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Sample records for high-purity factor ix

  1. Inactivation and clearance of viruses during the manufacture of high purity factor IX.

    PubMed

    Johnston, A; Macgregor, A; Borovec, S; Hattarki, M; Stuckly, K; Anderson, D; Goss, N H; Oates, A; Uren, E

    2000-09-01

    Haemophilia is a bleeding disorder characterised by a deficiency in Factor IX. Replacement therapy in the form of a Factor IX concentrate is a widely accepted practice. In this paper we describe a double virus inactivated chromatographic process for producing a high purity Factor IX product, MonoFIX((R))-VF. The process involves separation of the prothrombin complex by cryoprecipitation, fraction I precipitation and DEAE-cellulose adsorption, further ion-exchange chromatography of crude Factor IX, followed by solvent/detergent treatment. Heparin affinity chromatography is then used to further purify Factor IX. Final nanofiltration is sequential through 35 nm then 15 nm membrane filters. The principal virus inactivation/removal steps are solvent/detergent treatment and nanofiltration and the partitioning of relevant and model viruses provides further reduction in virus load through the production process.Solvent/detergent treatment was shown to achieve log reduction factors of 4.5 for HIV-1, 5.1 for Sindbis virus, 6.1 for vesicular stomatitis virus (VSV), 5.1 for bovine viral diarrhoea virus (BVDV) and 5.3 for pseudorabies virus (PRV). BVDV is a model for hepatitis C virus (HCV), and pseudorabies virus (PRV), like hepatitis B virus (HBV) is an enveloped DNA virus. Using scaled down models of the production process, we have also demonstrated the neutralization/partitioning of at least 6 logs of hepatitis A virus (HAV) during cryoprecipitation, Fraction I precipitation, and the DEAE adsorption and elution step, and a further 1.6 log reduction in HAV load as a result of heparin affinity chromatography. The log reduction factors for HAV as a result of the second ion-exchange chromatography step and as a result of enhanced neutralisation associated with solvent/detergent treatment were not significant. Nanofiltration was shown to contribute a further log reduction factor of 6.7 for HAV and 5.8 for BVDV indicating that log reduction factors of this order would be obtained

  2. Polymorphism of normal factor IX detected by mouse monoclonal antibodies.

    PubMed Central

    Wallmark, A; Ljung, R; Nilsson, I M; Holmberg, L; Hedner, U; Lindvall, M; Sjögren, H O

    1985-01-01

    Hemophilia B is an X-chromosomal recessive disease due to deficiency of coagulation factor IX. Three monoclonal antibodies against factor IX were prepared and used to develop immunoradiometric assays (IRMAs) of factor IX antigen (IX-Ag). IX-Ag was measured in 65 normal individuals with one IRMA based on polyclonal anti-IX antibodies and two IRMAs based on three monoclonal anti-IX antibodies. One of the monoclonal antibodies differed in specificity since it neutralized less than 50% of the clotting activity of factor IX (IX-C), whereas the other two monoclonal antibodies neutralized 80-95%. When the former antibody was used as the solid phase in IRMA, two groups of normal individuals were distinguished: group A with measurable IX-Ag, and group B without demonstrable IX-Ag. There were no differences between the groups either in IX-C or in IX-Ag measured with polyclonal antibodies. A subgroup comprising only women could be distinguished in group A, in whom intermediate IX-Ag concentrations were found. Family studies showed the group B variant of normal factor IX to be transmitted according to the pattern of X-linked recessive inheritance. The allelic frequency of group A was 0.66, and that of group B was 0.34. PMID:3873655

  3. High purity tungsten targets

    NASA Technical Reports Server (NTRS)

    1975-01-01

    High purity tungsten, which is used for targets in X-ray tubes was considered for space processing. The demand for X-ray tubes was calculated using the growth rates for dental and medical X-ray machines. It is concluded that the cost benefits are uncertain.

  4. Identification of the endothelial cell binding site for factor IX.

    PubMed Central

    Cheung, W F; van den Born, J; Kühn, K; Kjellén, L; Hudson, B G; Stafford, D W

    1996-01-01

    We previously demonstrated that the primary region of factor IX and IXa responsible for saturable specific binding to bovine aortic endothelial cells resides in residues 3-11 at the amino terminus of factor IX. We also demonstrated that mutations of lysine to alanine at residue 5, factor IX K5A, or valine to lysine at residue 10, factor IX V10K, resulted in a molecule unable to bind to endothelial cells. Moreover, a mutation with lysine to arginine at residue 5, factor IX K5R, resulted in a factor IX molecule with increased affinity for the endothelial cell binding site. In this paper we report that collagen IV is a strong candidate for the factor IX binding site on endothelial cells. Factor IX and factor IX K5R compete with 125I-labeled factor IX for binding to tetrameric collagen IV immobilized on microtiter plates, while factor X, factor VII, and factor IX K5A or V10K fail to compete. The Kd for wild-type factor IX binding to collagen IV in the presence of heparin was 6.8 +/- 2 nM, and the Kd for factor IX K5R was 1.1 +/- 0.2 nM, which agrees well with our previously published Kd values of 7.4 and 2.4 nM for binding of the same proteins to endothelial cells. Our working assumption is that we have identified the endothelial cell binding site and that it is collagen IV. Its physiological relevance remains to be determined. PMID:8855310

  5. Nb-3{sub Sn} layers on high-purity Nb cavities with very high quality factors and accelerating gradients

    SciTech Connect

    G. Muller; Peter Kneisel; D. Mansen; H. Piel; J. Pouryamout; R.W. Roth

    1996-06-01

    We have optimized the vapor diffusion technique to coat high-purity Nb cavities up to RRR=1000 with a micronthick Nb3Sn layer without loss of the thermal stabilization of defects. Systematic measurements on samples have shown no change of RRR of the bulk Nb and homogeneously nucleated growth of the Nb3Sn layers. Rinsing of such layers just with high pressure water resulted in low field emission activity and residual surface resistance values in the nW range, i.e. comparable to the best Nb surfaces. Single-cell 1.5 GHz cavities provided Q0 values up to 1011 at 2 K and above 1010 at 4.2 K, which stayed nearly constant up to peak electric surface fields of 10 MV/m but decreased to about 109 at 20 MV/m. No field emission and no quench could be observed in these cavities up to the maximum achievable accelerating gradients of about 15 MV/m at 2 K as limited by the available rf power. The performance of the Nb3Sn cavities at 4.2 K exceeds the design value of the CEBAF Nb cavities at 2 K. First results on a five-cell cavity are promising.

  6. Cleavage and activation of human factor IX by serine proteases

    SciTech Connect

    Enfield, D.L.; Thompson, A.R.

    1984-10-01

    Human factor IX circulates as a single-chain glycoprotein. Upon activation in vitro, it is cleaved into disulfide-linked light and heavy chains and an activation peptide. After reduction of activated /sup 125/I-factor IX, the heavy and light chains are readily identified by gel electrophoresis. A direct, immunoradiometric assay for factor IXa was developed to assess activation of factor IX for proteases that cleaved it. The assay utilized radiolabeled antithrombin III with heparin to identify the active site and antibodies to distinguish factor IX. After cleavage of factor IX by factor XIa, factor VIIa-tissue thromboplastin complex, or the factor X-activating enzyme from Russell's viper venom, antithrombin III bound readily to factor IXa. Cleavage of /sup 125/I-factor IX by trypsin, chymotrypsin, and granulocyte elastase in the presence of calcium yielded major polypeptide fragments of the sizes of the factor XIa-generated light and heavy chains. When the immunoradiometric assay was used to assess trypsin-cleaved factor IX, the product bound antithrombin III, but not maximally. After digesting with insolubilized trypsin, clotting activity confirmed activation. In evaluating activation of factor IX, physical evidence of activation cleavages does not necessarily correlate with generation of an active site.

  7. Labeled factor IX kinetics in patients with hemophilia-B

    SciTech Connect

    Smith, K.J.; Thompson, A.R.

    1981-09-01

    Labeled factor IX was infused five time into four patients with hemophilia-B. Ten-minute plasma recovery average 35% (SD +/- 2) and the mean T 1/2 beta-phase elimination was 23 hr (+/- 5). No alteration in the postinfusion 125I-factor-IX could be detected by radioautography of plasma samples run on polyacrylamide gels or on crossed-immunoelectrophoresis. Label was excreted into the urine as free 125I-iodide. Kinetics were similar when the labeled preparation was infused alone or with a commercial concentrate containing unlabeled factor IX. Infusion of factor IX in man is best described by a two-compartment open pharmacokinetic model where factor IX is distributed in a space larger than the plasma volume.

  8. Production of high purity radiothallium

    DOEpatents

    Lebowitz, Elliot; Greene, Margaret W.

    1976-11-23

    The method of producing high purity thallium-201 for use as a myocardial scanning agent comprising the steps of irradiating a thallium target with protons to give the reaction .sup.203 Tl(p,3n) .sup.201.sub.Pb, separating in ion exchange columns the lead from the thallium isotopes, permitting the lead to decay, and then purifying the thallium solution and converting the thallium present to thallous form in which it can be used.

  9. Preparation of high purity phosphorus

    DOEpatents

    Rupp, Arthur F.; Woo, David V.

    1981-01-01

    High purity phosphorus and phosphorus compounds are prepared by first reacting H.sub.3 PO.sub.4 with a lead compound such as PbO to form Pb.sub.3 (PO.sub.4).sub.2. The Pb.sub.3 (PO.sub.4).sub.2 is reduced with H.sub.2 at a temperature sufficient to form gaseous phosphorus which can be recovered as a high purity phosphorus product. Phosphorus compounds can be easily prepared by reacting the phosphorus product with gaseous reactants. For example, the phosphorus product is reacted with gaseous Cl.sub.2 to form PCl.sub.5. PCl.sub.5 is reduced to PCl.sub.3 by contacting it in the gaseous phase with solid elemental phosphorus. POCl.sub.3 can be prepared by contacting PCl.sub.5 in the gaseous phase with solid P.sub.2 O.sub.5. The general process is particularly suitable for the preparation of radiophosphorus compounds.

  10. Challenges of the management of severe hemophilia A with inhibitors: two case reports emphasizing the potential interest of a high-purity human Factor VIII/von Willebrand factor concentrate and individually tailored prophylaxis guided by thrombin-generation test.

    PubMed

    Mathieu, Sophie; Crampe, Carine; Dargaud, Yesim; Lavigne-Lissalde, Géraldine; Escuriola-Ettingshausen, Carmen; Tardy, Brigitte; Meley, Roland; Thouvenin, Sandrine; Stephan, Jean L; Berger, Claire

    2015-12-01

    Severe hemophilia A is an X-linked bleeding disorder. Immune tolerance induction (ITI) is the best strategy of treatment when patients develop inhibitors. The objective is to illustrate the benefit of a high-purity human factor VIII/von Willebrand factor (VWF) concentrate (Octanate) in the management of ITI. We also wanted to raise the potential interest of laboratory assays such as thrombin-generation test (TGT) and epitope mapping. Two patients were treated during ITI, first with a recombinant FVIII and then with plasma-derived factor VIII without success, and, finally, with Octanate. Bypassing agents were used based on the results of TGT. Epitope mapping was performed during ITI therapy. These observations suggest the potential contribution of Octanate in the management of ITI in difficult cases. The use of bypassing agents can be necessary in prophylaxis or to treat bleedings, and may be guided by TGT results. Epitope mapping is used to describe the inhibitor. This article shows a decrease of the inhibitor directed against the C2 domain after initiation of Octanate. A high-purity human factor VIII/von Willebrand factor concentrate (Octanate) may be a valuable therapeutical option for ITI therapy. TGT and epitope mapping could be of help in the management of ITI. PMID:26517064

  11. New polymorphic variants of human blood clotting factor IX

    SciTech Connect

    Surin, V.L.; Luk`yanenko, A.V.; Tagiev, A.F.; Smirnova, O.V.; Plutalov, O.V.; Berlin, Yu.A.

    1995-04-01

    The polymorphism of Alu-repeats, which are located in the introns of the human factor IX gene (copies 1-3), was studied. To identify polymorphic variants, direct sequencing of PCR products that contained appropriate repeats was used. In each case, 20 unrelated X chromosomes were studied. A polymorphic Dra I site was found near the 3{prime}-end of Alu copy 3 within the region of the polyA tract. A PCR-based testing system with internal control of restriction hydrolysis was suggested. Testing 81 unrelated X chromosomes revealed that the frequency of the polymorphic Dra I site is 0.23. Taq I polymorphism, which was revealed in Alu copy 4 of factor IX gene in our previous work, was found to be closely linked to Dra I polymorphism. Studies in linkage between different types of polymorphisms of the factor IX gene revealed the presence of a rare polymorphism in intron a that was located within the same minisatellite region as the known polymorphic insertion 50 bp/Dde I. However, the size of the insertion in our case was 26 bp. Only one polymorphic variant was found among over 150 unrelated X chromosomes derived from humans from Moscow and its vicinity. 10 refs., 4 figs., 1 tab.

  12. Monoclonal antibodies to coagulation factor IX define a high-frequency polymorphism by immunoassays.

    PubMed Central

    Smith, K J

    1985-01-01

    Monoclonal antibodies have been used to demonstrate a polymorphism of human plasma coagulation factor IX antigen in double antibody solid-phase immunoradiometric assays. This polymorphism is detected in an assay where a monoclonal antibody (A-1) adsorbed to microtiter wells is used to bind factor IX from diluted plasma samples. Plasma samples with the factor IX polymorphism have less than 0.2 U/ml of apparent antigen when tested with the A-1 antibody, while assays with other monoclonal antibodies and assays with goat antisera to factor IX show normal amounts of factor IX antigen. Factor IX coagulant activity was normal in samples from donors with the polymorphism. The thin-layer polyacrylamide gel isoelectric focusing pattern of factor IX purified from a donor with the factor IX polymorphism (IXp) was identical to that obtained with factor IX prepared from a donor who did not have the polymorphism (IXn). Purified radiolabeled factor IX prepared from a donor with the polymorphism showed a Ka for the A-1 antibody that was threefold less than that measured for IXn. The gene frequency of IXp in male blood donors is 0.25. This polymorphism may be useful as a marker for the X chromosome in genetic studies on plasma samples. Further studies are necessary to determine the explanation for decreased reaction of IXp with the A-1 monoclonal antibody. Images Fig. 1 PMID:9556657

  13. High purity silica reflective heat shield development

    NASA Technical Reports Server (NTRS)

    Nachtscheim, P. R.; Blome, J. C.

    1976-01-01

    A hyperpure vitreous silica material is being developed for use as a reflective and ablative heat shield for planetary entry. Various purity grades and forms of raw materials were evaluated along with various processing methods. Slip casting of high purity grain was selected as the best processing method, resulting in a highly reflective material in the wavelength bands of interest (the visible and ultraviolet regions). The selected material was characterized with respect to optical, mechanical and physical properties using a limited number of specimens. The process has been scaled up to produce a one-half scale heat shield (18 in. dia.) (45.72 cm) for a Jupiter entry vehicle. This work is now being extended to improve the structural safety factor of the heat shield by making hyperpure silica material tougher through the addition of silica fibers.

  14. The endothelial cell binding determinant of human factor IX resides in the. gamma. -carboxyglutamic acid domain

    SciTech Connect

    Toomey, J.R.; Roberts, H.R.; Stafford, D.W. ); Smith, K.J. United Blood Services, Albuquerque, NM )

    1992-02-18

    The blood coagulation factor IX(a) binds specifically to a site on endothelial cells with a K{sub d} of 2.0-3.0 nM. A number of previous studies have attempted to define the region(s) of factor IX(a) that mediate this interaction. These studies suggested that there are two regions of factor IX(a), the {gamma}-carboxyglutamic acid (Gla) domain and the epidermal growth factor like (EGF-like) domains, that mediate high-affinity binding to endothelial cells. Recently, however, the participation of the EGF1 domain has been excluded from the interaction. This indicated that if there was an EGF component of factor IX contributing to the binding affinity, then it must be in the second EGF-like domain. In order to further evaluate this relationship, the authors performed competitive binding experiments between {sup 125}I plasma factor IX and a set of six chimeric proteins composed of portions of factor VII and factor IX. The data suggest that the high-affinity interaction between factor IX and the endothelial cell binding site is mediated by the factor IX Gla domain and that the factor IX EGF domains are not involved in binding specificity.

  15. Characterization of the clotting activities of structurally different forms of activated factor IX. Enzymatic properties of normal human factor IXa alpha, factor IXa beta, and activated factor IX Chapel Hill.

    PubMed Central

    Griffith, M J; Breitkreutz, L; Trapp, H; Briet, E; Noyes, C M; Lundblad, R L; Roberts, H R

    1985-01-01

    Two structurally different forms of activated human Factor IX (Factor IXa alpha and IXa beta) have been previously reported to have essentially identical clotting activity in vitro. Although it has been shown that activated Factor IX Chapel Hill, an abnormal Factor IX isolated from the plasma of a patient with mild hemophilia B, and normal Factor IXa alpha are structurally very similar, the clotting activity of activated Factor IX Chapel Hill is much lower (approximately fivefold) than that of normal Factor IXa beta. In the present study we have prepared activated Factor IX by incubating human Factor IX with calcium and Russell's viper venom covalently bound to agarose. Fractionation of the activated Factor IX by high-performance liquid chromatography demonstrated the presence of both Factors IXa alpha and IXa beta. On the basis of active site concentration, determined by titration with antithrombin III, the clotting activities of activated Factor IX Chapel Hill and IXa alpha were similar, but both activities were less than 20% of the clotting activity of Factor IXa beta. Activated Factor IX activity was also measured in the absence of calcium, phospholipid, and Factor VIII, by determination of the rate of Factor X activation in the presence of polylysine. In the presence of polylysine, the rates of Factor X activation by activated Factor IX Chapel Hill, Factor IXa alpha, and Factor IXa beta were essentially identical. We conclude that the clotting activity of activated Factor IX Chapel Hill is reduced when compared with that of Factor IXa beta but essentially normal when compared with that of Factor IXa alpha. PMID:3871202

  16. APPARATUS FOR HIGH PURITY METAL RECOVERY

    DOEpatents

    Magel, T.T.

    1959-02-10

    An apparatus is described for preparing high purity metal such as uranium, plutonium and the like from an impure mass of the same metal. The apparatus is arranged so that the impure metal is heated and swept by a stream of hydrogen gas bearing a halogen such as iodine. The volatiie metal halide formed is carried on to a hot filament where the metal halide is decomposed and the molten high purity metal is collected in a rceeiver below

  17. Evidence for a prevalent dimorphism in the activation peptide of human coagulation factor IX.

    PubMed Central

    McGraw, R A; Davis, L M; Noyes, C M; Lundblad, R L; Roberts, H R; Graham, J B; Stafford, D W

    1985-01-01

    We have independently isolated and characterized cDNA and genomic clones for the human coagulation factor IX. Sequence analysis in both cases indicates that threonine is encoded by the triplet ACT as the third residue of the activation peptide. This is in agreement with some earlier reports but in disagreement with others that show the alanine triplet GCT at this position. The discrepancy can thus be accounted for by natural variation of a single nucleotide in the normal population. Amino acid sequence analyses of activated factor IX from plasma samples of four individuals yielded two cases of alanine and two cases of threonine at the third position of the activation peptide. In factor IX from pooled plasma and in factor IX from a heterozygous individual, however, both alanine and threonine were found. Taken together, the findings show that a prevalent nondeleterious dimorphism exists in the activation peptide of human coagulation factor IX. PMID:3857619

  18. High purity silane and silicon production

    NASA Technical Reports Server (NTRS)

    Breneman, William C. (Inventor)

    1987-01-01

    Silicon tetrachloride, hydrogen and metallurgical silicon are reacted at about 400.degree.-600.degree. C. and at pressures in excess of 100 psi, and specifically from about 300 up to about 600 psi to form di- and trichlorosilane that is subjected to disproportionation in the presence of an anion exchange resin to form high purity silane. By-product and unreacted materials are recycled, with metallurgical silicon and hydrogen being essentially the only consumed feed materials. The silane product may be further purified, as by means of activated carbon or cryogenic distillation, and decomposed in a fluid bed or free space reactor to form high purity polycrystalline silicon and by-product hydrogen which can be recycled for further use. The process results in simplified waste disposal operations and enhances the overall conversion of metallurgical grade silicon to silane and high purity silicon for solar cell and semiconductor silicon applications.

  19. Transforming the treatment for hemophilia B patients: update on the clinical development of recombinant fusion protein linking recombinant coagulation factor IX with recombinant albumin (rIX-FP).

    PubMed

    Santagostino, Elena

    2016-05-01

    Recombinant fusion protein linking recombinant coagulation factor IX with recombinant albumin (rIX-FP; Idelvion®(†)) is an innovative new treatment designed to extend the half-life of factor IX (FIX) and ease the burden of care for hemophilia B patients. The rIX-FP clinical development program - PROLONG-9FP - is in its advanced phases, with pivotal studies in previously treated adults, adolescents, and pediatrics now completed. Across all age groups studied, rIX-FP has demonstrated a markedly improved pharmacokinetic profile compared with plasma-derived and recombinant FIX treatments, with a 30-40% higher incremental recovery, an approximately 5-fold longer half-life, a lower clearance, and a greater area under the curve. rIX-FP has been very well tolerated with an excellent safety profile. In the pivotal studies, there have been no reports of FIX inhibitors or antidrug antibodies, and few treatment-related adverse events have been observed. Prophylactic regimens of rIX-FP administered once weekly to once every 14 days have been highly effective. When used for surgical prophylaxis, a single infusion of rIX-FP has been sufficient to maintain hemostasis, even during major orthopedic surgery. An ongoing study is now enrolling previously untreated patients and evaluating the possibility of extending the dosing interval to every 21 days. There is little doubt that rIX-FP will transform the treatment of hemophilia B. PMID:27288064

  20. Recombinant Human Factor IX Produced from Transgenic Porcine Milk

    PubMed Central

    Lee, Meng-Hwan; Lin, Yin-Shen; Tu, Ching-Fu; Yen, Chon-Ho

    2014-01-01

    Production of biopharmaceuticals from transgenic animal milk is a cost-effective method for highly complex proteins that cannot be efficiently produced using conventional systems such as microorganisms or animal cells. Yields of recombinant human factor IX (rhFIX) produced from transgenic porcine milk under the control of the bovine α-lactalbumin promoter reached 0.25 mg/mL. The rhFIX protein was purified from transgenic porcine milk using a three-column purification scheme after a precipitation step to remove casein. The purified protein had high specific activity and a low ratio of the active form (FIXa). The purified rhFIX had 11.9 γ-carboxyglutamic acid (Gla) residues/mol protein, which approached full occupancy of the 12 potential sites in the Gla domain. The rhFIX was shown to have a higher isoelectric point and lower sialic acid content than plasma-derived FIX (pdFIX). The rhFIX had the same N-glycosylation sites and phosphorylation sites as pdFIX, but had a higher specific activity. These results suggest that rhFIX produced from porcine milk is physiologically active and they support the use of transgenic animals as bioreactors for industrial scale production in milk. PMID:24955355

  1. A study of reported factor IX use around the world.

    PubMed

    Stonebraker, J S; Bolton-Maggs, P H B; Brooker, M; Farrugia, A; Srivastava, A

    2011-05-01

    Replacement therapy has significantly improved the life expectancy and lifestyle of people with haemophilia. The objectives of this article were to study the reported factor IX (FIX) use on a country-by-country basis and address the following question: Does the reported FIX use vary by national economies? We obtained data on the reported number of international units (IUs) of FIX used for 90 countries from the Marketing Research Bureau and the World Federation of Hemophilia. Results show that the reported FIX use varies considerably across national economies, even among the wealthiest of countries.Trends suggest that the reported FIX usage increases with increasing economic capacity and has been increasing over time. Trends also suggest that consumption of FIX has been increasing at a greater rate in high income countries. Given these trends, there will likely be an overall increase in the amount of FIX concentrates used in the treatment of haemophilia B. We also found that FIX use both in terms of IUs per capita and IUs per person provide a complete picture of the level of haemophilia care within a country. Such information is critical for planning efforts of national healthcare agencies to determine realistic budget priorities and pharmaceutical manufacturers to determine adequate production levels of FIX concentrates. By improving the data collection and surveillance of FIX use for the treatment of people with haemophilia B, we can identify trends and needs of patients and highlight best treatment practices among countries. PMID:21299742

  2. High purity silica reflecting heat shield development

    NASA Technical Reports Server (NTRS)

    Congdon, W.

    1974-01-01

    A reflecting heat shield composed of fused silica in which the scattering results from the refractive index mismatch between silica particles and the voids introduced during the fabrication process is developed. Major considerations and conclusions of the development are: the best material to use is Type A, which is capable of ultra-high-purity and which does not show the 0.243 micrometer absorption band; the reflection efficiency of fused silica is decreased at higher temperatures due to the bathochromic shift of the ultraviolet cut-off; for a given silica material, over the wavelength region and particle sizes tested, the monodisperse particle size configurations produce higher reflectances than continuous particle size configurations; and the smaller monodisperse particle size configurations give higher reflectance than the larger ones. A reflecting silica configuration that is an efficient reflector of shock layer radiation at high ablation temperatures is achieved by tailoring the matrix for optimum scattering and using an ultra-high-purity material.

  3. Derivation of high-purity oligodendroglial progenitors.

    PubMed

    Hatch, Maya N; Nistor, Gabriel; Keirstead, Hans S

    2009-01-01

    Oligodendrocytes are a type of glial cells that play a critical role in supporting the central nervous system (CNS), in particular insulating axons within the CNS by wrapping them with a myelin sheath, thereby enabling saltatory conduction. They are lost, and myelin damaged - demyelination - in a wide variety of neurological disorders. Replacing depleted cell types within demyelinated areas, however, has been shown experimentally to achieve remyelination and so help restore function. One method to produce oligodendrocytes for cellular replacement therapies is through the use of progenitor or stem cells. The ability to differentiate progenitor or stem cells into high-purity fates not only permits the generation of specific cells for transplantation therapies, but also provides powerful tools for studying cellular mechanisms of development. This chapter outlines methods of generating high-purity OPCs from multipotent neonatal progenitor or human embryonic stem cells. PMID:19378196

  4. Method of high purity silane preparation

    DOEpatents

    Tsuo, Y. Simon; Belov, Eugene P.; Gerlivanov, Vadim G.; Zadde, Vitali V.; Kleschevnikova, Solomonida I.; Korneev, Nikolai N.; Lebedev, Eugene N.; Pinov, Akhsarbek B.; Ryabenko, Eugene A.; Strebkov, Dmitry S.; Chernyshev, Eugene A.

    2000-01-01

    A process for the preparation of high purity silane, suitable for forming thin layer silicon structures in various semiconductor devices and high purity poly- and single crystal silicon for a variety of applications, is provided. Synthesis of high-purity silane starts with a temperature assisted reaction of metallurgical silicon with alcohol in the presence of a catalyst. Alcoxysilanes formed in the silicon-alcohol reaction are separated from other products and purified. Simultaneous reduction and oxidation of alcoxysilanes produces gaseous silane and liquid secondary products, including, active part of a catalyst, tetra-alcoxysilanes, and impurity compounds having silicon-hydrogen bonds. Silane is purified by an impurity adsorption technique. Unreacted alcohol is extracted and returned to the reaction with silicon. Concentrated mixture of alcoxysilanes undergoes simultaneous oxidation and reduction in the presence of a catalyst at the temperature -20.degree. C. to +40.degree. C. during 1 to 50 hours. Tetra-alcoxysilane extracted from liquid products of simultaneous oxidation and reduction reaction is directed to a complete hydrolysis. Complete hydrolysis of tetra-alcoxysilane results in formation of industrial silica sol and alcohol. Alcohol is dehydrated by tetra-alcoxysilane and returned to the reaction with silicon.

  5. Factor VIII/factor IX prophylaxis for severe hemophilia.

    PubMed

    Carcao, Manuel; Srivastava, Alok

    2016-01-01

    Experience with clotting factor concentrate (CFC) replacement products over several decades has shown that regular replacement (prophylaxis) is the only way to prevent musculoskeletal damage in hemophilia and impact the natural history of hemophilia. Yet there is a lack of data on the optimal age to start such replacement therapy and the regimens to be used. While very early administration of high doses is certainly more effective in preventing bleeding, cost and compliance are major constraints all over the world. Starting prophylaxis with even lower doses comparable to that used in episodic therapies leads to major reduction in bleeding. Recognition of the clinical heterogeneity of hemophilia even among patients with a label of severe hemophilia in terms of their spontaneous bleeding has led to efforts aimed at individualizing CFC replacement, based on clinical responses or pharmacokinetic data of the CFC. The importance of long-term outcome assessment being combined with CFC replacement therapy cannot be overemphasized. PMID:26805901

  6. Method for preparing high purity vanadium

    DOEpatents

    Schmidt, Frederick; Carlson, O. Norman

    1986-09-09

    A method for preparing high purity vanadium having a low silicon content has been developed. Vanadium pentoxide is reduced with a stoichiometric, or slightly deficient amount of aluminum to produce a vanadium-aluminum alloy containing an excess of oxygen. Silicon is removed by electron-beam melting the alloy under oxidizing conditions to promote the formation of SiO which is volatile at elevated temperatures. Excess oxygen is removed by heating the alloy in the presence of calcium metal to form calcium oxide.

  7. High-purity thermoacoustic isotope enrichment.

    PubMed

    Swift, G W; Geller, D A; Backhaus, S N

    2014-08-01

    In a tube many wavelengths long, thermoacoustic separation of a gas mixture can produce very high purities. A flexible wall allows a spatially continuous supply of acoustic power into such a long tube. Coiling the tube and immersing it in a fluid lets a single-wavelength, circulating, traveling pressure wave in the fluid drive all the wavelengths in the tube wall and gas. Preliminary measurements confirm many aspects of the concept with neon ((20)Ne and (22)Ne) and highlight some challenges of practical implementation. PMID:25096099

  8. Method for preparing high purity vanadium

    DOEpatents

    Schmidt, F.; Carlson, O.N.

    1984-05-16

    A method for preparing high purity vanadium having a low silicon content has been developed. Vanadium pentoxide is reduced with a stoichiometric, or slightly deficient amount of aluminum to produce a vanadium-aluminum alloy containing an excess of oxygen. Silicon is removed by electron-beam melting the alloy under oxidizing conditions to promote the formation of SiO which is volatile at elevated temperatures. Excess oxygen is removed by heating the alloy in the presence of calcium metal to form calcium oxide.

  9. The Conundrum of "Warfarin Hypersensitivity": Prolonged Partial Thromboplastin Time From Factor IX Propeptide Mutation.

    PubMed

    Sekhri, Arunabh; Lisinschi, Adriana; Furqan, Muhammad; Palaniswamy, Chandrasekar; Mukhi, Nikhil; Gupta, Ridhi; Nelson, John C

    2016-01-01

    Carboxylation of glutamic acid residues of vitamin K dependent clotting factors (II, VII, IX, and X) is essential to their biological functioning. Binding of these factors to γ-glutamyl carboxylase enzyme for carboxylation reaction is mediated by wild-type propeptide, a small sequence of amino acids that precede the actual polypeptide. Missense mutations at certain residue severely decrease the affinity of mutated propeptide for the enzyme. Such mutations are reported to occur at codon-10 of factor IX propeptide, a clinically silent metabolic event in normal conditions. However in the presence of warfarin, such mutations and resultant decrease affinity of factor IX propeptide for the enzyme that causes severe selective decrease in factor IX activity. This can potentially leads to life-threatening bleeding complications and known as one of the causes of warfarin hypersensitivity. It is imperative to recognize such cases early on to avoid additional warfarin therapy. Recurrent bleeding episodes, subtherapeutic to therapeutic range international normalized ratio values with relatively prolong partial thromboplastin time should raise the suspicion of underlying factor IX propeptide mutations. PMID:24832385

  10. Concurrent acquired inhibitors to factor VIII and IX, a laboratory artifact: a case report

    PubMed Central

    Doma, Saša Anžej; Hillarp, Andreas; Pajič, Tadej; Andoljšek, Dušan; Černelč, Peter; Preldžnik Zupan, Irena

    2016-01-01

    Acquired inhibitors to coagulation factors other than factor VIII are extremely rare. We describe a case of a 59-year-old woman with abnormal bleeding, diagnosed with concurrent inhibitor antibodies to factor VIII and IX by Bethesda testing. We demonstrate that anti-FVIII antibodies of a very high titre are capable of disturbing the aPTT-based Bethesda assay, resulting in falsely-positive antibodies to factor IX. The case also illustrates the usefulness of the immunological assay (ELISA) in complementing the inhibitor diagnosis. PMID:27346976

  11. Workshop on Preserving High Purity Uranium-233

    SciTech Connect

    Krichinsky, Alan M; Giaquinto, Joseph; Canaan, R Douglas {Doug}

    2016-01-01

    A workshop was held on at the MARC X conference to provide a forum for the scientific community to communicate needs for high-purity 233U and its by-products in order to preserve critical items otherwise slated for downblending and disposal. Currently, only a small portion of the U.S. holdings of separated 233U is being preserved. However, many additional kilograms of 233U (>97% pure) still are destined to be downblended which will permanently destroy their potential value for many other applications. It is not likely that this material will ever be replaced due to a lack of operating production capability. Summaries of information conveyed at the workshop and feedback obtained from the scientific community are presented herein.

  12. Processing to obtain high-purity gallium

    NASA Astrophysics Data System (ADS)

    Bautista, Renato G.

    2003-03-01

    Gallium has become increasingly popular as a substrate material for electronic devices. Aside from ore, gallium can be obtained from such industrial sources as the Bayer process caustic liquor that is a byproduct of bauxite processing, flue dust removed from the fume-collection system in plants that produce aluminum by the electrolytic process, zinc refinery residues, gallium scrap materials, and coal fly ash. The purification process for gallium can start with solvent-extraction processes where the concentrations of impurities, especially metals, are reduced to the ppm range. This article describes how ultra-purification techniques can be employed to reduce the undesirable impurities to the low ppb range. The various procedures described give an idea as to the extent of work needed to obtain and prepare high-purity gallium for electronic application.

  13. Manic depressive illness not linked to factor IX region in an independent series of pedigrees.

    PubMed

    Gejman, P V; Detera-Wadleigh, S; Martinez, M M; Berrettini, W H; Goldin, L R; Gelernter, J; Hsieh, W T; Gershon, E S

    1990-12-01

    We studied seven informative kindreds segregating for manic depressive illness (MDI), consistent with X-chromosome transmission of the trait (families do not show affective disease in both a father and a son), using markers mapped to the region of Xq27-Xq28. The lod scores were consistently below -2 in the region extending from about 10 cM centromeric from the Factor IX locus (F9) to the colorblindness region. This study does not replicate previous reports of linkage of MDI to Factor IX (Xq27) and colorblindness region (Xq28) chromosomal markers in other kindreds. PMID:1980485

  14. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial.

