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Sample records for factor ix concentrate

  1. Coagulation Factor IX concentrate: method of preparation and assessment of potential in vivo thrombogenicity in animal models.

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    Menache, D; Behre, H E; Orthner, C L; Nunez, H; Anderson, H D; Triantaphyllopoulos, D C; Kosow, D P

    1984-12-01

    Thrombosis and/or disseminated intravascular coagulation (DIC) are complications specifically associated with the use of factor IX complex in some patients. Assuming that these complications might result from zymogen overload, we have produced, using diethylaminoethyl (DEAE)-Sephadex (Pharmacia, Piscataway, NJ) and sulfated dextran chromatography, a factor IX concentrate (coagulation factor IX) that is essentially free of prothrombin, factor VII, and factor X. Factor IX specific activity is at least 5 U/mg protein, a 250-fold purification compared to plasma. Amounts of factors II, VII, and X are less than 5 units each per 100 units of factor IX. The concentrate is essentially free of activated clotting factors and contains no added heparin. In the rabbit stasis model, a dose of 200 factor IX U/kg was less thrombogenic than 100 factor IX U/kg of the DEAE-Sephadex eluate from which the concentrate was derived. Infusion of 200 factor IX U/kg did not induce DIC in the nonstasis rabbit model, whereas 100 factor IX U/kg of the DEAE-Sephadex eluate resulted in DIC in this model. Several factor IX lots were found to have shortened nonactivated partial thromboplastin times (PTTs), but were nonthrombogenic in both animal models. These data indicate that coagulation factor IX concentrate is less thrombogenic than factor IX complex.

  2. Efficacy of a high-purity factor IX concentrate in hemophilia B patients undergoing surgery Eficácia do concentrado de alta pureza do fator IX em pacientes cirúrgicos portadores de hemofilia B

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    Vesa Rasi

    2002-04-01

    Full Text Available A plasma derived, high purity, solvent-detergent treated and subsequently nanofiltered factor IX concentrate (BEMOFIL was evaluated in 19 hemophilia B patients, including four with severe, thirteen with mild or moderate type of disease and two hemophilia B carriers undergoing 31 surgical procedures. The mean in vivo recovery was 52 %, range 36 - 76 %. The mean preoperative plasma factor IX activity after the initial loading dose was 0.86 IU mL-1, range 0.59 - 1.32 IU mL-1. In eight major orthopedic procedures, the mean usage of factor IX was 44600 IU or 574 IU kg-1 during the hospital stay, mean 11.6 days. Thromboprophylaxis was not used. The hemostatic efficacy was evaluated good in all cases and there were no thromboembolic complications. In conclusion, BEMOFIL used as bolus dosing was found to be safe and effective in achieving hemostasis in subjects with hereditary F IX deficiency undergoing surgery.O concentrado de fator IX ( Bemofil , um derivado plasmático de alta pureza tratado com solventes- detergente e nano-filtrado , foi avaliado em 19 pacientes portadores de Hemofilia B .Quatro pacientes apresentavam a forma grave da moléstia, 13 a forma leve e moderada e dois portadores em um total de 31 atos cirúrgicos.A recuperação média "in vivo" foi de 52% (36-76%. A atividade plasmática média pré-operatória do fator IX após a dose inicial foi de 0,86 UI ml -1 , média de 0,59 - 1,32 UI ml-1. Em oito procedimentos ortopédicos extensos , a média de utilização do fator IX foi de 44.600 UI ou 574 UI kg -1 durante a hospitalização que teve a média de 11,6 dias. A tromboprofilaxia não foi utilizada. A eficácia hemostática avaliada em todos os casos foi boa ,e não ocorreu nenhum tipo de complicação tromboembólica. Concluímos que o Bemofil em bolus foi considerado seguro e eficaz para a hemostasia em pacientes portadores de hemofilia B que necessitam de um procedimento cirúrgico.

  3. Coagulation Factor IX for Hemophilia B Therapy


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    Orlova, N.; Kovnir, S.; Vorobiev, I.; Gabibov, A.

    2012-01-01

    Factor IX is a zymogen enzyme of the blood coagulation cascade. Inherited absence or deficit of the IX functional factor causes bleeding disorder hemophilia B, which requires constant protein replacement therapy. Reviewed herein are the current state in the manufacturing of FIX, improved variants of the recombinant protein for therapy, transgenic organisms for obtaining FIX, and the advances in the gene therapy of hemophilia B.

  4. Evaluation of factor IX deficiency by interdigitated electrode (IDE)

    Science.gov (United States)

    Gopinath, Subash C. B.; Hashim, Uda; Uda, M. N. A.

    2017-03-01

    Factor IX deficiency is the main cause of hemophilia A and B. This a severe excessive bleeding disorder that can even kill the patient if not treated with the right prescription of Factor IX hormone to stop the bleeding. The bleeding can be caused by an injury or even a sudden bleeding in some very rare cases. To find the Factor IX effectiveness and to understand the deficiency more carefully for the future of medicine, experiments are conducted to test the Factor IX using the Interdigitated Electrode (IDE) and gold Nanoparticle with the help of Nanoelectrical technology.

  5. Thermodynamics of mixtures containing amines. IX. Application of the concentration-concentration structure factor to the study of binary mixtures containing pyridines

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    Gonzalez, Juan Antonio, E-mail: jagl@termo.uva.es [G.E.T.E.F. Dpto Termodinamica y Fisica Aplicada, Facultad de Ciencias, Universidad de Valladolid, Valladolid 47071 (Spain); Cobos, Jose Carlos; Garcia de la Fuente, Isaias; Mozo, Ismael [G.E.T.E.F. Dpto Termodinamica y Fisica Aplicada, Facultad de Ciencias, Universidad de Valladolid, Valladolid 47071 (Spain)

    2009-10-10

    Binary mixtures formed by a pyridine base and an alkane, or an aromatic hydrocarbon, or a 1-alkanol have been studied in the framework of the concentration-concentration structure factor, S{sub CC}(0), formalism. Deviations between experimental data and those provided by the DISQUAC model are discussed. Systems containing alkanes are characterized by homocoordination. In pyridine + alkane mixtures, S{sub CC}(0) decreases with the chain length of the longer alkanes, due to size effects. For a given alkane, S{sub CC}(0) also decreases with the number of CH{sub 3}- groups in the pyridine base. This has been interpreted assuming that the number of amine-amine interactions available to be broken upon mixing also decreases similarly, probably as steric hindrances exerted by the methyl groups of the aromatic amine increase with the number of these groups. Homocoordination is higher in mixtures with 3,5-dimethylpyridine than in those with 2,6-dimethylpyridine. That is, steric effects exerted by methyl groups in positions 3 and 5 are stronger than when they are in positions 2 and 6. Similarly, from the application of the DISQUAC (dispersive-quasichemical) model, it is possible to conclude that homocoordination is higher in systems with 3- or 4-methylpyridine than in those involving 2-methylpyridine. Systems including aromatic hydrocarbons are nearly ideal, which seems to indicate that there is no specific interaction in such solutions. Mixtures with 1-alkanols show heterocoordination. This reveals the existence of interactions between unlike molecules, characteristic of alkanol + amine mixtures. Methanol systems show the lowest S{sub CC}(0) values due, partially, to size effects. This explains the observed decrease of homocoordination in such solutions in the order: pyridine > 2-methylpyridine > 2,6-dimethylpyridine. Moreover, as the energies of the OH-N hydrogen bonds are practically independent of the pyridine base considered when mixed with methanol, it suggests that

  6. Immunoaffinity purification of factor IX (Christmas factor) by using conformation-specific antibodies directed against the factor IX-metal complex.

    OpenAIRE

    1985-01-01

    Factor IX is a vitamin K-dependent blood clotting zymogen that is functionally defective or absent in patients with hemophilia B. A method of immunoaffinity chromatography has been developed for a one-step high yield purification of factor IX directly from plasma. The technique utilizes conformation-specific antibodies that bind solely to the metal-stabilized factor IX conformer, but not to the conformer of factor IX found in the absence of metal ions. Anti-factor IX-Ca(II) antibodies were im...

  7. New polymorphic variants of human blood clotting factor IX

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    Surin, V.L.; Luk`yanenko, A.V.; Tagiev, A.F.; Smirnova, O.V. [Hematological Research Center, Moscow (Russian Federation); Plutalov, O.V.; Berlin, Yu.A. [Shemyakin Institute of Bioorganic Chemistry, Moscow (Russian Federation)

    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.

  8. Recombinant Human Factor IX Produced from Transgenic Porcine Milk

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

    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 precipitat...

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

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    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.

  10. Molecular interactions between coagulation factor IX and low density lipoprotein receptor-related protein

    NARCIS (Netherlands)

    Rohlena, Jakub

    2004-01-01

    Factor IX is an essential blood haemostatic protein, which is apparent from the observation that the absence of functional FIX is associated with the severe bleeding disorder haemophilia B. To achieve its full enzymatic activity, the serine protease precursor factor IX must first be activated into

  11. Recombinant human factor IX produced from transgenic porcine milk.

    Science.gov (United States)

    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.

  12. Recombinant Human Factor IX Produced from Transgenic Porcine Milk

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    Meng-Hwan Lee

    2014-01-01

    Full Text Available 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.

  13. Prevention and Reversal of Antibody Responses Against Factor IX in Gene Therapy for Hemophilia B

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    Sushrusha eNayak

    2011-12-01

    Full Text Available Intramuscular (IM administration of an adeno-associated viral (AAV vector represents a simple and safe method of gene transfer for treatment of the X-linked bleeding disorder hemophilia B (factor IX, F.IX, deficiency. However, the approach is hampered by an increased risk of immune responses against F.IX. Previously, we demonstrated that the drug cocktail of immune suppressants rapamycin, IL-10, and a specific peptide (encoding a dominant CD4+ T cell epitope caused an induction of regulatory T cells (Treg with a concomitant apoptosis of antigen-specific effector T cells (J. Thromb. Haemost. 7:1523, 2009. This protocol was effective in preventing inhibitory antibody formation against human F.IX (hF.IX in muscle gene transfer to C3H/HeJ hemophilia B mice (with targeted F9 gene deletion. Here, we show that this protocol can also be used to reverse inhibitor formation. IM injection of AAV1-hF.IX vector resulted in inhibitors of on average 8-10 BU within 1 month. Subsequent treatment with the tolerogenic cocktail accomplished a rapid reduction of hF.IX-specific antibodies to <2 BU, which lasted for >4.5 months. Systemic hF.IX expression increased from undetectable to >200 ng/ml, and coagulation times improved. In addition, we developed an alternative prophylactic protocol against inhibitor formation that did not require knowledge of T cell epitopes, consisting of daily oral administration of rapamycin for 1-month combined with frequent, low-dose intravenous injection of hF.IX protein. Experiments in T cell receptor transgenic mice showed that the route and dosing schedule of drug administration substantially affected Treg induction. When combined with intravenous antigen administration, oral delivery of rapamycin had to be performed daily in order to induce Treg, which were suppressive and phenotypically comparable to natural Treg.

  14. An important role for the activation peptide domain in controlling factor IX levels in the blood of haemophilia B mice.