    PubMed

    Santagostino, Elena; Martinowitz, Uri; Lissitchkov, Toshko; Pan-Petesch, Brigitte; Hanabusa, Hideji; Oldenburg, Johannes; Boggio, Lisa; Negrier, Claude; Pabinger, Ingrid; von Depka Prondzinski, Mario; Altisent, Carmen; Castaman, Giancarlo; Yamamoto, Koji; Álvarez-Roman, Maria-Teresa; Voigt, Christine; Blackman, Nicole; Jacobs, Iris

    2016-04-01

    A global phase 3 study evaluated the pharmacokinetics, efficacy, and safety of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 63 previously treated male patients (12-61 years) with severe hemophilia B (factor IX [FIX] activity ≤2%). The study included 2 groups: group 1 patients received routine prophylaxis once every 7 days for 26 weeks, followed by either 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively; group 2 patients received on-demand treatment of bleeding episodes for 26 weeks and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. The mean terminal half-life of rIX-FP was 102 hours, 4.3-fold longer than previous FIX treatment. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg weekly and 75 IU/kg every 2 weeks, respectively. There was 100% reduction in median annualized spontaneous bleeding rate (AsBR) and 100% resolution of target joints when subjects switched from on-demand to prophylaxis treatment with rIX-FP (P< .0001). The median AsBR was 0.00 for all prophylaxis regimens. Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection. No patient developed an inhibitor, and no safety concerns were identified. These results indicate rIX-FP is safe and effective for preventing and treating bleeding episodes in patients with hemophilia B at dosing regimens of 40 IU/kg weekly and 75 IU/kg every 2 weeks. This trial was registered atwww.clinicaltrials.govas #NCT0101496274. PMID:26755710

  15. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial

    PubMed Central

    Martinowitz, Uri; Lissitchkov, Toshko; Pan-Petesch, Brigitte; Hanabusa, Hideji; Oldenburg, Johannes; Boggio, Lisa; Negrier, Claude; Pabinger, Ingrid; von Depka Prondzinski, Mario; Altisent, Carmen; Castaman, Giancarlo; Yamamoto, Koji; Álvarez-Roman, Maria-Teresa; Voigt, Christine; Blackman, Nicole; Jacobs, Iris

    2016-01-01

    A global phase 3 study evaluated the pharmacokinetics, efficacy, and safety of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 63 previously treated male patients (12-61 years) with severe hemophilia B (factor IX [FIX] activity ≤2%). The study included 2 groups: group 1 patients received routine prophylaxis once every 7 days for 26 weeks, followed by either 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively; group 2 patients received on-demand treatment of bleeding episodes for 26 weeks and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. The mean terminal half-life of rIX-FP was 102 hours, 4.3-fold longer than previous FIX treatment. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg weekly and 75 IU/kg every 2 weeks, respectively. There was 100% reduction in median annualized spontaneous bleeding rate (AsBR) and 100% resolution of target joints when subjects switched from on-demand to prophylaxis treatment with rIX-FP (P < .0001). The median AsBR was 0.00 for all prophylaxis regimens. Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection. No patient developed an inhibitor, and no safety concerns were identified. These results indicate rIX-FP is safe and effective for preventing and treating bleeding episodes in patients with hemophilia B at dosing regimens of 40 IU/kg weekly and 75 IU/kg every 2 weeks. This trial was registered at www.clinicaltrials.gov as #NCT0101496274. PMID:26755710

  16. Somatic mosaicism and female-to-female transmission in a kindred with hemophilia B (factor IX deficiency)

    SciTech Connect

    Taylor, S.A.M.; Deugau, K.V.; Lillicrap, D.P. )

    1991-01-01

    Studies have shown that hemophilia B (Christmas disease; factor IX deficiency) results from many different mutations in the factor IX gene, of which {gt}95% are single nulceotide substitutions. This study has identified a previously unreported form of hemophilia B in a patient who was a somatic mosaic for a guanine-to-cytosine transversion at nucleotide 31,170 in the factor IX gene. This point mutation changes the codon for residue 350 in the catalytic domain of factor IX from a cysteine to a serine. The authors used differential termination of primer extension to confirm and measure the degree of mosaicism. The study shows that a varying proportion of cells from hepatic, renal, smooth muscle, and hematopoietic populations possessed normal as well as mutant factor IX sequences. These results indicate that the mutation in this patient occurred either as an uncorrected half-chromatid mutation in the female gamete or as a replication or postreplication error in the initial mitotic divisions of the zygote preceding implantation. In addition, this kindred also contains two females in successive generations who have moderately severe factor IX deficiency. The molecular pathogenesis of this latter phenomenon has been studied and seems to relate to the unaccompanied expression of the mutant factor IX gene consequent upon a second, as yet undefined, genetic event that has prevented inactivation of sequences including the mutant factor IX gene on the X chromosome inherited from the affected male.

  17. Improved Induction of Immune Tolerance to Factor IX by Hepatic AAV-8 Gene Transfer

    PubMed Central

    Cooper, Mario; Nayak, Sushrusha; Hoffman, Brad E.; Terhorst, Cox; Cao, Ou

    2009-01-01

    Abstract Gene therapy for hemophilia B has been shown to result in long-term expression and immune tolerance to factor IX (F.IX) after in vivo transduction of hepatocytes with adeno-associated viral (AAV-2) vectors in experimental animals. An optimized protocol was effective in several strains of mice with a factor 9 gene deletion (F9−/−). However, immune responses against F.IX were repeatedly observed in C3H/HeJ F9−/− mice. We sought to establish a gene transfer protocol that results in sustained expression without a requirement for additional manipulation of the immune system. Compared with AAV-2, AAV-8 was more efficient in transgene expression and induction of tolerance to F.IX in three different strains of wild-type mice. At equal vector doses, AAV-8 induced transgene product-specific regulatory CD4+CD25+FoxP3+ T cells at significantly higher frequency. Moreover, sustained correction of hemophilia B in C3H/HeJ F9−/− mice without antibody formation was documented in all animals treated with ≥4 × 1011 vector genomes (VG)/kg and in 80% of mice treated with 8 × 1010 VG/kg. Therefore, it is possible to develop a gene transfer protocol that reliably induces tolerance to F.IX largely independent of genetic factors. A comparison with other studies suggests that additional parameters besides plateau levels of F.IX expression contributed to the improved success rate of tolerance induction. PMID:19309290

  18. Dynamic shear deformation in high purity Fe

    SciTech Connect

    Cerreta, Ellen K; Bingert, John F; Trujillo, Carl P; Lopez, Mike F; Gray, George T

    2009-01-01

    The forced shear test specimen, first developed by Meyer et al. [Meyer L. et al., Critical Adiabatic Shear Strength of Low Alloyed Steel Under Compressive Loading, Metallurgical Applications of Shock Wave and High Strain Rate Phenomena (Marcel Decker, 1986), 657; Hartmann K. et al., Metallurgical Effects on Impact Loaded Materials, Shock Waves and High Strain rate Phenomena in Metals (Plenum, 1981), 325-337.], has been utilized in a number of studies. While the geometry of this specimen does not allow for the microstructure to exactly define the location of shear band formation and the overall mechanical response of a specimen is highly sensitive to the geometry utilized, the forced shear specimen is useful for characterizing the influence of parameters such as strain rate, temperature, strain, and load on the microstructural evolution within a shear band. Additionally, many studies have utilized this geometry to advance the understanding of shear band development. In this study, by varying the geometry, specifically the ratio of the inner hole to the outer hat diameter, the dynamic shear localization response of high purity Fe was examined. Post mortem characterization was performed to quantify the width of the localizations and examine the microstructural and textural evolution of shear deformation in a bcc metal. Increased instability in mechanical response is strongly linked with development of enhanced intergranular misorientations, high angle boundaries, and classical shear textures characterized through orientation distribution functions.

  19. High-purity silicon crystal growth investigations

    NASA Technical Reports Server (NTRS)

    Ciszek, T. F.; Schuyler, T.; Hurd, J. L.; Fearheiley, M.; Evans, C.; Elder, R.

    1986-01-01

    Information is given on evaporation and segregation contributions to impurity profiles of floating zone crystals (FZ); high-purity silicon float zoning (FZ); minority-carrier lifetime measurement of heavily doped silicon crystals; the effect of some crystal growth parameters on minority-carrier lifetime; and defect investigations by X-ray topography in graphical and tabular form. It was concluded that evaporation contributes substantially to impurity reduction when FZ or cold-crucible growth is conducted in a vacuum; boron and gallium may be more favorable dopants than indium or aluminum for obtaining high minority-carrier lifetimes; minority-carrier lifetimes greater than 100 microseconds are feasible at a 2 times 10 to the 17th power cm-3 doping level; minority-carrier lifetime decreases with increasing crystal cooling rate and also with the presence of dislocations; the method used to clean silicon feed rods affects lifetime; and microdefect densities in dislocation-free FZ crystals appear to be lower with Ga doping than with B doping.

  20. Biaxial deformation in high purity aluminum

    DOE PAGESBeta

    Livescu, V.; Bingert, J. F.; Liu, C.; Lovato, M. L.; Patterson, B. M.

    2015-09-25

    The convergence of multiple characterization tools has been applied to investigate the relationship of microstructure on damage evolution in high purity aluminum. The extremely coarse grain size of the disc-shaped sample provided a quasi-two dimensional structure from which the location of surface-measured features could be inferred. In particular, the role of pre-existing defects on damage growth was accessible due to the presence of casting porosity in the aluminum. Micro tomography, electron backscatter diffraction, and digital image correlation were applied to interrogate the sample in three dimensions. Recently micro-bulge testing apparatus was used to deform the pre-characterized disc of aluminum inmore » biaxial tension, and related analysis techniques were applied to map local strain fields. Subsequent post-mortem characterization of the failed sample was performed to correlate structure to damaged regions. We determined that strain localization and associated damage was most strongly correlated with grain boundary intersections and plastic anisotropy gradients between grains. Pre-existing voids played less of an apparent role than was perhaps initially expected. Finally, these combined techniques provide insight to the mechanism of damage initiation, propagation, and failure, along with a test bed for predictive damage models incorporating anisotropic microstructural effects.« less

  1. Biaxial deformation in high purity aluminum

    SciTech Connect

    Livescu, V.; Bingert, J. F.; Liu, C.; Lovato, M. L.; Patterson, B. M.

    2015-09-25

    The convergence of multiple characterization tools has been applied to investigate the relationship of microstructure on damage evolution in high purity aluminum. The extremely coarse grain size of the disc-shaped sample provided a quasi-two dimensional structure from which the location of surface-measured features could be inferred. In particular, the role of pre-existing defects on damage growth was accessible due to the presence of casting porosity in the aluminum. Micro tomography, electron backscatter diffraction, and digital image correlation were applied to interrogate the sample in three dimensions. Recently micro-bulge testing apparatus was used to deform the pre-characterized disc of aluminum in biaxial tension, and related analysis techniques were applied to map local strain fields. Subsequent post-mortem characterization of the failed sample was performed to correlate structure to damaged regions. We determined that strain localization and associated damage was most strongly correlated with grain boundary intersections and plastic anisotropy gradients between grains. Pre-existing voids played less of an apparent role than was perhaps initially expected. Finally, these combined techniques provide insight to the mechanism of damage initiation, propagation, and failure, along with a test bed for predictive damage models incorporating anisotropic microstructural effects.

  2. High-purity germanium crystal growing

    SciTech Connect

    Hansen, W.L.; Haller, E.E.

    1982-10-01

    The germanium crystals used for the fabrication of nuclear radiation detectors are required to have a purity and crystalline perfection which is unsurpassed by any other solid material. These crystals should not have a net electrically active impurity concentration greater than 10/sup 10/cm/sup -3/ and be essentially free of charge trapping defects. Such perfect crystals of germanium can be grown only because of the highly favorable chemical and physical properties of this element. However, ten years of laboratory scale and commercial experience has still not made the production of such crystals routine. The origin and control of many impurities and electrically active defect complexes is now fairly well understood but regular production is often interrupted for long periods due to the difficulty of achieving the required high purity or to charge trapping in detectors made from crystals seemingly grown under the required conditions. The compromises involved in the selection of zone refining and crystal grower parts and ambients is discussed and the difficulty in controlling the purity of key elements in the process is emphasized. The consequences of growing in a hydrogen ambient are discussed in detail and it is shown how complexes of neutral defects produce electrically active centers.

  3. Fixing human factor IX (fIX): correction of a cryptic RNA splice enables the production of biologically active fIX in the mammary gland of transgenic mice.

    PubMed Central

    Yull, F; Harold, G; Wallace, R; Cowper, A; Percy, J; Cottingham, I; Clark, A J

    1995-01-01

    Transgenic mice and sheep secrete only low levels of human factor IX in their milk because of an aberrant splicing of the transgene RNA in the mammary gland. Removal of the cryptic 3' splice site prevents this splicing and leads to the production of relatively high levels of factor IX. The purified protein is fully active showing that the mammary gland is capable of the efficient post-translational modification of this protein and that transgenic animals are a suitable means of its production. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7479906

  4. Nonacog gamma, a novel recombinant factor IX with low factor IXa content for treatment and prophylaxis of bleeding episodes.

    PubMed

    Turecek, Peter L; Abbühl, Brigitt; Tangada, Srilatha D; Chapman, Miranda; Gritsch, Herbert; Rottensteiner, Hanspeter; Schrenk, Gerald; Mitterer, Artur; Dietrich, Barbara; Höllriegl, Werner; Schiviz, Alexandra; Horling, Frank; Reipert, Birgit M; Muchitsch, Eva-Maria; Pavlova, Borislava G; Scheiflinger, Friedrich

    2015-03-01

    Nonacog gamma is a new recombinant factor IX to treat factor IX deficiency. It is indicated for control of bleeding episodes, perioperative management and routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children with hemophilia B. Nonacog gamma was first approved in the USA in June 2013 under the trade name RIXUBIS followed by market approvals in Australia and the EU in 2014, and marketing authorization decision is pending in Japan. Nonacog gamma is derived from a recombinant Chinese hamster ovary cell line using a state of the art biotechnological manufacturing process. Recombinant factor IX is produced by Baxter's protein-free fermentation technology, which was first developed for ADVATE. The product is purified and formulated in the absence of any human or animal-derived protein. Nonacog gamma was characterized both in comprehensive in vitro and in vivo non-clinical studies as well as in an extensive clinical trial program. PMID:25660348

  5. Expression of human factor IX in rat capillary endothelial cells: Toward somatic gene therapy for hemophilia B

    SciTech Connect

    Shounan Yao; Wilson, J.M.; Nabel, E.G.; Kurachi, Sumiko; Hachiya, H.L.; Kurachi, Kotoku )

    1991-09-15

    In aiming to develop a gene therapy approach for hemophilia B, the authors expressed and characterized human factor IX in rat capillary endothelial cells (CECs). Moloney murine leukemia virus-derived retrovirus vectors that contain human factor IX cDNA linked to heterologous promoters and the neomycin-resistant gene were constructed and employed to prepare recombinant retroviruses. Rat CECs and NIH 3T3 cells infected with these viruses were selected with the neomycin analogue, G418 sulfate, and tested for expression of factor IX. A construct with the factor IX cDNA under direct control by long terminal repeat gave the highest level of expression as quantitated by immunoassays as well as clotting activity assays. A single RNA transcript of 4.4 kilobases predicted by the construct and a recombinant factor IX were found. The recombinant human factor IX produced showed full clotting activity, demonstrating that CECs have an efficient mechanism for posttranslational modifications, including {gamma}-carboxylation, essential for its biological activity. These results, in addition to other properties of the endothelium, including large number of cells, accessibility, and direct contact with the circulating blood, suggest that CECs can serve as an efficient drug delivery vehicle producing factor IX in a somatic gene therapy for hemophilia B.

  6. Factor IX Amagasaki: A new mutation in the catalytic domain resulting in the loss of both coagulant and esterase activities

    SciTech Connect

    Miyata, Toshiyuki; Iwanaga, Sadaaki ); Sakai, Toshiyuki; Sugimoto, Mitsuhiko; Naka, Hiroyuki; Yamamoto, Kazukuni; Yoshioka, Akira; Fukui, Hiromu ); Mitsui, Kotoko; Kamiya, Kensyu; Umeyama, Hideaki )

    1991-11-26

    Factor IX Amagasaki (AMG) is a naturally occurring mutant of factor IX having essentially no coagulant activity, even though normal levels of antigen are detected in plasma. Factor IX AMG was purified from the patient's plasma by immunoaffinity chromatography with an anti-factor IX monoclonal antibody column. Factor IX AMG was cleaved normally by factor VIIa-tissue factor complex, yielding a two-chain factor IXa. Amino acid composition and sequence analysis of one of the tryptic peptides isolated from factor IX AMG revealed that Gly-311 had been replaced by Glu. The authors identified a one-base substitution of guanine to adenine in exon VIII by amplifying exon VIII using the polymerase chain reaction method and sequencing the product. This base mutation also supported the replacement of Gly-311 by Glu. In the purified system, factor IXa AMG did not activate for factor X in the presence of factor VIII, phospholipids, and Ca{sup 2+}, and no esterase activity toward Z-Arg-p-nitrobenzyl ester was observed. The model building of the serine protease domain of factor IXa suggests that the Gly-311 {yields} Glu exchange would disrupt the specific conformational state in the active site environment, resulting in the substrate binding site not forming properly. This is the first report to show the experimental evidence for importance of a highly conserved Gly-142 (chymotrypsinogen numbering) located in the catalytic site of mammalian serine proteases so far known.

  7. Characteristics of GRIFFIN high-purity germanium clover detectors

    NASA Astrophysics Data System (ADS)

    Rizwan, U.; Garnsworthy, A. B.; Andreoiu, C.; Ball, G. C.; Chester, A.; Domingo, T.; Dunlop, R.; Hackman, G.; Rand, E. T.; Smith, J. K.; Starosta, K.; Svensson, C. E.; Voss, P.; Williams, J.

    2016-06-01

    The Gamma-Ray Infrastructure For Fundamental Investigations of Nuclei, GRIFFIN, is a new experimental facility for radioactive decay studies at the TRIUMF-ISAC laboratory. The performance of the 16 high-purity germanium (HPGe) clover detectors that will make up the GRIFFIN spectrometer is reported. The energy resolution, efficiency, timing resolution, crosstalk and preamplifier properties of each crystal were measured using a combination of analog and digital data acquisition techniques. The absolute efficiency and add-back factors are determined for the energy range of 80-3450 keV. The detectors show excellent performance with an average over all 64 crystals of a FWHM energy resolution of 1.89(6) keV and relative efficiency with respect to a 3 in . × 3 in . NaI detector of 41(1)% at 1.3 MeV.

  8. In Vivo Gene Therapy of Hemophilia B: Sustained Partial Correction in Factor IX-Deficient Dogs

    NASA Astrophysics Data System (ADS)

    Kay, Mark A.; Rothenberg, Steven; Landen, Charles N.; Bellinger, Dwight A.; Leland, Frances; Toman, Carol; Finegold, Milton; Thompson, Arthur R.; Read, M. S.; Brinkhous, Kenneth M.; Woo, Savio L. C.

    1993-10-01

    The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which results in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B patients, preclinical efficacy studies were done in a hemophilia B dog model. When the canine factor IX complementary DNA was transduced directly into the hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting. factor resulted in reductions of whole blood clotting and partial thromboplastin times of the treated animals. Thus, long-term treatment of hemophilia B patients may be feasible by direct hepatic gene therapy in vivo.

  9. High-purity silicon for solar cell applications

    NASA Technical Reports Server (NTRS)

    Dosaj, V. D.; Hunt, L. P.; Schei, A.

    1978-01-01

    The article discusses the production of solar cells from high-purity silicon. The process consists of reducing the level of impurities in the raw materials, preventing material contamination before and after entering the furnace, and performing orders-of-magnitude reduction of metal impurity concentrations. The high-purity raw materials are considered with reference to carbon reductants, silica, and graphite electrodes. Attention is also given to smelting experiments used to demonstrate, in an experimental-scale furnace, the production of high-purity SoG-Si. It is found that high-purity silicon may be produced from high-purity quartz and chemically purified charcoal in a 50-kVA arc furnace. The major contamination source is shown to be impurities from the carbon reducing materials.

  10. An unusual complication in a gravida with factor IX deficiency: case report with review of the literature.

    PubMed

    Guy, G P; Baxi, L V; Hurlet-Jensen, A; Chao, C R

    1992-09-01

    Factor IX deficiency (hemophilia B, Christmas disease) is an X-linked recessive coagulation disorder. It occurs in one out of every 25,000-30,000 male births and requires even rarer genetic circumstances for phenotypic expression in females. We report the occurrence of a large, late-trimester subchorionic hematoma in a gravida with factor IX deficiency and with laboratory evidence of consumptive coagulopathy during treatment. The patient was managed conservatively and had a successful outcome at term. The only four reported cases of antepartum management of factor IX deficiency in the English literature are reviewed. PMID:1495722

  11. Ares I-X Flight Test Development Challenges and Success Factors

    NASA Technical Reports Server (NTRS)

    Askins, Bruce; Davis, Steve; Olsen, Ronald; Taylor, James

    2010-01-01

    The NASA Constellation Program's Ares I-X rocket launched successfully on October 28, 2009 collecting valuable data and providing risk reduction for the Ares I project. The Ares I-X mission was formulated and implemented in less than four years commencing with the Exploration Systems Architecture Study in 2005. The test configuration was founded upon assets and processes from other rocket programs including Space Shuttle, Atlas, and Peacekeeper. For example, the test vehicle's propulsion element was a Shuttle Solid Rocket Motor. The Ares I-X rocket comprised a motor assembly, mass and outer mold line simulators of the Ares I Upper Stage, Orion Spacecraft and Launch Abort System, a roll control system, avionics, and other miscellaneous components. The vehicle was 327 feet tall and weighed approximately 1,800,000 pounds. During flight the rocket reached a maximum speed of Mach 4.8 and an altitude of 150,000 feet. The vehicle demonstrated staging at 130,000 feet, tested parachutes for recovery of the motor, and utilized approximately 900 sensors for data collection. Developing a new launch system and preparing for a safe flight presented many challenges. Specific challenges included designing a system to withstand the environments, manufacturing large structures, and re-qualifying heritage hardware. These and other challenges, if not mitigated, may have resulted in test cancellation. Ares I-X succeeded because the mission was founded on carefully derived objectives, led by decisive and flexible management, implemented by an exceptionally talented and dedicated workforce, and supported by a thorough independent review team. Other major success factors include the use of proven heritage hardware, a robust System Integration Laboratory, multi-NASA center and contractor team, concurrent operations, efficient vehicle assembly, effective risk management, and decentralized element development with a centralized control board. Ares I-X was a technically complex test that

  12. Why does the human factor IX gene have a G + C content of 40%?

    PubMed Central

    Bottema, C D; Bottema, M J; Ketterling, R P; Yoon, H S; Janco, R L; Phillips, J A; Sommer, S S

    1991-01-01

    The factor IX gene has a G + C content of approximately 40% in all mammalian species examined. In human factor IX, C----T and G----A transitions at the dinucleotide CpG are elevated at least 24-fold relative to other transitions. Can the G + C content be explained solely by this hot spot of mutation? Using our mathematical model, we show that the elevation of mutation at CpG cannot alone lower the G + C content below 45%. To search for other hot spots of mutation that might contribute to the reduction of G + C content, we assessed the relative rates of base substitution in our sample of 160 families with hemophilia B. Seventeen independent single-base substitutions are reported herein for a total of 96 independent point mutations in our sample. The following conclusions emerge from the analysis of our data and, where appropriate, the data of others: (1) Transversions at CpG are elevated an estimated 7.7-fold relative to other transversions. (2) The mutation rates at non-CpG dinucleotides are remarkably uniform; none of the observed rates are either more than twofold above the median for transitions or more than threefold above the median for transversions. (3) The pattern of recent mutation is compatible with the pattern during mammalian evolution that has maintained the G + C content of the factor IX gene at approximately 40%. PMID:1897528

  13. Role of enhanced half-life factor VIII and IX in the treatment of haemophilia.

    PubMed

    Mahdi, Ali J; Obaji, Samya G; Collins, Peter W

    2015-06-01

    Treatment of congenital haemophilia with factor VIII and IX concentrates often requires frequent infusions. This has obvious implications in establishing effective administration strategies and, in turn, adherence. To overcome these issues, three main technologies--polyethylene-glycol, Fc-neonatal IgG1 and albumin fusion products--have emerged into various stages of clinical development. Published data indicates an approximately 1·5- and fivefold increase in half-life of factor VIII and IX, respectively, compared to standard recombinant concentrates. Studies into efficacy and safety are starting to be published. Monitoring and optimal use of these new concentrates remains unknown. Weekly factor IX prophylaxis appears to be a feasible prophylactic regimen in haemophilia B patients. Weekly longer-acting FVIII is unlikely to provide adequate prophylaxis in most patients with haemophilia A but may reduce the frequency of infusions. Ongoing clinical trials and real life experience will help shape how these products can be used in practice and their cost effectiveness. The drive for convenience however should not overshadow the ultimate goal of prophylaxis, namely, preventing bleeding and arthropathy. PMID:25754016

  14. Production of High Purity Niobium Ingots at CBMM

    SciTech Connect

    Moura, Lourenco de; Faria Sousa, Clovis Antonio de; Burgos Cruz, Edmundo

    2011-03-31

    CBMM is a fully integrated company, from the mine to the end line of the production chain, supplying different niobium products to the world market: ferroniobium, nickelniobium, niobium pentoxide and high purity metallic niobium. This high purity metallic niobium has long been known to exhibit superconductivity below 9.25 Kelvin. This characteristic has the potential to bring technological benefits for many different areas such as medicine, computing and environment. This paper presents the raw material requirements as well as CBMM experience on producing high purity niobium ingots. The results prove that CBMM material can be the best solution for special applications such as low cost superconductive radiofrequency cavities.

  15. Pharmacokinetics, thrombogenicity and safety of a double viral inactivated factor IX concentrate compared with a prothrombin complex concentrate.

    PubMed

    Ruiz-Sáez, A; Hong, A; Arguello, A; Echenagucia, M; Boadas, A; Fabbrizzi, F; Minichilli, F; Bosch, N B

    2005-11-01

    Therapeutic options for developing countries have to assure an optimum safety and efficacy and low-cost antihaemophilic concentrates. A single blind randomized crossover study was carried out in 12 previously treated HB patients, comparing the pharmacokinetics (PK), thrombogenicity (TG) and safety of two plasma-derived double-inactivated (solvent/detergent heating at 100 degrees C, 30 min) factor IX (FIX) concentrates, UMAN COMPLEX DI (product A) [plasma-derived prothrombin concentrates (PCC)] and a high purity FIX concentrate AIMAFIX DI (product B, HPFIX). In a non-bleeding state, they received one single intravenous dose 50 IU FIX kg(-1) of PCC or HPFIX, and after a wash-out period of 14 days, the other product. We evaluated acute tolerance and determined PK parameters based on FIX levels measured over a 50 h postinfusion period. We studied fibrinogen, platelets, antithrombin, F1 + 2, TAT, D-dimer, over a 360 min postinfusion period. Ten cases remained in on-demand treatment for 6 months, five with PCC and five with HPFIX. PK and anti-FIX inhibitors were repeated at 3 and 6 months. No inhibitors were detected. PK values (PCC vs. HPFIX): clearence (CL; mL h(-1) kg(-1)) 5.2 +/- 1.4 vs. 6.5 +/- 1.4; the volume of distribution at steady state (mL kg(-1)) 154.9 +/- 54.9 vs. 197.5 +/- 72.5; mean residence time (h) 29.7 +/- 8.1 vs. 30.7 +/- 9.2; T(1/2) (h) 22.3 +/- 7 vs. 23.5 +/- 12.3; incremental recovery (IR; U dL(-1) U(-1) kg(-1)) 0.96 +/- 0.17 vs. 0.76 +/- 0.13. HPFIX showed significant lower IR and higher CL. There were no differences in PK at 3 and 6 months. In TG, significant increments in TAT and F1 + 2 at 30 min and 6 h were found with PCC. Product B PK results agrees with reported results for other HPFIX preparations. Use of PCC product A has to consider its thrombogenic activity. PMID:16236107

  16. Improved muscle-derived expression of human coagulation factor IX from a skeletal actin/CMV hybrid enhancer/promoter.

    PubMed

    Hagstrom, J N; Couto, L B; Scallan, C; Burton, M; McCleland, M L; Fields, P A; Arruda, V R; Herzog, R W; High, K A

    2000-04-15

    Hemophilia B is caused by the absence of functional coagulation factor IX (F.IX) and represents an important model for treatment of genetic diseases by gene therapy. Recent studies have shown that intramuscular injection of an adeno-associated viral (AAV) vector into mice and hemophilia B dogs results in vector dose-dependent, long-term expression of biologically active F.IX at therapeutic levels. In this study, we demonstrate that levels of expression of approximately 300 ng/mL (6% of normal human F.IX levels) can be reached by intramuscular injection of mice using a 2- to 4-fold lower vector dose (1 x 10(11) vector genomes/mouse, injected into 4 intramuscular sites) than previously described. This was accomplished through the use of an improved expression cassette that uses the cytomegalovirus (CMV) immediate early enhancer/promoter in combination with a 1.2-kilobase portion of human skeletal actin promoter. These results correlated with enhanced levels of F.IX transcript and secreted F.IX protein in transduced murine C2C12 myotubes. Systemic F.IX expression from constructs containing the CMV enhancer/promoter alone was 120 to 200 ng/mL in mice injected with 1 x 10(11) vector genomes. Muscle-specific promoters performed poorly for F.IX transgene expression in vitro and in vivo. However, the incorporation of a sequence from the alpha-skeletal actin promoter containing at least 1 muscle-specific enhancer and 1 enhancer-like element further improved muscle-derived expression of F.IX from a CMV enhancer/promoter-driven expression cassette over previously published results. These findings will allow the design of a clinical protocol for therapeutic levels of F.IX expression with lower vector doses, thus enhancing efficacy and safety of the protocol. (Blood. 2000;95:2536-2542) PMID:10753832

  17. Recombinant to modified factor VIII and factor IX - chromogenic and one-stage assays issues.

    PubMed

    Kitchen, S; Kershaw, G; Tiefenbacher, S

    2016-07-01

    The recent development of modified recombinant factor VIII (FVIII) and factor IX (FIX) therapeutic products with extended half-lives will create challenges for the haemostasis laboratory in obtaining recovery estimates of these products in clinical samples using existing assays. The new long-acting therapeutic concentrates contain molecular modifications of Fc fusion, site-specific of polyethylene glycol or albumin fusion. The optimum methods for monitoring each new product will need to be assessed individually and laboratories should select an assay which gives similar results to the assay used to assign potency to the product in question. For some extended half-life FVIII and FIX products some one stage assays are entirely unsuitable for monitoring purposes. For most products and assay reagents studied so far, and reviewed in this manuscript, chromogenic FVIII or FIX assays can be safely used with conventional plasma standards. If one stage assays are used then they should be performed using carefully selected reagents/methods which have been shown to recover activity close to the labelled potency for the specific product being monitored. PMID:27405680

  18. G244E in the canine factor IX gene leads to severe haemophilia B in Rhodesian Ridgebacks.

    PubMed

    Mischke, R; Kühnlein, P; Kehl, A; Langbein-Detsch, I; Steudle, F; Schmid, A; Dandekar, T; Czwalinna, A; Müller, E

    2011-01-01

    Haemophilia B in Rhodesian Ridgebacks is currently the most important canine haemophilia in Germany. The aim of this study was to define the underlying genetic defect. Genetic studies were performed including six phenotypically affected male dogs (factor IX activity: approximately 1%), four suspected carriers (factor IX activity 48-69%, one confirmed by affected offspring), and 12 healthy dogs. Comparison of the entire coding region of the canine factor IX DNA sequences and exon-intron junctions from affected dogs with the wild type canine factor IX DNA revealed a G-A missense mutation in exon 7. This mutation results in a glycine (GGA) to glutamic acid (GAA) exchange in the catalytic domain of the haemophilic factor IX. All affected dogs were hemizygous for the detected mutation and carriers were heterozygous, whereas none of the Rhodesian Ridgebacks with normal factor IX activity showed the mutation. No further alterations in the sequences between affected dogs and the healthy control group could be observed. None of the Rhodesian Ridgebacks with undefined haemophilia B status (n=30) and no individual of three other dog breeds (Doberman Pinscher: n=20; German Wire haired Pointer: n=20; Labrador: n=25) showed the presence of the mutation. Amino acid sequence alignment and protein structural modelling analysis indicate that the detected mutation causes a relevant functional defect. The results of this study suggest that the detected mutation is responsible for a severe form of haemophilia B in Rhodesian Ridgebacks. PMID:20303304

  19. Analysis of trace halocarbon contaminants in ultra high purity helium

    NASA Technical Reports Server (NTRS)

    Fewell, Larry L.

    1994-01-01

    This study describes the analysis of ultra high purity helium. Purification studies were conducted and containment removal was effected by the utilization of solid adsorbent purge-trap systems at cryogenic temperatures. Volatile organic compounds in ultra high purity helium were adsorbed on a solid adsorbent-cryogenic trap, and thermally desorbed trace halocarbon and other contaminants were analyzed by combined gas chromatography-mass spectrometry.

  20. Delta Doping High Purity CCDs and CMOS for LSST

    NASA Technical Reports Server (NTRS)

    Blacksberg, Jordana; Nikzad, Shouleh; Hoenk, Michael; Elliott, S. Tom; Bebek, Chris; Holland, Steve; Kolbe, Bill

    2006-01-01

    A viewgraph presentation describing delta doping high purity CCD's and CMOS for LSST is shown. The topics include: 1) Overview of JPL s versatile back-surface process for CCDs and CMOS; 2) Application to SNAP and ORION missions; 3) Delta doping as a back-surface electrode for fully depleted LBNL CCDs; 4) Delta doping high purity CCDs for SNAP and ORION; 5) JPL CMP thinning process development; and 6) Antireflection coating process development.

  1. Hemophilia as a defect of the tissue factor pathway of blood coagulation: Effect of factors VIII and IX on factor X activation in a continuous-flow reactor

    SciTech Connect

    Repke, D.; Gemmell, C.H.; Guha, A.; Turitto, V.T.; Nemerson, Y. ); Broze, G.J. Jr. )

    1990-10-01

    The effect of factors VIII and IX on the ability of the tissue factor-factor VIIa complex to activate factor X was studied in a continuous-flow tubular enzyme reactor. Tissue factor immobilized in a phospholipid bilayer on the inner surface of the tube was exposed to a perfusate containing factors VIIa, VIII, IX, and X flowing at a wall shear rate of 57, 300, or 1130 sec{sup {minus}1}. The addition of factors VIII and IX at their respective plasma concentrations resulted in a further 2{endash}-to 3{endash}fold increase. The direct activation of factor X by tissue factor-factor VIIa could be virtually eliminated by the lipoprotein-associated coagulation inhibitor. These results suggest that the tissue factor pathway, mediated through factors VIII and IX, produces significant levels of factor Xa even in the presence of an inhibitor of the tissue factor-factor VIIa complex; moreover, the activation is dependent on local shear conditions. These findings are consistent both with a model of blood coagulation in which initiation of the system results from tissue factor and with the bleeding observed in hemophilia.

  2. The rates and patterns of deletions in the human factor IX gene

    SciTech Connect

    Ketterling, R.P.; Vielhaber, E.L.; Lind, T.J.; Thorland, E.C.; Sommer S.S. )

    1994-02-01

    Deletions are commonly observed in genes with either segments of highly homologous sequences or excessive gene length. However, in the factor IX gene and in most genes, deletions (of [ge]21 bp) are uncommon. The authors have analyzed DNA from 290 families with hemophilia B (203 independent mutations) and have found 12 deletions >20 bp. Eleven of these are >2 kb (range >3-163 kb), and one is 1.1 kb. The junctions of the four deletions that are completely contained within the factor IX gene have been determined. A novel mutation occurred in patient HB128: the data suggest that a 26.8-kb deletion occurred between two segments of alternating purines and pyrimidines and that a 2.3-kb sense strand segment derived from the deleted region was inserted. For a sample of 203 independent mutations, the authors estimate the [open quotes]baseline[close quotes] rates of deletional mutation per base pair per generation as a function of size. The rate for large (>2 kb)I deletions is exceedingly low. For every mutational event in which a given base is at the junction of a large deletion, there are an estimated 58 microdeletions (<20 bp) and 985 single-base substitutions at that base. Analysis of the nine reported deletion junctions in the factor IX gene literature reveals that (i) five are associated with inversion, orphan sequences, or sense strand insertions; (ii) four are simple deletions that display an excess of short direct repeats at their junctions; (iii) there is no dramatic clustering of junctions within the gene; and (iv) with the exception of alternating purines and pyrimidines, deletion junctions are not preferentially associated with repetitive DNA. 58 refs., 5 figs., 5 tabs.

  3. Recent developments in high purity niobium metal production at CBMM

    NASA Astrophysics Data System (ADS)

    Abdo, Gustavo Giovanni Ribeiro; Sousa, Clovis Antonio de Faria; Guimarães, Rogério Contato; Ribas, Rogério Marques; Vieira, Alaércio Salvador Martins; Menezes, Andréia Duarte; Fridman, Daniel Pallos; Cruz, Edmundo Burgos

    2015-12-01

    CBMM is a global supplier of high quality niobium products including pure niobium, the focus of this paper. CBMM's position has been consolidated over three decades of producing high purity niobium metal ingots. The company supplies, among other products, commercial and reactor grade niobium ingots. One of the main uses of CBMM's ingots is for the manufacture of particle accelerators (superconducting radio frequency - SRF - cavities), where the purity and homogeneity of niobium metal is essentially important for good performance. CBMM constantly strives to improve process controls and product quality, and is currently implementing innovations in production, research and development to further improve ingot quality. The main aim is to reduce the content of interstitial elements, such as nitrogen (N), oxygen (O), carbon (C), and hydrogen (H), starting with the raw materials through the final step of ingot production. CBMM held the first trial to produce the world's largest-diameter niobium ingot (as cast 535 mm). The results of this initial trial presented very low levels of interstitial impurities (N, O, C, H), allowing the achievement of residual resistivity ratio (RRR) values very close to 300 in a six-melt process in an electron beam furnace. These values were reached with 850 ppm of tantalum. SRF cavities will be produced with this material in order to study the effect of low impurities and high RRR on the Q factor and accelerating gradient.

  4. High-purity silica reflecting heat shield development

    NASA Technical Reports Server (NTRS)

    Congdon, W. M.

    1974-01-01

    A high-purity, fused-silica reflecting heat shield for the thermal protection of outer-planet probes was developed. Factors that strongly influence the performance of a silica heat shield were studied. Silica-bonded silica configurations, each prepared by a different technique, were investigated and rated according to its relative merits. Slip-casting was selected as the preferred fabrication method because it produced good reflectivity and good strength, and is relatively easy to scale up for a full-size outer-planet probe. The slips were cast using a variety of different particle sizes: continuous particle-size slips; monodisperse particle-size slips; and blends of monodisperse particle-size slips were studied. In general, smaller particles gave the highest reflectance. The monodisperse slips as well as the blend slips gave a higher reflectance than the continuous particle-size slips. An upgraded and fused natural quartz was used to study the effects of microstructure on reflectance and as the baseline to ascertain the increase in reflectance obtained from using a higher-purity synthetic material.

  5. Recent developments in high purity niobium metal production at CBMM

    SciTech Connect

    Abdo, Gustavo Giovanni Ribeiro Sousa, Clovis Antonio de Faria Guimarães, Rogério Contato Ribas, Rogério Marques Vieira, Alaércio Salvador Martins Menezes, Andréia Duarte Fridman, Daniel Pallos Cruz, Edmundo Burgos

    2015-12-04

    CBMM is a global supplier of high quality niobium products including pure niobium, the focus of this paper. CBMM’s position has been consolidated over three decades of producing high purity niobium metal ingots. The company supplies, among other products, commercial and reactor grade niobium ingots. One of the main uses of CBMM’s ingots is for the manufacture of particle accelerators (superconducting radio frequency – SRF – cavities), where the purity and homogeneity of niobium metal is essentially important for good performance. CBMM constantly strives to improve process controls and product quality, and is currently implementing innovations in production, research and development to further improve ingot quality. The main aim is to reduce the content of interstitial elements, such as nitrogen (N), oxygen (O), carbon (C), and hydrogen (H), starting with the raw materials through the final step of ingot production. CBMM held the first trial to produce the world’s largest-diameter niobium ingot (as cast 535 mm). The results of this initial trial presented very low levels of interstitial impurities (N, O, C, H), allowing the achievement of residual resistivity ratio (RRR) values very close to 300 in a six-melt process in an electron beam furnace. These values were reached with 850 ppm of tantalum. SRF cavities will be produced with this material in order to study the effect of low impurities and high RRR on the Q factor and accelerating gradient.

  6. Synthesis and properties of high-purity alumina

    SciTech Connect

    Martin, E.S.; Weaver, M.L. . Chemical Systems Div.)

    1993-07-01

    High-purity alumina is intended primarily for the high-pressure sodium-vapor lamp envelope market and other specialty alumina applications such as abrasives, catalysts, and structural ceramics. High-purity alumina must calcine to Al[sub 2]O[sub 3] with minimal metal impurities ([>=]99.99% Al[sub 2]O[sub 3]). Sulfate and chloride impurities are also undesirable. High-purity alumina should have less than 20ppm alkali and alkaline-earth metals, and less than 10 ppm each in transition-metal impurities. A process for synthesizing alumina by converting pure aluminum metal to aluminum hydroxide and the resultant alumina properties are described.

  7. Analysis of the N-glycans of recombinant human Factor IX purified from transgenic pig milk

    PubMed Central

    Gil, Geun-Cheol; Velander, William H; Van Cott, Kevin E

    2008-01-01

    Glycosylation of recombinant proteins is of particular importance because it can play significant roles in the clinical properties of the glycoprotein. In this work, the N-glycan structures of recombinant human Factor IX (tg-FIX) produced in the transgenic pig mammary gland were determined. The majority of the N-glycans of transgenic pig-derived Factor IX (tg-FIX) are complex, bi-antennary with one or two terminal N-acetylneuraminic acid (Neu5Ac) moieties. We also found that the N-glycan structures of tg-FIX produced in the porcine mammary epithelial cells differed with respect to N-glycans from glycoproteins produced in other porcine tissues. tg-FIX contains no detectable Neu5Gc, the sialic acid commonly found in porcine glycoproteins produced in other tissues. Additionally, we were unable to detect glycans in tg-FIX that have a terminal Galα(1,3)Gal disaccharide sequence, which is strongly antigenic in humans. The N-glycan structures of tg-FIX are also compared to the published N-glycan structures of recombinant human glycoproteins produced in other transgenic animal species. While tg-FIX contains only complex structures, antithrombin III (goat), C1 inhibitor (rabbit), and lactoferrin (cow) have both high mannose and complex structures. Collectively, these data represent a beginning point for the future investigation of species-specific and tissue/cell-specific differences in N-glycan structures among animals used for transgenic animal bioreactors. PMID:18456721

  8. Characterisation of two AGATA asymmetric high purity germanium capsules

    NASA Astrophysics Data System (ADS)

    Colosimo, S. J.; Moon, S.; Boston, A. J.; Boston, H. C.; Cresswell, J. R.; Harkness-Brennan, L.; Judson, D. S.; Lazarus, I. H.; Nolan, P. J.; Simpson, J.; Unsworth, C.

    2015-02-01

    The AGATA spectrometer is an array of highly segmented high purity germanium detectors. The spectrometer uses pulse shape analysis in order to track Compton scattered γ-rays to increase the efficiency of nuclear spectroscopy studies. The characterisation of two high purity germanium detector capsules for AGATA of the same A-type has been performed at the University of Liverpool. This work will examine the uniformity of performance of the two capsules, including a comparison of the resolution and efficiency as well as a study of charge collection. The performance of the capsules shows good agreement, which is essential for the efficient operation of the γ-ray tracking array.

  9. Preparation of high purity copper fluoride by fluorinating copper hydroxyfluoride

    NASA Technical Reports Server (NTRS)

    King, R. B.; Lundquist, J. R.

    1969-01-01

    Copper fluoride containing no more than 50 ppm of any contaminating element was prepared by the fluorination of copper hydroxyfluoride. The impurity content was obtained by spark source mass spectrometry. High purity copper fluoride is needed as a cathode material for high energy density batteries.

  10. Electrochemical study of aluminum corrosion in boiling high purity water

    NASA Technical Reports Server (NTRS)

    Draley, J. E.; Legault, R. A.

    1969-01-01

    Electrochemical study of aluminum corrosion in boiling high-purity water includes an equation relating current and electrochemical potential derived on the basis of a physical model of the corrosion process. The work involved an examination of the cathodic polarization behavior of 1100 aluminum during aqueous oxidation.

  11. Low cost routes to high purity silicon and derivatives thereof

    SciTech Connect

    Laine, Richard M; Krug, David James; Marchal, Julien Claudius; Mccolm, Andrew Stewart

    2013-07-02

    The present invention is directed to a method for providing an agricultural waste product having amorphous silica, carbon, and impurities; extracting from the agricultural waste product an amount of the impurities; changing the ratio of carbon to silica; and reducing the silica to a high purity silicon (e.g., to photovoltaic silicon).

  12. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    NASA Astrophysics Data System (ADS)

    Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

    2013-06-01

    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

  13. Inhibitors of propagation of coagulation (factors VIII, IX and XI): a review of current therapeutic practice

    PubMed Central

    Franchini, Massimo; Mannucci, Pier Mannuccio

    2011-01-01

    The management of patients with congenital haemophilia who develop alloantibodies against factors of the propagation phase of blood coagulation, commonly known as inhibitors, is the most important challenge facing haemophilia caregivers at present, as this complication not only compromises the efficacy of replacement therapy but also consumes an enormous amount of economic resources. Development of inhibitors further complicates the clinical course of severe haemophilia, with a prevalence of up to 30% in patients with haemophilia A (factor VIII deficiency) and up to 5% in those with haemophilia B (factor IX deficiency) and haemophilia C (factor XI deficiency). While the short-term goal of treatment of patients who develop alloantibodies is the control of bleeding, the eradication of the inhibitor is the main long-term goal. The management of severe bleeding episodes and the eradication of the autoantibody are also the mainstays of treatment of patients with acquired haemophilia, a rare but life-threatening haemorrhagic condition characterized by the development of inhibitory autoantibodies against coagulation factor VIII. The most recent options available for treating patients with congenital haemophilia complicated by inhibitors and acquired haemophilia because of autoantibodies against factor VIII are summarized in this review article. PMID:21204915

  14. Preparation and properties of high purity Mg-Y biomaterials.

    PubMed

    Peng, Qiuming; Huang, Yuanding; Zhou, Le; Hort, Norbert; Kainer, Karl Ulrich

    2010-01-01

    An effective zone solidification method has been found to prepare high purity Mg-Y biomaterials. The corrosion and mechanical properties of the purified middle region are improved remarkably compared with common casting method. The average gain size and secondary dendrite space decrease from the top layer to the bottom layer of the ingot. The oxides, defects and precipitates are mainly enriched in the top layer of the ingot under the impulsion of high thermal gradient. These results are in agreement with that simulated by finite elemental method using FLOW-3D software. It is confirmed that the mode of scallop symmetric solidification attributes to the purifying process. This zone solidification method not only contributes to high purity Mg-based biomaterials, but also provides a new approach to prepare high performance Mg alloys. PMID:19800117

  15. High-Purity Silicon Seeds for Silane Pyrolysis

    NASA Technical Reports Server (NTRS)

    Hsu, G. C.; Rohatgi, N. K.; Morrison, A.

    1985-01-01

    Seed particles for fluidized-bed production of silicon made by new contamination-free, economical method. In new method, large particles of semiconductor-grade silicon fired at each other by high-speed streams of gas and thereby break up into particles of suitable size for fluidized bed. No foreign materials introduced, and leaching unnecessary. Method used to feed fluidized-bed reactor for continuous production of high-purity silicon.

  16. Dimensional stability of high-purity Invar 36

    NASA Astrophysics Data System (ADS)

    Sokolowski, Witold M.; Jacobs, Stephen F.; Lane, Marc S.; O'Donnell, Timothy P.; Hsieh, Cheng

    1993-12-01

    High performance requirements for the Imaging Science Subsystem/Narrow Angle Camera (NAC) instrument on the NASA/Jet Propulsion Laboratory (JPL) Cassini spacecraft impose very stringent demands for dimensional stability of metering rods in the camera's athermalizing system. Invar 36 was chosen as a baseline material because it possibly could meet these requirements through high purity control and appropriate thermomechanical processes. A powder metallurgy process appears to be the manufacturing method to ensure high purity and cleanliness of this material. Therefore, a powder metallurgy manufacturer was contacted and high purity (HP) Invar 36 was produced per JPL engineering requirements. Several heat treatments were established and heat treated HP Invar 36 samples were evaluated. Coefficient of thermal expansion (CTE), thermal hysteresis and temporal stability test results are reported here. The test results indicate that JPL has succeeded in obtaining possibly the most dimensionally stable (lowest CTE plus lowest temporal change) Invar 36 material ever produced. CTE < 1 ppm/ degree(s)C are reported here along with temporal stability < 1 ppm/year. These dimensional stability properties will meet the requirements for metering rods on the NAC.

  17. Recombinant Factor IX Fc Fusion Protein Maintains Full Procoagulant Properties and Exhibits Prolonged Efficacy in Hemophilia B Mice

    PubMed Central

    Toby, Garabet G.; Liu, Tongyao; Buyue, Yang; Zhang, Xin; Bitonti, Alan J.; Pierce, Glenn F.; Sommer, Jurg M.; Jiang, Haiyan; Peters, Robert T.

    2016-01-01

    Introduction Hemophilia B is an inherited X chromosome–linked disorder characterized by impaired blood clotting owing to the absence of functional coagulation factor IX. Due to the relatively short half-life of factor IX, patients with hemophilia B require frequent factor IX infusions to maintain prophylaxis. We have developed a recombinant factor IX (rFIX) fused to the Fc region of IgG (rFIXFc) with an extended half-life in animals and humans. Materials and Methods Procoagulant properties of rFIXFc and rFIX (BENEFIX®) were compared to determine the effect of the Fc region on rFIXFc hemostatic function. Specifically, we assessed rFIXFc activation, intermolecular interactions within the Xase complex, inactivation by antithrombin III (AT) and thrombin generation potential compared with rFIX. We also assessed the acute and prophylactic efficacy profiles of rFIXFc and rFIX in vivo in hemophilia B mouse bleeding models. Results and Conclusions The activation by factor XIa or factor VIIa/tissue factor, inhibition by AT, interaction profiles with phospholipids, affinities for factor VIIIa within the context of the Xase complex, and thrombin generation profiles were similar for rFIXFc and rFIX. Xase complexes formed with either molecule exhibited similar kinetic profiles for factor Xa generation. In acute efficacy models, mice infused with rFIXFc or rFIX were equally protected from bleeding. However, in prophylactic efficacy models, protection from bleeding was maintained approximately three times longer in rFIXFc-dosed mice than in those given rFIX; this prolonged efficacy correlates with the previously observed half-life extension. We conclude that rFIXFc retains critical FIX procoagulant attributes and that the extension in rFIXFc half-life translates into prolonged efficacy in hemophilia B mice. PMID:26840952

  18. Factor IXMadrid 2: a deletion/insertion in factor IX gene which abolishes the sequence of the donor junction at the exon IV-intron d splice site.

    PubMed Central

    Solera, J; Magallón, M; Martin-Villar, J; Coloma, A

    1992-01-01

    DNA from a patient with severe hemophilia B was evaluated by RFLP analysis, producing results which suggested the existence of a partial deletion within the factor IX gene. The deletion was further localized and characterized by PCR amplification and sequencing. The altered allele has a 4,442-bp deletion which removes both the donor splice site located at the 5' end of intron d and the two last coding nucleotides located at the 3' end of exon IV in the normal factor IX gene; this fragment has been replaced by a 47-bp sequence from the normal factor IX gene, although this fragment has been inserted in inverted orientation. Two homologous sequences have been discovered at the ends of the deleted DNA fragment. Images Figure 1 PMID:1346483

  19. Effective gene therapy for haemophilic mice with pathogenic factor IX antibodies

    PubMed Central

    Markusic, David M; Hoffman, Brad E; Perrin, George Q; Nayak, Sushrusha; Wang, Xiaomei; LoDuca, Paul A; High, Katherine A; Herzog, Roland W

    2013-01-01

    Formation of pathogenic antibodies is a major problem in replacement therapies for inherited protein deficiencies. For example, antibodies to coagulation factors (‘inhibitors’) seriously complicate treatment of haemophilia. While immune tolerance induction (ITI) protocols have been developed, inhibitors against factor IX (FIX) are difficult to eradicate due to anaphylactic reactions and nephrotic syndrome and thus substantially elevate risks for morbidity and mortality. However, hepatic gene transfer with an adeno-associated virus (AAV) serotype 8 vector expressing FIX (at levels of ≥4% of normal) rapidly reversed pre-existing high-titre inhibitors in haemophilia B mice, eliminated antibody production by B cells, desensitized from anaphylaxis (even if protein therapy was resumed) and provided long-term correction. High levels of FIX protein suppressed memory B cells and increased Treg induction, indicating direct and indirect mechanisms of suppression of inhibitor formation. Persistent presence of Treg was required to prevent relapse of antibodies. Together, these data suggest that hepatic gene transfer-based ITI provides a safe and effective alternative to eradicate inhibitors. This strategy may be broadly applicable to reversal of antibodies in different genetic diseases. PMID:24106230

  20. The GALATEA test-facility for high purity germanium detectors

    NASA Astrophysics Data System (ADS)

    Abt, I.; Caldwell, A.; Dönmez, B.; Garbini, L.; Irlbeck, S.; Majorovits, B.; Palermo, M.; Schulz, O.; Seitz, H.; Stelzer, F.

    2015-05-01

    GALATEA is a test facility designed to investigate bulk and surface effects in high purity germanium detectors. A vacuum tank houses a cold volume with the detector inside. A system of three precision motorized stages allows an almost complete scan of the detector. The main feature of GALATEA is that there is no material between source and detector. This allows the usage of alpha and beta sources to study surface effects. A 19-fold segmented true-coaxial germanium detector was used for commissioning. A first analysis of data obtained with an alpha source is presented here.

  1. Method and apparatus for producing high purity silicon

    DOEpatents

    Olson, Jerry M.

    1984-01-01

    A method for producing high purity silicon includes forming a copper silie alloy and positioning the alloy within an enclosure. A filament member is also placed within the enclosure opposite the alloy. The enclosure is then filled with a chemical vapor transport gas adapted for transporting silicon. Finally, both the filament member and the alloy are heated to temperatures sufficient to cause the gas to react with silicon at the alloy surface and deposit the reacted silicon on the filament member. In addition, an apparatus for carrying out this method is also disclosed.

  2. Neutron energy determination with a high-purity germanium detector

    NASA Technical Reports Server (NTRS)

    Beck, Gene A.

    1992-01-01

    Two areas that are related to planetary gamma-ray spectrometry are investigated. The first task was the investigation of gamma rays produced by high-energy charged particles and their secondaries in planetary surfaces by means of thick target bombardments. The second task was the investigation of the effects of high-energy neutrons on gamma-ray spectral features obtained with high-purity Ge-detectors. For both tasks, as a function of the funding level, the experimental work was predominantly tied to that of other researchers, whenever there was an opportunity to participate in bombardment experiments at large or small accelerators for charged particles.

  3. A novel method to synthesize high purity, nanostructured copper

    SciTech Connect

    Hodge, A M; Wang, Y M; Barbee, T W

    2005-08-30

    Nanostructured high purity (99.999%) copper foils, 10 cm in diameter and 22-25 microns thick were produced using nanoscale multilayer technology. The foils were produced using five different layer thicknesses ranging from 1.25 to 43.6 nm (18,000 to 520 layers). This process delivers the ability to produce multiple large-scale samples during a single deposition run with very small residual stresses. Tensile and indentation tests demonstrate that the material produced is a high strength copper ({sigma}{sub y} {approx} 540-690 MPa).

  4. Sensitivity of the reaction time of the resonance thrombogram for factor VIII:C and factor IX deficiencies in the blood of dogs with haemophilia A or B.

    PubMed

    Mischke, R

    2000-09-01

    The sensitivity of the reaction time of the resonance thrombogram (RTG-r) was examined for two instruments based on 105 canine samples with a reduced factor VIII:C activity and 26 samples with a reduced factor IX activity. These samples were taken from dogs suffering from haemophilia A (n=18) or B (n=3) before and at different times after the substitution therapy with fresh frozen plasma. The RTG-r sensitivity was low; with reference to the total of all examined samples, it was between 0.39 and 0.65 for the factor VIII:C activity and between 0.46 and 0.62 for the factor IX activity, depending on the instrument and the testing procedure used. Low sensitivity was shown especially by the fact that even some of the samples with a factor VIII:C activity < 5% showed false negative results. Moreover, the correlation found between RTG-r and factor VIII:C activity (Spearman's rank correlation coefficient, r(S)=-0.556 to -0.700) as well as between factor IX activity and RTG-r (r(S)=-0.380 to -0.612) was only moderate. The low sensitivity of the RTG towards a reduced activity of the haemophilia factors VIII:C and IX contradicts the exclusive use of the RTG for monitoring haemophilic dogs as well as a global screening test for the haemostasis of dogs. PMID:11012705

  5. Factor IX[sub Madrid 2]: A deletion/insertion in Facotr IX gene which abolishes the sequence of the donor junction at the exon IV-intron d splice site

    SciTech Connect

    Solera, J. ); Magallon, M.; Martin-Villar, J. ); Coloma, A. )

    1992-02-01

    DNA from a patient with severe hemophilia B was evaluated by RFLP analysis, producing results which suggested the existence of a partial deletion within the factor IX gene. The deletion was further localized and characterized by PCR amplification and sequencing. The altered allele has a 4,442-bp deletion which removes both the donor splice site located at the 5[prime] end of intron d and the two last coding nucleotides located at the 3[prime] end of exon IV in the normal factor IX gene; this fragment has been inserted in inverted orientation. Two homologous sequences have been discovered at the ends of the deleted DNA fragment.

  6. Molecular Basis and Therapeutic Strategies to Rescue Factor IX Variants That Affect Splicing and Protein Function.

    PubMed

    Tajnik, Mojca; Rogalska, Malgorzata Ewa; Bussani, Erica; Barbon, Elena; Balestra, Dario; Pinotti, Mirko; Pagani, Franco

    2016-05-01

    Mutations that result in amino acid changes can affect both pre-mRNA splicing and protein function. Understanding the combined effect is essential for correct diagnosis and for establishing the most appropriate therapeutic strategy at the molecular level. We have identified a series of disease-causing splicing mutations in coagulation factor IX (FIX) exon 5 that are completely recovered by a modified U1snRNP particle, through an SRSF2-dependent enhancement mechanism. We discovered that synonymous mutations and missense substitutions associated to a partial FIX secretion defect represent targets for this therapy as the resulting spliced-corrected proteins maintains normal FIX coagulant specific activity. Thus, splicing and protein alterations contribute to define at the molecular level the disease-causing effect of a number of exonic mutations in coagulation FIX exon 5. In addition, our results have a significant impact in the development of splicing-switching therapies in particular for mutations that affect both splicing and protein function where increasing the amount of a correctly spliced protein can circumvent the basic functional defects. PMID:27227676

  7. Computationally designed liver-specific transcriptional modules and hyperactive factor IX improve hepatic gene therapy

    PubMed Central

    Nair, Nisha; Rincon, Melvin Y.; Evens, Hanneke; Sarcar, Shilpita; Dastidar, Sumitava; Samara-Kuko, Emira; Ghandeharian, Omid; Man Viecelli, Hiu; Thöny, Beat; De Bleser, Pieter; Chuah, Marinee K.

    2014-01-01

    The development of the next-generation gene therapy vectors for hemophilia requires using lower and thus potentially safer vector doses and augmenting their therapeutic efficacy. We have identified hepatocyte-specific transcriptional cis-regulatory modules (CRMs) by using a computational strategy that increased factor IX (FIX) levels 11- to 15-fold. Vector efficacy could be enhanced by combining these hepatocyte-specific CRMs with a synthetic codon-optimized hyperfunctional FIX-R338L Padua transgene. This Padua mutation boosted FIX activity up to sevenfold, with no apparent increase in thrombotic risk. We then validated this combination approach using self-complementary adenoassociated virus serotype 9 (scAAV9) vectors in hemophilia B mice. This resulted in sustained supraphysiologic FIX activity (400%), correction of the bleeding diathesis at clinically relevant, low vector doses (5 × 1010 vector genomes [vg]/kg) that are considered safe in patients undergoing gene therapy. Moreover, immune tolerance could be induced that precluded induction of inhibitory antibodies to FIX upon immunization with recombinant FIX protein. PMID:24637359

  8. Prolonged activity of factor IX as a monomeric Fc fusion protein.

    PubMed

    Peters, Robert T; Low, Susan C; Kamphaus, George D; Dumont, Jennifer A; Amari, John V; Lu, Qi; Zarbis-Papastoitsis, Greg; Reidy, Thomas J; Merricks, Elizabeth P; Nichols, Timothy C; Bitonti, Alan J

    2010-03-11

    Treatment of hemophilia B requires frequent infusions of factor IX (FIX) to prophylax against bleeding episodes. Hemophilia B management would benefit from a FIX protein with an extended half-life. A recombinant fusion protein (rFIXFc) containing a single FIX molecule attached to the Fc region of immunoglobulin G was administered intravenously and found to have an extended half-life, compared with recombinant FIX (rFIX) in normal mice, rats, monkeys, and FIX-deficient mice and dogs. Recombinant FIXFc protein concentration was determined in all species, and rFIXFc activity was measured in FIX-deficient animals. The half-life of rFIXFc was approximately 3- to 4-fold longer than that of rFIX in all species. In contrast, in mice in which the neonatal Fc receptor (FcRn) was deleted, the half-life of rFIXFc was similar to rFIX, confirming the increased circulatory time was due to protection of the rFIXFc via the Fc/FcRn interaction. Whole blood clotting time in FIX-deficient mice was corrected through 144 hours for rFIXFc, compared with 72 hours for rFIX; similar results were observed in FIX-deficient dogs. Taken together, these studies show the enhanced pharmacodynamic and pharmacokinetic properties of the rFIXFc fusion protein and provide the basis for evaluating rFIXFc in patients with hemophilia B. PMID:20056791

  9. Molecular Basis and Therapeutic Strategies to Rescue Factor IX Variants That Affect Splicing and Protein Function

    PubMed Central

    Bussani, Erica; Barbon, Elena; Pinotti, Mirko; Pagani, Franco

    2016-01-01

    Mutations that result in amino acid changes can affect both pre-mRNA splicing and protein function. Understanding the combined effect is essential for correct diagnosis and for establishing the most appropriate therapeutic strategy at the molecular level. We have identified a series of disease-causing splicing mutations in coagulation factor IX (FIX) exon 5 that are completely recovered by a modified U1snRNP particle, through an SRSF2-dependent enhancement mechanism. We discovered that synonymous mutations and missense substitutions associated to a partial FIX secretion defect represent targets for this therapy as the resulting spliced-corrected proteins maintains normal FIX coagulant specific activity. Thus, splicing and protein alterations contribute to define at the molecular level the disease-causing effect of a number of exonic mutations in coagulation FIX exon 5. In addition, our results have a significant impact in the development of splicing-switching therapies in particular for mutations that affect both splicing and protein function where increasing the amount of a correctly spliced protein can circumvent the basic functional defects. PMID:27227676

  10. Influence of factor VIII:C and factor IX activity in plasmas of haemophilic dogs on the activated partial thromboplastin time measured with two commercial reagents.

    PubMed

    Mischke, R

    2000-05-01

    The present study is based on 145 plasma samples with a reduced activity of factor VIII:C (range: 0.009-0.62 IU mL-1) and 28 samples with a reduced factor IX activity (range: 0.035-0.55 IU mL-1). The samples were collected from dogs with haemophilia A (n=22) or haemophilia B (n=3), some of these during substitution therapy. For all samples the activated partial thromboplastin time (APTT) was measured with two commercial reagents containing kaolin as a contact activator. In each case, the deficiency of factor VIII:C or IX was reflected in abnormal results of the APTT. This was true for both reagents. A significant correlation (P < 0.001) was found between factor VIII:C activity and APTT (reagent 1, Pathromtin(R); Spearman's rank correlation coefficient, rS=-0.731, reagent 2, PTT-Reagenz; rS=-0.875) as well as between factor IX activity and APTT (reagent 1, rS=-0.819; reagent 2, rS=-0.955]. In each case, the relationship between coagulation factor activity and APTT could be proven most precisely by geometric regression. The results of this study illustrate the applicability of commercial APTT test kits as a sensitive screening test of factor VIII:C and IX deficiencies in canine plasma. PMID:10792470

  11. The compressibility of high purity YbB2.

    PubMed

    Kalkan, B; Suzer, S; Ozdas, E

    2012-08-29

    The compressibility and phase stability of Y bB(2) are investigated under high pressure using high-resolution synchrotron x-ray diffraction in a diamond anvil cell. The bulk modules of high purity Y bB(2) is obtained as ∼182 GPa using the Birch-Murnaghan equation of state. The patterns measured up to 20 GPa and the pressure dependence of normalized lattice parameters, a/a(0) and c/c(0), reveal that the compressibility of Y bB(2) is low and fairly isotropic, and this material can be classified as a hard material. X-ray photoemission studies demonstrate that Yb in Y bB(2) has a mostly trivalent valence state at room temperature. Moreover, sample preparation details provide a new insight into the high purity synthesis of Y bB(2) at ambient pressure and moderate temperatures. The presented structural and compressibility results are in agreement with the available theoretical and experimental data on binary rare-earth borides and can serve as a reliable reference for future studies. PMID:22850355

  12. Missense mutations and evolutionary conservation of amino acids: evidence that many of the amino acids in factor IX function as "spacer" elements.

    PubMed Central

    Bottema, C D; Ketterling, R P; Ii, S; Yoon, H S; Phillips, J A; Sommer, S S

    1991-01-01

    We report 31 point mutations in the factor IX gene and explore the relationship between the level of evolutionary conservation of an amino acid and the probability of a mutation causing hemophilia B. From our total sample of 125 hemophiliacs and from those reported by others, we identify 95 independent missense mutations, 94 of which occur at amino acids that are evolutionarily conserved in the available mammalian factor IX sequences. The likelihood of a missense mutation causing hemophilia B depends on whether the residue is also conserved in the factor IX-related proteases: factor VII, factor X, and protein C. Most of the possible missense mutations in generically conserved residues (i.e., those conserved in factor IX and in all the related proteases) should cause disease. In contrast, missense mutations in factor IX-specific residues (i.e., those conserved in human, cow, dog, and mouse factor IX but not in the related proteases) are sixfold less likely to cause disease. Missense mutations at nonconserved residues are 33-fold less likely to cause disease. At least three models are compatible with these observations. A comparison of sequence alignments from four and nine species of factor IX and an examination of the missense mutations occurring at CpG residues suggest a model in which most residues fall on opposite ends of a spectrum. In about 40% of residues, virtually any missense mutation in a minority of the residues will cause disease, while virtually no missense mutations will cause disease in most of the remaining residues. Thus, many of the residues in factor IX are spacers; that is, the main chains are presumably necessary to keep other amino acid interactions in register, but the nature of the side chain is unimportant. PMID:1680287

  13. The first EGF domain of coagulation factor IX attenuates cell adhesion and induces apoptosis.

    PubMed

    Ishikawa, Tomomi; Kitano, Hisataka; Mamiya, Atsushi; Kokubun, Shinichiro; Hidai, Chiaki

    2016-07-01

    Coagulation factor IX (FIX) is an essential plasma protein for blood coagulation. The first epidermal growth factor (EGF) motif of FIX (EGF-F9) has been reported to attenuate cell adhesion to the extracellular matrix (ECM). The purpose of the present study was to determine the effects of this motif on cell adhesion and apoptosis. Treatment with a recombinant EGF-F9 attenuated cell adhesion to the ECM within 10 min. De-adhesion assays with native FIX recombinant FIX deletion mutant proteins suggested that the de-adhesion activity of EGF-F9 requires the same process of FIX activation as that which occurs for coagulation activity. The recombinant EGF-F9 increased lactate dehydrogenase (LDH) activity release into the medium and increased the number of cells stained with annexin V and activated caspase-3, by 8.8- and 2.7-fold respectively, indicating that EGF-F9 induced apoptosis. Activated caspase-3 increased very rapidly after only 5 min of administration of recombinant EGF-F9. Treatment with EGF-F9 increased the level of phosphorylated p38 mitogen-activated protein kinase (MAPK), but not that of phosphorylated MAPK 44/42 or c-Jun N-terminal kinase (JNK). Inhibitors of caspase-3 suppressed the release of LDH. Caspase-3 inhibitors also suppressed the attenuation of cell adhesion and phosphorylation of p38 MAPK by EGF-F9. Our data indicated that EGF-F9 activated signals for apoptosis and induced de-adhesion in a caspase-3 dependent manner. PMID:27129300

  14. Development of high purity niobium used in SRF accelerating cavity

    NASA Astrophysics Data System (ADS)

    Chen, Lin; Xie, Wei-Ping; Li, Ming-Yang; He, Ji-Lin; Fan, Hui-Ru; Zhang, Bao-Cheng; He, Fei-Si; Zhao, Kui; Chen, Jia-Er; Liu, Ke-Xin

    2008-12-01

    Niobium is widely used in SRF (Superconducting Radio Frequency) cavities due to its excellent superconductivity and workability. With the continuous development of technology, higher demands of material are raised. One of the key issues is that RRR (Residual Resistance Ratio) of the Nb material should be more than 300, which requires that the Nb ingot have even higher RRR. This article introduces the development and the experimental results of high purity niobium in OTIC in Ningxia (Ningxia Orient Tantalum Industry Co. Ltd.), and the test results of the single cell TESLA (Tera Electron volt energy Superconducting Linear Accelerator) shaped cavity manufactured by Peking University using Nb material from OTIC. Supported by National Basic Research Program of China (2002CB713600)

  15. Secondary emission conductivity of high purity silica fabric

    NASA Technical Reports Server (NTRS)

    Belanger, V. J.; Eagles, A. E.

    1977-01-01

    High purity silica fabrics were proposed for use as a material to control the effects of electrostatic charging of satellites at synchronous altitudes. These materials exhibited very quiet behavior when placed in simulated charging environments as opposed to other dielectrics used for passive thermal control which exhibit varying degrees of electrical arcing. Secondary emission conductivity is proposed as a mechanism for this superior behavior. Design of experiments to measure this phenomena and data taken on silica fabrics are discussed as they relate to electrostatic discharge (ESD) control on geosynchronous orbit spacecraft. Studies include the apparent change in resistivity of the material as a function of the electron beam energy, flux intensity, and the effect of varying electric fields impressed across the material under test.

  16. Physical and mechanical metallurgy of high purity Nb accelerator cavities.

    SciTech Connect

    Wright, N. T.; Bieler, T. R.; Pourgoghart , F.; Compton, C.; Hartwig, K. T.; Baars, D.; Zamiri, A.; Chandrasekaran, S.; Darbandi, P.; Jiang, H.; Skoug, E.; Balachandran, S.; Ice, G. E.; Liu, W.; Michigan State Univ.; Texas A & M Univ.; ORNL

    2010-01-01

    In the past decade, high Q values have been achieved in high purity Nb superconducting radio frequency (SRF) cavities. Fundamental understanding of the physical metallurgy of Nb that enables these achievements is beginning to reveal what challenges remain to establish reproducible and cost-effective production of high performance SRF cavities. Recent studies of dislocation substructure development and effects of recrystallization arising from welding and heat treatments and their correlations with cavity performance are considered. With better fundamental understanding of the effects of dislocation substructure evolution and recrystallization on electron and phonon conduction, as well as the interior and surface states, it will be possible to design optimal processing paths for cost-effective performance using approaches such as hydroforming, which minimizes or eliminates welds in a cavity.

  17. Precipitation of hydrides in high purity niobium after different treatments

    SciTech Connect

    Barkov, F.; Romanenko, A.; Trenikhina, Y.; Grassellino, A.

    2013-01-01

    Precipitation of lossy non-superconducting niobium hydrides represents a known problem for high purity niobium in superconducting applications. Using cryogenic optical and laser confocal scanning microscopy we have directly observed surface precipitation and evolution of niobium hydrides in samples after different treatments used for superconducting RF cavities for particle acceleration. Precipitation is shown to occur throughout the sample volume, and the growth of hydrides is well described by the fast diffusion-controlled process in which almost all hydrogen is precipitated at $T=140$~K within $\\sim30$~min. 120$^{\\circ}$C baking and mechanical deformation are found to affect hydride precipitation through their influence on the number of nucleation and trapping centers.