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    Begbie, Megan E; Mamdani, Asif; Gataiance, Sharon; Eltringham-Smith, Louise J; Bhakta, Varsha; Hortelano, Gonzalo; Sheffield, William P

    2005-12-01

    The factors responsible for the removal of injected factor IX (fIX) from the blood of individuals with haemophilia B are only partly understood, and may include binding to endothelial or subendothelial sites, passive extravasation related to size or charge, or interactions requiring fIX activation. To investigate these issues, we have produced and characterised recombinant fIX proteins with amino acid changes: delta155-177, an internal deletion which removes most of the activation peptide while retaining the activation cleavage sites; S365A, which inactivates the serine protease activity of fIXa; and K5A, previously shown to eliminate fIX binding of endothelial/subendothelial collagen IV. All proteins were expressed in stably transfected HEK 293 cells, purified by immunoaffinity chromatography, and compared to the wild type HEK 293-derived protein (fIX (WT)). Mutant fIX proteins K5A and delta155-177 exhibited 72 and 202% of the specific activity of fIX (WT), respectively; S365A was without activity. Following intravenous injection in haemophilia B (fIX knockout) mice, recoveries did not differ for fIX (WT) and delta155-177, but were higher for K5A and S365A. The terminal catabolic half-life of delta155-177, alone among the mutants, was increased, by 45% versus fIX (WT). Nine hours post-injection, the observed areas under the clearance curve (AUCs) of delta155-177 and K5, but not S365A, were elevated 2-fold. delta155-177 was equally effective as fIX (WT) in reducing blood loss following tail vein transection in haemophilia B mice. Our results suggest that deletion of the multiple sites of fIX post-translational modification found within the activation peptide eliminated important fIX clearance motifs.

  15. Regulation of human clotting factor IX cDNA expression in transgenic mice

    Institute of Scientific and Technical Information of China (English)

    胡以平; 邱信芳; 薛京伦; 刘祖洞

    1995-01-01

    To study the expression of human dotting factor IX cDNA in transgenic mice,Which is an es-sential work on gene therapy for hemophilia B,3 recombinant constructions containing different lengths ofhuman dotting factor IX cDNA have been introduced into the cultured cells.All of the recombinant constructionswere found to he expressed well in vitro.They were then microinjected into the male pronudei of the fertilizedmouse eggs respectively for generating trahsgenic mice.Unfortunately,none of them was expressed in any transgenicmice.These results show that the expression of the human clotting factor IX cDNA in the transgenic mice canbe determined by cis regulatory element(s).As compared With the results from other related works,it is sug-gested that the cis regulatory element(s)is resided in the 5’-end non-coding region.

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

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    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 stru...

  17. Isolation of a human anti-haemophilic factor IX cDNA clone using a unique 52-base synthetic oligonucleotide probe deduced from the amino acid sequence of bovine factor IX.

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    Jaye, M; de la Salle, H; Schamber, F; Balland, A; Kohli, V; Findeli, A; Tolstoshev, P; Lecocq, J P

    1983-04-25

    A unique 52mer oligonucleotide deduced from the amino acid sequence of bovine Factor IX was synthesized and used as a probe to screen a human liver cDNA bank. The Factor IX clone isolated shows 5 differences in nucleotide and deduced amino acid sequence as compared to a previously isolated clone. In addition, precisely one codon has been deleted.Images

  18. Optimization of The Electroporation Conditions for Transfection of Human Factor IX into The Goat Fetal Fibroblasts

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    Amir Amiri Yekta

    2013-01-01

    Full Text Available Objective: Electroporation is the most common method used for the transfection of DNA. Although this method has been attributed for various cell using different buffer compositions, the effects of DNA concentration on the transfection efficiency has not yet been studied. Here the correlation between the efficiency of electroporation reaction and increments of DNA concentration has been investigated. Following this investigation, a study was set out to produce a transgenic goat which is capable of secreting recombinant human coagulation factor IX in its milk.Materials and Methods: In this experimental study, a linearized recombinant vector (pBC1 entailing human coagulation factor IX (5.7 kb cDNA was introduced into goat fetal fibroblast cells (three sub passages via electroporation in four separate experiments (while other variables were kept constant, beginning with 10 μg DNA per pulse in the first experiment and increments of 10 μg/pulse for the next three reactions. Thereafter, polymerase chain reaction (PCR-positive cell culture plates were diluted by several factors for further analysis of the transfected wells. Subsequently, positive cells were isolated for fluorescence in situ hybridization. Logistic regression model was used for data analyzing. Significance was defined as p< 0.05.Results: The results showed no significant difference among three first concentrations except for group 1 (10 μg/pulse and group 3 (30 μg/pulse, but there was a significant difference between these groups and the fourth group (p<0.05, as this group (40 μg/pulse statistically showed the highest rate of transfection. As the fluorescence in situ hybridization (FISH results indicated the transgene was integrated in a single position in PCR positive cells.Conclusion: Increasing amount of using the vector 40μg/pulse efficiently increased the number of transfected cells. Besides of voltage and buffer strength which had been previously shown to play a critical role

  19. Purification, crystallization and preliminary crystallographic analysis of AHP IX-bp, a zinc ion and pH-dependent coagulation factor IX binding protein from Agkistrodon halys Pallas venom.

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    Zang, Jianye; Teng, Maikun; Niu, Liwen

    2003-04-01

    A new coagulation factor IX binding protein, AHP IX-bp, has been purified from Agkistrodon halys Pallas venom and estimated to be an AB heterodimer of about 25 kDa consisting of two chains (an A chain of 15.5 kDa and a B chain of 15 kDa) linked by one or more disulfide bonds. The N-terminal sequence of AHP IX-bp has been determined and aligned with C-type lectin-like proteins. The protein has a high sequence similarity to some snake-venom C-type lectin-like proteins. AHP IX-bp binds to coagulation factor IX but not to coagulation factor X. Moreover, AHP IX-bp shows binding to coagulation factor IX in both zinc ion-dependent and pH-dependent manners. The affinity between AHP IX-bp and coagulation factor IX is higher under neutral or weakly alkaline conditions than under weakly acidic conditions. Single crystals of AHP IX-bp grown at pH 6.5 and 7.5 diffract X-rays to 2.0 and 1.8 A resolution, respectively. Both crystals are isomorphous and belong to the space group P1; only one AB heterodimer is present in the unit cell.

  20. Characterization of three abnormal factor IX variants (Bm Lake Elsinore, Long Beach, and Los Angeles) of hemophilia-B. Evidence for defects affecting the latent catalytic site.

    OpenAIRE

    P. Usharani; Warn-Cramer, B J; Kasper, C K; BAJAJ, S. P.

    1985-01-01

    Abnormal factor IX variant proteins were isolated from the plasmas of three unrelated severe hemophilia-B families that had been previously shown to contain functionally impaired molecules immunologically similar to normal factor IX. The families studied were: (1) a patient with markedly prolonged ox brain prothrombin time, designated factor IX Bm Lake Elsinore (IXBmLE); (b) three patients (brothers) with moderately prolonged ox brain prothrombin time, designated factor IX Long Beach (IXLB); ...

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

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    Shounan Yao; Wilson, J.M.; Nabel, E.G.; Kurachi, Sumiko; Hachiya, H.L.; Kurachi, Kotoku (Univ. of Michigan, Ann Arbor (United States))

    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.

  2. EFFECT OF ORAL CONTRACEPTIVES (LD AND CILEST ON CLOTTING FACTORS VIII AND IX

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    H.R. Sadeghipour Roudsari

    1997-10-01

    Full Text Available Based on epidemiologic data, women who take oral contraceptives seem to have an increased risk of developing thromboembollic disease. The thrombotic effects of oral contraceptive (OC are probably mediated, at least partly through their effects on the coagulation system. Plasma levels of several clotting factors have been shown to be elevated in OC users, and this increase is graduated according to the dose of estrogen. In this study, fifty healthy and non smoking women, aged 18-35 years, were randomly assigned to treatment with 2 different OCs: a monophasic pill containing 30 pg of ethinyl estradiol plus 150µg levonorgestrel (LD and a monophasic pill containing 35µg ethinylestradiol plus 250pg norgestimate (Cilest. Factor VIII plasma values were significantly decreased (P<0.05 only in women treated with the preparation LD, but the levels of factor VIII were not significantly different in the group treated with Cilest. Factor IX plasma values were significantly increased (P<0.05 only in women treated with the preparation Cilest, but the levels of factor Ix were not significantly different in the group treated with LD. In LD and cilest users factors VIII and IX were not significantly changed (P<0.05 in overweight and obese subjects in comparison to normal weight.

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

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    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.

  4. Molecular Analysis of Factor VIII and Factor IX Genes in Hemophilia Patients: Identification of Novel Mutations and Molecular Dynamics Studies

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    Al-Allaf, Faisal A.; Taher, Mohiuddin M.; Abduljaleel, Zainularifeen; Bouazzaoui, Abdellatif; Athar, Mohammed; Bogari, Neda M.; Abalkhail, Halah A.; Owaidah, Tarek MA.

    2017-01-01

    Background Hemophilias A and B are X-linked bleeding disorders caused by mutations in the factor VIII and factor IX genes, respectively. Our objective was to identify the spectrum of mutations of the factor VIII and factor IX genes in Saudi Arabian population and determine the genotype and phenotype correlations by molecular dynamics (MD) simulation. Methods For genotyping, blood samples from Saudi Arabian patients were collected, and the genomic DNA was amplified, and then sequenced by Sanger method. For molecular simulations, we have used softwares such as CHARMM (Chemistry at Harvard Macromolecular Mechanics; http://www.charmm-gui.org) and GROMACS. In addition, the secondary structure was determined based on the solvent accessibility for the confirmation of the protein stability at the site of mutation. Results Six mutations (three novel and three known) were identified in factor VIII gene, and six mutations (one novel and five known) were identified in factor IX gene. The factor VIII novel mutations identified were c.99G>T, p. (W33C) in exon 1, c.2138 DelA, p. (N713Tfs*9) in eon14, also a novel mutation at splicing acceptor site of exon 23 c.6430 - 1G>A. In factor IX, we found a novel mutation c.855G>C, p. (E285D) in exon 8. These novel mutations were not reported in any factor VIII or factor IX databases previously. The deleterious effects of these novel mutations were confirmed by PolyPhen2 and SIFT programs. Conclusion The protein functional and structural studies and the models built in this work would be appropriate for predicting the effects of deleterious amino acid substitutions causing these genetic disorders. These findings are useful for genetic counseling in the case of consanguineous marriages which is more common in the Saudi Arabia. PMID:28270892

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

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    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

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

    Science.gov (United States)

    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

  7. Once-weekly prophylactic dosing of recombinant factor IX improves adherence in hemophilia B

    Science.gov (United States)

    Djambas Khayat, Claudia

    2016-01-01

    Regular prophylactic treatment in severe hemophilia should be considered an optimal treatment. There is no general agreement on the optimal prophylaxis regimen, and adherence to prophylaxis is a main challenge due to medical, psychosocial, and cost controversies. Improved approaches in prophylaxis regimen of hemophilia B are needed to make patients’ lives easier. There is some evidence to support the efficacy of once-weekly prophylaxis. Longer sampling schedules are required for the determination of pharmacokinetic (PK) properties of factor IX (FIX). The half-life of FIX seems to be longer than previously described and is expected to be 34 hours. The clinical significance of maintaining a 1% trough level is widely debated in hemophilia B. The overall relationship between factor concentrate levels and incidence of joint bleeding was found to be very weak. Data also indicate that the distribution of FIX into an extravascular FIX compartment may contribute to hemostasis independently of circulating plasma FIX levels. Clinical assessment of the frequency and severity of bleeds remain an important measure of the efficacy of treatment. Role of PK-guided therapy remains to be established. Two prospective randomized studies had evaluated the efficacy and safety of 100 IU/kg once-weekly prophylaxis with nonacog alfa, and this prophylaxis regimen was found to be associated with lower annual bleeding rate compared with on-demand treatment in adolescents and adults with moderately severe-to-severe hemophilia B. Secondary prophylaxis therapy with 100 IU/kg nonacog alfa once weekly reduced annual bleeding rate by 89.4% relative to on-demand treatment. Residual FIX may be supportive of effectiveness. Once-weekly prophylaxis was well tolerated in the two studies, with a safety profile similar to that reported during the on-demand treatment period. To individually tailor treatment to clinical response and to minimize costs of factor concentrate, it would be of interest to

  8. Anion-exchange purification of recombinant factor IX from cell culture supernatant using different chromatography supports.