  18. Springback in Deep Drawn High Purity Niobium for Superconductor Cavities

    SciTech Connect

    Ganapati Rao Myneni; Peter Kneisel

    2005-09-01

    Superconducting radio frequency (SRF) cavities made from deep drawn high-purity niobium have become a popular approach for the design of particle accelerators. A number of current accelerators use this technology and it is a leading candidate for future designs. The development of this technology has required significant advances in many scientific fields including metallurgy, high vacuum physics, surface science, and forming. Recently proposed modifications to the current process for fabrication of these cavities has resulted in increased concern about the distribution of deformation, residual stress patterns, and springback. This presentation will report on the findings of a recently initiated program to study plastic flow and springback in the fabrication of these cavities and the influence of metallurgical variables including grain size and impurity content.

  19. Study on the Properties of High Purity Germanium Crystals

    NASA Astrophysics Data System (ADS)

    Yang, G.; Mei, H.; Guan, Y. T.; Wang, G. J.; Mei, D. M.; Irmscher, K.

    2015-05-01

    In the crystal growth lab of South Dakota University, we are growing high purity germanium (HPGe) crystals and using the grown crystals to make radiation detectors. As the detector grade HPGe crystals, they have to meet two critical requirements: an impurity level of ∼109 to 10 atoms /cm3 and a dislocation density in the range of ∼102 to 104 / cm3. In the present work, we have used the following four characterization techniques to investigate the properties of the grown crystals. First of all, an x-ray diffraction method was used to determine crystal orientation. Secondly, the van der Pauw Hall effect measurement was used to measure the electrical properties. Thirdly, a photo-thermal ionization spectroscopy (PTIS) was used to identify what the impurity atoms are in the crystal. Lastly, an optical microscope observation was used to measure dislocation density in the crystal. All of these characterization techniques have provided great helps to our crystal activities.

  20. Dislocation distribution in large high-purity germanium crystal

    NASA Astrophysics Data System (ADS)

    Mei, Hao; Wang, Guojian; Mei, Dongming; Huang, Mianliang; Yang, Gang; Guan, Yutong; Cubed Collaboration

    2014-03-01

    We investigated the impacts of growth rate, time-temperature profile, thermal gradient on the dislocation distribution in large high-purity germanium crystal (12 cm in diameter) grown via Czochralski along <100>orientation. The time-temperature profiles of the crystal grown at different input power were investigated using direct measurements and computational modeling. The effect of crystallization speed on dislocation density is discussed from the context of thermal gradient during growth. Several samples from the grown crystals were used for this investigation. We measured dislocation density across the entire cross-section of the grown crystal through the microscope. By measuring and calculating the dislocation density, we were able to identify the denseness and the type of dislocation, which allows us to study how the thermal stress impacts the dislocation generation and distribution across the large grown crystals. This work is supported by DOE grant DE-FG02-10ER46709 and the state of South Dakota.

  1. Stable and high-level production of recombinant Factor IX in human hepatic cell line.

    PubMed

    de Castilho Fernandes, Andrielle; Fontes, Aparecida; Gonsales, Nathalia; Swiech, Kamilla; Picanco-Castro, Virginia; Faca, Sandra; Covas, Dimas

    2011-01-01

    Hemophilia B is a genetic disease of the coagulation system that affects one in 30,000 males worldwide. Recombinant human Factor IX (rhFIX) has been used for hemophilia B treatment, but the amount of active protein generated by these systems is inefficient, resulting in a high-cost production of rhFIX. In this study, we developed an alternative for rhFIX production. We used a retrovirus system to obtain two recombinant cell lines. We first tested rhFIX production in the human embryonic kidney 293 cells (293). Next, we tested a hepatic cell line (HepG2) because FIX is primarily expressed in the liver. Our results reveal that intracellular rhFIX expression was more efficient in HepG2/rhFIX (46%) than in 293/rhFIX (21%). The activated partial thromboplastin time test showed that HepG2/rhFIX expressed biologically active rhFIX 1.5 times higher than 293/rhFIX (P = 0.016). Recovery of rhFIX from the HepG2 by reversed-phase chromatography was straightforward. We found that rhFIX has a pharmacokinetic profile similar to that of FIX purified from human plasma when tested in hemophilic B model. HepG2/rhFIX cell line produced the highest levels of rhFIX, representing an efficient in vitro expression system. This work opens up the possibility of significantly reducing the costs of rhFIX production, with implications for expanding hemophilia B treatment in developing countries. PMID:21838798

  2. In silico designing of hyper-glycosylated analogs for the human coagulation factor IX.

    PubMed

    Ghasemi, Fahimeh; Zomorodipour, Alireza; Karkhane, Ali Asghar; Khorramizadeh, M Reza

    2016-07-01

    N-glycosylation is a process during which a glycan moiety attaches to the asparagine residue in the N-glycosylation consensus sequence (Asn-Xxx-Ser/Thr), where Xxx can be any amino acid except proline. Introduction of a new N-glycosylation site into a protein backbone leads to its hyper-glycosylation, and may improve the protein properties such as solubility, folding, stability, and secretion. Glyco-engineering is an approach to facilitate the hyper-glycosylation of recombinant proteins by application of the site-directed mutagenesis methods. In this regard, selection of a suitable location on the surface of a protein for introduction of a new N-glycosylation site is a main concern. In this work, a computational approach was conducted to select suitable location(s) for introducing new N-glycosylation sites into the human coagulation factor IX (hFIX). With this aim, the first 45 residues of mature hFIX were explored to find out suitable positions for introducing either Asn or Ser/Thr residues, to create new N-glycosylation site(s). Our exploration lead to detection of five potential positions, for hyper-glycosylation. For each suggested position, an analog was defined and subjected for N-glycosylation efficiency prediction. After generation of three-dimensional structures, by homology-based modeling, the five designed analogs were examined by molecular dynamic (MD) simulations, to predict their stability levels and probable structural distortions caused by amino acid substitutions, relative to the native counterpart. Three out of five suggested analogs, namely; E15T, K22N, and R37N, reached equilibration state with relatively constant Root Mean Square Deviation values. Additional analysis on the data obtained during MD simulations, lead us to conclude that, R37N is the only qualified analog with the most similar structure and dynamic behavior to that of the native counterpart, to be considered for further experimental investigations. PMID:27356208

  3. Ultrasound-targeted hepatic delivery of factor IX in hemophiliac mice

    PubMed Central

    Anderson, C D; Moisyadi, S; Avelar, A; Walton, C B; Shohet, R V

    2016-01-01

    Ultrasound-targeted microbubble destruction (UTMD) was used to direct the delivery of plasmid and transposase-based vectors encoding human factor IX (hFIX) to the livers of hemophilia B (FIX−/−) mice. The DNA vectors were incorporated into cationic lipid microbubbles, injected intravenously, and transfected into hepatocytes by acoustic cavitation of the bubbles as they transited the liver. Ultrasound parameters were identified that produced transfection of hepatocytes in vivo without substantial damage or bleeding in the livers of the FIX-deficient mice. These mice were treated with a conventional expression plasmid, or one containing a piggyBac transposon construct, and hFIX levels in the plasma and liver were evaluated at multiple time points after UTMD. We detected hFIX in the plasma by western blotting from mice treated with either plasmid during the 12 days after UTMD, and in the hepatocytes of treated livers by immunofluorescence. Reductions in clotting time and improvements in the percentage of FIX activity were observed for both plasmids, conventional (4.15±1.98%), and transposon based (2.70±.75%), 4 to 5 days after UTMD compared with untreated FIX (−/−) control mice (0.92±0.78%) (P=0.001 and P=0.012, respectively). Reduced clotting times persisted for both plasmids 12 days after treatment (reflecting percentage FIX activity of 3.12±1.56%, P=0.02 and 3.08±0.10%, P=0.001, respectively). Clotting times from an additional set of mice treated with pmGENIE3-hFIX were evaluated for long-term effects and demonstrated a persistent reduction in average clotting time 160 days after a single treatment. These data suggest that UTMD could be a minimally invasive, nonviral approach to enhance hepatic FIX expression in patients with hemophilia. PMID:26960037

  4. Potency determination of factor VIII and factor IX for new product labelling and postinfusion testing: challenges for caregivers and regulators.

    PubMed

    Dodt, J; Hubbard, A R; Wicks, S J; Gray, E; Neugebauer, B; Charton, E; Silvester, G

    2015-07-01

    A workshop organized by the European Medicines Agency and the European Directorate for the Quality of Medicines and HealthCare was held in London, UK on November 28-29, 2013, to provide an overview of the current knowledge of the characterization of new factor VIII (FVIII) and factor IX (FIX) concentrates with respect to potency assays and testing of postinfusion material. The objective was to set the basis for regulatory authorities' discussion on the most appropriate potency assay for the individual products, and European Pharmacopoeia (Ph. Eur.) discussion on whether to propose revision of the Ph. Eur. monographs with respect to potency assays in the light of information on new FVIII and FIX concentrates. The workshop showed that for all products valid assays vs. the international concentrate standards were obtained and potency could be expressed in International Units. The Ph. Eur. chromogenic potency assay gave valid assay results which correlate with in vivo functionality of rFVIII products. For some modified rFVIII products and all modified rFIX products, one-stage clotting assay methods result in different potencies depending on the activated partial thromboplastin time reagent. As a consequence, monitoring of patients' postinfusion levels is challenging but it was pointed out that manufacturers are responsible for providing the users with appropriate information for use and laboratory testing of their product. Strategies to avoid misleading determination of patents' plasma levels, e.g. information on suitable assays, laboratory standards or correction factors were discussed. PMID:25623631

  5. Characterization of IXINITY® (Trenonacog Alfa), a Recombinant Factor IX with Primary Sequence Corresponding to the Threonine-148 Polymorph

    PubMed Central

    Monroe, Dougald M.; Jenny, Richard J.; Van Cott, Kevin E.; Saward, Laura L.

    2016-01-01

    The goal of these studies was to extensively characterize the first recombinant FIX therapeutic corresponding to the threonine-148 (Thr-148) polymorph, IXINITY (trenonacog alfa [coagulation factor IX (recombinant)]). Gel electrophoresis, circular dichroism, and gel filtration were used to determine purity and confirm structure. Chromatographic and mass spectrometry techniques were used to identify and quantify posttranslational modifications. Activity was assessed as the ability to activate factor X (FX) both with and without factor VIIIa (FVIIIa) and in a standard clotting assay. All results were consistent across multiple lots. Trenonacog alfa migrated as a single band on Coomassie-stained gels; activity assays were normal and showed <0.002 IU of activated factor IX (FIXa) per IU of FIX. The molecule has >97%  γ-carboxylation and underwent the appropriate structural change upon binding calcium ions. Trenonacog alfa was activated normally with factor XIa (FXIa); once activated it bound to FVIIIa and FXa. When activated to FIXa, it was inhibited efficiently by antithrombin. Glycosylation patterns were similar to plasma-derived FIX with sialic acid content consistent with the literature reports of good pharmacokinetic performance. These studies have shown that trenonacog alfa is a highly pure product with a primary sequence and posttranslational modifications consistent with the common Thr-148 polymorphism of plasma-derived FIX. PMID:26997955

  6. Characterization of IXINITY® (Trenonacog Alfa), a Recombinant Factor IX with Primary Sequence Corresponding to the Threonine-148 Polymorph.

    PubMed

    Monroe, Dougald M; Jenny, Richard J; Van Cott, Kevin E; Buhay, Shelly; Saward, Laura L

    2016-01-01

    The goal of these studies was to extensively characterize the first recombinant FIX therapeutic corresponding to the threonine-148 (Thr-148) polymorph, IXINITY (trenonacog alfa [coagulation factor IX (recombinant)]). Gel electrophoresis, circular dichroism, and gel filtration were used to determine purity and confirm structure. Chromatographic and mass spectrometry techniques were used to identify and quantify posttranslational modifications. Activity was assessed as the ability to activate factor X (FX) both with and without factor VIIIa (FVIIIa) and in a standard clotting assay. All results were consistent across multiple lots. Trenonacog alfa migrated as a single band on Coomassie-stained gels; activity assays were normal and showed <0.002 IU of activated factor IX (FIXa) per IU of FIX. The molecule has >97%  γ-carboxylation and underwent the appropriate structural change upon binding calcium ions. Trenonacog alfa was activated normally with factor XIa (FXIa); once activated it bound to FVIIIa and FXa. When activated to FIXa, it was inhibited efficiently by antithrombin. Glycosylation patterns were similar to plasma-derived FIX with sialic acid content consistent with the literature reports of good pharmacokinetic performance. These studies have shown that trenonacog alfa is a highly pure product with a primary sequence and posttranslational modifications consistent with the common Thr-148 polymorphism of plasma-derived FIX. PMID:26997955

  7. Observing bulk diamond spin coherence in high-purity nanodiamonds.

    PubMed

    Knowles, Helena S; Kara, Dhiren M; Atatüre, Mete

    2014-01-01

    Nitrogen-vacancy (NV) centres in diamond are attractive for research straddling quantum information science, nanoscale magnetometry and thermometry. Whereas ultrapure bulk diamond NVs sustain the longest spin coherence times among optically accessible spins, nanodiamond NVs exhibit persistently poor spin coherence. Here we introduce high-purity nanodiamonds accommodating record-long NV coherence times, >60 μs, observed through universal dynamical decoupling. We show that the main contribution to decoherence comes from nearby nitrogen impurities rather than surface states. We protect the NV spin free precession, essential to d.c. magnetometry, by driving solely these impurities into the motional narrowing regime. This extends the NV free induction decay time from 440 ns, longer than that in type Ib bulk diamond, to 1.27 μs, which is comparable to that in type IIa (impurity-free) diamond. These properties allow the simultaneous exploitation of both high sensitivity and nanometre resolution in diamond-based emergent quantum technologies. PMID:24270582

  8. High Purity Zirconium Tetrafluoride For Fluoride Glass Applications

    NASA Astrophysics Data System (ADS)

    Withers, Howard P.; Monk, V. A.; Cooper, G. A.

    1989-06-01

    A totally anhydrous process has been developed for the preparation of high purity zirconium tetrafluoride for use in low loss fluoride glass applications. The ZrF4 purityis 99.99997% with respect to all transition elements (excluding HO based on analysis by spark source mass spectrometry (SSMS) and graphite furnace/atomic absorption spectroscopy (GF/AA). The only transition elements detected by these techniques were Fe, Ni and Cr, while Co and Cu were consistently below the detection limits. The anhydrous nature of the process, which is strictly maintained by the choice of reactants, affords product with very low oxide and hydroxide content. Total oxygen concentrations of less than 10 ppm have been measured by the inert gas fusion technique. A ZBLAN glass composition prepared using this ZrF4 showed extremely low UV absorption having an absorption constant of 1 cm-1 at 198 nm. ZrF4 from this process was also used in a ZBLAN glass fiber whose minimum optical loss was measured at 6.3 dB/km over 150 meters of fiber. The process is straightforward to scale up and has also been demonstrated to be useful for the preparation of HfF4, BaF2, A1F3 and LaF3.

  9. Improved scheme for the analysis of high-purity talc.

    PubMed

    Norwitz, G; Gordon, H

    1977-01-01

    An improved method is proposed for the determination of silica, magnesium oxide, R(2)O(3), ferric oxide, calcium oxide, and aluminium oxide in high-purity talc. In the method for silica and magnesium oxide, the sample is fused with sodium carbonate and the cooled melt is dissolved with perchloric acid in such a manner that it floats free from the crucible (in previous schemes for the analysis of talc there are frequently mechanical losses due to the difficulty of removing the magnesium silicate melt from the crucible). The solution is then evaporated to fumes of perchloric acid and the silica is filtered off and ignited. The magnesium oxide is determined in the filtrate by precipitation as magnesium ammonium phosphate and a correction is made for the calcium which is precipitated along with the magnesium ammonium phosphate. R(2)O(3) is determined after treatment of the sample with nitric and hydrofluoric acids and evaporation to fumes of perchloric acid. Iron oxide and calcium oxide are determined by atomic absorption, after treatment with nitric and hydrofluoric acids and evaporation to fumes of perchloric acid. Al(2)O(3) is calculated by difference. PMID:18962055

  10. Modified matrix volatilization setup for characterization of high purity germanium.

    PubMed

    Meruva, Adisesha Reddy; Raparthi, Shekhar; Kumar, Sunil Jai

    2016-01-01

    Modified matrix volatilization (MV) method has been described to characterize high purity germanium material of 7 N (99.99999%) purity. Transport of both, the chlorine gas generated in-situ in this method and the argon gas (carrier) is fine controlled by means of a mass flow controller. This enabled both uniform reaction of chlorine gas with the germanium matrix and smooth removal of germanium matrix as its chloride. This resulted in improvement in the reproducibility of the analytical results. The use of quartz reaction vessel has lead to the reduction in the process blank levels. The combined effect of these modifications in the MV setup has resulted in very consistent and low process blanks and hence improved detection limits of this method. Applicability of the method has been expanded to rare earth elements and other elements after examining their recoveries. The quantification is done by using inductively coupled plasma quadrupole mass spectrometer (ICP-QMS) and continuum source graphite furnace atomic absorption spectrometry (CS-GFAAS). In the absence of certified reference materials for high pure germanium, the accuracy of the method is established by spike recovery tests. The precision of the method has been found to vary from 1 to 30% for concentrations between 1 and 30 ng g(-1). The limits of detection (LOD) for the target analytes are found to be between 18 and 0.033 ng g(-1). PMID:26695261

  11. Spectroscopic Determination of Trace Contaminants in High Purity Oxygen

    NASA Technical Reports Server (NTRS)

    Hornung, Steven D.

    2011-01-01

    Oxygen used for extravehicular activities (EVA) must be free of contaminants because a difference in a few tenths of a percent of argon or nitrogen content can mean significant reduction in available EVA time. These inert gases build up in the extravehicular mobility unit because they are not metabolized or scrubbed from the atmosphere. Measurement of oxygen purity above 99.5% is problematic, and currently only complex instruments such as gas chromatographs or mass spectrometers are used for these determinations. Because liquid oxygen boil-off from the space shuttle will no longer be available to supply oxygen for EVA use, other concepts are being developed to produce and validate high purity oxygen from cabin air aboard the International Space Station. A prototype optical emission technique capable of detecting argon and nitrogen below 0.1% in oxygen was developed at White Sands Test Facility. This instrument uses a glow discharge in reduced pressure gas to produce atomic emission from the species present. Because the atomic emission lines from oxygen, nitrogen, and argon are discrete and in many cases well-separated, trace amounts of argon and nitrogen can be detected in the ultraviolet and visible spectrum. This is a straightforward, direct measurement of the target contaminants and may lend itself to a device capable of on-orbit verification of oxygen purity. System design and optimized measurement parameters are presented.

  12. Permeation of oxygen through high purity, large grain silver

    NASA Technical Reports Server (NTRS)

    Outlaw, R. A.; Peregoy, W. K.; Hoflund, Gar B.

    1987-01-01

    The permeation of high purity, large grain Ag membranes by oxygen has been studied over the temperature range 400 to 800 C. The permeability was found to be quite linear and repeatable, but the magnitude was 3.2 times smaller than that determined by past research. Since previous investigators studied substantially less pure Ag and conducted experiments within much poorer vacuum environments (which indicates that their grain boundary density was much greater), the data presented here suggest oxygen transport through the membrane is primarily by grain boundary diffusion. The diffusivity measurements were found to exhibit two distinct linear regions, one above and one below a critical temperature of 630 C. The high-temperature data have an activation energy (11.1 kcal/mole) similar to that reported by others, but the low-temperature data have a higher activation energy (15.3 kcal/mole), which can be explained by impurity trapping in the grain boundaries. Vacuum desorption of the oxygen-saturated Ag was found to occur at a threshold of 630 C, which is consistent with the onset of increased mobility within the grain boundaries.

  13. High-purity Cu nanocrystal synthesis by a dynamic decomposition method

    NASA Astrophysics Data System (ADS)

    Jian, Xian; Cao, Yu; Chen, Guozhang; Wang, Chao; Tang, Hui; Yin, Liangjun; Luan, Chunhong; Liang, Yinglin; Jiang, Jing; Wu, Sixin; Zeng, Qing; Wang, Fei; Zhang, Chengui

    2014-12-01

    Cu nanocrystals are applied extensively in several fields, particularly in the microelectron, sensor, and catalysis. The catalytic behavior of Cu nanocrystals depends mainly on the structure and particle size. In this work, formation of high-purity Cu nanocrystals is studied using a common chemical vapor deposition precursor of cupric tartrate. This process is investigated through a combined experimental and computational approach. The decomposition kinetics is researched via differential scanning calorimetry and thermogravimetric analysis using Flynn-Wall-Ozawa, Kissinger, and Starink methods. The growth was found to be influenced by the factors of reaction temperature, protective gas, and time. And microstructural and thermal characterizations were performed by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and differential scanning calorimetry. Decomposition of cupric tartrate at different temperatures was simulated by density functional theory calculations under the generalized gradient approximation. High crystalline Cu nanocrystals without floccules were obtained from thermal decomposition of cupric tartrate at 271°C for 8 h under Ar. This general approach paves a way to controllable synthesis of Cu nanocrystals with high purity.

  14. Expression of human factor IX in rabbit hepatocytes by retrovirus-mediated gene transfer: Potential for gene therapy of hemophilia B

    SciTech Connect

    Thompson, A.R. Puget Sound Blood Center, Seattle, WA ); Darlington, G. ); Armentano, D.; Woo, S.L.C.

    1990-08-01

    Hemophilia B (Christmas disease) is a chromosome X-linked blood clotting disorder which results when factor IX is deficient or functionally defective. The enzyme is synthesized in the liver, and the existence of animal models for this genetic disease will permit the development of somatic gene therapy protocols aimed at transfer of the functional gene into the liver. The authors report the construction of an N2-based recombinant retroviral vector, NCMVFIX, for efficient transfer and expression of human factor IX cDNA in primary rabbit hepatocytes. In this construct the human cytomegalovirus immediate early promoter directs the expression of factor IX. Hepatocytes were isolated from 3-week-old New Zealand White rabbits, infected with the recombinant virus, and analyzed for secretion of active factor IX. The infected rabbit hepatocytes produced human factor IX that is indistinguishable from enzyme derived from normal human plasma. The recombinant protein is sufficiently {gamma}-carboxylated and is functionally active in clotting assays. These results establish the feasibility of using infected hepatocytes for the expression of this protein and are a step toward the goal of correcting hemophilia B by hepatic gene transfer.

  15. The propeptide region of clotting factor IX is a signal for a vitamin K dependent carboxylase: evidence from protein engineering of amino acid -4.

    PubMed Central

    Galeffi, P; Brownlee, G G

    1987-01-01

    Homologous "propeptide" regions are present in a family of vitamin K-dependent mammalian proteins, including clotting factors II, VII, IX, X, protein C, protein S and bone "gla" proteins. To test the hypothesis that the propeptide is a signal for the correct gamma-carboxylation of the adjacent gamma-carboxy region, we have mutated amino acid -4 of human factor IX from an arginine to a glutamine residue, by M13-directed site-specific mutagenesis of a cDNA clone. After expression of mutant factor IX in dog kidney cells, we find that it is secreted into the medium in a precursor form containing the propeptide, and is inefficiently gamma-carboxylated compared to the control, wild-type, recombinant factor IX. This result supports the hypothesis that the propeptide region is required for efficient gamma-carboxylation of factor IX in dog kidney cells. Furthermore, it confirms previous results that arginine at amino acid -4 is required for correct propeptide processing. Images PMID:3684602

  16. Results of a phase I/II open-label, safety and efficacy trial of coagulation factor IX (recombinant), albumin fusion protein in haemophilia B patients

    PubMed Central

    Martinowitz, U; Lissitchkov, T; Lubetsky, A; Jotov, G; Barazani-Brutman, T; Voigt, C; Jacobs, I; Wuerfel, T; Santagostino, E

    2015-01-01

    Introduction rIX-FP is a coagulation factor IX (recombinant), albumin fusion protein with more than fivefold half-life prolongation over other standard factor IX (FIX) products available on the market. Aim This prospective phase II, open-label study evaluated the safety and efficacy of rIX-FP for the prevention of bleeding episodes during weekly prophylaxis and assessed the haemostatic efficacy for on-demand treatment of bleeding episodes in previously treated patients with haemophilia B. Methods The study consisted of a 10–14 day evaluation of rIX-FP pharmacokinetics (PK), and an 11 month safety and efficacy evaluation period with subjects receiving weekly prophylaxis treatment. Safety was evaluated by the occurrence of related adverse events, and immunogenic events, including development of inhibitors. Efficacy was evaluated by annualized spontaneous bleeding rate (AsBR), and the number of injections to achieve haemostasis. Results Seventeen subjects participated in the study, 13 received weekly prophylaxis and 4 received episodic treatment only. No inhibitors were detected in any subject. The mean and median AsBR were 1.25, and 1.13 respectively in the weekly prophylaxis arm. All bleeding episodes were treated with 1 or 2 injections of rIX-FP. Three prophylaxis subjects who were treated on demand prior to study entry had >85% reduction in AsBR compared to the bleeding rate prior to study entry. Conclusion This study demonstrated the efficacy for weekly routine prophylaxis of rIX-FP to prevent spontaneous bleeding episodes and for the treatment of bleeding episodes. In addition no safety issues were detected during the study and an improved PK profile was demonstrated. PMID:25990590

  17. The Hydrometallurgical Extraction and Recovery of High-Purity Silver

    NASA Astrophysics Data System (ADS)

    Hoffmann, James E.

    2012-06-01

    -bearing inputs, will be described in detail to demonstrate how typical chemical engineering unit process and unit operations have supplanted classic smelting and fire refining techniques. The Kennecott Copper Company, which has operated a hydrometallurgical circuit successfully for the recovery of high-purity silver from the slimes wet chlorination residue, has permitted me to provide some operation information and results using the technology. Both Phelps Dodge and Kennecott should be recognized for their forward-looking attitude in undertaking the conversion of conceptual chemistry into successful, full-scale plants. The process as employed at Phelps Dodge is discussed at length in reference (J.E. Hoffmann and B. Wesstrom: Hydrometallurgy, 1994, vol. 94, pp. 69-105).

  18. Coronary artery bypass grafting in a patient with hemophilia B: continuous recombinant factor IX infusion as per the Japanese guidelines for replacement therapy.

    PubMed

    Suzuki, Tomoyuki; Kawamoto, Shunsuke; Kumagai, Kiichiro; Adachi, Osamu; Kanda, Keisuke; Ishikawa, Masaaki; Okitsu, Yoko; Harigae, Hideo; Kurosawa, Shin; Saiki, Yoshikatsu

    2016-08-01

    We herein report our experience of successfully managing the hemostatic system by controlling serum factor IX levels throughout the perioperative period in a patient with hemophilia B. Coronary artery bypass grafting with cardiopulmonary bypass was planned for a 52-year-old man with moderate severity of hemophilia B. During surgery, recombinant factor IX (rFIX; BeneFIX(®) Pfizer Japan inc., Tokyo, Japan) was administered by bolus infusion followed by continuous infusion as per the guidelines of the Japanese Society on Thrombosis and Hemostasis. The operative course was uneventful without any considerable bleeding or complications. PMID:25523881

  19. SIMULTANEOUS PRODUCTION OF HIGH-PURITY HYDROGEN AND SEQUESTRATION-READY CO2 FROM SYNGAS

    SciTech Connect

    Linda Denton; Hana Lorethova; Tomasz Wiltowski; Court Moorefield; Parag Kulkarni; Vladimir Zamansky; Ravi Kumar

    2003-12-01

    This final report summarizes the progress made on the program ''Simultaneous Production of High-Purity Hydrogen and Sequestration-Ready CO{sub 2} from Syngas (contract number DE-FG26-99FT40682)'', during October 2000 through September of 2003. GE Energy and Environmental Research (GE-EER) and Southern Illinois University (SIU) at Carbondale conducted the research work for this program. This program addresses improved methods to efficiently produce simultaneous streams of high-purity hydrogen and separated carbon dioxide from synthesis gas (syngas). The syngas may be produced through either gasification of coal or reforming of natural gas. The process of production of H{sub 2} and separated CO{sub 2} utilizes a dual-bed reactor and regenerator system. The reactor produces hydrogen and the regenerator produces separated CO{sub 2}. The dual-bed system can be operated under either a circulating fluidized-bed configuration or a cyclic fixed-bed configuration. Both configurations were evaluated in this project. The experimental effort was divided into lab-scale work at SIU and bench-scale work at GE-EER. Tests in a lab-scale fluidized bed system demonstrated the process for the conversion of syngas to high purity H{sub 2} and separated CO{sub 2}. The lab-scale system generated up to 95% H{sub 2} (on a dry basis). Extensive thermodynamic analysis of chemical reactions between the syngas and the fluidized solids determined an optimum range of temperature and pressure operation, where the extent of the undesirable reactions is minimum. The cycling of the process between hydrogen generation and oxygen regeneration has been demonstrated. The fluidized solids did not regenerate completely and the hydrogen purity in the reuse cycle dropped to 70% from 95% (on a dry basis). Changes in morphology and particle size may be the most dominant factor affecting the efficiency of the repeated cycling between hydrogen production and oxygen regeneration. The concept of simultaneous

  20. A cleaner two-step synthesis of high purity diallyldimethylammonium chloride monomers for flocculant preparation.

    PubMed

    Tian, Bing-hui; Fan, Bin; Peng, Xian-jia; Luan, Zhao-kun

    2005-01-01

    In order to improve the flocculation efficiency of polydiallyldimethylammonium chloride (PDADMAC), high molecular weight PDADMAC should be prepared from high purity diallyldimethylammonium chloride(DADMAC) monomers. In this paper, a cleaner method with microwave irradiation and alkali solidification was proposed for preparing high pure DADMAC by selective heating under low temperature, and the prepared high purity DADMAC is characterized using FTIR and atomic absorption spectrometry. The new method provides a solution to the key technical problem of PDADMAC synthesis. Comparing with the conventional methods, the results showed that the advantages of the novel synthesis include: (a) high purity DADMAC is improved from 57% to 71%; (b) reaction time of tertiary amine preparation is shortened from 6 h to 7 min; (c) water instead of acetone was used as reaction medium; (d) toxic by-products, wastewater and waste gas are eliminated. Flocculant made from the synthesized high purity DADMAC monomers was proved more efficient in flocculation tests. PMID:16313006

  1. High purity germanium crystal growth at the University of South Dakota

    NASA Astrophysics Data System (ADS)

    Wang, Guojian; Mei, Hao; Mei, Dongming; Guan, Yutong; Yang, Gang

    2015-05-01

    High-purity germanium crystal growth is challenging work, requiring the control of individual crystal properties such as the impurity distribution, the dislocation density, and the crystalline structure. Currently, we grow high-purity germanium crystals by the Czochralski method in our laboratory in order to understand the details of the growing process, especially for large diameter crystals. In this paper, we report the progress of detector-grade germanium crystal growth at the University of South Dakota.

  2. Liver gene therapy by lentiviral vectors reverses anti-factor IX pre-existing immunity in haemophilic mice.

    PubMed

    Annoni, Andrea; Cantore, Alessio; Della Valle, Patrizia; Goudy, Kevin; Akbarpour, Mahzad; Russo, Fabio; Bartolaccini, Sara; D'Angelo, Armando; Roncarolo, Maria Grazia; Naldini, Luigi

    2013-11-01

    A major complication of factor replacement therapy for haemophilia is the development of anti-factor neutralizing antibodies (inhibitors). Here we show that liver gene therapy by lentiviral vectors (LVs) expressing factor IX (FIX) strongly reduces pre-existing anti-FIX antibodies and eradicates FIX inhibitors in haemophilia B mice. Concomitantly, plasma FIX levels and clotting activity rose to 50-100% of normal. The treatment was effective in 75% of treated mice. FIX-specific plasma cells (PCs) and memory B cells were reduced, likely because of memory B-cell depletion in response to constant exposure to high doses of FIX. Regulatory T cells displaying FIX-specific suppressive capacity were induced in gene therapy treated mice and controlled FIX-specific T helper cells. Gene therapy proved safer than a regimen mimicking immune tolerance induction (ITI) by repeated high-dose FIX protein administration, which induced severe anaphylactoid reactions in inhibitors-positive haemophilia B mice. Liver gene therapy can thus reverse pre-existing immunity, induce active tolerance to FIX and establish sustained FIX activity at therapeutic levels. These data position gene therapy as an attractive treatment option for inhibitors-positive haemophilic patients. PMID:24106222

  3. Identification and Genetic Analysis of a Factor IX Gene Intron 3 Mutation in a Hemophilia B Pedigree in China

    PubMed Central

    Cao, Dong-Hua; Liu, Xiao-Li; Mu, Kai; Ma, Xiang-Wei; Sun, Jing-Li; Bai, Xiao-Zhong; Lin, Chang-Kun; Jin, Chun-Lian

    2014-01-01

    Objective: Hemophilia B is caused by coagulation defects in the factor IX gene located in Xq27.1 on the X chromosome. A wide range of mutations, showing extensive molecular heterogeneity, have been described in hemophilia B patients. Our study was aimed at genetic analysis and prenatal diagnosis of hemophilia B in order to further elucidate the pathogenesis of the hemophilia B pedigree in China. Materials and Methods: Polymerase chain reaction amplification and direct sequencing of all the coding regions was conducted in hemophilia B patients and carriers. Prenatal diagnosis of the proband was conducted at 20 weeks. Results: We identified the novel point mutation 10.389 A>G, located upstream of the intron 3 acceptor site in hemophilia B patients. The fetus of the proband’s cousin was identified as a carrier. Conclusion: Our identification of a novel mutation in the F9 gene associated with hemophilia B provides novel insight into the pathogenesis of this genetically inherited disorder and also represents the basis of prenatal diagnosis. PMID:25330515

  4. Fibronectin-Alginate microcapsules improve cell viability and protein secretion of encapsulated Factor IX-engineered human mesenchymal stromal cells.

    PubMed

    Sayyar, Bahareh; Dodd, Megan; Marquez-Curtis, Leah; Janowska-Wieczorek, Anna; Hortelano, Gonzalo

    2015-01-01

    Continuous delivery of proteins by engineered cells encapsu-lated in biocompatible polymeric microcapsules is of considerable therapeutic potential. However, this technology has not lived up to expectations due to inadequate cell--matrix interactions and subsequent cell death. In this study we hypoth-esize that the presence of fibronectin in an alginate matrix may enhance the viability and functionality of encapsulated human cord blood-derived mesenchymal stromal cells (MSCs) expressing the human Factor IX (FIX) gene. MSCs were encapsulated in alginate-PLL microcapsules containing 10, 100, or 500 μg/ml fibronectin to ameliorate cell survival. MSCs in microcapsules with 100 and 500 μg/ml fibronectin demonstrated improved cell viability and proliferation and higher FIX secretion compared to MSCs in non-supplemented microcapsules. In contrast, 10 μg/ml fibronectin did not significantly affect the viability and protein secretion from the encapsulated cells. Differentiation studies demonstrated osteogenic (but not chondrogenic or adipogenic) differentiation capability and efficient FIX secretion of the enclosed MSCs in the fibronectin-alginate suspension culture. Thus, the use of recombinant MSCs encapsulated in fibronectin-alginate microcapsules in basal or osteogenic cultures may be of practical use in the treatment of hemophilia B. PMID:24564349

  5. CRISPR/Cas9-mediated somatic correction of a novel coagulator factor IX gene mutation ameliorates hemophilia in mouse.