    Science.gov (United States)

    Ribeiro, Daniel A; Passos, Douglas F; Ferraz, Helen C; Castilho, Leda R

    2013-11-01

    Both recombinant and plasma-derived factor IX concentrates are used in replacement therapies for the treatment of haemophilia B. In the present work, the capture step for a recombinant FIX (rFIX) purification process was investigated. Different strong anion-exchange chromatography media (the resins Q Sepharose(®) FF and Fractogel(®) TMAE, the monolith CIM(®) QA and the membrane adsorber Sartobind(®) Q) were tested for their rFIX binding capacity under dynamic conditions. In these experiments, crude supernatant from CHO cells was used, thus in the presence of supernatant contaminants and mimicking process conditions. The highest dynamic binding capacity was obtained for the monolith, which was then further investigated. To study pseudoaffinity elution of functional rFIX with Ca(2+) ions, a design of experiments to evaluate the effects of pH, NaCl and CaCl2 on yield and purification factor was carried out. The effect of pH was not statistically significant, and a combination of no NaCl and 45mM CaCl2 yielded a good purification factor combined with a high yield of active rFIX. Under these conditions, activity yield of rFIX was higher than the mass yield, confirming selective elution of functional, γ-carboxylated rFIX. Scaling-up of this process 8 fold resulted in very similar process performance. Monitoring of the undesired activated FIX (FIXa) revealed that the FIXa/FIX ratio (1.94%) was higher in the eluate than in the loaded sample, but was still within an acceptable range. HCP and DNA clearances were high (1256 and 7182 fold, respectively), indicating that the proposed process is adequate for the intended rFIX capture step. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Enhancement of pulmonary tumour seeding by human coagulation factors II, IX, X--an investigation into the possible mechanisms involved.

    OpenAIRE

    Purushotham, A D; McCulloch, P.; George, W. D.

    1991-01-01

    Warfarin inhibits metastasis in the animal model and injection of the Warfarin-dependent coagulation factor complex II, IX, X enhances pulmonary metastasis in the same model. We have studied two possible mechanisms responsible for the observed effect. Mtln3, rat mammary carcinoma cells, radiolabelled with 5-(125) Iodo-2'-deoxyuridine (IUDR) were injected intravenously in female Fisher 344 rats either alone or in combination with factor complex II, IX, X or bovine serum albumin. Following sacr...

  10. Effects of genetic fusion of factor IX to albumin on in vivo clearance in mice and rabbits.

    Science.gov (United States)

    Sheffield, William P; Mamdani, Asif; Hortelano, Gonzalo; Gataiance, Sharon; Eltringham-Smith, Louise; Begbie, Megan E; Leyva, Rina A; Liaw, Peter S; Ofosu, Frederick A

    2004-08-01

    Individuals with haemophilia B require replacement therapy with recombinant or plasma-derived coagulation factor IX (fIX). More benefit per injected dose might be obtained if fIX clearance could be slowed. The contribution of overall size to fIX clearance was explored, using genetic fusion to albumin. Recombinant murine fIX (MIX), and three proteins with C-terminal epitope tags were expressed in HEK 293 cells: tagged MIX (MIXT), tagged mouse serum albumin (MSAT) and MFUST, in which MIX and MSAT were fused in a single polypeptide chain. Proteins MFUST and MIXT were two- to threefold less active in clotting assays than MIX. In mice, the area under the clearance curve (AUC) was reduced for MFUST compared with MSAT or plasma-derived MSA (pd-MSA); the terminal catabolic half-life (t(0.5)) did not differ amongst the three proteins. Two minutes after injection, >40% of the injected MFUST was found in the liver, compared with <10% of either MSAT or pd-MSA. In rabbits, the AUC for MFUST was reduced compared to MIXT, MSAT, or pd-MSA, while the t(0.5) of the fusion protein fell between that of MIXT and MSAT or pd-MSA. Similar results were obtained with non-radioactive fused or non-fused recombinant human fIX in fIX knockout mice. The clearance behaviour of the fusion protein thus more closely resembled that of fIX than that of albumin despite a modest increase in terminal half-life, suggesting that fIX-specific interactions that are important in determining clearance were maintained in spite of the increased size of the fusion protein.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ketterling, R.P.; Vielhaber, E.L.; Lind, T.J.; Thorland, E.C.; Sommer S.S. (Mayo Clinic/Foundation, Rochester, MN (United States))

    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.

  12. Crystal Structure of the Fab Fragment of an Anti-factor IX Antibody 10C12

    Institute of Scientific and Technical Information of China (English)

    SHI Xiao-Li; ZENG Tu; HUANG Ming-Dong

    2008-01-01

    10C12 is an anticoagulant antibody identified from a phage display single-chain Fv human antibody library. It can be directed at the calcium-stabilized Gla domain of Factor-IX, an important coagulation factor in intrinsic pathway of blood coagulation cascade, and interfere with membrane anchoring of Factor IX, thus inhibiting blood coagulation function. 10C12 has been demonstrated as an effective anti-coagulant in attenuating thrombosis in several different animal models. Here, we report the crystal structure of the Fab fragment of 10C12. The crystal contains two Fab molecules in the asymmetric unit with identical conformation, forming a lattice with large cavities. In addition, comparison of this free Fab with the antigen-bound structure of 10C12 shows no change in CDR conformations and the relative disposition of the variable subunits of H and L chains, suggesting the rigid conformation of this 10C12 Fab and a lock-and-key mechanism of antibody-antigen recognition for 10C 12.

  13. Encapsulation of factor IX-engineered mesenchymal stem cells in fibrinogen-alginate microcapsules enhances their viability and transgene secretion.

    Science.gov (United States)

    Sayyar, Bahareh; Dodd, Megan; Wen, Jianping; Ma, Shirley; Marquez-Curtis, Leah; Janowska-Wieczorek, Anna; Hortelano, Gonzalo

    2012-01-01

    Cell microencapsulation holds significant promise as a strategy for cellular therapies; however, inadequate survival and functionality of the enclosed cells limit its application in hemophilia treatment. Here, we evaluated the use of alginate-based microcapsules to enhance the viability and transgene secretion of human cord blood-derived mesenchymal stem cells in three-dimensional cultures. Given the positive effects of extracellular matrix molecules on mesenchymal stem cell growth, we tested whether fibrinogen-supplemented alginate microcapsules can improve the efficiency of encapsulated factor IX-engineered mesenchymal stem cells as a treatment of hemophilia B. We found that fibrinogen-supplemented alginate microcapsules (a) significantly enhanced the viability and proliferation of factor IX-engineered mesenchymal stem cells and (b) increased factor IX secretion by mesenchymal stem cells compared to mesenchymal stem cells in nonsupplemented microcapsules. Moreover, we observed the osteogenic, but not chondrogenic or adipogenic, differentiation capability of factor IX-engineered cord blood mesenchymal stem cells and their efficient factor IX secretion while encapsulated in fibrinogen-supplemented alginate microcapsules. Thus, the use of engineered mesenchymal stem cells encapsulated in fibrinogen-modified microcapsules may have potential application in the treatment of hemophilia or other protein deficiency diseases.

  14. Systemic delivery of factor IX messenger RNA for protein replacement therapy

    Science.gov (United States)

    Ramaswamy, Suvasini; Tonnu, Nina; Tachikawa, Kiyoshi; Limphong, Pattraranee; Vega, Jerel B.; Karmali, Priya P.; Chivukula, Pad; Verma, Inder M.

    2017-01-01

    Safe and efficient delivery of messenger RNAs for protein replacement therapies offers great promise but remains challenging. In this report, we demonstrate systemic, in vivo, nonviral mRNA delivery through lipid nanoparticles (LNPs) to treat a Factor IX (FIX)-deficient mouse model of hemophilia B. Delivery of human FIX (hFIX) mRNA encapsulated in our LUNAR LNPs results in a rapid pulse of FIX protein (within 4–6 h) that remains stable for up to 4–6 d and is therapeutically effective, like the recombinant human factor IX protein (rhFIX) that is the current standard of care. Extensive cytokine and liver enzyme profiling showed that repeated administration of the mRNA–LUNAR complex does not cause any adverse innate or adaptive immune responses in immune-competent, hemophilic mice. The levels of hFIX protein that were produced also remained consistent during repeated administrations. These results suggest that delivery of long mRNAs is a viable therapeutic alternative for many clotting disorders and for other hepatic diseases where recombinant proteins may be unaffordable or unsuitable. PMID:28202722

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

    Science.gov (United States)

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

    2008-07-01

    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 Galalpha(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.

  16. Survey of the anti-factor IX immunoglobulin profiles in patients with hemophilia B using a fluorescence-based immunoassay.

    Science.gov (United States)

    Boylan, B; Rice, A S; Neff, A T; Manco-Johnson, M J; Kempton, C L; Miller, C H

    2016-10-01

    Essentials Studies characterizing neutralizing antibodies (inhibitors) in hemophilia B (HB) are lacking. The current study describes anti-factor (F) IX antibody profiles in 37 patients who have HB. Anti-FIX IgG4 levels exhibited a strong positive correlation with Nijmegen-Bethesda results. These data will help to more clearly define, predict, and treat alloantibody formation in HB.

  17. Enhancement of pulmonary tumour seeding by human coagulation factors II, IX, X--an investigation into the possible mechanisms involved.

    Science.gov (United States)

    Purushotham, A D; McCulloch, P; George, W D

    1991-09-01

    Warfarin inhibits metastasis in the animal model and injection of the Warfarin-dependent coagulation factor complex II, IX, X enhances pulmonary metastasis in the same model. We have studied two possible mechanisms responsible for the observed effect. Mtln3, rat mammary carcinoma cells, radiolabelled with 5-(125) Iodo-2'-deoxyuridine (IUDR) were injected intravenously in female Fisher 344 rats either alone or in combination with factor complex II, IX, X or bovine serum albumin. Following sacrifice at various intervals, measured lung radioactivity was significantly higher (20%) in animals administered cells with the factor complex than in the other two groups (P less than 0.001, ANOVA and Student's t-test). These results indicate increased entrapment of tumour cells in the pulmonary microcirculation. In a second experiment, rat factor complex II, IX, X was prepared, and Mtln3 cells were then injected in female Fisher 344 rats alone or in combination with either human factor complex or rat factor complex. Following sacrifice, the number of pulmonary nodules in animals receiving cells with rat factor complex was similar to that in animals receiving human factor complex, and significantly higher than that in the control (P less than 0.001, ANOVA and Mann-Whitney), indicating that the observed enhancement of pulmonary seeding is unrelated to the xenogeneic properties of the human factor complex.