    PubMed

    Guan, Yuting; Ma, Yanlin; Li, Qi; Sun, Zhenliang; Ma, Lie; Wu, Lijuan; Wang, Liren; Zeng, Li; Shao, Yanjiao; Chen, Yuting; Ma, Ning; Lu, Wenqing; Hu, Kewen; Han, Honghui; Yu, Yanhong; Huang, Yuanhua; Liu, Mingyao; Li, Dali

    2016-01-01

    The X-linked genetic bleeding disorder caused by deficiency of coagulator factor IX, hemophilia B, is a disease ideally suited for gene therapy with genome editing technology. Here, we identify a family with hemophilia B carrying a novel mutation, Y371D, in the human F9 gene. The CRISPR/Cas9 system was used to generate distinct genetically modified mouse models and confirmed that the novel Y371D mutation resulted in a more severe hemophilia B phenotype than the previously identified Y371S mutation. To develop therapeutic strategies targeting this mutation, we subsequently compared naked DNA constructs versus adenoviral vectors to deliver Cas9 components targeting the F9 Y371D mutation in adult mice. After treatment, hemophilia B mice receiving naked DNA constructs exhibited correction of over 0.56% of F9 alleles in hepatocytes, which was sufficient to restore hemostasis. In contrast, the adenoviral delivery system resulted in a higher corrective efficiency but no therapeutic effects due to severe hepatic toxicity. Our studies suggest that CRISPR/Cas-mediated in situ genome editing could be a feasible therapeutic strategy for human hereditary diseases, although an efficient and clinically relevant delivery system is required for further clinical studies. PMID:26964564

  6. Variations among Japanese of the factor IX gene (F9) detected by PCR-denaturing gradient gel electrophoresis

    SciTech Connect

    Satoh, Chiyoko; Takahashi, Norio; Asakawa, Junichi; Hiyama, Keiko; Kodaira, Meiko )

    1993-01-01

    In the course of feasibility studies to examine the efficiencies and practicalities of various techniques for screening for genetic variations, the human coagulation factor IX (F9) genes of 63 Japanese families were examined by PCR-denaturing gradient gel electrophoresis (PCR-DGGE). Four target sequences with lengths of 983-2,891 bp from the F9 genes of 126 unrelated individuals from Hiroshima and their 100 children were amplified by PCR, digested with restriction enzymes to approximately 500-bp fragments, and examined by DGGE - a total of 6,724 bp being examined per individual. GC-rich sequences (GC-clamps) of 40 bp were attached to both ends of the target sequences, as far as was feasible. Eleven types of new nucleotide substitutions were detected in the population, none of which produced RFLPs or caused hemophilia B. By examining two target sequences in a single lane, approximately 8,000 bp in a diploid individual could be examined. This approach is very effective for the detection of variations in DNA and is applicable to large-scale population studies. 46 refs., 3 figs., 1 tab.

  7. Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B.

    PubMed

    Su, Jin; Zhu, Liqing; Sherman, Alexandra; Wang, Xiaomei; Lin, Shina; Kamesh, Aditya; Norikane, Joey H; Streatfield, Stephen J; Herzog, Roland W; Daniell, Henry

    2015-11-01

    Antibodies (inhibitors) developed by hemophilia B patients against coagulation factor IX (FIX) are challenging to eliminate because of anaphylaxis or nephrotic syndrome after continued infusion. To address this urgent unmet medical need, FIX fused with a transmucosal carrier (CTB) was produced in a commercial lettuce (Simpson Elite) cultivar using species specific chloroplast vectors regulated by endogenous psbA sequences. CTB-FIX (∼1 mg/g) in lyophilized cells was stable with proper folding, disulfide bonds and pentamer assembly when stored ∼2 years at ambient temperature. Feeding lettuce cells to hemophilia B mice delivered CTB-FIX efficiently to the gut immune system, induced LAP(+) regulatory T cells and suppressed inhibitor/IgE formation and anaphylaxis against FIX. Lyophilized cells enabled 10-fold dose escalation studies and successful induction of oral tolerance was observed in all tested doses. Induction of tolerance in such a broad dose range should enable oral delivery to patients of different age groups and diverse genetic background. Using Fraunhofer cGMP hydroponic system, ∼870 kg fresh or 43.5 kg dry weight can be harvested per 1000 ft(2) per annum yielding 24,000-36,000 doses for 20-kg pediatric patients, enabling first commercial development of an oral drug, addressing prohibitively expensive purification, cold storage/transportation and short shelf life of current protein drugs. PMID:26302233

  8. Temperature sensitivity of surface channel effects on high-purity germanium detectors

    NASA Astrophysics Data System (ADS)

    Hull, E. L.; Pehl, R. H.; Madden, N. W.; Luke, P. N.; Cork, C. P.; Malone, D. L.; Xing, J. S.; Komisarcik, K.; Vanderwerp, J. D.; Friesel, D. L.

    1995-02-01

    The temperature sensitivity of surface channel effects on planar high-purity germanium detectors was measured using 60-keV gamma-ray scanning techniques, as part of a radiation damage study. When measured in this manner, the surface effects on most detectors showed extreme temperature sensitivity in the 72-95 K region. The effect of the surface channel increased with increasing temperature to such an extent that the efficiency, as measured by the count rate in the 1332-keV peak from a 60Co source, decreased by a factor of over two in some cases. Since the peak efficiency for the 1332-keV gamma ray decreased as the temperature increased throughout the operating range (72-120 K) the effect of the surface channel must continue to increase beyond the temperature (95 K) at which the 60-keV scan loses its sensitivity because of the strong attenuation of these much lower energy gamma rays. Radiation damage had no measurable effect on the surface characteristics. No correlation between the surface effects and the resolution changes of the 1332-keV peak was observed.

  9. Construction of a Bacillus amyloliquefaciens strain for high purity levan production.

    PubMed

    Feng, Jun; Gu, Yanyan; Han, Lifang; Bi, Kexin; Quan, Yufeng; Yang, Chao; Zhang, Wei; Cao, Mingfeng; Wang, Shufang; Gao, Weixia; Sun, Yang; Song, Cunjiang

    2015-06-01

    Bacillus amyloliquefaciens NK-1 has the potential to produce levan and poly-gamma-glutamic acid (γ-PGA) simultaneously. However, it is not possible to purify each single product from the same strain because the extraction process is identical. We deleted the pgs cluster (for γ-PGA synthesis) from the NK-1 strain and constructed a γ-PGA-deficient NK-ΔLP strain. Nuclear magnetic results showed that the NK-ΔLP strain could produce high purity levan product. However, its levan titer was only 1.96 g L(-1) in the basal medium. Single-factor experimental and response surface methodology was used to optimize the culture condition, leading to levan titer of 13.9 and 22.6 g L(-1) in flask culture and in a 5-L bioreactor, respectively. The levan purity can reach to 92.7% after 48 h cultivation. Furthermore, the relationship between levanase (LevB) and levan molecular weight was studied. The results showed that LevB resulted in the production of low molecular weight levan and its expression level determined the ratio of high and low molecular weight levan. We also deleted the sac cluster (for levan synthesis) from the NK-1 strain and constructed a levan-deficient NK-L strain. The NK-L strain exhibited increased purity of γ-PGA product from 79.5 to 91.2%. PMID:25953857

  10. Development, fabrication and test of a high purity silica heat shield

    NASA Technical Reports Server (NTRS)

    Rusert, E. L.; Drennan, D. N.; Biggs, M. S.

    1978-01-01

    A highly reflective hyperpure ( 25 ppm ion impurities) slip cast fused silica heat shield material developed for planetary entry probes was successfully scaled up. Process development activities for slip casting large parts included green strength improvements, casting slip preparation, aggregate casting, strength, reflectance, and subscale fabrication. Successful fabrication of a one-half scale Saturn probe (shape and size) heat shield was accomplished while maintaining the silica high purity and reflectance through the scale-up process. However, stress analysis of this original aggregate slip cast material indicated a small margin of safety (MS. = +4%) using a factor of safety of 1.25. An alternate hyperpure material formulation to increase the strength and toughness for a greater safety margin was evaluated. The alternate material incorporates short hyperpure silica fibers into the casting slip. The best formulation evaluated has a 50% by weight fiber addition resulting in an 80% increase in flexural strength and a 170% increase in toughness over the original aggregate slip cast materials with comparable reflectance.

  11. Leakage current in high-purity germanium detectors with amorphous semiconductor contacts

    NASA Astrophysics Data System (ADS)

    Looker, Q.; Amman, M.; Vetter, K.

    2015-03-01

    Amorphous semiconductor electrical contacts on high-purity Ge radiation detectors have become a valuable technology because they are simple to fabricate, result in thin dead layers, block both electron and hole injection, and can readily be finely segmented as needed for applications requiring imaging or particle tracking. Though significant numbers of detectors have been successfully produced for a variety of applications using the amorphous semiconductor contact technology, there remains a need to better understand the dependence of performance characteristics, particularly leakage current, on the fabrication process parameters so that the performance can be better optimized. To this end, we have performed a systematic study of leakage current on RF-sputter-deposited amorphous-Ge (a-Ge) and amorphous-Si (a-Si) contacts as a function of process and operational parameters including sputter gas pressure and composition, number of detector temperature cycles, and time spent at room temperature. The study focused primarily on the current resulting from electron injection at the contact. Significant findings from the study include that a-Si produces lower electron injection than a-Ge, the time the detector spends at room temperature rather than the number of temperature cycles experienced by the detector is the primary factor associated with leakage current change when the detector is warmed, and the time stability of the a-Ge contact depends on the sputter gas pressure with a higher pressure producing more stable characteristics.

  12. Mechanical Properties of High Purity Niobium - Novel Measurements

    SciTech Connect

    Ganapati Myneni

    2003-09-01

    One of the procedures to improve the performance of superconducting niobium cavities is a heat treatment for several hours in an ultrahigh vacuum at temperatures between 800C and 1400C for hydrogen degassing or post-purification, respectively. However, it was recently observed with Spallation Neutron Source Project (SNS) prototype cavities, that a heat treatment at 800 C for even 1 hour degraded the mechanical properties of RRR niobium, in particular the yield strength. This lower strength resulted in cavity deformations during handling thus affecting both their resonant frequency and field profile. In addition to lowering the yield strength, it was observed in some lots of material that the Young's modulus was also apparently reduced by a factor of 2 as a result of the hydrogen outgassing at 800 C. Surprisingly, material received at other national laboratories exhibited similar anomalous behavior even without any heat treatments in vacuum. Based on these observations a multi-institutional collaborative basic research activity on high RRR niobium (determination of Nb yield strength as a function of grain size, work hardening, chemical composition, and heat treatment temperature) has been initiated by JLAB to gain a better understanding of the material properties affecting the mechanical behavior In this contribution, a brief review of the measurements at JLAB, at the Materials Science and Engineering Department of the University of Virginia, at the Analytical Chemistry and Metallurgy Divisions of the National Institute of Standard and Technology, Gaithersburg and in the Department of Physics, SUNY, Albany are presented. The measurements include yield strength, hardness, ultrasonic velocity, crystallographic structure, microstructure, determination of interstitial contents using internal friction; particular emphasis is placed on determining the hydrogen concentration in the niobium via Cold Neutron Prompt Gamma-Ray Activation Analysis and Neutron Incoherent

  13. Impurity distribution in high purity germanium crystal and its impact on the detector performance

    NASA Astrophysics Data System (ADS)

    Wang, Guojian; Amman, Mark; Mei, Hao; Mei, Dongming; Irmscher, Klaus; Guan, Yutong; Yang, Gang

    High-purity germanium crystals were grown in a hydrogen atmosphere using the Czochralski method. The axial and radial distributions of impurities in the crystals were measured by Hall effect and Photo-thermal ionization spectroscopy (PTIS). Amorphous semiconductor contacts were deposited on the germanium crystals to make detectors. Three planar detectors were fabricated from three crystals with different net carrier concentrations (1.7, 7.9 and 10x1010 cm-3). We evaluated the electrical and spectral performance of three detectors. Measurements of gamma-ray spectra from 137Cs, 241Am and 60Co sources demonstrate that the detectors have excellent energy resolution. The relationship between the impurities and detector's energy resolution was analyzed. Keywords: High-purity germanium crystal, High-purity germanium detector This work is supported by DOE grant DE-FG02-10ER46709 and the state of South Dakota..

  14. Coagulation Factor IX Mediates Serotype-Specific Binding of Species A Adenoviruses to Host Cells ▿ †

    PubMed Central

    Lenman, Annasara; Müller, Steffen; Nygren, Mari I.; Frängsmyr, Lars; Stehle, Thilo; Arnberg, Niklas

    2011-01-01

    Human species A adenoviruses (HAdVs) comprise three serotypes: HAdV-12, -18, and -31. These viruses are common pathogens and cause systemic infections that usually involve the airways and/or intestine. In immunocompromised individuals, species A adenoviruses in general, and HAdV-31 in particular, cause life-threatening infections. By combining binding and infection experiments, we demonstrate that coagulation factor IX (FIX) efficiently enhances binding and infection by HAdV-18 and HAdV-31, but not by HAdV-12, in epithelial cells originating from the airways or intestine. This is markedly different from the mechanism for HAdV-5 and other human adenoviruses, which utilize coagulation factor X (FX) for infection of host cells. Surface plasmon resonance experiments revealed that the affinity of the HAdV-31 hexon-FIX interaction is higher than that of the HAdV-5 hexon-FX interaction and that the half-lives of these interactions are profoundly different. Moreover, both HAdV-31–FIX and HAdV-5–FX complexes bind to heparan sulfate-containing glycosaminoglycans (GAGs) on target cells, but binding studies utilizing cells expressing specific GAGs and GAG-cleaving enzymes revealed differences in GAG dependence and specificity between these two complexes. These findings add to our understanding of the intricate infection pathways used by human adenoviruses, and they may contribute to better design of HAdV-based vectors for gene and cancer therapy. Furthermore, the interaction between the HAdV-31 hexon and FIX may also serve as a target for antiviral treatment. PMID:21976659

  15. A two-component system regulates gene expression of the type IX secretion component proteins via an ECF sigma factor

    PubMed Central

    Kadowaki, Tomoko; Yukitake, Hideharu; Naito, Mariko; Sato, Keiko; Kikuchi, Yuichiro; Kondo, Yoshio; Shoji, Mikio; Nakayama, Koji

    2016-01-01

    The periodontopathogen Porphyromonas gingivalis secretes potent pathogenic proteases, gingipains, via the type IX secretion system (T9SS). This system comprises at least 11 components; however, the regulatory mechanism of their expression has not yet been elucidated. Here, we found that the PorY (PGN_2001)-PorX (PGN_1019)-SigP (PGN_0274) cascade is involved in the regulation of T9SS. Surface plasmon resonance (SPR) analysis revealed a direct interaction between a recombinant PorY (rPorY) and a recombinant PorX (rPorX). rPorY autophosphorylated and transferred a phosphoryl group to rPorX in the presence of Mn2+. These results demonstrate that PorX and PorY act as a response regulator and a histidine kinase, respectively, of a two component system (TCS), although they are separately encoded on the chromosome. T9SS component-encoding genes were down-regulated in a mutant deficient in a putative extracytoplasmic function (ECF) sigma factor, PGN_0274 (SigP), similar to the porX mutant. Electrophoretic gel shift assays showed that rSigP bound to the putative promoter regions of T9SS component-encoding genes. The SigP protein was lacking in the porX mutant. Co-immunoprecipitation and SPR analysis revealed the direct interaction between SigP and PorX. Together, these results indicate that the PorXY TCS regulates T9SS-mediated protein secretion via the SigP ECF sigma factor. PMID:26996145

  16. A two-component system regulates gene expression of the type IX secretion component proteins via an ECF sigma factor.

    PubMed

    Kadowaki, Tomoko; Yukitake, Hideharu; Naito, Mariko; Sato, Keiko; Kikuchi, Yuichiro; Kondo, Yoshio; Shoji, Mikio; Nakayama, Koji

    2016-01-01

    The periodontopathogen Porphyromonas gingivalis secretes potent pathogenic proteases, gingipains, via the type IX secretion system (T9SS). This system comprises at least 11 components; however, the regulatory mechanism of their expression has not yet been elucidated. Here, we found that the PorY (PGN_2001)-PorX (PGN_1019)-SigP (PGN_0274) cascade is involved in the regulation of T9SS. Surface plasmon resonance (SPR) analysis revealed a direct interaction between a recombinant PorY (rPorY) and a recombinant PorX (rPorX). rPorY autophosphorylated and transferred a phosphoryl group to rPorX in the presence of Mn(2+). These results demonstrate that PorX and PorY act as a response regulator and a histidine kinase, respectively, of a two component system (TCS), although they are separately encoded on the chromosome. T9SS component-encoding genes were down-regulated in a mutant deficient in a putative extracytoplasmic function (ECF) sigma factor, PGN_0274 (SigP), similar to the porX mutant. Electrophoretic gel shift assays showed that rSigP bound to the putative promoter regions of T9SS component-encoding genes. The SigP protein was lacking in the porX mutant. Co-immunoprecipitation and SPR analysis revealed the direct interaction between SigP and PorX. Together, these results indicate that the PorXY TCS regulates T9SS-mediated protein secretion via the SigP ECF sigma factor. PMID:26996145

  17. Recombinant factor IX (BAX326) in previously treated paediatric patients with haemophilia B: a prospective clinical trial.

    PubMed

    Urasinski, T; Stasyshyn, O; Andreeva, T; Rusen, L; Perina, F G; Oh, M S; Chapman, M; Pavlova, B G; Valenta-Singer, B; Abbuehl, B E

    2015-03-01

    A newly developed recombinant factor IX (BAX326(1) ) was investigated for prophylactic use in paediatric patients aged <12 years with severe (FIX level <1%) or moderately severe (FIX level 1-2%) haemophilia B. The aim of this prospective clinical trial was to assess the safety, haemostatic efficacy and pharmacokinetic profile of BAX326 in previously treated paediatric patients. BAX326 was administered as prophylaxis twice a week for a period of 6 months, and on demand for treatment of bleeds. Safety was assessed by the occurrence of related AEs, thrombotic events and immunologic assessments. Efficacy was evaluated by annualized bleeding rate (ABR), and by treatment response rating (excellent, good, fair, none). PK was assessed over 72 h. None of the 23 treated paediatric subjects had treatment-related SAEs or AEs. There were no thrombotic events, inhibitory or specific binding antibodies against FIX, rFurin or CHO protein. Twenty-six bleeds (19 non-joint vs. 7 joint bleeds) occurred (mean ABR 2.7 ± 3.14, median 2.0), of which 23 were injury-related. Twenty subjects (87%) did not experience any bleeds of spontaneous aetiology. Haemostatic efficacy of BAX326 was excellent or good for >96% of bleeds (100% of minor, 88.9% of moderate and 100% of major bleeds); the majority (88.5%) resolved after 1-2 infusions. Longer T1/2 and lower IR were observed in younger children (<6 years) compared to those aged 6 to 12 years. BAX326 administered as prophylactic treatment as well as for controlling bleeds is efficacious and safe in paediatric patients aged <12 years with haemophilia B. PMID:25495591

  18. Use of factor IX concentrates in active teenagers with hemophilia B.

    PubMed

    Tagariello, Giuseppe

    2004-06-01

    This paper addresses issues specific to the treatment of teenagers with hemophilia B. All teenagers, including those with hemophilia, are at high risk of being exposed to accident-related trauma because of activities inherent within normal adolescent development. To reduce the impact of recurrent joint bleeds, studies have shown that prophylaxis should be started at an early age, with treatment individualized due to variability in patient pharmacokinetics and product recoveries. A key factor in the acceptance and success of prophylaxis in teenagers is the training given at hemophilia treatment centers regarding self-treatment dosing and infusion schedules. Both plasma-derived and recombinant products are appropriate in this cohort, depending on the patient's and family's experiences and preferences. PMID:15322451

  19. Production of high-purity radium-223 from legacy actinium-beryllium neutron sources.

    PubMed

    Soderquist, Chuck Z; McNamara, Bruce K; Fisher, Darrell R

    2012-07-01

    Radium-223 is a short-lived alpha-particle-emitting radionuclide with potential applications in cancer treatment. Research to develop new radiopharmaceuticals employing (223)Ra has been hindered by poor availability due to the small quantities of parent actinium-227 available world-wide. The purpose of this study was to develop innovative and cost-effective methods to obtain high-purity (223)Ra from (227)Ac. We obtained (227)Ac from two surplus actinium-beryllium neutron generators. We retrieved the actinium/beryllium buttons from the sources and dissolved them in a sulfuric-nitric acid solution. A crude actinium solid was recovered from the solution by coprecipitation with thorium fluoride, leaving beryllium in solution. The crude actinium was purified to provide about 40 milligrams of actinium nitrate using anion exchange in methanol-water-nitric acid solution. The purified actinium was then used to generate high-purity (223)Ra. We extracted (223)Ra using anion exchange in a methanol-water-nitric acid solution. After the radium was separated, actinium and thorium were then eluted from the column and dried for interim storage. This single-pass separation produces high purity, carrier-free (223)Ra product, and does not disturb the (227)Ac/(227)Th equilibrium. A high purity, carrier-free (227)Th was also obtained from the actinium using a similar anion exchange in nitric acid. These methods enable efficient production of (223)Ra for research and new alpha-emitter radiopharmaceutical development. PMID:22697483

  20. Production of High-purity Radium-223 from Legacy Actinium-Beryllium Neutron Sources

    SciTech Connect

    Z. Soderquist, Chuck; K. McNamara, Bruce; R. Fisher, Darrell

    2012-06-01

    Radium-223 is a short-lived alpha-particle-emitting radionuclides with potential applications in cancer treatment. Research to develop new radiopharmaceuticals employing 223Ra has been hindered by poor availability due to the small quantities of parent actinium-227 available world-wide. The purpose of this study was to develop innovative and cost-effective methods to obtain high-purity 223Ra from 227Ac. We obtained 227Ac from two surplus actinium-beryllium neutron generators. We retrieved the actinium/beryllium buttons from the sources and dissolved them in a sulfuric-nitric acid solution. A crude actinium solid was recovered from the solution by coprecipitation with thorium fluoride, leaving beryllium in solution. The crude actinium was purified to provide about 40 milligrams of actinium nitrate using anion exchange in methanol-water-nitric acid solution. The purified actinium was then used to generate high-purity 223Ra. We extracted 223Ra using anion exchange in a methanol-water-nitric acid solution. After the radium was separated, actinium and thorium were then eluted from the column and dried for interim storage. This single-pass separation produces high purity, carrier-free 223Ra product, and does not disturb the 227Ac/227Th equilibrium. A high purity, carrier-free 227Th was also obtained from the actinium using a similar anion exchange in nitric acid. These methods enable efficient production of 223Ra for research and new alpha-emitter radiopharmaceutical development.

  1. Structure and texture of electrolytic superconducting coatings of high-purity niobium

    NASA Astrophysics Data System (ADS)

    Kolosov, V. N.; Shevyrev, A. A.

    2014-08-01

    Modes of epitaxial growth of electrolytic superconducting coatings of high-purity niobium on substrates of niobium, molybdenum, and tungsten have been investigated. The dynamics of changes in the structure and texture of the coatings depending on the method of treatment of substrates, cathode current density, and thickness of the deposited niobium layer has been studied.

  2. Low temperature recombination and trapping analysis in high purity gallium arsenide by microwave photodielectric techniques

    NASA Technical Reports Server (NTRS)

    Khambaty, M. B.; Hartwig, W. H.

    1972-01-01

    Some physical theories pertinent to the measurement properties of gallium arsenide are presented and experimental data are analyzed. A model for explaining recombination and trapping high purity gallium arsenide, valid below 77 K is assembled from points made at various places and an appraisal is given of photodielectric techniques for material property studies.

  3. Factor IX assay

    MedlinePlus

    ... LE, Heslop HE, Weitz JI, Anastasi J, eds. Hematology: Basic Principles and Practice . 6th ed. Philadelphia, PA: ... LE, Heslop HE, Weitz JI, Anastasi J, eds. Hematology: Basic Principles and Practice . 6th ed. Philadelphia, PA: ...

  4. Factor IX assay

    MedlinePlus

    ... B. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, eds. Hematology: ... disorders. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, eds. Hematology: ...

  5. Performance of a compact multi-crystal high-purity germanium detector array for measuring coincident gamma-ray emissions

    NASA Astrophysics Data System (ADS)

    Howard, Chris; Daigle, Stephen; Buckner, Matt; Erikson, Luke E.; Runkle, Robert C.; Stave, Sean C.; Champagne, Arthur E.; Cooper, Andrew; Downen, Lori; Glasgow, Brian D.; Kelly, Keegan; Sallaska, Anne

    2015-05-01

    The Multi-sensor Airborne Radiation Survey (MARS) detector is a 14-crystal array of high-purity germanium (HPGe) detectors housed in a single cryostat. The array was used to measure the astrophysical S-factor for the 14N(p,γ)15O* reaction for several transition energies at an effective center-of-mass energy of 163 keV. Owing to the granular nature of the MARS detector, the effect of gamma-ray summing was greatly reduced in comparison to past experiments which utilized large, single-crystal detectors. The new S-factor values agree within their uncertainties with the past measurements. Details of the analysis and detector performance are presented.

  6. Performance of A Compact Multi-crystal High-purity Germanium Detector Array for Measuring Coincident Gamma-ray Emissions

    SciTech Connect

    Howard, Chris; Daigle, Stephen; Buckner, Matt; Erikson, Luke E.; Runkle, Robert C.; Stave, Sean C.; Champagne, Art; Cooper, Andrew; Downen, Lori; Glasgow, Brian D.; Kelly, Keegan; Sallaska, Anne

    2015-02-18

    The Multi-sensor Airborne Radiation Survey (MARS) detector is a 14-crystal array of high-purity germanium (HPGe) detectors housed in a single cryostat. The array was used to measure the astrophysical S-factor for the 14N(p,γ)15O* reaction for several transition energies at an effective center of mass energy of 163 keV. Owing to the segmented nature of the MARS detector, the effect of gamma-ray summing was greatly reduced in comparison to past experiments which utilized large, single-crystal detectors. The new S-factor values agree within the uncertainties with the past measurements. Details of the analysis and detector performance will be presented.

  7. Preliminary study on non-viral transfection of F9 (factor IX) gene by nucleofection in human adipose-derived mesenchymal stem cells

    PubMed Central

    Olmedillas López, Susana; Garcia-Arranz, Mariano; Garcia-Olmo, Damian

    2016-01-01

    Background. Hemophilia is a rare recessive X-linked disease characterized by a deficiency of coagulation factor VIII or factor IX. Its current treatment is merely palliative. Advanced therapies are likely to become the treatment of choice for the disease as they could provide a curative treatment. Methods. The present study looks into the use of a safe non-viral transfection method based on nucleofection to express and secrete human clotting factor IX (hFIX) where human adipose tissue derived mesenchymal stem cells were used as target cells in vitro studies and NOD. Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice were used to analyze factor IX expression in vivo studies. Previously, acute liver injury was induced by an injected intraperitoneal dose of 500 mg/kg body weight of acetaminophen. Results. Nucleofection showed a percentage of positive cells ranging between 30.7% and 41.9% and a cell viability rate of 29.8%, and cells were shown to secrete amounts of hFIX between 36.8 and 71.9 ng/mL. hFIX levels in the blood of NSG mice injected with ASCs transfected with this vector, were 2.7 ng/mL 48 h after injection. Expression and secretion of hFIX were achieved both in vitro cell culture media and in vivo in the plasma of mice treated with the transfected ASCs. Such cells are capable of eventually migrating to a previously damaged target tissue (the liver) where they secrete hFIX, releasing it to the bloodstream over a period of at least five days from administration. Conclusions. The results obtained in the present study may form a preliminary basis for the establishment of a future ex vivo non-viral gene/cellular safe therapy protocol that may eventually contribute to advancing the treatment of hemophilia. PMID:27114871

  8. Title IX Resource Guide

    ERIC Educational Resources Information Center

    Office for Civil Rights, US Department of Education, 2015

    2015-01-01

    Title IX of the Education Amendments of 1972 (Title IX) prohibits discrimination based on sex in education programs and activities in federally funded schools at all levels. If any part of a school district or college receives any Federal funds for any purpose, all of the operations of the district or college are covered by Title IX. The essence…

  9. Confirmation of warfarin resistance of naturally occurring VKORC1 variants by coexpression with coagulation factor IX and in silico protein modelling

    PubMed Central

    2014-01-01

    Background VKORC1 has been identified some years ago as the gene encoding vitamin K epoxide reductase (VKOR) – the target protein for coumarin derivates like warfarin or phenprocoumon. Resistance against warfarin and other coumarin-type anticoagulants has been frequently reported over the last 50 years in rodents due to problems in pest control as well as in thrombophilic patients showing variable response to anticoagulant treatment. Many different mutations have already been detected in the VKORC1 gene leading to warfarin resistance in rats, mice and in humans. Since the conventional in vitro dithiothreitol (DTT)-driven VKOR enzymatic assay often did not reflect the in vivo status concerning warfarin resistance, we recently developed a cell culture-based method for coexpression of VKORC1 with coagulation factor IX and subsequent measurement of secreted FIX in order to test warfarin inhibition in wild-type and mutated VKORC1. Results In the present study, we coexpressed wild-type factor IX with 12 different VKORC1 variants which were previously detected in warfarin resistant rats and mice. The results show that amino acid substitutions in VKORC1 maintain VKOR activity and are associated with warfarin resistance. When we projected in silico the amino acid substitutions onto the published three-dimensional model of the bacterial VKOR enzyme, the predicted effects matched well the catalytic mechanism proposed for the bacterial enzyme. Conclusions The established cell-based system for coexpression of VKORC1 and factor IX uses FIX activity as an indicator of carboxylation efficiency. This system reflects the warfarin resistance status of VKORC1 mutations from anticoagulant resistant rodents more closely than the traditional DTT-driven enzyme assay. All mutations studied were also predicted to be involved in the reaction mechanism. PMID:24491178

  10. An improved procedure for high purity gaseous peroxyacyl nitrate production: Use of heavy lipid solvents

    NASA Astrophysics Data System (ADS)

    Gaffney, J. S.; Fajer, R.; Senum, G. I.

    An improved procedure is described for the production of peroxyacyl nitrates (PAN's) in the gas phase. The method of Nielsen et al. (1982) has been modified to yield PAN's of high purity with no further Chromatographic purification required. Extraction of PAN's from the nitration of the peracids is accomplished by use of a heavy lipid solvent ( n-tridecane). This solvent's low vapor pressure allows the simple separation and preparation of high purity gaseous PAN's (> 98 %) as determined by Fourier transform infrared spectroscopy (FTIR). Using this method infrared integrated band strengths are reported for peroxyacetyl nitrate (PAN) perdeutero-peroxyacetyl nitrate (PAN-D 3) and peroxyproprionyl nitrate (PPN). The method allows facile production of large amounts of gaseous PAN's for smog chamber and laboratory studies, lexicological and health effects research, as well as for calibration of PAN analyses.

  11. Fabrication of novel cryomill for synthesis of high purity metallic nanoparticles

    NASA Astrophysics Data System (ADS)

    Kumar, Nirmal; Biswas, Krishanu

    2015-08-01

    The successful preparation of free standing metal nanoparticles with high purity in bulk quantity is the pre-requisite for any potential application. This is possible by using ball milling at cryogenic temperature. However, the most of ball mills available in the market do not allow preparing high purity metal nanoparticles by this route. In addition, it is not possible to carry out in situ measurements of process parameters as well as diagnostic of the process. In the present investigation, we present a detailed study on the fabrication of a cryomill, which is capable of avoiding contaminations in the product. It also provides in situ measurements and diagnostic of the low temperature milling process. Online monitoring of the milling temperature and observation of ball motion are the important aspects in the newly designed mill. The nanoparticles prepared using this fabricated mill have been found to be free standing and also free from contaminations.

  12. Comparison of Deformation in High-Purity Single/Large Grain and Polycrystalline Niobium Superconducting Cavities

    SciTech Connect

    Ganapati Rao Myneni; Peter Kneisel

    2005-07-10

    The current approach for the fabrication of superconducting radio frequency (SRF) cavities is to roll and deep draw sheets of polycrystalline high-purity niobium. Recently, a new technique was developed at Jefferson Laboratory that enables the fabrication of single-crystal high-purity Nb SRF cavities. To better understand the differences between SRF cavities fabricated out of fine-grained polycrystalline sheet in the standard manner and single crystal cavities fabricated by the new technique, two half-cells were produced according to the two different procedures and compared using a variety of analytical techniques including optical microscopy, scanning laser confocal microscopy, profilometry, and X-ray diffraction. Crystallographic orientations, texture, and residual stresses were determined in the samples before and after forming and this poster presents the results of this ongoing study.

  13. Characterization of a high-purity germanium detector for small-animal SPECT

    PubMed Central

    Johnson, Lindsay C; Campbell, Desmond L; Hull, Ethan L; Peterson, Todd E

    2011-01-01

    We present an initial evaluation of a mechanically-cooled, high-purity germanium double-sided strip detector as a potential gamma camera for small-animal SPECT. It is 90 mm in diameter and 10 mm thick with two sets of 16 orthogonal strips that have a 4.5 mm width with a 5 mm pitch. We found an energy resolution of 0.96% at 140 keV, an intrinsic efficiency of 43.3% at 122 keV and a FWHM spatial resolution of approximately 1.5 mm. We demonstrated depth-of-interaction estimation capability through comparison of pinhole acquisitions with a point source on and off axis. Finally, a flood-corrected-flood image exhibited a strip-level uniformity of less than 1%. This high-purity germanium offers many desirable properties for small-animal SPECT. PMID:21852723

  14. Crystal growth and detector performance of large size high-purity Ge crystals

    NASA Astrophysics Data System (ADS)

    Wang, Guojian; Amman, Mark; Mei, Hao; Mei, Dongming; Irmscher, Klaus; Guan, Yutong; Yang, Gang

    2015-03-01

    High-purity germanium crystals with 12 cm in diameter were grown in a hydrogen atmosphere using the Czochralski method. The dislocation density of the crystals was determined to be in the range of 2000 - 4200 cm-2, which meets a requirement for use as a radiation detector. The axial and radial distributions of impurities in the crystals were measured by Hall effect and Photo-thermal ionization spectroscopy (PTIS). Two detectors were also fabricated from one of the crystals with different techniques and then evaluated for electrical and spectral performance. Measurements of gamma-ray spectra from 137Cs, 241Am and 60Co sources demonstrate that the detectors have excellent energy resolution. Keywords: High-purity germanium crystal, Czochralski method This work is supported by DOE grant DE-FG02-10ER46709 and the state of South Dakota.

  15. The effectiveness of circulating aeration in air and high purity oxygen systems for control of VOC emissions from aeration basins

    SciTech Connect

    Zhu, H.; Keener, T.C.; Bishop, P.L.; Orton, T.L.; Wang, M.; Siddiqui, K.F.

    1997-12-31

    A simple steady state circulating aeration system (CAS) model has been used to study the effects of volatility and degradability on the fate of VOCs in both air and high purity oxygen (HPO) systems. With increase of circulation ratio in an air CAS, air emissions by stripping can be significantly reduced for compounds of low degradabilities and high volatilities. Enhancement of biodegradation is more significant for compounds of high degradabilities and volatilities. A large portion of VOCs will remain in the wastewater when circulation ratio is high, especially for VOCs that are difficult to degrade. In HPO systems, emissions by stripping are much less than air systems. However, VOCs will remain in the wastewater if they have poor degradabilities. Volatilities of VOCs are not important in HPO systems. Due to their wide range and large uncertainties, degradation rate constants are a major factor determining the effectiveness of a CAS for VOC emission control

  16. Synthesis of high purity nitride powders. (Latest citations from Engineered Materials abstracts). NewSearch

    SciTech Connect

    Not Available

    1994-10-01

    The bibliography contains citations concerning the synthesis and preparation of high purity nitride powders. Citations discuss the preparation of powders using chemical vapor deposition, carbothermic reactions, plasmochemical reactions, pyrolysis, sol gel processes, and self-propagating high-temperature synthesis. Citations concern boron nitrides, carbonitrides, aluminum nitrides, silicon nitrides, and titanium nitrides. (Contains a minimum of 246 citations and includes a subject term index and title list.)