  18. 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

    Energy Technology Data Exchange (ETDEWEB)

    Solera, J. (Unidades de Genetica Molecular, Madrid (Spain)); Magallon, M.; Martin-Villar, J. (Hemofilia Hospital, Madrid (Spain)); Coloma, A. (Departamento deBioquimica de la Facultad de Medicina de la Universidad Autonoma, Madrid (Spain))

    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.

  19. Evaluation of engineered AAV capsids for hepatic factor IX gene transfer in murine and canine models.

    Science.gov (United States)

    Markusic, David M; Nichols, Timothy C; Merricks, Elizabeth P; Palaschak, Brett; Zolotukhin, Irene; Marsic, Damien; Zolotukhin, Sergei; Srivastava, Arun; Herzog, Roland W

    2017-05-01

    Adeno-associated virus (AAV) gene therapy vectors have shown the best outcomes in human clinical studies for the treatment of genetic diseases such as hemophilia. However, these pivotal investigations have also identified several challenges. For example, high vector doses are often used for hepatic gene transfer, and cytotoxic T lymphocyte responses against viral capsid may occur. Therefore, achieving therapy at reduced vector doses and other strategies to reduce capsid antigen presentation are desirable. We tested several engineered AAV capsids for factor IX (FIX) expression for the treatment of hemophilia B by hepatic gene transfer. These capsids lack potential phosphorylation or ubiquitination sites, or had been generated through molecular evolution. AAV2 capsids lacking either a single lysine residue or 3 tyrosine residues directed substantially higher coagulation FIX expression in mice compared to wild-type sequence or other mutations. In hemophilia B dogs, however, expression from the tyrosine-mutant vector was merely comparable to historical data on AAV2. Evolved AAV2-LiC capsid was highly efficient in hemophilia B mice but lacked efficacy in a hemophilia B dog. Several alternative strategies for capsid modification improve the in vivo performance of AAV vectors in hepatic gene transfer for correction of hemophilia. However, capsid optimization solely in mouse liver may not predict efficacy in other species and thus is of limited translational utility.

  20. Expression of human coagulation Factor IX in transgenic tomato (Lycopersicon esculentum).

    Science.gov (United States)

    Zhang, Hui; Zhao, Lingxia; Chen, Yuhui; Cui, Lijie; Ren, Weiwei; Tang, Kexuan

    2007-10-01

    In the present study, a plant binary expression vector PG-pRD12-hFIX (where PG is polygalacturonase) harbouring the hFIX (human coagulation Factor IX) gene was constructed and introduced into tomato (Lycopersicon esculentum) via Agrobacterium tumefaciens-mediated transformation. After kanamycin selection, 32 putative independent transgenic tomato plants were regenerated. PCR and Southern-blot analyses confirmed the transgenic status of some plants. RT (reverse transcription)-PCR analysis for the expression of the introduced gene (hFIX) demonstrated that the hFIX gene was expressed specifically in fruits of the tomato. Western-blot analysis confirmed the presence of a 56 kDa band specific to hFIX in the transformed tomatoes. ELISA results showed that the expression of hFIX protein reached a maximum of 15.84 ng/g fresh weight in mature fruit. A blood-clotting assay demonstrated the clotting activity of the expressed hFIX protein in transgenic tomato fruits. This is the first report on the expression of hFIX in plants, and our research provides potentially valuable knowledge for further development of the plant-derived therapeutic proteins.

  1. In vitro differentiation of mouse ES cells into hepatocytes with coagulation factors VIII and IX expression profiles

    Institute of Scientific and Technical Information of China (English)

    MENG; Ying; HUANG; Shaoliang; MIN; Jun; GUO; Zhongmin

    2006-01-01

    Coagulation factors II, V, VII, VIII, IX and X are produced by hepatocytes. So factors VIII and IX deficiencies, which result in hemophilia A and B, have the potential to respond to cellular re- placement therapy. Embryonic stem (ES) cells provide a unique source for therapeutic applications. Here, E14 mouse ES cells have been induced into hepatocytes in vitro. Morphology revealed that ES-derived hepatic-like cells were round or polyhedral shaped with distinct boundary of individual cells, and some arranged in trabeculae. These cells expressed endodermal- or liver-specific mRNA --transthyretin (TTR), α1-anti-trypsin (AAT), α-fetoprotein (AFP), albumin (ALB), glucose-6- phoshpatase (G6P) and tyrosine aminotransferase (TAT). Approximately (85.1(0.5)% of the ES-de- rived cells was stained positive green with ICG uptake. These cells were also stained magenta as a result of PAS reaction. In this paper, expression of coagulation factors VIII and IX mRNA in the ES-derived cells is documented. Therefore, ES cells might be developed as substitute donor cells for the therapy of coagulation factor deficiencies.

  2. Construction and high expression of retroviral vector with human clotting factor IX cDNA in vitro

    Institute of Scientific and Technical Information of China (English)

    卢大儒; 邱信芳; 郑冰; 邱晓赟; 薛京伦

    1995-01-01

    The construction of the high liter and highly expressed safety retroviral vector carrying human clotting factor IX cDNA is reported. Retroviral vectors LNCTX, LIXSN and LCTXSN, driven by hCMV, LTR and hCMV combined with LTR promoter respectively, were constructed, based on the retroviral vector LNL6, and transferred into packaging cell line PA317 with electroporalion. Human dolling factor IX was delected in the cultured cells transduced with LNCIX and LIXSN but not in the cells transduced with LCIXSN. The viral titer of PA317/LNC1X was 800000 CFU per mL. With ELISA detection, it was found that the cells transduced with this vector can express human clotting factor IX at the level of 3.3μg per 106 cells in 24 h in human fibrosarcoma cells HT-1080 and 2.5μg per 106 cells in 24 h in hemophilia B patients’ skin fibroblast HSF cells, and more than 80% of them were biologically active. The viral liter and expression of human FIX were increased, and the construction of retroviral vector backbone was improved

  3. A study of gene transfer and expression of human clotting factor IX in Hemophilia B mice mediated by mini-adenoviral vector

    Institute of Scientific and Technical Information of China (English)

    高啸波; 叶晨波; 侍鼎; 陈立; 邱信芳; 薛京伦

    2003-01-01

    Vector Gti'IX containing human clotting factor IX cDNA with intron 1 (hFIX mini-gene or Fi'IX) driven by CMV promoter was constructed based on the mini-adenoviral vector GT2073 (mini-Ad vector) with all viral protein coding sequences deleted. Mini-Ad packaging cell 293Cre4 was first transduced with Gti'IX, and then was transfected with helper-adenovirus AdLC8, thus mini-Ad virions AdGTi'IX were obtained. At the same time, previous normal adenoviral vector pAdSPi'IX containing viral genome and hFIX mini-gene was constructed, and then previous adenovirus (pre-Ad) AdSPi'IX was obtained as control. The ratio of helper-adenovirus among purified virons AdGTi'IX was less than 0.8%. 3T3 cells were transfected with AdGTi'IX and AdSPi'IX at a MOI of 50 per cell and ELISA result showed that transient expression level in vitro was 1.4±0.2 μg /106@24 h and 1.6±0.3 μg/106@24 h respectively. Each hemophilia B (FIX knock-out) mouse received celiac injection of 1×1010pfu AdGTi'IX or AdSPi'IX. The highest expression level of hFIX in mouse plasma was 590 ng/mL and 690 ng/mL respectively, and the expression time lasted for 16 weeks and 9 weeks respectively. The bleeding time reduced from over 30 min to 7.5 min, and 5-min blood lost reduced from 430 μL to 60 μL. The results of anti-Ad IgG assays indicated that immune response triggered by AdGTi'IX was obviously weaker than that triggered by AdSPi'IX. These results indicated that, compared with previous adenovirus (pre-Ad), the mini-Ad vector system prolonged the expression time of hFIX and reduced immune response, thus offering a promising result for further pre-clinical study.

  4. A simple technique to reduce epistaxis and nasopharyngeal trauma during nasotracheal intubation in a child with factor IX deficiency having dental restoration.

    Science.gov (United States)

    Delgado, Anita V; Sanders, John C

    2004-10-01

    Epistaxis and airway trauma are often associated with nasotracheal intubation. We describe a patient with Factor IX deficiency who required nasotracheal intubation. An inexpensive, nonproprietary, rapid technique was used to reduce the trauma of intubation.

  5. Sustained expression of coagulation factor IX by modified cord blood-derived mesenchymal stromal cells.

    Science.gov (United States)

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

    2014-01-01

    Hemophilia B patients are subject to frequent and spontaneous bleeding caused by a deficiency of clotting factor IX (FIX). Mesenchymal stromal cells (MSCs) have been used in cellular therapies as a result of their immunomodulatory properties, the ability to home to sites of injury and their amenability to various ex vivo modifications, including lentiviral-mediated gene transfer. MSCs were isolated from human umbilical cord blood and differentiated into adipogenic, chondrogenic and osteogenic lineages. A lentiviral DNA vector containing the human FIX gene was generated using traditional restriction enzyme digest and ligation techniques to generate viable replication-incompetent lentiviral particles that were used to transduce MSCs. Quantitative measurement of FIX expression was conducted using an enzyme-linked immunosorbent assay. The over-expression of FIX was sustained in vitro at levels > 4 µg/10(6) cells/24 h and FIX coagulant activity was > 2.5 mIU/10(6) cells/24 h for the 6-week duration of study. Lentiviral modification of cells with a multiplicity of infection of 10 did not adversely affect the potential of cord blood (CB) MSCs to differentiate to adipocytes, chondrocytes and osteoblastic cells, and the expression of functional FIX was sustained after differentiation and was similar to that in nondifferentiated cells. Modification of human CB MSCs with a lentiviral vector resulted in sustained high FIX expression in vitro after differentiation to adipogenic, chondrogenic and osteoblastic cells. These modified MSCs could have applications in cellular therapies for hemophilia B. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Expression of the human coagulation factor IX in the bone marrow mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Azadehsadat Azadbakhsh

    2014-05-01

    Full Text Available Background: Mesenchymal stem cells (MSCs are appropriate target for gene and cell-based therapy of hemophilia B patients. MSCs possess several unique properties such as capability of differentiating into multiple lineages and lower immunogenecity in transplant procedure that make them attractive candidates for cell and gene therapy. One of the challenges in the gene therapy is the low expression level of transgene. To improve expression, strong regulatory elements in the context of vectors could contribute to improve efficacy of gene therapy strategies. In this study four human factor IX (hFIX-expressing plasmids equipped with various combination of human -globin (hBG introns and Kozak sequence were transfected into the MSCs and expression of the hFIX was evaluated in vitro. Material and Methods: MSCs were obtained from tibias and the femora of rats and phenotypic characterization of the MSCs was determined by flow cytometry. Four hFIX-expressing plasmids were introduced into the culture-expanded MSCs using transfection agent. 48 hours after transfection, ability of the MSCs for expression of the hFIX and efficacies of the plasmids were evaluated by performing sandwich ELISA on cultured media as well as semi-quantitative RT-PCR. All analyses were performed with One-way ANOVA using SPSS software. Results:The highest expression level of the hFIX was obtained from intron-less and hBG intron-I containing construct. The highest biological activity was obtained from hBG intron-I,II containing construct. Conclusion:Successful expression of the hFIX was obtained from recombinant MSCs. MSCs were able to splice heterologous hBG intron-I from the hFIX-cDNA. Application of thehBG introns reduced the hFIX expression levels, probably due to improper splicing of the hBG introns.