  17. Synthesis of high purity nitride powders. (Latest citations from Engineered Materials abstracts). Published Search

    SciTech Connect

    1995-12-01

    The bibliography contains citations concerning the synthesis and preparation of high purity nitride powders. Citations discuss the preparation of powders using chemical vapor deposition, carbothermic reactions, plasmochemical reactions, pyrolysis, sol gel processes, and self-propagating high-temperature synthesis. Citations concern boron nitrides, carbonitrides, aluminum nitrides, silicon nitrides, and titanium nitrides.(Contains 50-250 citations and includes a subject term index and title list.) (Copyright NERAC, Inc. 1995)

  18. High purity liquid phase epitaxial GaAs for radiation detectors

    SciTech Connect

    Wynne, D.I.; Haller, E.E.; Rossington Tull, C.S.

    1998-12-31

    The authors report on the growth of high purity n-GaAs using Liquid Phase Epitaxy (LPE) and the fabrication of room temperature p-i-n radiation detectors. The epilayers are grown from a Ga solvent in a graphite boat in a pure hydrogen atmosphere. Growth is started at a temperature of approximately 800 C. The best epilayers show a net-residual-donor concentration of 2 {times} 10{sup 13} cm{sup {minus}3}, confirmed by Hall effect measurements. The residual donors have been analyzed by far infrared spectroscopy and found to be sulfur and silicon. Epilayers with thicknesses of up to 120 {micro}m have been deposited on 650 {micro}m thick semi-insulating GaAs substrates and on 500 {micro}m thick n{sup +}-type GaAs substrates. The authors report the results obtained with Schottky barrier diodes fabricated from these high purity n-type GaAs epilayers and operated as X-ray detectors. The Schottky barrier contacts consisted of evaporated circular gold contacts on epilayers on n{sup +} substrates. The ohmic contacts were formed by evaporated and alloyed Ni-Ge-Au films on the back of the substrate. Several of the diodes exhibit currents of the order of 1 to 10 nA at reverse biases depleting approximately 50 {micro}m of the epilayer. This very encouraging result, demonstrating the possibility for fabricating GaAs p-i-n diodes with depletion layers in high purity GaAs instead of semi-insulating GaAs, is supported by similar results obtained by several other groups. The consequences of using high purity instead of semi-insulating GaAs will be much reduced charge carrier trapping. Diode electrical characteristics and detector performance results using {sup 55}Fe and {sup 241}Am radiation will be discussed.

  19. Synthesis of high purity carbide powders. (Latest citations from Engineered Materials abstracts). Published Search

    SciTech Connect

    Not Available

    1994-08-01

    The bibliography contains citations concerning the synthesis and preparation of high purity carbide powders. Articles discuss techniques of powder manufacture such as chemical vapor deposition, plasma arc reactions, sintering, hot pressing, combustion synthesis, precipitation, chemical reaction, self-propagating high temperature synthesis, shock or explosive compaction, and aerosol formation. Citations concern silicon carbides, titanium carbides, and other carbide materials and composites. (Contains 250 citations and includes a subject term index and title list.)

  20. Aluminium. II - A review of deformation properties of high purity aluminium and dilute aluminium alloys.

    NASA Technical Reports Server (NTRS)

    Reed, R. P.

    1972-01-01

    The elastic and plastic deformation behavior of high-purity aluminum and of dilute aluminum alloys is reviewed. Reliable property data, including elastic moduli, elastic coefficients, tensile, creep, fatigue, hardness, and impact are presented. Single crystal tensile results are discussed. Rather comprehensive reference lists, containing publications of the past 20 years, are included for each of the above categories. Defect structures and mechanisms responsible for mechanical behavior are presented. Strengthening techniques (alloys, cold work, irradiation, quenching, composites) and recovery are briefly reviewed.

  1. Molecular interactions of the intrinsic activation complex of coagulation: binding of native and activated human factors IX and X to defined phospholipid vesicles.

    PubMed

    Burri, B J; Edgington, T S; Fair, D S

    1987-02-20

    The assembly of proteins of the intrinsic activation complex has been partially elucidated. In the present study we examine the association of gamma-carboxylated serine proteinase zymogens factors IX and X, and their proteolytically activated counterparts factors IXa and Xa to unilamellar lipid vesicles of defined composition using three types of physical measurement. Utilizing relative light scatter to estimate the dissociation constants for binding in the presence of calcium ions, it appears that factor IXa (0.93 +/- 0.37 microM) may preferentially associate with phospholipids relative to factor IX (0.35 +/- 0.08 microM). In contrast, factor X (0.34 +/- 0.14 microM), the substrate for factor IXa, appears to bind to phospholipid with a higher affinity than factor Xa (0.58 +/- 0.13 microM). These observations are compatible with the hypothesized dynamics where the forward 'traffic' is facilitated by favoring the association of factor IXa with factor X. The dissociation constants were estimated by molecular exclusion chromatography (1.1 - 2.5 microM) and do not reflect these relative and ordered differences in association with lipid vesicles. Quasi-elastic light scatter analyses indicate that each protein appears to saturate the same vesicle surface, consistent with competition for similar surface lipids, although the molecular shell formed by factor Xa (36 A) is smaller, suggesting that it has a different packing on the phospholipid surface than the other proteins (64-79 A). The pattern of preferential affinities for phospholipid is consistent with a kinetically functional forward traffic through the reaction precursors to products, and suggests that these preferential affinities may assist in the ordering of the four proteins in the intrinsic activation complex. PMID:3493031

  2. Integration of High-Purity Carbon Nanotube Solution into Electronic Devices

    NASA Astrophysics Data System (ADS)

    Tulevski, George; IBM TJ Watson Reserach Center Team

    Due to their exceptional electronic properties, carbon nanotubes (cnt) are leading candidates to be employed as channel materials in future nanoelectronic devices. A key bottleneck to realizing device integration is the sorting of carbon nanotubes, namely the isolation of high-purity, semiconducting cnt solutions. This talk will describe our efforts in using polymer-based sorting methods to isolate high-density and high-purity semiconducting cnt solutions. We explore the dependence of starting material and polymer to cnt ratio on the effectiveness of the separation. We confirm optically and electrically that the semiconducting purity is >99.99% through several thousand individual device measurements. In addition to single-cnt devices, thin-film transistors were also fabricated and tested. Due to the high purity of the solutions, device switching (~105 ION/IOFF) was observed at channel lengths below the percolation threshold (<500 nm). Operating below the percolation threshold allows for devices with much higher current densities and effective mobilities as transport is now the result of direct transport as opposed to hopping between cnts.

  3. Synthesis and Characterization of High-Purity Tellurium Nanowires via Self-seed-Assisted Growth Approach

    NASA Astrophysics Data System (ADS)

    Li, Ying; Zhao, Wen-yu; Mu, Xin; Liu, Xing; He, Dan-qi; Zhu, Wan-ting; Zhang, Qing-jie

    2016-03-01

    Nanowires have attracted intense attention in recent years due to their novel physical properties. In this work, we prepare high-purity tellurium nanowires through the self-seed-assisted growth method previously developed by us. The tellurium seeds were firstly synthesized by reducing Na2TeO3 in the ice water with NaBH4. The high-purity tellurium nanowires with a diameter of 40-50 nm and a length of several tens of micrometers were then grown on tellurium seeds by reducing Na2TeO3 with hydrazine hydrate. X-ray diffraction, scanning electron microscopy and transmission electron microscopy were employed to characterize the crystal structure, microstructure, and growth direction of tellurium seeds and nanowires. The effects of temperature, time, surfactant and tellurium seeds on microstructures of tellurium nanowires has also been investigated. The synthesis conditions of tellurium seeds and nanowires was optimized. The selected area electron diffraction pattern confirms that the growth direction of tellurium nanowires is parallel to [0001] direction. It was discovered that high-purity tellurium nanowires with high aspect ratio can be synthesized by precisely controlling the temperature to adjust the nucleation rate of the tellurium nuclei, selecting the appropriate surfactant to induce the coordination along the macromolecular chain, and using tellurium seeds as the templates of the epitaxial growth of tellurium nuclei.

  4. Synthesis and Characterization of High-Purity Bismuth Nanowires via Seed-Assisted Growth Approach

    NASA Astrophysics Data System (ADS)

    Mu, Xin; Zhao, Wen-Yu; He, Dan-Qi; Zhou, Hong-Yu; Zhu, Wan-Ting; Zhang, Qing-Jie

    2015-06-01

    Nanowires are considered as high-performance thermoelectric materials with large Seebeck coefficients due to quantum confinement and low thermal conductivity because of enhanced boundary scattering of phonons. In this work, a seed-assisted growth method has been developed to synthesize high-purity bismuth nanowires. The bismuth seeds were first synthesized by reducing BiCl3 in the ice water with NaBH4. The high-purity bismuth nanowires about 40-50 nm in diameter and several tens of micrometers in length were then grown on bismuth seeds by reducing NaBiO3 with ethylene glycol. X-ray diffraction, scanning electron microscopy, and transmission electron microscopy were employed to characterize the crystal structure, microstructure, and growth direction of the bismuth seeds and nanowires. The effects of temperature, reductant, and bismuth seeds template on the microstructures of the bismuth nanowires were also investigated. The synthesis conditions of bismuth seeds and nanowires were optimized. The selected area electron diffraction pattern confirms that the growth direction of bismuth nanowires is parallel to [] direction. It was discovered that high-purity bismuth nanowires with high aspect ratio can be synthesized by precisely controlling the temperature to adjust the nucleation rate of the bismuth nuclei, selecting the appropriate reductant to maintain a low nucleation rate, and using bismuth seeds as the template of the epitaxial growth of the bismuth nuclei.

  5. Migration of grain boundaries and triple junctions in high-purity aluminum during annealing after slight cold rolling

    SciTech Connect

    Yin, Wenhong; Wang, Weiguo; Fang, Xiaoying; Qin, Congxiang; Xing, Xiaoguang

    2015-09-15

    Grain orientations and grain boundary migrations near triple junctions in a high purity aluminum were analyzed by electron back scattered diffraction. The results indicate that there are good correlations between the Schmid factors or Taylor factors and the misorientation values of point to original point in grains near the triple junctions in a slightly deformed sample. Grains with higher Schmid factors or lower Taylor factors typically correspond to higher misorientation values near the triple junctions. In a subsequent annealing at 400 °C, both grain boundaries and triple junctions migrate, but the former leave ghost lines. During such migration, a grain boundary grows from the grain with lower Schmid factor (higher Taylor factor) into the grain with higher Schmid factor (lower Taylor factor). Usually, the amount of migration of a grain boundary is considerably greater than that of a triple junction, and the grain boundary becomes more curved after migration. These observations indicate that the triple junctions have drag effects on grain boundary migration. - Highlights: • Polycrystalline aluminum with fine grains about 30 μm were used. • Off-line in situ EBSD was used to identify TJs before and after annealing. • Grains with higher SFs have higher misorientation values near TJs after deformation. • Grain boundaries grow from hard grains into soft grains during annealing. • Triple junctions have drag effects on grain boundaries migration.

  6. Evolutionary pattern of mutation in the factor IX genes of great apes: How does it compare to the pattern of recent germline mutation in patients with hemophilia B?

    SciTech Connect

    Grouse, L.H.; Ketterling, R.P.; Sommer, S.S.

    1994-09-01

    Most mutations causing hemophilia B have arisen within the past 150 years. By correcting for multiple biases, the underlying rates of spontaneous germline mutation have been estimated in the factor IX gene. From these rates, an underlying pattern of mutation has emerged. To determine if this pattern compares to a underlying pattern found in the great apes, sequence changes were determined in intronic regions of the factor IX gene. The following species were studied: Gorilla gorilla, Pan troglodytes (chimpanzee), Pongo pygmacus (orangutan) and Homo sapiens. Intronic sequences at least 200 bp from a splice junction were randomly chosen, amplified by cross-species PCR, and sequenced. These regions are expected to be subject to little if any selective pressure. Early diverged species of Old World monkeys were also studied to help determine the direction of mutational changes. A total of 62 sequence changes were observed. Initial data suggest that the average pattern since evolution of the great apes has a paucity of transitions at CpG dinucleotides and an excess of microinsertions to microdeletions when compared to the pattern observed in humans during the past 150 years (p<.05). A larger study is in progress to confirm these results.

  7. Production of transgenic goats expressing human coagulation factor IX in the mammary glands after nuclear transfer using transfected fetal fibroblast cells.

    PubMed

    Amiri Yekta, Amir; Dalman, Azam; Eftekhari-Yazdi, Poopak; Sanati, Mohammad Hossein; Shahverdi, Abdol Hossein; Fakheri, Rahman; Vazirinasab, Hamed; Daneshzadeh, Mohammad Taghi; Vojgani, Mahdi; Zomorodipour, Alireza; Fatemi, Nayeralsadat; Vahabi, Zeinab; Mirshahvaladi, Shahab; Ataei, Fariba; Bahraminejad, Elmira; Masoudi, Najmehsadat; Rezazadeh Valojerdi, Mojtaba; Gourabi, Hamid

    2013-02-01

    There are growing numbers of recombinant proteins that have been expressed in milk. Thus one can consider the placement of any gene of interest under the control of the regulatory elements of a milk protein gene in a dairy farm animal. Among the transgene introducing techniques, only nuclear transfer (NT) allows 100 % efficiency and bypasses the mosaicism associated with counterpart techniques. In this study, in an attempt to produce a transgenic goat carrying the human coagulation factor IX (hFIX) transgene, goat fetal fibroblasts were electroporated with a linearized marker-free construct in which the transgene was juxtaposed to β-casein promoter designed to secret the recombinant protein in goat milk. Two different lines of transfected cells were used as donors for NT to enucleated oocytes. Two transgenic goats were liveborn. DNA sequencing of the corresponding transgene locus confirmed authenticity of the cloning procedure and the complementary experiments on the whey demonstrated expression of human factor IX in the milk of transgenic goats. In conclusion, our study has provided the groundwork for a prosperous and promising approach for large-scale production and therapeutic application of hFIX expressed in transgenic goats. PMID:22869287

  8. Dielectric Performance of a High Purity HTCC Alumina at High Temperatures - a Comparison Study with Other Polycrystalline Alumina

    NASA Technical Reports Server (NTRS)

    Chen, Liangyu

    2014-01-01

    A very high purity (99.99+%) high temperature co-fired ceramic (HTCC) alumina has recently become commercially available. The raw material of this HTCC alumina is very different from conventional HTCC alumina, and more importantly there is no glass additive in this alumina material for co-firing processing. Previously, selected HTCC and LTCC (low temperature co-fired ceramic) alumina materials were evaluated at high temperatures as dielectric and compared to a regularly sintered 96% polycrystalline alumina (96% Al2O3), where 96% alumina was used as the benchmark. A prototype packaging system based on regular 96% alumina with Au thickfilm metallization successfully facilitated long term testing of high temperature silicon carbide (SiC) electronic devices for over 10,000 hours at 500 C. In order to evaluate this new high purity HTCC alumina for possible high temperature packaging applications, the dielectric properties of this HTCC alumina substrate were measured and compared with those of 96% alumina and a previously tested LTCC alumina from room temperature to 550 C at frequencies of 120 Hz, 1 KHz, 10 KHz, 100 KHz, and 1 MHz. A parallel-plate capacitive device with dielectric of the HTCC alumina and precious metal electrodes were used for measurements of the dielectric constant and dielectric loss of the co-fired alumina material in the temperature and frequency ranges. The capacitance and AC parallel conductance of the capacitive device were directly measured by an AC impedance meter, and the dielectric constant and parallel AC conductivity of the dielectric were calculated from the capacitance and conductance measurement results. The temperature and frequency dependent dielectric constant, AC conductivity, and dissipation factor of the HTCC alumina substrate are presented and compared to those of 96% alumina and a selected LTCC alumina. Other technical advantages of this new co-fired material for possible high packaging applications are also discussed.

  9. Sequence-specific sup 1 H NMR assignments, secondary structure, and location of the calcium binding site in the first epidermal growth factor like domain of blood coagulation factor IX

    SciTech Connect

    Huang, L.H.; Cheng, H.; Sweeney, W.V. ); Pardi, A. ); Tam, J.P. )

    1991-07-30

    Factor IX is a blood clotting protein that contains three regions, including a {gamma}-carboxyglutamic acid (Gla) domain, two tandemly connected epidermal growth factor like (EGF-like) domains, and a serine protease region. The protein exhibits a high-affinity calcium binding site in the first EGF0like domain, in addition to calcium binding in the Gla domain. The first EGF-like domain, factor IX (45-87), has been synthesized. Sequence-specific resonance assignment of the peptide has been made by using 2D NMR techniques, and its secondary structure has been determined. The protein is found to have two antiparallel {beta}-sheets, and preliminary distance geometry calculations indicate that the protein has two domains, separated by Trp{sup 28}, with the overall structure being similar to that of EGF. An NMR investigation of the calcium-bound first EGF-like domain indicates the presence and location of a calcium binding site involving residues on both strands of one of the {beta}-sheets as well as the N-terminal region of the peptide. These results suggest that calcium binding in the first EGF-like domain could induce long-range (possibly interdomain) conformational changes in factor IX, rather than causing structural alterations in the EGF-like domain itself.

  10. Characterization of high-purity arsine and gallium arsenide epilayers grown by MOCVD

    NASA Astrophysics Data System (ADS)

    Feng, Jun; Clement, Ryan; Raynor, Mark

    2008-11-01

    Impurities present in the metal organic chemical vapor deposition (MOCVD) process gases and precursors can have a significant effect on the performance of III-V compound semiconductor devices. High-purity arsine purified using chemical, adsorption and distillation techniques, has been characterized for impurities by using high sensitivity gas analysis methods and low temperature photoluminescence (PL) of GaAs epilayers. Permanent gas, hydrocarbon and dopant impurities can all be removed using these purification methods to below the detection limit of instrumentation (low nmol mol -1-pmol mol -1, depending on method). Capability to remove water vapor to single digit nmol mol -1 levels is also demonstrated and cylinder depletion studies show that gas-phase arsine, with consistently low H 2O, can be delivered from the cylinder, even well after phase break. Low temperature PL measurements are made on 10 μm GaAs/GaAs grown with three different arsine sources. Well-resolved near-band emission characteristics of high-purity n-type GaAs is obtained with high-purity distilled arsine. PL of epilayers grown with less pure arsine show the presence of Ge as well as elevated levels of Mg and Zn, incorporated from the trimethylgallium. The incorporation of O from an arsine cylinder containing H 2O at 200 nmol mol -1 results in reduced full width at half maximum (FWHM) of the near-band emission and decreased ( D0, X) and ( F, X) intensity, highlighting the importance of minimizing H 2O impurity.

  11. High Purity Americium-241 for Fuel Cycle R&D Program

    SciTech Connect

    Dr. Paul A. Lessing

    2011-07-01

    Previously the U.S. Department of Energy released Am-241 for various applications such as smoke detectors and Am-Be neutron sources for oil wells. At this date there is a shortage of usable, higher purity Am-241 in metal and oxide form available in the United States. Recently, the limited source of Am-241 has been from Russia with production being contracted to existing customers. The shortage has resulted in the price per gram rising dramatically over the last few years. DOE-NE currently has need for high purity Am-241 metal and oxide to fabricate fuel pellets for reactor testing in the Fuel Cycle R&D program. All the available high purity americium has been gathered from within the DOE system of laboratories. However, this is only a fraction of the projected needs of FCRD over the next 10 years. Therefore, FCR&D has proposed extraction and purification concepts to extract Am-241 from a mixed AmO2-PuO2 feedstock stored at the Savannah River Site. The most simple extraction system is based upon high temperature reduction using lanthanum metal with concurrent evaporation and condensation to produce high purity Am metal. Metallic americium has over a four order of magnitude higher vapor pressure than plutonium. Results from small-scale reduction experiments are presented. These results confirm thermodynamic predictions that at 1000 deg C metallic lanthanum reduces both PuO2 and AmO2. Faster kinetics are expected for temperatures up to about 1500 deg C.

  12. Formation and evolution of tweed structures on high-purity aluminum polycrystalline foils under cyclic tension

    SciTech Connect

    Kuznetsov, P. V.; Vlasov, I. V.; Sklyarova, E. A.; Smekalina, T. V.

    2015-10-27

    Peculiarities of formation and evolution of tweed structures on the surface of high-purity aluminum polycrystalline foils under cyclic tension were studied using an atom force microscope and a white light interferometer. Tweed structures of micron and submicron sizes were found on the foils at different number of cycles. In the range of 42,000 < N < 95,000 cycles destruction of tweed patterns is observed, which leads to their disappearance from the surface of the foils. Formation of tweed structures of various scales is discussed in terms of the Grinfeld instability.

  13. Formation of High-Purity Indium Oxide Nanoparticles and Their Application to Sensitive Detection of Ammonia

    PubMed Central

    Bhardwaj, Sanjeev K.; Bhardwaj, Neha; Kukkar, Manil; Sharma, Amit L.; Kim, Ki-Hyun; Deep, Akash

    2015-01-01

    High-purity In2O3 nanoparticles were recovered from scrap indium tin oxide substrates in a stepwise process involving acidic leaching, liquid-liquid extraction with a phosphine oxide extractant, and combustion of the organic phase. The morphological and structural parameters of the recovered nanoparticles were investigated to support the formation of the desired products. These In2O3 nanoparticles were used for sensitive sensing of ammonia gas using a four-probe electrode device. The proposed sensor offered very quick response time (around 10 s) and highly sensitive detection of ammonia (at a detection limit of 1 ppm). PMID:26694415

  14. Corrosion behavior of surface films on boron-implanted high purity iron and stainless steels

    NASA Technical Reports Server (NTRS)

    Kim, H. J.; Carter, W. B.; Hochman, R. F.; Meletis, E. I.

    1985-01-01

    Boron (dose, 2 x 10 to the 17th ions/sq cm) was implanted into high purity iron, AISI 316 austenitic stainless steel, and AISI 440C martensitic stainless steel, at 40 keV. The film structure of implanted samples was examined and characterized by contrast and diffraction analyses utilizing transmission electron microscopy. The effect of B(+) ion implantation on the corrosion behavior was studied using the potentiodynamic polarization technique. Tests were performed in deaerated 1 N H2SO4 and 0.1 M NaCl solutions. Scanning electron microscopy was used to examine the morphology of the corroded surfaces after testing.

  15. Method for growing low defect, high purity crystalline layers utilizing lateral overgrowth of a patterned mask

    NASA Technical Reports Server (NTRS)

    Morrison, Andrew D. (Inventor); Daud, Taher (Inventor)

    1986-01-01

    A method for growing a high purity, low defect layer of semiconductor is described. This method involves depositing a patterned mask of a material impervious to impurities of the semiconductor on a surface of a blank. When a layer of semiconductor is grown on the mask, the semiconductor will first grow from the surface portions exposed by the openings in the mask and will bridge the connecting portions of the mask to form a continuous layer having improved purity, since only the portions overlying the openings are exposed to defects and impurities. The process can be iterated and the mask translated to further improve the quality of grown layers.

  16. Effects of annealing on texture evolution of cross shear rolled high-purity Al foils

    NASA Astrophysics Data System (ADS)

    Wang, L.; Liu, Y.; Song, X.; He, J.; Zuo, L.

    2015-04-01

    The effects of annealing on recrystallization texture of cross shear rolled high-purity Al foil were investigated by orientation distribution functions (ODFs) and electron backscattered diffraction (EBSD). The results show that the intermediate annealing is beneficial to the development of the cube texture. The cube texture can be promoted by annealing, and the critical annealing temperature is about 280 °C. The cubic orientation grains firstly nucleate, and then expand into other grains with a high growth speed, and large angle grain boundary ratio increases, finally can swallow up most of the original grains, which results in the cube texture

  17. High-purity separation of cancer cells by optically induced dielectrophoresis.

    PubMed

    Chen, Hsiu-Hsiang; Lin, Mai-Wei; Tien, Wan-Ting; Lai, Chin-Pen; Weng, Kuo-Yao; Ko, Ching-Huai; Lin, Chun-Chuan; Chen, Jyh-Chern; Tiao, Kuo-Tung; Chen, Tse-Ching; Chen, Shin-Cheh; Yeh, Ta-Sen; Cheng, Chieh-Fang

    2014-04-01

    Detecting and concentrating cancer cells in peripheral blood is of great importance for cancer diagnosis and prognosis. Optically induced dielectrophoresis (ODEP) can achieve high resolution and low optical intensities, and the electrode pattern can be dynamically changed by varied light patterns. By changing the projected light pattern, it is demonstrated to separate high-purity gastric cancer cell lines. Traditionally, the purity of cancer cell isolation by negative selection is 0.9% to 10%; by positive selection it is 50% to 62%. An ODEP technology is proposed to enhance the purity of cancer cell isolation to about 77%. PMID:24723112

  18. Preparation and Evaluation of High-Purity La2O3

    NASA Astrophysics Data System (ADS)

    Lee, Gwang Seop; Uchikoshi, Masahito; Mimura, Kouji; Isshiki, Minoru

    2010-06-01

    A separation procedure based on extraction chromatography using the di(2-ethylhexyl) phosphoric acid (D2EHPA) impregnated resin, anion exchange with DIAION SA 10 resin, and oxalate precipitation has been developed for the preparation of high-purity La2O3 in hydrochloric acid media at a high La concentration. The metallic impurities Ce, Pr, Nd, Sm, K, Mg, Ca, Zn, Cu, Co, Mn, Pb, Al, In, and Fe, but not Bi, were removed efficiently from La by extraction chromatography using a D2EHPA impregnated resin. The Bi was separated from the La by anion exchange (DIAION SA 10) separation. Thus, a high-purity LaCl3 solution was obtained by anion exchange separation and extraction chromatography. La2O3 was prepared from the purified LaCl3 solution by oxalate precipitation. Glow discharge mass spectrometry was applied for purity evaluation of the prepared La2O3. The purity of the prepared La2O3 was more than 99.9998 pct total rare earth oxide.

  19. Process for producing high purity isoolefins and dimers thereof by dissociation of ethers

    DOEpatents

    Smith, Jr., Lawrence A.; Jones, Jr., Edward M.; Hearn, Dennis

    1984-01-01

    Alkyl tertiary butyl ether or alkyl tertiary amyl ether is dissociated by vapor phase contact with a cation acidic exchange resin at temperatures in the range of 150.degree. to 250.degree. F. at LHSV of 0.1 to 20 to produce a stream consisting of unreacted ether, isobutene or isoamylene and an alcohol corresponding to the alkyl radical. After the alcohol is removed, the ether/isoolefin stream may be fractionated to obtain a high purity isoolefin (99+%) or the ether/isoolefin stream can be contacted in liquid phase with a cation acidic exchange resin to selectively dimerize the isoolefin in a highly exothermic reaction, followed by fractionation of the dimerization product to produce high purity diisoolefin (97+%). In the case where the alkyl is C.sub.3 to C.sub.6 and the corresponding alcohol is produced on dissociation of the ether, combined dissociation-distillation may be carried out such that isoolefin is the overhead product and alcohol the bottom.

  20. Process for producing high purity isoolefins and dimers thereof by dissociation of ethers

    DOEpatents

    Smith, L.A. Jr.; Jones, E.M. Jr.; Hearn, D.

    1984-05-08

    Alkyl tertiary butyl ether or alkyl tertiary amyl ether is dissociated by vapor phase contact with a cation acidic exchange resin at temperatures in the range of 150 to 250 F at LHSV of 0.1 to 20 to produce a stream consisting of unreacted ether, isobutene or isoamylene and an alcohol corresponding to the alkyl radical. After the alcohol is removed, the ether/isoolefin stream may be fractionated to obtain a high purity isoolefin (99+%) or the ether/isoolefin stream can be contacted in liquid phase with a cation acidic exchange resin to selectively dimerize the isoolefin in a highly exothermic reaction, followed by fractionation of the dimerization product to produce high purity diisoolefin (97+%). In the case where the alkyl is C[sub 3] to C[sub 6] and the corresponding alcohol is produced on dissociation of the ether, combined dissociation-distillation may be carried out such that isoolefin is the overhead product and alcohol the bottom. 2 figs.

  1. Isolation of high-purity anthocyanin mixtures and monomers from blueberries using combined chromatographic techniques.

    PubMed

    Wang, Erlei; Yin, Yongguang; Xu, Caina; Liu, Jingbo

    2014-01-31

    Research on the isolation and preparation of anthocyanins has intensified in recent years because of the requirements of quantitative and bioactive analyses. However, simple and effective methods for the scale purification of pure anthocyanins from natural products are rarely reported. In this study, high-purity anthocyanin mixtures and monomers were successfully isolated from wild blueberries using a combination of column chromatography and semi-preparative HPLC. We established an effective elution system to separate high-purity anthocyanin mixtures with aqueous ethanol containing 0.01% HCl first in an Amberlite XAD-7HP column (ethanol/H2O=35:65) and then in a Sephadex LH-20 column (ethanol/H2O=25:75). Crude anthocyanin extracts were isolated using the Amberlite column, and a purity of 32% was obtained based on UV-vis analysis. Three fractions of anthocyanin mixtures were isolated from the crude extracts using the Sephadex column with purities ranging from 59% to 68%. Three pure monomeric anthocyanins of malvidin-3-O-glucoside, petunidin-3-O-glucoside, and delphinidin-3-O-glucoside were also isolated by semi-preparative HPLC and identified by HPLC-DAD-ESI-MS/MS. The purities of these anthocyanins were determined by analytical HPLC and estimated to be 97.7%, 99.3%, and 95.4%, respectively. The results of this study may help promote the purification of anthocyanins from most blueberry varieties as well as from other plant materials. PMID:24433700

  2. Characterization of high purity Silicon derived from Rice husk through improved Leaching process

    NASA Astrophysics Data System (ADS)

    Yusuf, Gbadebo; Awodugba, Ayodeji; Raimi, Adepoju; Babatola, Babatunde

    2014-03-01

    Rice husk is an abundant source of silicon and silicon compounds. High purity Silicon are required in high technology products such as semiconductors and solar cell. In this work, the possibility of obtaining pure silicon compounds through leaching process was investigated. Mesoporous silica nanoparticles with amorphous morphology have been synthesized from rice husk which was further subjected to improved leaching process to obtain pure silicon. XRD analysis shows the crystal structure of the as-received RHA with major reflections or peaks of crystalline quartz from ICSD powder diffraction occur at Bragg 2 θ angles of 20.856°, 26.636° and 36.541°. The purity of silicon obtained in terms of silica content was improved by leaching in 10 wt% hydrochloric acid. Advance future works on characterizing the electrical properties of the refined Rice Husk will eventually add value to the Rice Husk Silicon product and make it more attractive not only to the Photovoltaic industry but also other industries that require high purity silicon at reasonable cost. We wish to thank the Managements of Osun state Polytechnic-Iree and Ladoke Akintola University of Technology-Ogbomoso for creating enabling environment for this research work.

  3. In-line System to Produce High-Purity Acid Solutions.

    PubMed

    Masunaga, Hiroto; Higo, Yuji; Ishii, Mizuo; Maruyama, Noboru; Yamazaki, Shigeo

    2016-01-01

    Herein, we report a new device that generates a high-purity acid solution. It comprises three compartments divided by anion-exchange membranes and filled with ion-exchange resins. Fluorochemical cation-exchange membranes, which tolerate electrochemical wear and permit bulk flow, are inserted between each electrode and the anion-exchange resin. A bipolar boundary is a composite boundary comprising anion and cation exchangers. This device has four bipolar boundaries to separate the location of acid generation from the location where water is electrolyzed. It can tolerate high pressures, resist degradation due to electrolysis at the electrodes, and produce high-purity acid solutions that are free from gases and cationic impurities. The acid solution is generated on the basis of an electrokinetic phenomenon at the surfaces of ion-exchange resins and membranes in an electric field; its concentration can be controlled at rates from 0.01 to 100 μmol/min by adjusting the electrical current applied to the device. PMID:27302592

  4. The behavior of high-purity, low-density air plasma sprayed thermal barrier coatings

    SciTech Connect

    Helminiak, Yanar NM

    2009-12-01

    Research on the behavior of high-purity, low-density (85%) air plasma sprayed (APS) thermal barrier coatings (TBC) with NiCoCrAlY bond coats deposited by argon-shrouded plasma spraying is described. The microstructure of the APS topcoats is one variable in this study intended to maximize the coating thicknesses that can be applied without spallation and to minimize the thermal conduction through the YSZ layer. The specimens were evaluated using cyclic oxidation tests and important properties of the TBCs, such as resistance to sintering and phase transformation, were determined. The high purity resulted in top coats which are highly resistant to sintering and transformation from the metastable tetragonal phase to the equilibrium mixture of monoclinic and cubic phases. The porous topcoat microstructure also resulted in significant durability during thermal cycling. The actual failure mechanisms of the APS coatings were found to depend on topcoat thickness, CTE of the superalloy substrate and the nature of the thermal exposure.

  5. Recyclable Strategy for the Production of High-Purity Galacto-oligosaccharides by Kluyveromyces lactis.

    PubMed

    Sun, Huaisheng; You, Shengping; Wang, Mengfan; Qi, Wei; Su, Rongxin; He, Zhimin

    2016-07-20

    A recyclable strategy for the production of high-purity (>95%) galacto-oligosaccharides (GOS) was developed using Kluyveromyces lactis in both the synthesis and purification steps. For the synthesis of GOS, ethanol-permeabilized cells (p-cells) of K. lactis were used because the enhanced permeability facilitated the mass transfer of the substrate and the release of oligosaccharide products. For the purification of GOS, non-permeabilized K. lactis cells (np-cells) were preferred as a result of their intrinsic cell membrane barrier toward GOS, which led to the selective consumption of carbohydrate. In this way, undesired glucose, galactose, and lactose in the raw GOS solution can be completely removed. This strategy is recyclable not only because of the high stability and reusability of p-cells and np-cells but also because the ethanol, which is simultaneously generated during the purification, can be reused for the preparation of p-cells. The strategy proposed in this study is a promising candidate for the efficient production of high-purity GOS. PMID:27366924

  6. Secondary electron emission characteristics of ion-textured copper and high-purity isotropic graphite surfaces

    NASA Technical Reports Server (NTRS)

    Curren, A. N.; Jensen, K. A.

    1984-01-01

    Experimentally determined values of true secondary electron emission and relative values of reflected primary electron yield for untreated and ion textured oxygen free high conductivity copper and untreated and ion textured high purity isotropic graphite surfaces are presented for a range of primary electron beam energies and beam impingement angles. This investigation was conducted to provide information that would improve the efficiency of multistage depressed collectors (MDC's) for microwave amplifier traveling wave tubes in space communications and aircraft applications. For high efficiency, MDC electrode surfaces must have low secondary electron emission characteristics. Although copper is a commonly used material for MDC electrodes, it exhibits relatively high levels of secondary electron emission if its surface is not treated for emission control. Recent studies demonstrated that high purity isotropic graphite is a promising material for MDC electrodes, particularly with ion textured surfaces. The materials were tested at primary electron beam energies of 200 to 2000 eV and at direct (0 deg) to near grazing (85 deg) beam impingement angles. True secondary electron emission and relative reflected primary electron yield characteristics of the ion textured surfaces were compared with each other and with those of untreated surfaces of the same materials. Both the untreated and ion textured graphite surfaces and the ion treated copper surface exhibited sharply reduced secondary electron emission characteristics relative to those of untreated copper. The ion treated graphite surface yielded the lowest emission levels.

  7. Recycling of high purity selenium from CIGS solar cell waste materials.

    PubMed

    Gustafsson, Anna M K; Foreman, Mark R StJ; Ekberg, Christian

    2014-10-01

    Copper indium gallium diselenide (CIGS) is a promising material in thin film solar cell production. To make CIGS solar cells more competitive, both economically and environmentally, in comparison to other energy sources, methods for recycling are needed. In addition to the generally high price of the material, significant amounts of the metals are lost in the manufacturing process. The feasibility of recycling selenium from CIGS through oxidation at elevated temperatures was therefore examined. During oxidation gaseous selenium dioxide was formed and could be separated from the other elements, which remained in solid state. Upon cooling, the selenium dioxide sublimes and can be collected as crystals. After oxidation for 1h at 800°C all of the selenium was separated from the CIGS material. Two different reduction methods for reduction of the selenium dioxide to selenium were tested. In the first reduction method an organic molecule was used as the reducing agent in a Riley reaction. In the second reduction method sulphur dioxide gas was used. Both methods resulted in high purity selenium. This proves that the studied selenium separation method could be the first step in a recycling process aimed at the complete separation and recovery of high purity elements from CIGS. PMID:24472714

  8. Tertiarybutylarsine for Metalorganic Chemical Vapor Deposition Growth of High Purity, High Uniformity Films

    NASA Astrophysics Data System (ADS)

    Chui, H. C.; Biefeld, R. M.; Hammons, B. E.; Breiland, W. G.; Brennan, T. M.; Jones, E. D.; Moffat, H. K.; Kim, M. H.; Grodzinski, P.; Chang, K. H.; Lee, H. C.