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

    Science.gov (United States)

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

    2016-06-01

    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.

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

    Science.gov (United States)

    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 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.

  9. Characterization of three abnormal factor IX variants (Bm Lake Elsinore, Long Beach, and Los Angeles) of hemophilia-B. Evidence for defects affecting the latent catalytic site.

    Science.gov (United States)

    Usharani, P; Warn-Cramer, B J; Kasper, C K; Bajaj, S P

    1985-01-01

    Abnormal factor IX variant proteins were isolated from the plasmas of three unrelated severe hemophilia-B families that had been previously shown to contain functionally impaired molecules immunologically similar to normal factor IX. The families studied were: (1) a patient with markedly prolonged ox brain prothrombin time, designated factor IX Bm Lake Elsinore (IXBmLE); (b) three patients (brothers) with moderately prolonged ox brain prothrombin time, designated factor IX Long Beach (IXLB); and (c) a patient with normal ox brain prothrombin time designated factor IX Los Angeles (IXLA). Each variant molecule comigrates with normal factor IX (IXN) both in the sodium dodecyl sulfate and in the nondenaturing alkaline gel electrophoresis. All three variant proteins are indistinguishable from IXN in their amino acid compositions, isoelectric points, carbohydrate distributions and number of gamma-carboxyglutamic acid residues. Each variant protein undergoes a similar pattern of cleavage by factor XIa/Ca2+ and by factor VIIa/Ca2+/tissue factor, and is activated at a rate similar to that observed for IXN. All of the three variant proteins also react with an anti-IXN monoclonal antibody that interferes with the binding of activated IXN(IXaN) to thrombin-treated factor VIIIC. However, in contrast to IXaN, the cleaved IXBmLE has negligible activity (approximately 0.2%), and cleaved forms of IXLA and IXLB have significantly reduced activity (approximately 5-6%) in binding to antithrombin-III/heparin, and in activating factor VII (plus Ca2+ and phospholipid) or factor X (plus Ca2+ and phospholipid) +/- factor VIII. These data, taken together, strongly indicate that the defect in these three variant proteins resides near or within the latent catalytic site. This results in virtually a complete loss of catalytic activity of the cleaved IXBmLE molecule and approximately 95% loss of catalytic activity of the cleaved IXLA and IXLB molecules.

  10. A computer-based model to assess costs associated with the use of factor VIII and factor IX one-stage and chromogenic activity assays.

    Science.gov (United States)

    Kitchen, S; Blakemore, J; Friedman, K D; Hart, D P; Ko, R H; Perry, D; Platton, S; Tan-Castillo, D; Young, G; Luddington, R J

    2016-04-01

    Measurement of coagulation factor factor VIII (FVIII) and factor IX (FIX) activity can be associated with a high level of variability using one-stage assays based on activated partial thromboplastin time (APTT). Chromogenic assays show less variability, but are less commonly used in clinical laboratories. In addition, one-stage assay accuracy using certain reagent and instrument combinations is compromised by some modified recombinant factor concentrates. Reluctance among some in the hematology laboratory community to adopt the use of chromogenic assays may be partly attributable to lack of familiarity and perceived higher associated costs. To identify and characterize key cost parameters associated with one-stage APTT and chromogenic assays for FVIII and FIX activity using a computer-based cost analysis model. A cost model for FVIII and FIX chromogenic assays relative to APTT assays was generated using assumptions derived from interviews with hematologists and laboratory scientists, common clinical laboratory practise, manufacturer list prices and assay kit configurations. Key factors that contribute to costs are factor-deficient plasma and kit reagents for one-stage and chromogenic assays, respectively. The stability of chromogenic assay kit reagents also limits the cost efficiency compared with APTT testing. Costs for chromogenic assays might be reduced by 50-75% using batch testing, aliquoting and freezing of kit reagents. Both batch testing and aliquoting of chromogenic kit reagents might improve cost efficiency for FVIII and FIX chromogenic assays, but would require validation. Laboratory validation and regulatory approval as well as education and training in the use of chromogenic assays might facilitate wider adoption by clinical laboratories. © 2016 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

  11. Sustained and therapeutic delivery of factor IX in nude haemophilia B mice by encapsulated C2C12 myoblasts: concurrent tumourigenesis.

    Science.gov (United States)

    Hortelano, G; Wang, L; Xu, N; Ofosu, F A

    2001-03-01

    This study reports the generation of an immunodeficient murine model for haemophilia B, obtained by breeding factor IX-deficient mice with an immunodeficient mouse strain, and use of this mouse model to evaluate the long-term efficacy and safety of a gene therapy strategy for treating haemophilia B. Nude haemophilic mice were implanted with biocompatible microcapsules enclosing recombinant myoblasts secreting human factor IX. The activated partial thromboplastin time (APTT) of plasma of mice thus treated was invariably shortened 3 weeks after microcapsule implantation, and remained shortened for at least 77 days. Shortening of the APTT of the haemophilia mice coincided with the appearance of human factor IX in mice plasmas (up to 600 ng mL(-1) on day 77), and normalization of the tail-bleeding time. Thus, the microencapsulated myoblasts reversed the clinical phenotype of haemophilia B. In contrast, plasmas of immunocompetent haemophilic mice similarly implanted with microcapsules only showed a transient shortening of APTT, and coincident transient delivery of human factor IX antigen. Rapid disappearance of human factor IX from plasmas of immunocompetent mice also coincided with production of antibodies to the human transgene. Significantly, 86% of the nude haemophilia mice developed tumours of myoblast origin. Thus, while this study revealed the feasibility of this gene therapy approach to treat severe haemophilia B, it also highlights the importance of using safer cell lines to prevent tumour development.

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

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, A.R. (Univ. of Washington, Seattle (USA) Puget Sound Blood Center, Seattle, WA (USA)); Darlington, G. (Baylor College of Medicine, Houston, TX (USA)); 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.

  13. PpIX induces mitochondria-related apoptosis in murine leukemia L1210 cells.

    Science.gov (United States)

    Su, Xiaomin; Chen, Yan; Wang, Xiaobing; Wang, Yuan; Wang, Pan; Li, Long; Liu, Quanhong

    2014-07-01

    Protoporphyrin IX (PpIX), a well-known sensitizer that can enhance laser light or ultrasound induced cytotoxicity in photodynamic and sonodynamic therapy. However, PpIX alone could effectively cause anti-tumor effect and the underlying mechanisms are rarely been reported. Therefore, this study was to investigate the possible mechanism by which PpIX revealed anti-proliferative effect on murine leukemia L1210 cells. The accumulation of PpIX in L1210 cells and normal peripheral blood mononuclear cells (PBMCs) was evaluated with flow cytometry. The subcellular localization of PpIX and apoptosis-inducing factor (AIF) translocation were determined by confocal microscope. The cell viability was examined by MTT assay. Annexin V-PE/7-AAD and DAPI staining were used to detect apoptotic cells. The mitochondrial membrane potential (MMP) changes were tested by rhodamine123 staining. DNA damage was measured by comet assay. PpIX preferentially accumulated in L1210 cells compared to PBMCs and PpIX mainly located in the mitochondria of L1210 cells. PpIX at a concentration of 1 µg/ml or above exerted significant anti-tumor effect and the cell viability loss presented PpIX dose-dependent manner. Typical apoptotic features such as chromatin condensation were observed by DAPI staining. Annexin V-PE/7-AAD analysis showed 5 µg/ml PpIX could induce about 24% cell apoptosis, which was inhibited by cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore. In addition, the PpIX caused MMP loss, AIF translocation to nucleus and serious DNA damage were also suppressed by CsA. The results indicate mitochondria-dependent apoptosis were involved in PpIX caused cell damage on L1210 cells.

  14. A pilot study on potential plasma hypoxia markers in the radiotherapy of non-small cell lung cancer. Osteopontin, carbonic anhydrase IX and vascular endothelial growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Ostheimer, C.; Bache, M.; Guettler, A.; Vordermark, D. [Martin-Luther-University Halle-Wittenberg, Department of Radiation Oncology, Halle (Saale) (Germany); Kotzsch, M. [Technical University Dresden, Department of Pathology, Dresden (Germany)

    2014-03-15

    Hypoxic radioresistance plays a critical role in the radiotherapy of cancer and adversely impacts prognosis and treatment response. This prospective study investigated the interrelationship and the prognostic significance of several hypoxia-related proteins in non-small cell lung cancer (NSCLC) patients treated by radiotherapy ± chemotherapy. Pretreatment osteopontin (OPN), vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CA IX) plasma levels were determined by ELISA in 55 NSCLC (M0) patients receiving 66 Gy curative-intent radiotherapy or chemoradiation. Marker correlation, association with clinicopathological parameters and the prognostic value of a biomarker combination was evaluated. All biomarkers were linearly correlated and linked to different clinical parameters including lung function, weight loss (OPN), gross tumor volume (VEGF) and T stage (CA IX). High OPN (p = 0.03), VEGF (p = 0.02) and CA IX (p = 0.04) values were significantly associated with poor survival. Double marker combination additively increased the risk of death by a factor of 2 and high plasma levels of the triple combination OPN/VEGF/CA IX yielded a 5.9-fold risk of death (p = 0.009). The combined assessment of OPN/VEGF/CA IX correlated independently with prognosis (p = 0.03) in a multivariate Cox regression model including N stage, T stage and GTV. This pilot study suggests that a co-detection augments the prognostic value of single markers and that the integration of OPN, VEGF and CA IX into a hypoxic biomarker profile for the identification of patients with largely hypoxic and radioresistant tumors should be further evaluated. (orig.) [German] Hypoxische Radioresistenz spielt eine kritische Rolle in der Radiotherapie maligner Tumoren und beeinflusst Prognose und Therapieansprechen negativ. Diese prospektive Studie untersuchte den Zusammenhang und die prognostische Bedeutung einiger hypoxieassoziierter Proteine bei Patienten mit nicht-kleinzelligem Bronchialkarzinom

  15. Gene therapy for hemophilia B mediated by recombinant adeno-associated viral vector with hFIXR338A, a high catalytic activity mutation of human coagulation factor IX

    Institute of Scientific and Technical Information of China (English)

    LU; Huazhong; (

    2001-01-01

    [1]Chang, J., Jin, J., Lollar, P. et al., Changing residue 338 in human factor IX from arginine to alanine causes an increase in catalytic activity, J. Bio. Chem., 1998, 273 (20): 12089-12094.[2]Lai, L., Chen, L., Zhou, H. et al., Clinical phenotype and genetic stability of factor IX gene knock out mice, J. Fudan Uni., 1999, 38 (4): 435-438.[3]Wu, Z. J., Wu, X. B., Hou, Y. D., Generation of a recombinant herps simplex virus which can provide packaging function for recombinant adeno-associated virus, Chinese Sci. Bull., 1999, 44 (8): 715-719.[4]Snyder, R. O., Miao, C. H., Patijn, G. A. et al., Persistent and therapeutic concentrations of human factor IX in mice after hepatic gene transfer of recombinant AAV vectors, Nat. Genet., 1997, 16 (3): 270-276.[5]Lai, L. H., Chen, L., Wang, J. M. et al., Skeletal muscle-specific expression of human blood coagulation factor IX rescues factor IX deficiency mouse by AAV-mediated gene transfer, Science in China, Ser. C, 1999, 42 (6): 628-634.[6]Snyder, R. O., Miao, C., Meuse, L. et al., Correction of hemophilia B in canine and murine models using recombinant adeno-associated viral vectors, Nat. Med., 1999, 5 (1): 64-70.[7]Kung, S. H., Hagstrom, J. N., Cass, D. et al., Human factor IX corrects the bleeding diathesis of mice with hemophilia B, Blood, 1998, 91(3): 784-790.[8]Hirt, B., Selective extraction of polyoma DNA from infected mouse cell culture, J. Mol. Biol., 1967, 26: 365-369.[9]Sambrook, J., Fritsch, E., Maniatis, T., Molecular Cloning: A Laboratory Manual, New York: Cold Spring Harbor Laboratory Press, 1989, 6, 20-21.[10]Chao, H., Samulski, R. J., Bellinger, D. A. et al., Persistent expression of canine factor IX in hemophilia B canines, Gene Ther., 1999, 6: 1695-1704.[11]Kaufman, R. J., Advances toward gene therapy for hemophilia at the millennium, Hum. Gene Ther., 1999, 10 (13): 2091-2107.[12]Lu, D. R., Zhou, J. M., Zheng, B. et al., Stage I clinical trial of gene

  16. Abnormal joint and bone wound healing in hemophilia mice is improved by extending factor IX activity after hemarthrosis.

    Science.gov (United States)

    Sun, Junjiang; Hua, Baolai; Livingston, Eric W; Taves, Sarah; Johansen, Peter B; Hoffman, Maureane; Ezban, Mirella; Monroe, Dougald M; Bateman, Ted A; Monahan, Paul E

    2016-12-30

    Wound healing requires interactions between coagulation, inflammation, angiogenesis, cellular migration, and proliferation. Healing in dermal wounds of hemophilia B mice is delayed when compared to hemostatically normal wild type (WT) mice, with abnormal persistence of iron deposition, inflammation, and neovascularity. We observed healing following induced joint hemorrhage in WT and factor IX (FIX) knockout (FIX(-/-)) mice, examining also parameters previously studied in an excisional skin wound model. Hemostatically normal mice tolerated this joint bleeding challenge, cleared blood from the joint, and healed with minimal pathology, even if additional autologous blood was injected intra-articularly at the time of wounding. Following hemarthrosis, joint wound healing in hemophilia B mice was impaired and demonstrated similar abnormal histologic features as previously described in hemophilic dermal wounds. Therefore, studies of pathophysiology and therapy of hemophilic joint bleeding performed in hemostatically normal animals are not likely to accurately reflect the healing defect of hemophilia. We additionally explored the hypothesis that the use of a FIX replacement protein with extended circulating FIX activity could improve synovial and osteochondral wound healing in hemophilic mice, when compared to treatment with unmodified recombinant FIX (rFIX) in the established joint bleeding model. Significantly improved synovial wound healing and preservation of normal osteochondral architecture are achieved by extending FIX activity after hemarthrosis using glycoPEGylated FIX when compared to an equivalent dose of rFIX. These results suggest that treating joint bleeding only until hemostasis is achieved may not result in optimal joint healing, which is improved by extending factor activity.

  17. Modulating immunogenicity of factor IX by fusion to an immunoglobulin Fc domain: a study using a hemophilia B mouse model.

    Science.gov (United States)

    Levin, D; Lagassé, H A D; Burch, E; Strome, S; Tan, S; Jiang, H; Sauna, Z E; Golding, B

    2017-04-01

    Essentials Fc-fusion increases a therapeutic's half-life, but FcγR interactions may impact immunogenicity. Species-specific Fc-FcγR interactions allow for mechanistic in vivo studies using mouse models. Fc fusion modulates the immune response to factor IX in hemophilia B mice by eliciting Th1 bias. This model could inform future studies of IgE-associated anaphylaxis in hemophilia B patients. Background Fc fusion is a platform technology used to increase the circulating half-life of protein and peptide therapeutics. However, there are potential immunological consequences with this approach, such as changes in the molecule's immunogenicity as well as possible interactions with a repertoire of Fc receptors (FcR) that can modulate immune responses. Objectives/Methods Using a mouse hemophilia B (HB) model, we compared the immune responses to infusions of recombinant human factor IX (hFIX) and hFIX fused to mouse IgG2a-Fc (hFIX-mFc). The mFc was employed to allow species-specific Fc-FcγR interactions. Results Although treatment with hFIX-mFc altered the early development of anti-FIX IgG, no significant differences in anti-FIX antibody titers were observed at the end of the treatment regimen (5 weeks) or upon anamnestic response (5 months). However, treatment with hFIX-mFc elicited higher FIX-neutralizing antibody levels and resulted in reduced IgE titers compared with the hFIX-treated group. Additionally, differences in plasma cytokine levels and in vitro CD4(+) T-cell responses suggest that whereas hFIX treatment triggered a Th2-biased immune response, hFIX-mFc treatment induced Th1-biased CD4(+) T cells. We also show that hFIX-mFc bound to soluble FcγRs and engaged with FcγRs on different cell types, which may impact antigen presentation. Conclusions These studies provide a model system to study how Fc-fusion proteins may affect immune mechanisms. We used this model to demonstrate a plausible mechanism by which Fc fusion may modulate the IgE response to hFIX. This

  18. Preparation of a recombinant adeno-associated viral vector with a mutation of human factor IX in large scale and its expression in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A series of adeno-associated viral vectors conraining a mutation of human factor IX (hFIXR338A) with different regulation elements were constructed and used to transduce cell lines. The plasmids and the stable transduction cell clones with high expression level of hFIXR338Awere obtained by selecting and optimizing, and then, the recombinant adeno-associated viral vector with hFIXR338Awas prepared via novel rHSV/AAV hybrid virus packaging system on a large scale, which contained the capsid protein genes. A method for producing rAAV-hFIXR338A viral stocks on a large scale and higher fiter was established,which can be used for industrial purpose. The titer of rAAV-hFIXR338A was more than 1.25x1012 particle/mL, and then, a mammalian cell line, C2C12 and the factor IXknock-out mice were transfected with the rAAV-hFIXR338Ain vitro and in vivo. The results show that the high-level expression of rAAV-hFIXR338A was achieved in cell line and hemophilia B mice. It reached at (2551.32±92.14) ng@ (106cells)-1 @ (24 h)-1 in C2C12 cell in vitro and had a peak concentration of 463.28 ng/mL in mice treated with rAAV-hFIX R338A, which was as high as the expression of rAAV-hFIX -wt (2565.76±64.36) ng@ (106 cells)-1@ (24 h)-1 in C2C12 and 453.92 ng/mL in the mice treated with rAAV-hFIX-wt) in vitro and in vivo, there is no any difference between two groups, but the clotting activity of hFIXR338A is about 2.46times higher than that of hFIX-wt. It was first reported that a mutation of human factor IX was used into gene therapy research for hemophilia B, meanwhile, a novel packaging system, rAAV/HSV was used for preparation of rAAV-hFIX R338A on a large scale, which laid the foundation of industrial production for applying rAAV viral stocks to gene therapy clinical trial for hemophilia B mediated with rAAV-hFIX.``

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

    Science.gov (United States)

    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.

  20. Targeting of the human coagulation factor IX gene at rDNA locus of human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Xionghao Liu

    Full Text Available BACKGROUND: Genetic modification is a prerequisite to realizing the full potential of human embryonic stem cells (hESCs in human genetic research and regenerative medicine. Unfortunately, the random integration methods that have been the primary techniques used keep creating problems, and the primary alternative method, gene targeting, has been effective in manipulating mouse embryonic stem cells (mESCs but poorly in hESCs. METHODOLOGY/PRINCIPAL FINDINGS: Human ribosomal DNA (rDNA repeats are clustered on the short arm of acrocentric chromosomes. They consist of approximately 400 copies of the 45S pre-RNA (rRNA gene per haploid. In the present study, we targeted a physiological gene, human coagulation factor IX, into the rDNA locus of hESCs via homologous recombination. The relative gene targeting efficiency (>50% and homologous recombination frequency (>10(-5 were more than 10-fold higher than those of loci targeted in previous reports. Meanwhile, the targeted clones retained both a normal karyotype and the main characteristics of ES cells. The transgene was found to be stably and ectopically expressed in targeted hESCs. CONCLUSION/SIGNIFICANCE: This is the first targeting of a human physiological gene at a defined locus on the hESC genome. Our findings indicate that the rDNA locus may serve as an ideal harbor for transgenes in hESCs.

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

    Energy Technology Data Exchange (ETDEWEB)

    Satoh, Chiyoko; Takahashi, Norio; Asakawa, Junichi; Hiyama, Keiko; Kodaira, Meiko (Radiation Effects Research Foundation, Hiroshima (Japan))

    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.

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

    Directory of Open Access Journals (Sweden)

    Dong Hua Cao

    2014-09-01

    Full Text Available 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. 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.

  3. Clearance of protoporphyrin IX induced by 5-aminolevulinic acid from WiDr human colon carcinoma cells

    Science.gov (United States)

    Juzeniene, Asta; Kaliszewski, Miron; Bugaj, Andrzej; Moan, Johan

    2009-06-01

    5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is the most widely practiced form of PDT in dermatology. One of the advantages of ALA-PDT is that undesirable photosensitization lasts only for 24-48 h. In order to optimize ALA-PDT it is necessary to understand the mechanisms controlling intracellular PpIX clearance (efflux and transformation into heme) in order to decrease protoporphyrin IX (PpIX) clearance rates in the early stages of its production. The aim of this study was to investigate the factors controlling the clearance of intracellular PpIX. Fluorescence spectroscopy was used to study PpIX kinetics in WiDr cells initially treated with ALA. The clearance rate of PpIX in WiDr cells was faster after application of a low concentration of ALA (0.1 mM) than after application of high concentration of ALA (1 mM). PpIX was cleared faster from cells which initially were seeded at low densities than cells seeded at higher densities. The presence of the iron chelator deferoxamine reduced the clearance rate of PpIX, while the presence of ferrous sulfate acted oppositely. The decay rate of PpIX in WiDr cells was faster at higher temperature than at lower. The ferrochelatase activity at pH 7.2 was significantly greater than that at pH 6.7. ALA concentration, application time, cell density, temperature, pH, intracellular iron content, intracellular amount and localization of PpIX are factors controlling PpIX clearance.

  4. Efficient detection of factor IX mutations by denaturing high-performance liquid chromatography in Taiwanese hemophilia B patients, and the identification of two novel mutations

    Directory of Open Access Journals (Sweden)

    Pei-Chin Lin

    2014-04-01

    Full Text Available Hemophilia B (HB is an X-linked recessive disorder characterized by mutations in the clotting factor IX (FIX gene that result in FIX deficiency. Previous studies have shown a wide variation of FIX gene mutations in HB. Although the quality of life in HB has greatly improved mainly because of prophylactic replacement therapy with FIX concentrates, there exists a significant burden on affected families and the medical care system. Accurate detection of FIX gene mutations is critical for genetic counseling and disease prevention in HB. In this study, we used denaturing high-performance liquid chromatography (DHPLC, which has proved to be a highly informative and practical means of detecting mutations, for the molecular diagnosis of our patients with HB. Ten Taiwanese families affected by HB were enrolled. We used the DHPLC technique followed by direct sequencing of suspected segments to detect FIX gene mutations. In all, 11 FIX gene mutations (8 point mutations, 2 small deletions/insertions, and 1 large deletion, including two novel mutations (exon6 c.687–695, del 9 mer and c.460–461, ins T were found. According to the HB pedigrees, 25% and 75% of our patients were defined as familial and sporadic HB cases, respectively. We show that DHPLC is a highly sensitive and cost-effective method for FIX gene analysis and can be used as a convenient system for disease prevention.