    1997-12-01

    We have performed an extensive study of GaAs, Al0.22Ga0.78As, and In0.16Ga0.84As grown using tertiarybutylarsine (TBA) in an ultra-high purity metalorganic chemical vapor deposition multi-wafer reactor. Key results include: high purity TBA AlGaAs layers with the lowest p-type carrier concentrations (4 × 1014 cm-3) reported to date; 4K photoluminescence bound exciton linewidths as narrow as 4.3 meV; C, O. Si, and S concentrations below the secondary ion mass spectrometry detection limit; and InGaAs/GaAs quantum wells with 20K PL linewidths as narrow as 3.5 meV. We also observe a strong dependence of growth rates and doping efficiency on group-V partial pressure, possibly due to a competition between excess group-V species and group-Ill or Si species for group-Ill surface sites. Finally, we demonstrate record uniformity using TBA with an AlGaAs thickness variation of only ±1.4% across a 4 inch wafer.

  9. Surface preparation for high purity alumina ceramics enabling direct brazing in hydrogen atmospheres

    DOEpatents

    Cadden, Charles H.; Yang, Nancy Yuan Chi; Hosking, Floyd M.

    2001-01-01

    The present invention relates to a method for preparing the surface of a high purity alumina ceramic or sapphire specimen that enables direct brazing in a hydrogen atmosphere using an active braze alloy. The present invention also relates to a method for directly brazing a high purity alumina ceramic or sapphire specimen to a ceramic or metal member using this method of surface preparation, and to articles produced by this brazing method. The presence of silicon, in the form of a SiO.sub.2 -containing surface layer, can more than double the tensile bond strength in alumina ceramic joints brazed in a hydrogen atmosphere using an active Au-16Ni-0.75 Mo-1.75V filler metal. A thin silicon coating applied by PVD processing can, after air firing, produce a semi-continuous coverage of the alumina surface with a SiO.sub.2 film. Room temperature tensile strength was found to be proportional to the fraction of air fired surface covered by silicon-containing films. Similarly, the ratio of substrate fracture versus interface separation was also related to the amount of surface silicon present prior to brazing. This process can replace the need to perform a "moly-manganese" metallization step.

  10. Device to generate high purity hydroxide solution in-line for ion chromatography.

    PubMed

    Masunaga, Hiroto; Higo, Yuji; Ishii, Mizuo; Maruyama, Noboru; Yamazaki, Shigeo

    2016-05-01

    Herein, we report a new device that generates a high-purity hydroxide solution in line. The device's container has three compartments that are isolated from each other by two cation exchange (CE) membranes. In each end of the container, an electrode is installed. The three compartments are filled with ion exchange resins. A bipolar boundary is a composite boundary comprising anion- and cation-exchangers. This device has two bipolar boundaries, which are used to separate the location of hydroxide solution generation from the location where water is electrolyzed. Therefore, it can produce high-purity hydroxide solutions that are free from gases and anionic impurities. The hydroxide solution is generated on the basis of an electrokinetic phenomenon at the surfaces of ion-exchange resins and membranes in an electric field; NaOH concentration can be controlled at rates from 0.01 to 100mM per 1mL/min by adjusting the electrical current (0-200mA) applied to the device. As the generated solution is used as an eluent for a suppressed anion chromatography, the electrical conductivity of the effluent from the suppressor is as low as that of ultra-pure water. Thus, the noise of the base-line electrical conductivity is improved, and so the detection limit of anions on the sub-ng/mL order can be achieved. PMID:27063368

  11. Investigation of active slip systems in high purity single crystal niobium

    NASA Astrophysics Data System (ADS)

    Baars, Derek

    The superconducting radio-frequency (SRF) community uses high purity niobium to manufacture SRF cavities for a variety of accelerator applications. Cavities are either made from large-grain sheets cut directly from the ingot and formed, or the ingot microstructure is broken down to form polycrystalline sheets or tubes. Reducing the number of costly electron beam welds to assemble the cavities is also desired. A greater understanding of the active slip systems and their relation to subsequent dislocation substructure would be of use in all these areas, to better understand how large grain niobium deforms and to develop more accurate computational models that will aid in the design and use of more cost-effective forming methods. Studies of slip in high-purity niobium suggest that temperature, material purity, and crystal orientation affect which slip systems are active during deformation, though have not examined the somewhat lesser purity niobium used for SRF cavities. As a step toward these goals, two sets of SRF-purity single crystal niobium samples were deformed to 40% strain in tension at room temperature. The first set was cut and welded back together. The second set consisted of deliberately orientated samples that resolved shear stress onto desired slip systems to evaluate different combinations of slip. Determining likely active slip systems was complex, though the evidence suggests that {112} slip may be dominant at yield at room temperature as suggested by theory, though {110} slip could not be ruled out.

  12. Process for producing high purity silicon nitride by the direct reaction between elemental silicon and nitrogen-hydrogen liquid reactants

    DOEpatents

    Pugar, E.A.; Morgan, P.E.D.

    1987-09-15

    A process is disclosed for producing, at a low temperature, a high purity reaction product consisting essentially of silicon, nitrogen, and hydrogen which can then be heated to produce a high purity alpha silicon nitride. The process comprises: reacting together a particulate elemental high purity silicon with a high purity nitrogen-hydrogen reactant in its liquid state (such as ammonia or hydrazine) having the formula: N/sub n/H/sub (n+m)/ wherein: n = 1--4 and m = 2 when the nitrogen-hydrogen reactant is straight chain, and 0 when the nitrogen-hydrogen reactant is cyclic. High purity silicon nitride can be formed from this intermediate product by heating the intermediate product at a temperature of from about 1200--1700/degree/C for a period from about 15 minutes up to about 2 hours to form a high purity alpha silicon nitride product. The discovery of the existence of a soluble Si/endash/N/endash/H intermediate enables chemical pathways to be explored previously unavailable in conventional solid-state approaches to silicon-nitrogen ceramics

  13. Process for producing high purity silicon nitride by the direct reaction between elemental silicon and nitrogen-hydrogen liquid reactants

    DOEpatents

    Pugar, Eloise A.; Morgan, Peter E. D.

    1990-01-01

    A process is disclosed for producing, at a low temperature, a high purity reaction product consisting essentially of silicon, nitrogen, and hydrogen which can then be heated to produce a high purity alpha silicon nitride. The process comprises: reacting together a particulate elemental high purity silicon with a high purity nitrogen-hydrogen reactant in its liquid state (such as ammonia or hydrazine) having the formula: N.sub.n H.sub.(n+m) wherein: n=1-4 and m=2 when the nitrogen-hydrogen reactant is straight chain, and 0 when the nitrogen-hydrogen reactant is cyclic. High purity silicon nitride can be formed from this intermediate product by heating the intermediate product at a temperature of from about 1200.degree.-1700.degree. C. for a period from about 15 minutes up to about 2 hours to form a high purity alpha silicon nitride product. The discovery of the existence of a soluble Si-N-H intermediate enables chemical pathways to be explored previously unavailable in conventional solid state approaches to silicon-nitrogen ceramics.

  14. Experimental research of phase transition's kinetics in a liquid melt of high-purity aluminum

    NASA Astrophysics Data System (ADS)

    Vorontsov, V. B.; Zhuravlev, D. V.; Cherepanov, A. S.

    2015-08-01

    This scientific work is devoted to the studying of the genetic connection structures of solid and liquid phases. Fourier analysis of signals of acoustic emission (AE) accompanying melting high purity aluminum from the melting point up to t = 860°C was performed. Based on the results of previous studies cluster formations in the melt - the micro-regions, those retain crystallinity (areas with short-range order of symmetry) were considered as the source of AE. The experimental data allowed to follow the dynamics of disorder zones range order in the melt with increasing melt temperature up to their complete destruction. The presented results of spectral analysis of the signals were analyzed from the standpoint of the theory of cluster melting metals.

  15. Application of Thermodynamic Calculations to the Pyro-refining Process for Production of High Purity Bismuth

    NASA Astrophysics Data System (ADS)

    Mezbahul-Islam, Mohammad; Belanger, Frederic; Chartrand, Patrice; Jung, In-Ho; Coursol, Pascal

    2016-04-01

    The present work has been performed with the aim to optimize the existing process for the production of high purity bismuth (99.999 pct). A thermo-chemical database including most of the probable impurities of bismuth (Bi-X, X = Ag, Au, Al, Ca, Cu, Fe, Mg, Mn, Na, Ni, Pb, S, Sb, Sn, Si, Te, Zn) has been constructed to perform different thermodynamic calculations required for the refining process. Thermodynamic description for eight of the selected binaries, Bi-Ca, Cu, Mn, Ni, Pb, S, Sb, and Sn, has been given in the current paper. Using the current database, different thermodynamic calculations have been performed to explain the steps involved in the bismuth refining process.

  16. Effect of Sintering Temperature on the Synthesis of High Purity Cordierite

    SciTech Connect

    Choo, Y. P.; Chow, T. Y.; Mohamad, H.

    2008-03-17

    Cordierite is silicate material widely used in ceramic industry. The effect of sintering temperature to the properties of cordierite by sol gel method was studied with utilizing magnesium nitrate, aluminum nitrate, ethanol, and tetraethyl orthosilicate (TEOS) as starting materials. Gels are dried and sintered at different temperature (1000 deg. C, 1200 deg. C, 1300 deg. C and 1350 deg. C) then characterized by varies analysis techniques. XRD analysis shows that spinel, {mu}-cordierite and cristobalite are formed at 1000 deg. C which spinel as predominant phase. At 1200 deg. C, {mu}-cordierite occured as predominant phase, spinel, sapphirine and cristobalite are formed as minor phases. It also confirmed that high purity {alpha}-cordierite formed at 1300 deg. C and clearly observed at 1350 deg. C. Result of EDX analysis proved that magnesium, aluminum, silicon and oxygen was existed in the cordierite.

  17. The importance of Soret transport in the production of high purity silicon for solar cells

    NASA Technical Reports Server (NTRS)

    Srivastava, R.

    1985-01-01

    Temperature-gradient-driven diffusion, or Soret transport, of silicon vapor and liquid droplets is analyzed under conditions typical of current production reactors for obtaining high purity silicon for solar cells. Contrary to the common belief that Soret transport is negligible, it is concluded that some 15-20 percent of the silicon vapor mass flux to the reactor walls is caused by the high temperature gradients that prevail inside such reactors. Moreover, since collection of silicon is also achieved via deposition of silicon droplets onto the walls, the Soret transport mechanism becomes even more crucial due to size differences between diffusing species. It is shown that for droplets in the 0.01 to 1 micron diameter range, collection by Soret transport dominates both Brownian and turbulent mechanisms.

  18. In-growth of an electrically active defect in high-purity silicon after proton irradiation

    SciTech Connect

    Nylandsted Larsen, A.; Juul Pedersen, H.; Christian Petersen, M.; Privitera, V.; Gurimskaya, Y.; Mesli, A.

    2013-12-14

    Defect-related energy levels in the lower half of the band gap of silicon have been studied with transient-capacitance techniques in high-purity, carbon and oxygen lean, plasma-enhanced chemical-vapor deposition grown, n-and p-type silicon layers after 2-MeV proton irradiations at temperatures at or just below room temperature. The in-growth of a distinct line in deep-level transient spectroscopy spectra, corresponding to a level in the band gap at E{sub V} + 0.357 eV where E{sub V} is the energy of the valence band edge, takes place for anneal temperatures at around room temperature with an activation energy of 0.95 ± 0.08 eV. The line disappears at an anneal temperature of around 450 K. The corresponding defect is demonstrated not to contain boron, carbon, oxygen, or phosphorus. Possible defect candidates are discussed.

  19. URANIUM RECOVERY AND PURIFICATION PROCESS AND PRODUCTION OF HIGH PURITY URANIUM TETRAFLUORIDE

    DOEpatents

    Bailes, R.H.; Long, R.S.; Grinstead, R.R.

    1957-09-17

    A process is described wherein an anionic exchange technique is employed to separate uramium from a large variety of impurities. Very efficient and economical purification of contamimated uranium can be achieved by treatment of the contaminated uranium to produce a solution containing a high concentration of chloride. Under these conditions the uranium exists as an aniomic chloride complex. Then the uranium chloride complex is adsorbed from the solution on an aniomic exchange resin, whereby a portion of the impurities remain in the solution and others are retained with the uramium by the resin. The adsorbed impurities are then removed by washing the resin with pure concentrated hydrochloric acid, after which operation the uranium is eluted with pure water yielding an acidic uranyl chloride solution of high purity.

  20. Hot working of high purity Fe-C alloys in the α-range

    NASA Astrophysics Data System (ADS)

    Montheillet, F.; Le Coze, J.

    2010-07-01

    The influence of carbon in solid solution on the stress-strain curves of α-iron was investigated using model alloys prepared from high purity iron. Uniaxial compression tests were carried out within the ferritic domain at temperatures between 700 and 880 °C. Oscillating stress-strain curves observed at high temperatures and low strain rates indicate that discontinuous dynamic recrystallization takes place. The macroscopic strain rate sensitivities m and apparent activation energies Q associated with the flow stress are not significantly modified by carbon additions. By contrast, the "mesoscopic" parameters h and r associated with strain hardening and dynamic recovery, respectively, are strongly dependent on the carbon content. Finally, an estimation of the grain boundary mobilities during dynamic recrystallization was carried out from the above rheological data.

  1. Observation of Impact Ionization of Shallow States in Sub-Kelvin, High-Purity Germanium

    NASA Astrophysics Data System (ADS)

    Phipps, A.; Sadoulet, B.; Sundqvist, K. M.

    2016-07-01

    We report on the observation of impact ionization processes involving shallow impurity states in a sub-Kelvin, high-purity n-type germanium detector similar to those used by direct detection dark matter experiments such as the Cryogenic Dark Matter Search. An optical fiber is used to generate packets of charge carriers near one surface of the detector. The charge carriers drift to the opposite surface by application of an electric field. The resulting drift current is measured by a high-speed charge amplifier. The onset of impact ionization for both electron and hole transport is clearly observed in the drift current as the applied electric field is increased above ≈ 5 V/cm. We present the effective charge collection efficiency and trapping length as a function of applied electric field for electrons and holes. We estimate the impact ionization cross section to be on the order of 5× 10^{-13} mathrm {cm}^2.

  2. Physical and mechanical metallurgy of high purity Nb for accelerator cavities

    SciTech Connect

    Bieler, T. R.; Wright, N. T.; Pourboghrat, F.; Compton, C.; Hartwig, K. T.; Baars, D.; Zamiri, A.; Chandrasekaran, S.; Darbandi, P.; Jiang, H.; Skoug, E.; Balachandran, S.; Ice, Gene E; Liu, W.

    2010-01-01

    In the past decade, high Q values have been achieved in high purity Nb superconducting radio frequency (SRF) cavities. Fundamental understanding of the physical metallurgy of Nb that enables these achievements is beginning to reveal what challenges remain to establish reproducible and cost-effective production of high performance SRF cavities. Recent studies of dislocation substructure development and effects of recrystallization arising from welding and heat treatments and their correlations with cavity performance are considered. With better fundamental understanding of the effects of dislocation substructure evolution and recrystallization on electron and phonon conduction, as well as the interior and surface states, it will be possible to design optimal processing paths for cost-effective performance using approaches such as hydroforming, which minimizes or eliminates welds in a cavity.

  3. A Rapid and Cost-Effective Laser Based Synthesis of High Purity Cadmium Selenide Quantum Dots.

    PubMed

    Gondall, M A; Qahtan, Talal F; Dastageer, M A; Yamani, Z H; Anjum, D H

    2016-01-01

    A rapid and cost effective method is developed to synthesize high purity cadmium Selenide (CdSe) quantum dots in acetone medium using second harmonic of Nd:YAG nanosecond pulsed laser of 532 nm wavelength. The thermal agglomeration due the nanosecond pulse duration of the laser was successfully eliminated by using unfocussed laser beam and thereby providing a favorable conditions for the synthesis of quantum dots having the grain size of 3 nm. The morphological and optical characterizations like XRD, HRTEM, optical absorption of the synthesized CdSe quantum dots, reveal that the material possesses the similar characteristics of the one synthesized through cumbersome wet chemical methods. Relative to the CdSe bulk material, the synthesized CdSe quantum dots showed a blue shift in the measured band gap energy from near infrared spectral region to visible region, making this material very attractive for many solar energy harvesting applications like photo-catalysis and solar cells. PMID:27398538

  4. Observation of Impact Ionization of Shallow States in Sub-Kelvin, High-Purity Germanium

    NASA Astrophysics Data System (ADS)

    Phipps, A.; Sadoulet, B.; Sundqvist, K. M.

    2016-01-01

    We report on the observation of impact ionization processes involving shallow impurity states in a sub-Kelvin, high-purity n-type germanium detector similar to those used by direct detection dark matter experiments such as the Cryogenic Dark Matter Search. An optical fiber is used to generate packets of charge carriers near one surface of the detector. The charge carriers drift to the opposite surface by application of an electric field. The resulting drift current is measured by a high-speed charge amplifier. The onset of impact ionization for both electron and hole transport is clearly observed in the drift current as the applied electric field is increased above ≈ 5 V/cm. We present the effective charge collection efficiency and trapping length as a function of applied electric field for electrons and holes. We estimate the impact ionization cross section to be on the order of 5× 10^{-13} {cm}^2.

  5. Formation of recrystallization cube texture in high purity face-centered cubic metal sheets

    SciTech Connect

    Mao, W.

    1999-10-01

    An investigation on recrystallization textures in high purity face-centered cubic (fcc) aluminum, copper, and nickel indicated that the cube texture is a unique dominant final texture. In a macroview of rolling deformation, a balanced activation of four slip systems can result in certain stability of some substructure with cube orientation in the deformed matrix. In the stable substructure the dislocation density is very low, and the dislocation configuration is rather simple in comparison to other orientations so that the cube substructure can easily be transformed into cube recrystallization nuclei by a recovery process. A high orientation gradient and correspondingly high angle boundaries to the deformed matrix are usually expected around the cube nuclei, which, therefore, grow rapidly. After the primary recrystallization, the size of cube grains is much larger than the grains with other orientations, which will be expensed as the cube grains grow further, so that the cube texture can finally become a dominant texture component.

  6. Map showing high-purity silica sand of Middle Ordovician age in the Midwestern states

    USGS Publications Warehouse

    Ketner, Keith B.

    1979-01-01

    Certain quartz sands of Middle Ordovician age in the Midwestern States are well known for their purity and are exploited for a wide variety of industrial uses. The principal Middle Ordovician formations containing high-purity sands are the St. Peter Sandstone which crops out extensively from Minnesota to Arkansas; the Everton Formation principally of Arkansas; and the Oil Creek, McLish, and Tulip Creek Formations (all of the Simpson Group) of Oklahoma. The St. Peter and sandy beds in the other formations are commonly called "sandstones," but a more appropriate term is "sands" for in most fresh exposures they are completely uncemented or very weakly cemented. On exposure to air, uncemented sands usually become "case hardened" where evaporating ground water precipitates mineral matter at the surface; but this is a surficial effect. This report summarizes the available information on the extent of exposures, range of grain size, and chemical composition of the Middle Ordovician sands.

  7. The relationship between induction time for pitting and pitting potential for high purity aluminum.

    SciTech Connect

    Wall, Frederick Douglas; Vandenavyle, Justin J.; Martinez, Michael A.

    2003-08-01

    The objective of this study was to determine if a distribution of pit induction times (from potentiostatic experiments) could be used to predict a distribution of pitting potentials (from potentiodynamic experiments) for high-purity aluminum. Pit induction times were measured for 99.99 Al in 50 mM NaCl at potentials of -0.35, -0.3, -0.25, and -0.2 V vs. saturated calomel electrode. Analysis of the data showed that the pit germination rate generally was an exponential function of the applied potential; however, a subset of the germination rate data appeared to be mostly potential insensitive. The germination rate behavior was used as an input into a mathematical relationship that provided a prediction of pitting potential distribution. Good general agreement was found between the predicted distribution and an experimentally determined pitting potential distribution, suggesting that the relationships presented here provide a suitable means for quantitatively describing pit germination rate.

  8. Diffusion Resistant, High-Purity Wafer Carriers For SI Semiconductor Production

    SciTech Connect

    Tiegs, T.N.; Leaskey, L.

    2000-10-01

    The Cooperative Research and Development Agreement (CRADA) was directed towards development of diffusion resistant, high-purity wafer carriers for Si semiconductor production with improved properties compared to current materials. The determination of the infiltration behavior is important for controlling the fabrication process to. obtain consistent high-quality products. Ammonium molybdate or molybdenum carbide were found to be suitable as a precursor to produce SiC-MoSi{sub 2}-Si composites by Si infiltration into carbon preforms. Experiments on the pyrolysis of the preforms showed variable infiltration behavior by the molten Si (within the range of conditions in the present study). Further research is required to reproducibly and consistently fabricate flaw-free articles. The strength of the composites fabricated to-date was 325{+-}124 MPa, which is higher than current commercial products. Better process control should result in higher average strengths and reduce the variability.

  9. Production of carbon monoxide-free hydrogen and helium from a high-purity source

    DOEpatents

    Golden, Timothy Christopher; Farris, Thomas Stephen

    2008-11-18

    The invention provides vacuum swing adsorption processes that produce an essentially carbon monoxide-free hydrogen or helium gas stream from, respectively, a high-purity (e.g., pipeline grade) hydrogen or helium gas stream using one or two adsorber beds. By using physical adsorbents with high heats of nitrogen adsorption, intermediate heats of carbon monoxide adsorption, and low heats of hydrogen and helium adsorption, and by using vacuum purging and high feed stream pressures (e.g., pressures of as high as around 1,000 bar), pipeline grade hydrogen or helium can purified to produce essentially carbon monoxide -free hydrogen and helium, or carbon monoxide, nitrogen, and methane-free hydrogen and helium.

  10. Crystallographic Analysis of Nucleation at Hardness Indentations in High-Purity Aluminum

    NASA Astrophysics Data System (ADS)

    Xu, Chaoling; Zhang, Yubin; Lin, Fengxiang; Wu, Guilin; Liu, Qing; Juul Jensen, Dorte

    2016-08-01

    Nucleation at Vickers hardness indentations has been studied in high-purity aluminum cold-rolled 12 pct. Electron channeling contrast was used to measure the size of the indentations and to detect nuclei, while electron backscattering diffraction was used to determine crystallographic orientations. It is found that indentations are preferential nucleation sites. The crystallographic orientations of the deformed grains affect the hardness and the nucleation potentials at the indentations. Higher hardness gives increased nucleation probabilities. Orientation relationships between nuclei developed at different indentations within one original grain are analyzed and it is found that the orientation distribution of the nuclei is far from random. It is suggested that it relates to the orientations present near the indentation tips which in turn depend on the orientation of the selected grain in which they form. Finally, possible nucleation mechanisms are briefly discussed.

  11. Observation of Impact Ionization of Shallow States in Sub-Kelvin, High-Purity Germanium

    NASA Astrophysics Data System (ADS)

    Phipps, A.; Sadoulet, B.; Sundqvist, K. M.

    2016-07-01

    We report on the observation of impact ionization processes involving shallow impurity states in a sub-Kelvin, high-purity n-type germanium detector similar to those used by direct detection dark matter experiments such as the Cryogenic Dark Matter Search. An optical fiber is used to generate packets of charge carriers near one surface of the detector. The charge carriers drift to the opposite surface by application of an electric field. The resulting drift current is measured by a high-speed charge amplifier. The onset of impact ionization for both electron and hole transport is clearly observed in the drift current as the applied electric field is increased above ≈ 5 V/cm. We present the effective charge collection efficiency and trapping length as a function of applied electric field for electrons and holes. We estimate the impact ionization cross section to be on the order of 5× 10^{-13} {cm}^2.

  12. High Strain-Rate Response of High Purity Aluminum at Temperatures Approaching Melt

    SciTech Connect

    Grunschel, S E; Clifton, R J; Jiao, T

    2010-01-28

    High-temperature, pressure-shear plate impact experiments were conducted to investigate the rate-controlling mechanisms of the plastic response of high-purity aluminum at high strain rates (10{sup 6} s{sup -1}) and at temperatures approaching melt. Since the melting temperature of aluminum is pressure dependent, and a typical pressure-shear plate impact experiment subjects the sample to large pressures (2 GPa-7 GPa), a pressure-release type experiment was used to reduce the pressure in order to measure the shearing resistance at temperatures up to 95% of the current melting temperature. The measured shearing resistance was remarkably large (50 MPa at a shear strain of 2.5) for temperatures this near melt. Numerical simulations conducted using a version of the Nemat-Nasser/Isaacs constitutive equation, modified to model the mechanism of geometric softening, appear to capture adequately the hardening/softening behavior observed experimentally.

  13. Characterization of dislocation and defects for large high purity Ge crystals

    NASA Astrophysics Data System (ADS)

    Mei, Hao; Wang, Guojian; Guan, Yutong; Yang, Gang; Mei, Dongming; Cubed Collaboration

    2015-03-01

    Large diameter (~10 cm) high purity Germanium (HP-Ge) crystals have been growing via Czochralski method at University of South Dakota. We investigate the impacts of growth rate, time-temperature profile, and thermal gradient on the dislocation and defects distribution in HP-Ge crystals along <100>orientation. The dislocation density across the entire cross-section of a grown crystal is measured using microscope. Utilizing X-Ray Diffraction method, we obtain the rocking curves from the same crystal samples. We analyze the correlation between the full width at half maximum (FWHM) of the rocking curves and the dislocation densities from the optical observations (etch pits distribution). A model that describes the correlation of dislocation density, along the HP-Ge crystal, with the FWHM of the rock curves for XRD is established. We report these analytic results. This work is supported by DOE Grant DE-FG02-10ER46709 and the state of South.

  14. Effect of Rest Periods on Fatigue of High-Purity Aluminum

    NASA Technical Reports Server (NTRS)

    Berry, J. W.; Lemaitre, J.; Valluri, S. R.

    1958-01-01

    The effect of rest periods on the fatigue life of high-purity aluminum was investigated under two conditions. In one the specimens were tested at elevated temperatures and the rest periods were given at room temperature; in the second the specimens were tested at room temperature and the rest periods were given at elevated temperature. The results obtained indicated that the increase of life was negligible in the first condition, but an increase of life may be obtained in the second. In order to check this increase in fatigue life a second series of tests has been carried out on a different lot of specimens and again an increase in life was found. This increase of life appeared to be from 30 to 60 percent from the average of the results of 20 tests for each test condition.

  15. Preparation and characterization of (10)B boric acid with high purity for nuclear industry.

    PubMed

    Zhang, Weijiang; Liu, Tianyu; Xu, Jiao

    2016-01-01

    Boric acid is often added into coolant as neutron capture agent for pressurized water reactor, whose amount is influenced by its abundance and purity. Therefore, the preparation of enriched (10)B boric acid with high purity is beneficial to nuclear industry. (10)B is also used in developing tumor-specific boronated drugs in boron neutron capture therapy. The boronated drug can be administered to patient intravenously, intratumorally, or deposited at tumor site in surgical excision. Thus, enriched (10)B boric acid is of practical significance in the field of medicine. Self-made boron trifluoride-methanol-complex solution was selected as one of the experimental reagents, and the preparation of (10)B acid was realized by one-step reaction for the complexes with water and calcium chloride. The determination of electrical conductivity in reaction process proves that the optimum reaction time was 16-20 h. Furthermore, the effect of reaction time, ratio of calcium chloride to complex as well as the amount of water on the purity and yield of boric acid was investigated. Finally, the optimum reaction time was 20 h, the optimal solid-liquid ratio (molar ratio) was 3:1, and the amount of water was 1 L of deionized water for each mol of the complex. H2O2 was added in the reaction process to remove Fe(2+). After recrystallization, IR spectra of (10)B boric acid was measured and compared with standard to verify the product of boric acid. The feasibility of the preparation method was determined by the detection of XRD of boric acid. To observe the morphology by polarizing microscope, crystal structure was obtained. The purity of the final product is 99.95 %, and the yield is 96.47 %. The ion concentration of boric acid accords with the national standard of high purity, which was determined by ICP. PMID:27516940

  16. Recycling of high purity selenium from CIGS solar cell waste materials

    SciTech Connect

    Gustafsson, Anna M.K. Foreman, Mark R.StJ.; Ekberg, Christian

    2014-10-15

    Highlights: • A new method for recycling of selenium from CIGS solar cell materials is presented. • Separation of selenium as selenium dioxide after heating in oxygen atmosphere. • Complete selenium separation after oxidation of <63 μm particles at 800 °C for 1 h. • After reduction of selenium dioxide the selenium purity was higher than 99.999 wt%. - Abstract: Copper indium gallium diselenide (CIGS) is a promising material in thin film solar cell production. To make CIGS solar cells more competitive, both economically and environmentally, in comparison to other energy sources, methods for recycling are needed. In addition to the generally high price of the material, significant amounts of the metals are lost in the manufacturing process. The feasibility of recycling selenium from CIGS through oxidation at elevated temperatures was therefore examined. During oxidation gaseous selenium dioxide was formed and could be separated from the other elements, which remained in solid state. Upon cooling, the selenium dioxide sublimes and can be collected as crystals. After oxidation for 1 h at 800 °C all of the selenium was separated from the CIGS material. Two different reduction methods for reduction of the selenium dioxide to selenium were tested. In the first reduction method an organic molecule was used as the reducing agent in a Riley reaction. In the second reduction method sulphur dioxide gas was used. Both methods resulted in high purity selenium. This proves that the studied selenium separation method could be the first step in a recycling process aimed at the complete separation and recovery of high purity elements from CIGS.

  17. The Stress Corrosion Crack Growth Rate of Alloy 600 Heat Affected Zones Exposed to High Purity Water

    SciTech Connect

    George A. Young; Nathan Lewis

    2003-04-05

    Grain boundary chromium carbides improve the resistance of nickel based alloys to primary water stress corrosion cracking (PWSCC). However, in weld heat affected zones (HAZ's), thermal cycles from fusion welding can solutionize beneficial grain boundary carbides, produce locally high residual stresses and strains, and promote PWSCC. The present research investigates the crack growth rate of an A600 HAZ as a function of test temperature. The A600 HAZ was fabricated by building up a gas-tungsten-arc-weld deposit of EN82H filler metal onto a mill-annealed A600 plate. Fracture mechanics based, stress corrosion crack growth rate testing was performed in high purity water between 600 F and 680 F at an initial stress intensity factor of 40 ksi {radical}in and at a constant electrochemical potential. The HAZ samples exhibited significant SCC, entirely within the HAZ at all temperatures tested. While the HAZ samples showed the same temperature dependence for SCC as the base material (HAZ: 29.8 {+-} 11.2{sub 95%} kcal/mol vs A600 Base: 35.3 {+-} 2.58{sub 95%} kcal/mol), the crack growth rates were {approx} 30X faster than the A600 base material tested at the same conditions. The increased crack growth rates of the HAZ is attributed to fewer intergranular chromium rich carbides and to increased plastic strain in the HAZ as compared to the unaffected base material.

  18. Functions of AAV-CMV-F.IX And AAV-EF1alpha-F.IX in gene therapy for hemophilia B.

    PubMed

    Wiwanitkit, Viroj

    2007-02-01

    There has been substantial progress in using gene therapy to treat animals with hemophilia. Adeno-associated viral (AAV) gene transfer of coagulation factor IX to skeletal muscle and liver of murine and canine models of hemophilia has resulted in sustained systemic expression and, in several studies, in complete cure of the bleeding disorder. Two AAV vectors widely used at present are AAV-CMV-F.IX and AAV-EF1alpha-F.IX. This work compares the predicted molecular functions of AAV-CMV-F.IX and AAV-EF1alpha -F.IX by sequence docking and gene ontology. It is shown that both AAV-CMV-F.IX and AAV-EF1alpha -F.IX induce coagulation factor IXa activity; however, AAV-CMV-F.IX administration also yields coagulation factor XIa activity and AAV-EF1alpha -F.IX treatment results in coagulation factor Xa activity. Therefore, AAV-CMV-F.IX might be useful for factor XI deficiency. AAV-CMV-F.IX has several additional molecular functions and processes compared with AAV-CMV-F.IX. PMID:17266422

  19. Influence of strain rate and temperature on the structure/property behavior of high-purity titanium

    SciTech Connect

    Gray, G.T. III

    1997-05-01

    The effect of strain rate, temperature, grain size, and texture on the substructure and mechanical response of high-purity polycrystalline titanium is presented. The compressive stress-strain response of 20 and 240 {mu}m grain size high-purity Ti was found to depend on both the applied strain rate; 0.001 {le} {epsilon} {le} 7500 s{sup -1}, and the test temperature; 77 {le} T {le} 873 K. The rate of strain hardening in Ti is seen to increase with increasing strain rate. The substructure of high-purity Ti deformed at high-strain-rate or quasi-statically at 77K displayed a higher incidence of deformation twinning than during quasi-static deformation at 298K.

  20. Desensitization and immune tolerance induction in children with severe factor IX deficiency; inhibitors and adverse reactions to replacement therapy: a case-report and literature review.

    PubMed

    Bon, Andrea; Morfini, Massimo; Dini, Alessandro; Mori, Francesca; Barni, Simona; Gianluca, Sottilotta; de Martino, Maurizio; Novembre, Elio

    2015-01-01

    Hemophilia B is a rare X-linked recessive disorder with plasma factor IX (FIX) deficiency. 1-3% of patients treated with exogenous FIX-containing products develop inhibitors (i.e. polyclonal high affinity immunoglobulins) that neutralize the procoagulant activity of a specific coagulation factor. Although the incidence of inhibitors in hemophilia B patients is low, most are "high titer" and frequently associated with the development of severe allergic or anaphylactic reactions. Immune tolerance induction as a strategy for inhibitor eradication was first described in 1984. Unfortunately, the overall reported success of immune tolerance induction in FIX deficiency with inhibitors is approximately 25-40%.We report the case of a 2-year-old boy with hemophilia B severe FIX deficiency (<1%), inhibitor antibodies to FIX development, and a history of adverse reactions to FIX infusions, who underwent a successful desensitization and immune tolerance induction with a daily FIX infusion. With this regimen the inhibitor titer decreased with effective bleeding prevention. PMID:25887512

  1. Multidimensional Study on Spall Behavior of High-Purity Copper Under Sliding Detonation

    NASA Astrophysics Data System (ADS)

    Yang, Yang; Peng, Zhiqiang; Guo, Zhaoliang; Luo, Shuhong; Tang, Tiegang; Hu, Haibo; Zhang, Qingming

    2015-09-01

    The spall behaviors of high-purity copper samples with different heat treatment histories were investigated using optical microscopy and X-ray computer tomography (XRCT). The spall samples were obtained by sliding detonation experiments at low pressures (2 to 4 GPa). It was found that the spall planes created by sliding detonation in this experiment are similar to the spall planes created by plate impact test, except for more secondary damage residual around the main spall plane. The results of damage degree, the shape, and the distributions of voids obtained by the means of metallography (2D) and XRCT (3D) statistics were consistent. For similar microstructure, the maximum damage degree and damage zone width increase with increasing shock stress. Whereas the ranges of voids distribution parallel to the shock stress direction decreases with the increasing of shock stress. For the shock stress is similar, the shape of voids in annealed samples are closed to spheres, their mean flatness is 0.51. The voids in samples with thermo-mechanical treatment histories are sheet like with mean flatness 0.16. The difference in grain size (40 and 9 μm) may be the main reason of such difference.