  5. [Construction of nonsense-mutated eukaryotic expression vector of factor IX gene and its expression in COS-7 cells].

    Science.gov (United States)

    Nie, Xin; Yang, Lin-Hua; Chai, Bao-Feng; Shen, Quan; Zhang, Yuan; Zhang, Yao-Fang; Chen, Jian-Fang

    2010-06-01

    The purpose of this study was to construct 4 types of nonsense-mutated eukaryotic expression plasmids of fIX gene, using pcDNA3.1 plasmid containing fIX cDNA as template, and to identify, then to perform their expression in COS-7 cells. These stop mutants constructed by site-directed mutagenesis based on PCR, and further confirmed by DNA sequencing. COS-7 cells were transfected with either the wild-type or mutated fIX expression constructs, then the relative expression levels of fIX mRNA were detected by real time fluorescent quantitative PCR. The result showed that except the designed sites, there were no other nucleotide mutation in the sequences of four nonsense mutants. The results of real time PCR proved that the nonsense-mutated vectors can be effectively expressed in COS-7 cells. It is concluded that the nonsense-mutated eukaryotic expression vectors of fIX gene have been successfully constructed and can express in COS-7 cells, which provides the material basis for further researches on mechanism and treatment of FIX deficiency and the function defects caused by nonsense mutation.

  6. Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein.

    Science.gov (United States)

    McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D

    2014-07-01

    Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long-acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human- and animal-derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi-step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process-related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non-human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc.

  7. Sustained and therapeutic levels of human factor IX in hemophilia B mice implanted with microcapsules: key role of encapsulated cells.

    Science.gov (United States)

    Wen, Jianping; Vargas, Andrew Gómez; Ofosu, Frederick A; Hortelano, Gonzalo

    2006-03-01

    A gene therapy delivery system based on microcapsules enclosing recombinant cells engineered to secrete a therapeutic protein was explored in this study. In order to prevent immune rejection of the delivered cells, they were enclosed in non-antigenic biocompatible alginate microcapsules prior to being implanted intraperitoneally into mice. We have shown that encapsulated C2C12 myoblasts can temporarily deliver therapeutic levels of factor IX (FIX) in mice, but the C2C12 myoblasts elicited an immune response to FIX. In this study we report the use of mouse fetal G8 myoblasts secreting hFIX in hemophilia mice. Mouse G8 myoblasts were transduced with MFG-FIX vector. A pool of recombinant G8 myoblasts secreting approximately 1500 ng hFIX/10(6) cells/24 h in vitro were enclosed in biocompatible alginate microcapsules and implanted intraperitoneally into immunocompetent C57BL/6 and hemophilic mice. Circulating levels of hFIX in treated mice reached approximately 400 ng/ml for at least 120 days (end of experiment). Interestingly, mice treated with encapsulated G8 myoblasts did not develop anti-hFIX antibodies. Activated partial thromboplastin time (APTT) of plasmas obtained from treated hemophilic mice was reduced from 107 to 82 sec on day 60 post-treatment, and whole blood clotting time (WBCT) was also corrected from 7-9 min before treatment to 3-5 min following microcapsule implantation. Further, mice were protected against bleeding following major trauma. Thus, the FIX delivery in vivo was biologically active. Our findings suggest that the type of cells encapsulated play a key role in the generation of immune responses against the transgene. Further, a judicious selection of encapsulated cells is critical for achieving sustained gene expression. Our findings support the feasibility of encapsulated G8 myoblasts as a gene therapy approach for hemophilia B.

  8. Matrix Factorization and Matrix Concentration

    OpenAIRE

    Mackey, Lester

    2012-01-01

    Motivated by the constrained factorization problems of sparse principal components analysis (PCA) for gene expression modeling, low-rank matrix completion for recommender systems, and robust matrix factorization for video surveillance, this dissertation explores the modeling, methodology, and theory of matrix factorization.We begin by exposing the theoretical and empirical shortcomings of standard deflation techniques for sparse PCA and developing alternative methodology more suitable for def...

  9. Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell's Viper Bites with Coagulopathy.

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    Geoffrey K Isbister

    Full Text Available Russell's viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell's viper envenoming.In a prospective cohort of 146 patients with Russell's viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT, activated partial thromboplastin time (aPTT, coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39 y (16-82 y and 111 were male. The median peak INR was 6.8 (interquartile range [IQR]: 3.7 to >13, associated with low fibrinogen [median,3 at 6 h post-antivenom but had reduced to <2, by 24 h. The aPTT had also returned to close to normal (<50 sec at 24 h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02 and aPTT (r = 0.19, p = 0.03 were correlated (non-parametric Spearman analysis.Russell's viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48 h. Severity of clotting abnormalities was associated with venom concentrations.

  10. DNA Damage and Cell Cycle Arrest Induced by Protoporphyrin IX in Sarcoma 180 Cells

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    Qing Li

    2013-09-01

    Full Text Available Background: Porphyrin derivatives have been widely used in photodynamic therapy as effective sensitizers. Protoporphyrin IX (PpIX, a well-known hematoporphyrin derivative component, shows great potential to enhance light induced tumor cell damage. However, PpIX alone could also exert anti-tumor effects. The mechanisms underlying those direct effects are incompletely understood. This study thus investigated the putative mechanisms underlying the anti-tumor effects of PpIX on sarcoma 180 (S180 cells. Methods: S180 cells were treated with different concentrations of PpIX. Following the treatment, cell viability was evaluated by the 3-(4, 5- dimethylthiazol-2-yl-2, 5-diphenyltetrazoliumbromide (MTT assay; Disruption of mitochondrial membrane potential was measured by flow cytometry; The trans-location of apoptosis inducer factor (AIF from mitochondria to nucleus was visualized by confocal laser scanning microscopy; DNA damage was detected by single cell gel electrophoresis; Cell cycle distribution was analyzed by DNA content with flow cytometry; Cell cycle associated proteins were detected by western blotting. Results: PpIX (≥ 1 µg/ml significantly inhibited proliferation and reduced viability of S180 cells in a dose-dependent manner. PpIX rapidly and significantly triggered mitochondrial membrane depolarization, AIF (apoptosis inducer factor translocation from mitochondria to nucleus and DNA damage, effects partially relieved by the specific inhibitor of MPTP (mitochondrial permeability transition pore. Furthermore, S phase arrest and upregulation of the related proteins of P53 and P21 were observed following 12 and 24 h PpIX exposure. Conclusion: PpIX could inhibit tumor cell proliferation by induction of DNA damage and cell cycle arrest in the S phase.

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

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    Susana Olmedillas López

    2016-04-01

    Full Text Available 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.

  12. Gene therapy for hemophilia B mediated by recombinant adeno-associated viral vector with hFIXR338A, a high catalytic activity mutation of human coagulation factor IX

    Institute of Scientific and Technical Information of China (English)

    陆华中; 陈立; 王红卫; 伍志坚; 吴小兵; 王学峰; 王鸿利; 卢大儒; 邱信芳; 薛京伦

    2001-01-01

    A mutant human factor IX with arginine at 338 residual changed to alanine (hFIXR338A) by site-directed mutagenesis was introduced into AAV vectors, and a recombinant adeno-associ- ated viral vector containing hFIXR338A, prepared by rHSV/AAV hybrid helper virus system, was directly introduced to the hind leg muscle of factor IX knock out mice. The expression and the biological activity of human factor IX mutant, hFIXR338A, and the immune response against it in the treated mice were assayed and detected. The results showed that (i) the high-level expression of human factor IX mutant protein, hFIXR338A, has been detected in rAAV-hFIXR338A treated hemophilia B mice and lasted more than 15 weeks; (ii) the clotting activity of hFIXR338A in plasma is 34.2%± 5.23%, which is remarkably higher than that of (14.27% ± 3.4%) of wild type hFIX treated mice in the activated partial thromboplastin assay; (iii) immune response against factor IX R338A was absent, with no factor IX mutant protein (hFIXR338A) inhibitors development in the treated mice; and (iv) no local or systemic side-effects and toxicity associated with the gene transfer were found. It demonstrated the potential use of treating hemophilia B by recombinant adeno-associated viral vectors with mutant hFIXR338A gene, an alternative strategy for hemophilia B gene therapy to wild-type human factor IX.

  13. 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?

    Energy Technology Data Exchange (ETDEWEB)

    Grouse, L.H.; Ketterling, R.P.; Sommer, S.S. [Mayo Clinic/Foundation, Rochester, MN (United States)

    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.

  14. Hybrid retroviral vector with MCK enhancers inserted in LTR for stable and specific expression of human factor IX in skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    WANG Jian-min 王健民; HOU Jun 侯军; QIU Xin-fang 邱信芳; Kurachi Kotoku; XUE Jing-lun 薛京伦

    2004-01-01

    Background Retroviral vectors have been widely used to introduce foreign into various target cells in vitro, thus showing relatively high systemic delivery efficiency of various transgene products. The authors investigated the stability and efficiency of skeletal muscle-specific hybrid retroviral vectors in expression of human factor IX (FIX) in vitro and iv vivo. Methods FIX cDNA in LIXSN vector was replaced with a FIX minigene containing splicing donor and splicing acceptor sequence of first intron of human FIX gene. Two copies of muscle creatine kinase enhancer (MCK, Me2) were inserted in forward or reverse orientation at NheI site of 3' long terminal repeat (LTR), resulting in two hybrid vectors, which were designated as LMe2IXm2SN(F) and LMe2IXm2SN(R), respectively. The vectors were tested in vitro and in vivo for stability and muscle-specificity of factor IX expression with SCID mice. Results Muscle cells carrying vector with Me2 expressed significantly higher levels of FIX (up to 1800 ng/106.24h) than those without Me2, thus suggesting that Me2 could specifically increase expression level of FIX in muscle cells. Myoblasts transduced with LMe2IXm2SN(R) produced much less FIX in vivo in SCID mice than LMe2IXm2SN(F). One or two copies of Me2 sequence were deleted in myoblasts transduced with LMe2IXm2SN(R) without changing the orientation of Me2. Conclusions LTR inserted with MCK enhancers can specifically increase human FIX expression in skeletal muscle cells in vitro and in vivo, and MCK enhancer should be positioned in the same orientation as that of LTR promoter.