  2. Safety studies conducted on a proprietary high-purity aloe vera inner leaf fillet preparation, Qmatrix.

    PubMed

    Williams, Lonnie D; Burdock, George A; Shin, Eunju; Kim, Seunghyun; Jo, T H; Jones, Kenneth N; Matulka, Ray A

    2010-06-01

    The aloe vera plant has a long history of safe use for oral and topical applications. This publication describes safety studies conducted on a proprietary high-purity aloe vera inner leaf fillet preparation, Qmatrix. In a 13-week study in rats, Qmatrix was administered via gavage at 0, 500, 1000 and 2000 mg/kg body weight (bw)/day. There were no significant changes in food or water consumption, body weight, serum biochemistry or hematology at any of the doses tested. Sporadic, significant increases were observed in some of the measured urinalysis parameters; however, these variations were not treatment-related, as most were observed only in one sex, not dose-dependent and within historical control values. Organ weights were unaffected, except for a statistically significant, though not dose-dependent, increase in absolute and relative weights of the right kidney in males at 500 and 2000 mg/kg bw/day, respectively. Histopathological analysis revealed no abnormal signs. Qmatrix was non-mutagenic in an Ames test and a chromosomal aberration test at concentrations up to 10,000 microg/plate, and in an in vivo bone marrow micronucleus test at doses up to 5000 mg/kg bw/day. Based on these results, Qmatrix is not genotoxic in vitro or in vivo and; has an oral NOAEL greater than 2000 mg/kg bw/day following 90 days of oral exposure. PMID:20096744

  3. Optimization of extraction of high purity all-trans-lycopene from tomato pulp waste.

    PubMed

    Poojary, Mahesha M; Passamonti, Paolo

    2015-12-01

    The aim of this work was to optimize the extraction of pure all-trans-lycopene from the pulp fractions of tomato processing waste. A full factorial design (FFD) consisting of four independent variables including extraction temperature (30-50 °C), time (1-60 min), percentage of acetone in n-hexane (25-75%, v/v) and solvent volume (10-30 ml) was used to investigate the effects of process variables on the extraction. The absolute amount of lycopene present in the pulp waste was found to be 0.038 mg/g. The optimal conditions for extraction were as follows: extraction temperature 20 °C, time 40 min, a solvent composition of 25% acetone in n-hexane (v/v) and solvent volume 40 ml. Under these conditions, the maximal recovery of lycopene was 94.7%. The HPLC-DAD analysis demonstrated that, lycopene was obtained in the all-trans-configuration at a very high purity grade of 98.3% while the amount of cis-isomers and other carotenoids were limited. PMID:26041168

  4. Native oxidation of ultra high purity Cu bulk and thin films

    NASA Astrophysics Data System (ADS)

    Iijima, J.; Lim, J.-W.; Hong, S.-H.; Suzuki, S.; Mimura, K.; Isshiki, M.

    2006-12-01

    The effect of microstructure and purity on the native oxidation of Cu was studied by using angle-resolved X-ray photoelectron spectroscopy (AR-XPS) and spectroscopic ellipsometry (SE). A high quality copper film prepared by ion beam deposition under a substrate bias voltage of -50 V (IBD Cu film at Vs = -50 V) showed an oxidation resistance as high as an ultra high purity copper (UHP Cu) bulk, whereas a Cu film deposited without substrate bias voltage (IBD Cu film at Vs = 0 V) showed lower oxidation resistance. The growth of Cu 2O layer on the UHP Cu bulk and both types of the films obeyed in principle a logarithmic rate law. However, the growth of oxide layer on the IBD Cu films at Vs = 0 and -50 V deviated upward from the logarithmic rate law after the exposure time of 320 and 800 h, respectively. The deviation from the logarithmic law is due to the formation of CuO on the Cu 2O layer after a critical time.

  5. Effect of chromium on low-temperature deformation of high-purity iron

    NASA Technical Reports Server (NTRS)

    Kelley, M. J.; Stoloff, N. S.

    1976-01-01

    A series of very low interstitial Fe-Cr alloys containing 0, 1, 3, 5, and 10 wt% Cr were prepared by vacuum melting and fabricated under argon to 1.83 mm diam wires exposed in an alumina system to wet hydrogen for 200 h at 1423 K followed by 1000 h in ZrH2-purified hydrogen at 1573 K. The wires were then transverse-rolled into thin sheet and cut into tensile specimens subjected to electropolishing and strained to fracture in a series of cryogenic baths ranging from 4.2 K to room temperature. It is shown that small Cr additions lower the twinning stress so that yielding occurs by twinning rather than by slip. Cr in amounts up to 10 wt% has little effect on the yield strength of high-purity Fe between 147 and 300 K, and ductility is not greatly affected at any test temperature. Higher solute contents provide appreciable strengthening only at temperatures of 112 K and below.

  6. Determination of halogens and sulfur in high-purity polyimide by IC after digestion by MIC.

    PubMed

    Krzyzaniak, Sindy R; Santos, Rafael F; Dalla Nora, Flavia M; Cruz, Sandra M; Flores, Erico M M; Mello, Paola A

    2016-09-01

    In this work, a method for sample preparation of high-purity polyimide was proposed for halogens and sulfur determination by ion chromatography (IC) with conductivity detection and, alternatively, by inductively coupled plasma mass spectrometry (ICP-MS). A relatively high polyimide mass (600mg) was completely digested by microwave-induced combustion (MIC) using 20bar of O2 and 50mmolL(-1) NH4OH as absorbing solution. These conditions allowed final solutions with low carbon content (<10mgL(-1)) and suitable pH for analysis by both IC and ICP-MS. The accuracy was evaluated using a certified reference material of polymer for Cl, Br and S and spike recovery experiments for all analytes. No statistical difference (t-test, 95% of confidence level) was observed between the results obtained for Cl, Br and S by IC after MIC and the certified values. In addition, spike recoveries obtained for F, Cl, Br, I and S ranged from 94% to 101%. The proposed method was suitable for polyimide decomposition for further determination of halogens and sulfur by IC and by ICP-MS (Br and I only). Taking into account the lack of methods and the difficulty of bringing this material into solution, MIC can be considered as a suitable alternative for the decomposition of polyimide for routine quality control of halogens and sulfur using IC or ICP-MS. PMID:27343595

  7. Simulation study comparing high-purity germanium and cadmium zinc telluride detectors for breast imaging

    PubMed Central

    Campbell, DL; Peterson, TE

    2014-01-01

    We conducted simulations to compare the potential imaging performance for breast cancer detection with High-Purity Germanium (HPGe) and Cadmium Zinc Telluride (CZT) systems with 1% and 3.8% energy resolution at 140 keV, respectively. Using the Monte Carlo N-Particle (MCNP5) simulation package, we modelled both 5 mm-thick CZT and 10 mm-thick HPGe detectors with the same parallel-hole collimator for the imaging of a breast/torso phantom. Simulated energy spectra were generated, and planar images were created for various energy windows around the 140-keV photopeak. Relative sensitivity and scatter and the torso fractions were calculated along with tumour contrast and signal-to-noise ratios (SNR). Simulations showed that utilizing a ±1.25% energy window with an HPGe system better suppressed torso background and small-angle scattered photons than a comparable CZT system using a −5%/+10% energy window. Both systems provided statistically similar contrast and SNR, with HPGe providing higher relative sensitivity. Lowering the counts of HPGe images to match CZT count density still yielded equivalent contrast between HPGe and CZT. Thus, an HPGe system may provide equivalent breast imaging capability at lower injected radioactivity levels when acquiring for equal imaging time. PMID:25360792

  8. High purity isolation and quantification of semiconducting carbon nanotubes via column chromatography.

    PubMed

    Tulevski, George S; Franklin, Aaron D; Afzali, Ali

    2013-04-23

    The isolation of semiconducting carbon nanotubes (CNTs) to ultrahigh (ppb) purity is a prerequisite for their integration into high-performance electronic devices. Here, a method employing column chromatography is used to isolate semiconducting nanotubes to 99.9% purity. The study finds that by modifying the solution preparation step, both the metallic and semiconducting fraction are resolved and elute using a single surfactant system, allowing for multiple iterations. Iterative processing enables a far more rapid path to achieving the level of purities needed for high performance computing. After a single iteration, the metallic peak in the absorption spectra is completely attenuated. Although absorption spectroscopy is typically used to characterize CNT purity, it is found to be insufficient in quantifying solutions of high purity (>98 to 99%) due to low signal-to-noise in the metallic region of ultrahigh purity solutions. Therefore, a high throughput electrical testing method was developed to quantify the degree of separation by characterizing ∼4000 field-effect transistors fabricated from the separated nanotubes after multiple iterations of the process. The separation and characterization methods described here provide a path to produce the ultrahigh purity semiconducting CNT solutions needed for high performance electronics. PMID:23484490

  9. Preparation of high purity glasses in the Ga-Ge-As-Se system

    NASA Astrophysics Data System (ADS)

    Shiryaev, V. S.; Velmuzhov, A. P.; Tang, Z. Q.; Churbanov, M. F.; Seddon, A. B.

    2014-11-01

    Small additions of Ga to Ge-As-Se glasses are known to enhance rare earth ion solubility in Ge-As-Se chalcogenide glasses designed for active optical applications. The effect of variants and conditions for producing samples of an exemplar Ge16As17Se64Ga3 (atomic%) glass on optical transmission, and the content of limiting impurities, is investigated. To prepare the high-purity glass samples, chemical distillation for purification of the Ge-As-Se base-glass is used. Next, a new vapor phase transport approach of metallic Ga transfer in a GaI3 flow is developed to purify and add the batch of metallic gallium into the silica-glass reactor for the Ge-As-Se-Ga glass synthesis. A thermodynamic equilibrium based vapor phase transport model is discussed. In the best examples of these glasses, the content of residual impurities is: hydrogen - 0.15 ppm, oxygen - <1 ppm, and transition metals - less than 0.1 ppm.

  10. High-Purity Germanium Spectroscopy at Rates in Excess of 10^{6} Events/s

    SciTech Connect

    VanDevender, Brent A.; Dion, Michael P.; Fast, James E.; Rodriguez, Douglas C.; Taubman, Matthew S.; Wilen, Christopher D.; Wood, Lynn S.; Wright, Michael E.

    2014-10-01

    Abstract—In gamma spectroscopy, a compromise must be made between energy resolution and event-rate capability. Some foreseen nuclear material safeguards applications require a spectrometer with energy resolution typical of high purity germanium (HPGe) detectors, operated at rates up to and exceeding 106 events per second. We report the performance of an HPGe spectrometer adapted to run at such rates. Our system consists of a commercial semi-coaxial HPGe detector, a modified high-voltagerail, resistive-feedback, charge-sensitive preamplifier and a continuous waveform digitizer. Digitized waveforms are analyzed offline with a novel time-variant trapezoidal filter algorithm. Several time-invariant trapezoidal filters are run in parallel and the slowest one not rejected by instantaneous pileup conditions is used to measure each pulse height. We have attained full-widthat- half-maximum energy resolution of less than 8 keV measured at 662 keV with 1:08*106 per second incoming event rate and 38% throughput. An additional constraint on the width of the fast trigger filter removes a significant amount of edge pileup that passes the first pileup cut, reducing throughput to 26%. While better resolution has been reported by other authors, our throughput is over an order of magnitude higher than any other reported HPGe system operated at such an event rate.

  11. Determination of nitrogen monoxide in high purity nitrogen gas with an atmospheric pressure ionization mass spectrometer

    NASA Technical Reports Server (NTRS)

    Kato, K.

    1985-01-01

    An atmospheric pressure ionization mass spectrometric (API-MS) method was studied for the determination of residual NO in high purity N2 gas. The API-MS is very sensitive to NO, but the presence of O2 interferes with the NO measurement. Nitrogen gas in cylinders as sample gas was mixed with NO standard gas and/or O2 standard gas, and then introduced into the API-MS. The calibration curves of NO and O2 has linearity in the region of 0 - 2 ppm, but the slopes changed with every cylinder. The effect of O2 on NO+ peak was additive and proportional to O2 concentration in the range of 0 - 0.5 ppm. The increase in NO+ intensity due to O2 was (0.07 - 0.13)%/O2, 1 ppm. Determination of NO and O2 was carried out by the standard addition method to eliminate the influence of variation of slopes. The interference due to O2 was estimated from the product of the O2 concentration and the ratio of slope A to Slope B. Slope A is the change in the NO+ intensity with the O2 concentration. Slope B is the intensity with O2 concentration.

  12. Improving axion detection sensitivity in high purity germanium detector based experiments

    NASA Astrophysics Data System (ADS)

    Xu, Wenqin; Elliott, Steven

    2015-04-01

    Thanks to their excellent energy resolution and low energy threshold, high purity germanium (HPGe) crystals are widely used in low background experiments searching for neutrinoless double beta decay, e.g. the MAJORANA DEMONSTRATOR and the GERDA experiments, and low mass dark matter, e.g. the CDMS and the EDELWEISS experiments. A particularly interesting candidate for low mass dark matter is the axion, which arises from the Peccei-Quinn solution to the strong CP problem and has been searched for in many experiments. Due to axion-photon coupling, the postulated solar axions could coherently convert to photons via the Primakeoff effect in periodic crystal lattices, such as those found in HPGe crystals. The conversion rate depends on the angle between axions and crystal lattices, so the knowledge of HPGe crystal axis is important. In this talk, we will present our efforts to improve the HPGe experimental sensitivity to axions by considering the axis orientations in multiple HPGe crystals simultaneously. We acknowledge the support of the U.S. Department of Energy through the LANL/LDRD Program.

  13. GELATIO: a general framework for modular digital analysis of high-purity Ge detector signals

    NASA Astrophysics Data System (ADS)

    Agostini, M.; Pandola, L.; Zavarise, P.; Volynets, O.

    2011-08-01

    GELATIO is a new software framework for advanced data analysis and digital signal processing developed for the GERDA neutrinoless double beta decay experiment. The framework is tailored to handle the full analysis flow of signals recorded by high purity Ge detectors and photo-multipliers from the veto counters. It is designed to support a multi-channel modular and flexible analysis, widely customizable by the user either via human-readable initialization files or via a graphical interface. The framework organizes the data into a multi-level structure, from the raw data up to the condensed analysis parameters, and includes tools and utilities to handle the data stream between the different levels. GELATIO is implemented in C++. It relies upon ROOT and its extension TAM, which provides compatibility with PROOF, enabling the software to run in parallel on clusters of computers or many-core machines. It was tested on different platforms and benchmarked in several GERDA-related applications. A stable version is presently available for the GERDA Collaboration and it is used to provide the reference analysis of the experiment data.

  14. Evaluation of Electric Load Following Capability on Fuel Cell System Fueled by High-Purity Hydrogen

    NASA Astrophysics Data System (ADS)

    Doi, Yusuke; Park, Deaheum; Ishida, Masayoshi; Fujisawa, Akitoshi; Miura, Shinichi

    This paper describes the electrical response in load change concerning a fuel cell system fueled by high-purity hydrogen. The purpose of this study is that the fuel cell system is applied to make up for unstable electrical output of a photovoltaic system as a renewable energy. As an alternative method of secondary battery, the fuel cell system, which is able to continuously generate power as long as fuel is supplied, is expected to provide power with high reliability and stability. To evaluate the load-following capability of a polymer electrolyte fuel cell (PEFC) system, an experimental equipment was constructed with a 200W PEFC stack (number of cells: 20, cell area: 200cm2) which was supplied with hydrogen from a compressed hydrogen cylinder and a metal hydride canister. We measured the transient phenomenon of current and cell voltage when the PEFC stack was inputted step-up current loads that changed in the range of 0∼300mA/cm2. As a result, we have found that the PEFC system with both hydrogen supply sources is able to response at a time constant of 6.6∼11.6μsec under enough oxygen supply and a load below the PEFC rated power.

  15. Influence of Ta content in high purity niobium on cavity performance

    SciTech Connect

    P. Kneisel; G. Ciovati; G. R. Myneni; W. Singer; X. Singer; D. Proch; T. Carneiro

    2005-05-01

    In a previous paper [1] we have reported about initial tests of single cell 1500 MHz cavities made from high purity niobium with three different Ta contents of 160 ppm , {approx}600 ppm and {approx}1400 ppm. These cavities had been treated by buffered chemical polishing several times and 100 {micro}m, 200 {micro}m and 300 {micro}m of material had been removed from the surfaces. This contribution reports about subsequent tests following post purification heat treatments with Ti and ''in situ'' baking. As a result, all cavities exhibited increased quench fields due to the improved thermal conductivity after the heat treatment. After the ''in situ'' baking at 120 C for {approx} 40 hrs the always present Q-drop at high fields disappeared and further improvements in accelerating gradient could be realized. Gradients as high as E{sub acc} = 35 MV/m were achieved and there were no clear indications that the cavity performance was influenced by the Ta content in the material. A multi-cell cavity from the high Ta content material has been fabricated and initial results are reported.

  16. Formation process of high-purity Ge-on-insulator layers by Ge-condensation technique

    NASA Astrophysics Data System (ADS)

    Nakaharai, S.; Tezuka, T.; Hirashita, N.; Toyoda, E.; Moriyama, Y.; Sugiyama, N.; Takagi, S.

    2009-01-01

    Formation process of Ge-on-insulator (GOI) layers by Ge condensation with very high purity of Ge is clarified in terms of diffusion behaviors of Si and Ge in a SiGe layer. It is shown that the diffusion behavior affects the Ge condensation process, and the purity of GOI layer can be determined by the relation between oxidation and diffusion of Si. Experimental results support a model of GOI formation that the selective oxidation of Si in SiGe continues until the formation of a GOI layer with the residual Si fraction of less than 0.01%. Based on this model, we quantitatively clarify the reason why GOI layers can reach very low residual Si fraction without oxidizing Ge by calculating the diffusion behavior of Si during the Ge condensation process. As a result, we have found that the thermal diffusion of Si is sufficiently fast so that the selective oxidation of Si can continue during the GOI formation process until the averaged residual Si fraction in the SGOI layer becomes lower than 0.03%, which is essentially consistent with the experimental results. In addition, we have found that, even if the GOI layer is thick, the Ge purity of GOI layer can approach 100% infinitely in principle by enhancing the Si diffusion in SGOI compared to the oxidation rate of SGOI.

  17. Safety studies conducted on high-purity trans-resveratrol in experimental animals.

    PubMed

    Williams, Lonnie D; Burdock, George A; Edwards, James A; Beck, Mareike; Bausch, Jochen

    2009-09-01

    trans-Resveratrol is a naturally occurring polyphenolic compound found in a variety of foods, but predominantly in grapes. Safety studies were conducted on high-purity trans-resveratrol (Resvida), including skin and eye irritation, dermal sensitization, subchronic and reproductive toxicity, genotoxicity, and absorption, metabolism and excretion. Resvida was non-irritating to skin and eyes and non-sensitizing. It was non-mutagenic in a bacterial reverse mutation assay in Salmonella typhimurium and Escherichia coli, but exhibited clastogenic activity in a chromosomal aberration test in human lymphocytes. However, in an in vivo bone marrow micronucleus test in rats, Resvida was non-genotoxic. In a 28-day study, Resvida caused no adverse effects in rats at 50, 150 and 500 mg/kg bw/day. Similarly, in a 90-day study, Resvida did not cause any adverse effects in rats at up to 700 mg/kg bw/day; the highest dose tested. Resvida did not induce any adverse reproductive effects in an embryo-fetal toxicity study in rats at a dose of 750 mg/kg bw/day. Also, in vitro and in vivo absorption, metabolism, and excretion studies in Caco-2 cells, rat primary hepatocytes and male and female rats (in vivo) show that Resvida is readily absorbed, metabolized and excreted. These studies provide evidence that Resvida is well tolerated and non-toxic. PMID:19505523

  18. Industrial symbiosis: high purity recovery of metals from Waelz sintering waste by aqueous SO2 solution.

    PubMed

    Copur, Mehmet; Pekdemir, Turgay; Colak, Sabri; Künkül, Asim

    2007-10-22

    Sintering operation in the production of Zn, Cd, and Pb by Waelz process produces a powdery waste containing mainly (about 70%) ZnO, CdO, and PbO. The waste may be referred to as Waelz sintering waste (WSW). The aim of this study is to develop a process for the separation and recovery of the metals from WSW with high purities. The process is based on the dissolution of the WSW in aqueous SO2 solution. The research reported here concentrated on the effect of some important operational parameters on dissolution process. The parameters investigated and their ranges were as follows: SO(2) gas flow rate (V); 38-590 ml/min, stirring speed (W); 100-1000 rpm, reaction temperature (T); 13-60 degrees C, reaction time (t); 1-16 min, and solid-liquid ratio (S/L); 0.1-0.5 g/ml. The results showed that the dissolution rate increased with increasing W, V, and S/L and decreasing T. The best dissolution conditions were found to be V=325 ml/min, W=600 rpm, t=6 min, T=21 degrees C, and S/L=0.1g/ml. Separation of Zn from Cd involved precipitation of ZnSO3 from a mixture solution. The best pH level for the precipitation was observed to be 6. PMID:17482352

  19. High-energy proton radiation damage of high-purity germanium detectors

    NASA Technical Reports Server (NTRS)

    Pehl, R. H.; Varnell, L. S.; Metzger, A. E.

    1978-01-01

    Quantitative studies of radiation damage in high-purity germanium gamma-ray detectors due to high-energy charged particles have been carried out; two 1.0 cm thick planar detectors were irradiated by 6 GeV/c protons. Under proton bombardment, degradation in the energy resolution was found to begin below 7 x 10 to the 7th protons/sq cm and increased proportionately in both detectors until the experiment was terminated at a total flux of 5.7 x 10 to the 8th protons/sq cm, equivalent to about a six year exposure to cosmic-ray protons in space. At the end of the irradiation, the FWHM resolution measured at 1332 keV stood at 8.5 and 13.6 keV, with both detectors of only marginal utility as a spectrometer due to the severe tailing caused by charge trapping. Annealing these detectors after proton damage was found to be much easier than after neutron damage.

  20. Production of Ultrafine, High-purity Ceramic Powders Using the US Bureau of Mines Developed Turbomill

    NASA Technical Reports Server (NTRS)

    Hoyer, Jesse L.

    1993-01-01

    Turbomilling, an innovative grinding technology developed by the U.S. Bureau of Mines in the early 1960's for delaminating filler-grade kaolinitic clays, has been expanded into the areas of particle size reduction, material mixing, and process reaction kinetics. The turbomill, originally called an attrition grinder, has been used for particle size reduction of many minerals, including natural and synthetic mica, pyrophyllite, talc, and marble. In recent years, an all-polymer version of the turbomill has been used to produce ultrafine, high-purity, advanced ceramic powders such as SiC, Si3N4, TiB2, and ZrO2. In addition to particle size reduction, the turbomill has been used to produce intimate mixtures of high surface area powders and whiskers. Raw materials, TiN, AlN, and Al2O3, used to produce a titanium nitride/aluminum oxynitride (TiN/AlON) composite, were mixed in the turbomill, resulting in strength increases over samples prepared by dry ball milling. Using the turbomill as a leach vessel, it was found that 90.4 pct of the copper was extracted from the chalcopyrite during a 4-hour leach test in ferric sulfate versus conventional processing which involves either roasting of the ore for Cu recovery or leaching of the ore for several days.

  1. Electrical properties of as-grown and proton-irradiated high purity silicon

    NASA Astrophysics Data System (ADS)

    Krupka, Jerzy; Karcz, Waldemar; Kamiński, Paweł; Jensen, Leif

    2016-08-01

    The complex permittivity of as-grown and proton-irradiated samples of high purity silicon obtained by the floating zone method was measured as a function of temperature at a few frequencies in microwave spectrum by employing the quasi TE011 and whispering gallery modes excited in the samples under test. The resistivity of the samples was determined from the measured imaginary part of the permittivity. The resistivity was additionally measured at RF frequencies employing capacitive spectroscopy as well as in a standard direct current experiment. The sample of as-grown material had the resistivity of ∼85 kΩ cm at room temperature. The sample irradiated with 23-MeV protons had the resistivity of ∼500 kΩ cm at 295 K and its behavior was typical of the intrinsic material at room and at elevated temperatures. For the irradiated sample, the extrinsic conductivity region is missing and at temperatures below 250 K hopping conductivity occurs. Thermal cycle hysteresis of the resistivity for the sample of as-grown material is observed. After heating and subsequent cooling of the sample, its resistivity decreases and then slowly (∼50 h) returns to the initial value.

  2. Formation of formaldehyde and peroxides by air oxidation of high purity polyoxyethylene surfactants.

    PubMed

    Bergh, M; Magnusson, K; Nilsson, J L; Karlberg, A T

    1998-07-01

    Ethoxylated alcohols are non-ionic surfactants. The majority are used in household cleaners, laundry products, toiletries and in industrial and institutional cleaners. In previous studies, an ethoxylated non-ionic surfactant of technical quality showed allergenic activity in guinea pig experiments. Chemical analysis revealed a content of formaldehyde, a well-known contact allergen, and peroxides in the surfactant. Most cases of occupational contact dermatitis are considered to be of irritant origin, caused by contact with water and surfactants, but if allergenic autoxidation products can be formed, allergic contact dermatitis cannot be excluded. The sensitizing potential of a chemically defined high purity ethoxylated alcohol was investigated and oxidation under various storage and handling conditions was studied for this and a homologous product. The pure surfactant showed no significant allergenic activity on predictive testing in guinea pigs. When ethoxylated alcohols were stored in the refrigerator, their deterioration was limited. At room temperature, their content of peroxides and formaldehyde increased with time. Levels of formaldehyde above those capable of causing positive patch test reactions were found. Since such surfactants have wide applications, resulting exposure to formaldehyde could be more frequent than is generally realized, contributing to persistence of dermatitis in individuals allergic to formaldehyde. PMID:9686972

  3. Simulation study comparing high-purity germanium and cadmium zinc telluride detectors for breast imaging

    NASA Astrophysics Data System (ADS)

    Campbell, D. L.; Peterson, T. E.

    2014-11-01

    We conducted simulations to compare the potential imaging performance for breast cancer detection with High-Purity Germanium (HPGe) and Cadmium Zinc Telluride (CZT) systems with 1% and 3.8% energy resolution at 140 keV, respectively. Using the Monte Carlo N-Particle (MCNP5) simulation package, we modelled both 5 mm-thick CZT and 10 mm-thick HPGe detectors with the same parallel-hole collimator for the imaging of a breast/torso phantom. Simulated energy spectra were generated, and planar images were created for various energy windows around the 140 keV photopeak. Relative sensitivity and scatter and the torso fractions were calculated along with tumour contrast and signal-to-noise ratios (SNR). Simulations showed that utilizing a ±1.25% energy window with an HPGe system better suppressed torso background and small-angle scattered photons than a comparable CZT system using a -5%/+10% energy window. Both systems provided statistically similar contrast and SNR, with HPGe providing higher relative sensitivity. Lowering the counts of HPGe images to match CZT count density still yielded equivalent contrast between HPGe and CZT. Thus, an HPGe system may provide equivalent breast imaging capability at lower injected radioactivity levels when acquiring for equal imaging time.

  4. High-purity propionate production from glycerol in mixed culture fermentation.

    PubMed

    Chen, Yun; Wang, Ting; Shen, Nan; Zhang, Fang; Zeng, Raymond J

    2016-11-01

    High-purity propionate production from glycerol in mixed culture fermentation (MCF) induced by high ammonium concentration was investigated. Fed-batch experiments revealed that higher ammonium concentration (>2.9g/L) had simultaneous negative effects on acetate and propionate degradation. Propionate production and yield was up to 22.6g/L and 0.45g COD/g COD glycerol, respectively, with a purity of 96%. Sequential batch experiments demonstrated that the yields of propionate were 0.3±0.05, 0.32±0.01, and 0.34±0.03g COD/g COD at a glycerol concentration of 2.78, 4.38, and 5.56g/L, respectively, and the purity of propionate was 91-100%. Microbial community analysis showed that the phylum Firmicutes dominated the bacterial community at different glycerol concentrations. However, the Methanosaeta population decreased from 46% to 6% when glycerol concentration increased from 2.78 to 5.56g/L, resulting in lower acetate degradation rate. Thus, the present study might provide an alternative option for the production of propionate from glycerol via MCF. PMID:27544916

  5. Isolation of Ubiquitinated Proteins to High Purity from In Vivo Samples.

    PubMed

    Ramirez, Juanma; Min, Mingwei; Barrio, Rosa; Lindon, Catherine; Mayor, Ugo

    2016-01-01

    Ubiquitination pathways are widely used within eukaryotic cells. The complexity of ubiquitin signaling gives rise to a number of problems in the study of specific pathways. One problem is that not all processes regulated by ubiquitin are shared among the different cells of an organism (e.g., neurotransmitter release is only carried out in neuronal cells). Moreover, these processes are often highly temporally dynamic. It is essential therefore to use the right system for each biological question, so that we can characterize pathways specifically in the tissue or cells of interest. However, low stoichiometry, and the unstable nature of many ubiquitin conjugates, presents a technical barrier to studying this modification in vivo. Here, we describe two approaches to isolate ubiquitinated proteins to high purity. The first one favors isolation of the whole mixture of ubiquitinated material from a given tissue or cell type, generating a survey of the ubiquitome landscape for a specific condition. The second one favors the isolation of just one specific protein, in order to facilitate the characterization of its ubiquitinated fraction. In both cases, highly stringent denaturing buffers are used to minimize the presence of contaminating material in the sample. PMID:27613036

  6. Defect structural evolution in high purity tungsten irradiated with electrons using high voltage electron microscope

    NASA Astrophysics Data System (ADS)

    Fukuzumi, S.; Yoshiie, T.; Satoh, Y.; Xu, Q.; Mori, H.; Kawai, M.

    2005-08-01

    Four types of high purity tungsten were irradiated with 2 MeV electrons to 5 dpa using a high voltage electron microscope, and defect structural evolutions were examined as a function of the irradiation temperature and the concentration of impurity atoms. Three of materials were made by sintering of tungsten powder with purity of 99.999% (5N-W), 99.99% (PF-W) and 99.95% (N-W), and one was a chemical vapor deposited tungsten of 99.9999% (CVD-W) purity. The formation of interstitial type dislocation loops is observed above room temperature by electron irradiation. In sintered tungsten, the number density of loops increases with increasing density of impurity atoms, i.e., N-W > PF-W > 5N-W. The density of loops in CVD-W is relatively high, contrary to its purity. In CVD-W, a heterogeneous formation of loops is observed at above 573 K. Loops are aligned on layers, and no loops are formed between the layers. All four types of specimens have a change in slop of the temperature dependence of loop number density at around 500 K which is caused by impurity atoms. Results of radioactivation analysis and hardness testing are also presented.

  7. Effectiveness of a high purity chlorine dioxide solution in eliminating intracanal Enterococcus faecalis biofilm.

    PubMed

    Herczegh, Anna; Ghidan, Agoston; Friedreich, Dóra; Gyurkovics, Milán; Bendő, Zsolt; Lohinai, Zsolt

    2013-03-01

    We investigated the effectiveness of chlorine dioxide (ClO2) solution in comparison to sodium hypochlorite (NaOCl) and chlorhexidine gluconate (CHX) in the elimination of intracanal Enterococcus faecalis biofilm. Extracted human teeth were inoculated with E. faecalis. After preparation the canals were irrigated with ClO2, NaOCl, CHX or physiologic saline for control. Two and five days later bacterial samples were collected and streaked onto Columbia agar. CFU/mL were counted. The canal walls were investigated by scanning electron microscopy (SEM). The gas phase was investigated in an upside down Petri dish where E. faecalis was inoculated onto blood agar. The irrigants were placed on absorbent paper into the cover. Bacteria were detectable in the control group, but not in any of the irrigants groups. There was a massive reinfection 2 or 5 days after irrigation in the control group. The lowest reinfection was found after the ClO2 treatment. These findings were confirmed by SEM images. We observed an antibacterial effect of ClO2 and NaOCl gas phases on E. faecalis growth, but not of CHX. ClO2 eliminates intracanal biofilm and keeps canal nearly free from bacteria. We suggest the use of high purity ClO2 as a root canal irrigant in clinical practice. PMID:23529300

  8. Interaction between a high purity magnesium surface and PCL and PLA coatings during dynamic degradation.

    PubMed

    Chen, Ying; Song, Yang; Zhang, Shaoxiang; Li, Jianan; Zhao, Changli; Zhang, Xiaonong

    2011-04-01

    In this study, polycaprolactone (PCL) and polylactic acid (PLA) coatings were prepared on the surface of high purity magnesium (HPMs), respectively, and electrochemical and dynamic degradation tests were used to investigate the degradation behaviors of these polymer-coated HPMs. The experimental results indicated that two uniform and smooth polymer films with thicknesses between 15 and 20 µm were successfully prepared on the HPMs. Electrochemical tests showed that both PCL-coated and PLA-coated HPMs had higher free corrosion potentials (E(corr)) and smaller corrosion currents (I(corr)) in the modified simulated body fluid (m-SBF) at 37 °C, compared to those of the uncoated HPMs. Dynamic degradation tests simulating the flow conditions in coronary arteries were carried out on a specific test platform. The weight of the specimens and the pH over the tests were recorded to characterize the corrosion performance of those samples. The surfaces of the specimens after the dynamic degradation tests were also examined. The data implied that there was a special interaction between HPM and its polymer coatings during the dynamic degradation tests, which undermined the corrosion resistance of the coated HPMs. A model was proposed to illustrate the interaction between the polymer coatings and HPM. This study also suggested that this reciprocity may also exist on the implanted magnesium stents coated with biodegradable polymers, which is a potential obstacle for the further development of drug-eluting magnesium stents. PMID:21358027

  9. Development and validation of a reversed-phase high-performance liquid chromatography method for routine identification and purity assessment of high-purity steviol glycoside sweeteners.

    PubMed

    Bililign, Tsion; Moore, Jeffrey C; Tan, Shane; Leeks, Allan T

    2014-02-12

    The widespread application of stevia-based sweeteners in food products has resulted in the need for reliable analytical methods for measuring the purity and identity of high-purity steviol glycoside ingredients. The objective of this research was to develop and validate a new reversed-phase separation method capable of separating and quantifying nine steviol glycosides present in typical high-purity stevia extract ingredients. Results of the study established the linearity of the method at a correlation factor of 1.000 for the two major components and other minor components of this food ingredient. Method accuracy values were in the range of 99.1-100.9%. The percent relative standard deviation for six independent assay determinations was 1.0%. The method was determined to be robust for minor changes in column temperature, initial acetonitrile content, flow rate, and wavelength. The validated high-performance liquid chromatography method was found to be suitable to be included by USP as a Food Chemicals Codex compendial standard for steviol glycosides. PMID:24443893

  10. Identification of a point mutation in type IIB von Willebrand disease illustrating the regulation of von Willebrand factor affinity for the platelet membrane glycoprotein Ib-IX receptor

    SciTech Connect

    Ware, J.; Dent, J.A.; Azuma, Hiroyuki; Sugimoto, Mitsuhiko; Kyrle, P.A.; Yoshioka, Akira; Ruggeri, Z.M. )

    1991-04-01

    von Willebrand factor (vWF) supports platelet adhesion on thrombogenic surfaces by binding to platelet membrane glycoprotein (GP) Ib in the GP Ib-IX receptor complex. This interaction is physiologically regulated so that it does not occur between circulating vWF and platelets but, rather, only at a site of vascular injury. The abnormal vWF found in type IIB von Willebrand disease, however, has a characteristically increased affinity for GP Ib and binds to circulating platelets. The authors have analyzed the molecular basis of this abnormality by sequence analysis of a type IIB vWF cDNA and have identified a single amino acid change, Trp{sup 550} to Cys{sup 550}, located in the GP IB-binding domain of the molecule comprising residues 449-728. Bacterial expression of recombinant fragments corresponding to this vWF domain yielded molecules that, whether containing a normal Trp{sup 550} or a mutant Cys{sup 550} residue, bound directly to GP Ib in the absence of modulators and with similar affinity. These results identify a region of vWF that, although not thought to be directly involved in binding to GP Ib, may modulate the interaction through conformational changes.