  15. Crystallization and preliminary X-ray analysis of coagulation factor IX-binding protein from habu snake venom at pH 6.5 and 4.6

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Nobuhiro [Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8572 (Japan); Department of Biochemisty, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602 (Japan); Shikamoto, Yasuo; Fujimoto, Zui [Department of Biochemisty, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602 (Japan); Morita, Takashi [Department of Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588 (Japan); Mizuno, Hiroshi, E-mail: mizuno@affrc.go.jp [Department of Biochemisty, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602 (Japan); Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8572 (Japan)

    2005-01-01

    Crystals of habu coagulation factor IX-binding protein have been obtained at pH 6.5 and 4.6 and characterized by X-ray diffraction. Coagulation factor IX-binding protein isolated from Trimeresurus flavoviridis (IX-bp) is a C-type lectin-like protein. It is an anticoagulant protein consisting of homologous subunits A and B. The subunits both contain a Ca{sup 2+}-binding site with differing affinity (K{sub d} values of 14 and 130 µM at pH 7.5). These binding characteristics are pH-dependent; under acidic conditions, the affinity of the low-affinity site was reduced considerably. In order to identify which site has high affinity and also to investigate the Ca{sup 2+}-releasing mechanism, IX-bp was crystallized at pH 6.5 and 4.6. The crystals at pH 6.5 and 4.6 diffracted to 1.72 and 2.29 Å resolution, respectively; the former crystals belong to the monoclinic space group P2{sub 1}, with unit-cell parameters a = 60.7, b = 63.5, c = 66.9 Å, β = 117.0°, while the latter belong to the monoclinic space group C2, with a = 134.1, b = 37.8, c = 55.8 Å, β = 110.4°.

  16. The Role of Hypoxia-Inducible Factor-1α, Glucose Transporter-1, (GLUT-1 and Carbon Anhydrase IX in Endometrial Cancer Patients

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    Pawel Sadlecki

    2014-01-01

    Full Text Available Hypoxia-inducible factor-1α (HIF-1α, glucose transporter-1 (GLUT-1, and carbon anhydrase IX (CAIX are important molecules that allow adaptation to hypoxic environments. The aim of our study was to investigate the correlation between HIF-1α, GLUT-1, and CAIX protein level with the clinicopathological features of endometrial cancer patients. Materials and Methods. 92 endometrial cancer patients, aged 37–84, were enrolled to our study. In all patients clinical stage, histologic grade, myometrial invasion, lymph node, and distant metastases were determined. Moreover, the survival time was assessed. Immunohistochemical analyses were performed on archive formalin fixed paraffin embedded tissue sections. Results. High significant differences (P=0.0115 were reported between HIF-1α expression and the histologic subtype of cancer. Higher HIF-1α expression was associated with the higher risk of recurrence (P=0.0434. The results of GLUT-1 and CAIX expression did not reveal any significant differences between the proteins expression in the primary tumor and the clinicopathological features. Conclusion. The important role of HIF-1α in the group of patients with the high risk of recurrence and the negative histologic subtype of the tumor suggest that the expression of this factor might be useful in the panel of accessory pathomorphological tests and could be helpful in establishing more accurate prognosis in endometrial cancer patients.

  17. Cell-matrix Interactions of Factor IX (FIX)-engineered human mesenchymal stromal cells encapsulated in RGD-alginate vs. fibrinogen-alginate microcapsules.

    Science.gov (United States)

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

    2014-04-01

    The success of cell microencapsulation technology in tissue engineering and protein delivery applications depends on the viability and functionality of the encapsulated cells, which in turn are dependent upon cell/matrix interactions. In this work, we compared the viability of cord blood-derived mesenchymal stromal cells (CB MSCs), engineered to secrete factor IX (FIX) for hemophilia treatment, and encapsulated in arginine-glycine-aspartate (RGD)-alginate versus fibrinogen-alginate microcapsules. We evaluated the effect of the biomimetic matrix on cell attachment, proliferation, and secretion of FIX. Compared with nonsupplemented alginate matrix, RGD-alginate significantly enhanced the viability of the encapsulated MSCs. Further, cells in RGD-alginate displayed distinct attachment morphology, thus suggesting that RGD-alginate can potentially be used for the encapsulation of MSCs in tissue engineering applications that require enhanced cell attachment and viability. However, our data also showed that RGD-alginate microcapsules, in contrast to fibrinogen-alginate microcapsules, did not significantly improve cell proliferation of or FIX secretion by encapsulated MSCs. Our findings suggest that evidence of cell attachment alone may not accurately predict the functionality of cells in biomimetic microcapsules.

  18. The rates of G:C[yields]T:A and G:C[yields]C:G transversions at CpG dinucleotides in the human factor IX gene

    Energy Technology Data Exchange (ETDEWEB)

    Ketterling, R.P.; Vielhaber, E.; Sommer, S.S. (Mayo Clinic/Foundation, Rochester, MN (United States))

    1994-05-01

    The authors have identified eight independent transversions at CpG in 290 consecutive families with hemophilia B. These eight transversions account for 16.3% of all independent transversions in the sample, yet the expected frequency of CpG transversions at random in the factor IX gene is only 2.6% (P<0.1). The aggregate data suggest that the two types of CpG transversions (G:C[yields]T:A and G:C[yields]C:G) possess similar mutation rates (24.8 [times] 10[sup [minus]10] and 20.6 [times] 10[sup [minus]10], respectively), which are about fivefold greater than the comparable rates for transversions at non-CpG dinucleotides. The enhancement of transversions at CpG suggest that the model by which mutations occur at CpG may need to be reevaluated. The relationship, if any, between deamination of 5-methyl cytosine and enhancement of transversions at CpG remains to be defined. 28 refs., 2 tabs.

  19. Multicentre, randomized, open-label study of on-demand treatment with two prophylaxis regimens of recombinant coagulation factor IX in haemophilia B subjects.

    Science.gov (United States)

    Valentino, L A; Rusen, L; Elezovic, I; Smith, L M; Korth-Bradley, J M; Rendo, P

    2014-05-01

    Few randomized studies have reported on the use of factor IX (FIX) for secondary prophylaxis in haemophilia B patients. This study aimed to evaluate the efficacy and safety of two secondary prophylaxis regimens of recombinant coagulation FIX, nonacog alfa, compared with on-demand therapy. Male subjects aged 6-65 years with severe or moderately severe haemophilia B (FIX:C ≤ 2, n = 50) and ≥12 bleeding episodes (including ≥6 haemarthroses episodes) within 12 months of study participation were enrolled in this multicentre, randomized, open-label, four-period crossover trial. The primary measure was the annualized bleeding rate (ABR) of two prophylactic regimens vs. on-demand therapy. In the intent-to-treat group, mean ABR values were 35.1, 2.6 and 4.6 for the first on-demand period, the 50 IU kg(-1) twice-weekly period, and the 100 IU kg(-1) once-weekly period respectively. Differences in ABR between the first on-demand period and both prophylaxis regimens were significant (P < 0.0001); no significant differences were observed between prophylaxis regimens (P = 0.22). Seven serious adverse events occurred in five subjects, none related to study drug. Results demonstrated that secondary prophylaxis therapy with nonacog alfa 50 IU kg(-1) twice weekly or 100 IU kg(-1) once weekly reduced ABR by 89.4% relative to on-demand treatment. Both prophylaxis regimens demonstrated favourable safety profiles in subjects with haemophilia B.

  20. An Exon-Specific U1snRNA Induces a Robust Factor IX Activity in Mice Expressing Multiple Human FIX Splicing Mutants

    Directory of Open Access Journals (Sweden)

    Dario Balestra

    2016-01-01

    Full Text Available In cellular models we have demonstrated that a unique U1snRNA targeting an intronic region downstream of a defective exon (Exon-specific U1snRNA, ExSpeU1 can rescue multiple exon-skipping mutations, a relevant cause of genetic disease. Here, we explored in mice the ExSpeU1 U1fix9 toward two model Hemophilia B-causing mutations at the 5′ (c.519A > G or 3′ (c.392-8T > G splice sites of F9 exon 5. Hydrodynamic injection of wt-BALB/C mice with plasmids expressing the wt and mutant (hFIX-2G5′ss and hFIX-8G3′ss splicing-competent human factor IX (hFIX cassettes resulted in the expression of hFIX transcripts lacking exon 5 in liver, and in low plasma levels of inactive hFIX. Coinjection of U1fix9, but not of U1wt, restored exon inclusion of variants and in the intrinsically weak FIXwt context. This resulted in appreciable circulating hFIX levels (mean ± SD; hFIX-2G5′ss, 1.0 ± 0.5 µg/ml; hFIX-8G3′ss, 1.2 ± 0.3 µg/ml; and hFIXwt, 1.9 ± 0.6 µg/ml, leading to a striking shortening (from ≃100 seconds of untreated mice to ≃80 seconds of FIX-dependent coagulation times, indicating a hFIX with normal specific activity. This is the first proof-of-concept in vivo that a unique ExSpeU1 can efficiently rescue gene expression impaired by distinct exon-skipping variants, which extends the applicability of ExSpeU1s to panels of mutations and thus cohort of patients.

  1. Effect of Surface Topography on Stress Concentration Factor

    Institute of Scientific and Technical Information of China (English)

    CHENG Zhengkun; LIAO Ridong

    2015-01-01

    Neuber rule and Arola-Ramulu model are widely used to predict the stress concentration factor of rough specimens. However, the height parameters and effective valley radius used in these two models depend strongly on the resolution of the roughness-measuring instruments and are easily introduce measuring errors. Besides, it is difficult to find a suitable parameter to characterize surface topography to quantitatively describe its effect on stress concentration factor. In order to overcome these disadvantages, profile moments are carried out to characterize surface topography, surface topography is simulated by superposing series of cosine components, the stress concentration factors of different micro cosine-shaped surface topographies are investigated by finite element analysis. In terms of micro cosine-shaped surface topography, an equation using the second profile moment to estimate the stress concentration factor is proposed, predictions for the stress concentration factor using the proposed expression are within 10% error compared with the results of finite element analysis, which are more accurate than other models. Moreover, the proposed equation is applied to the real surface topography machined by turning. Predictions for the stress concentration factor using the proposed expression are within 10% of the maximum stress concentration factors and about 5% of the effective stress concentration factors estimated from the finite element analysis for three levels of turning surface topographies under different simulated scales. The proposed model is feasible in predicting the stress concentration factors of real machined surface topographies.

  2. Concentration and flux of bioaerosol and environmental factors

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The concentration and flux transportation of bioaerosol are analyzed using the data observed in Nanjing in July 1998. Some results are obtained: (i) the concentration and flux transportation of bioaerosol vary periodically with the cycle of the solar radiation and atmospheric turbulent intensity, (ii) The bioaerosol concentration is affected by both the bioaerosol flux transportation and the environmental factors. The bacterial concentration is obviously affected by the solar radiation while the fungi concentration is significantly affected by temperature.

  3. Effects of subchronic exposures to concentrated ambient particles in mice. IX. Integral assessment and human health implications of subchronic exposures of mice to CAPs.

    Science.gov (United States)

    Lippmann, Morton; Gordon, Terry; Chen, Lung Chi

    2005-04-01

    In order to examine the biologic plausibility of adverse chronic cardiopulmonary effects in humans associated with ambient particulate matter (PM) exposure, we exposed groups of normal mice (C57) and knockout mice that develop atherosclerotic plaque (ApoE-/- and ApoE-/- LDLr-/-) for 6 h/day, 5 days/wk for 5 or 6 mo during the spring/summer of 2003 to either filtered air or 10-fold concentrated ambient particles (CAPs) in Tuxedo, NY (average PM2.5 concentration during exposure = 110 microg/m3). Some of the mice had implanted electrocardiographic monitors. We demonstrated that: (1) this complex interdisciplinary study was technically feasible in terms of daily exposure, collection of air quality monitoring data, the collection, analysis, and interpretation of continuous data on cardiac function, and the collection and analyses of tissues of the animals sacrificed at the end of the study; (2) the daily variations in CAPs were significantly associated, in ApoE-/- mice, with daily variations in cardiac functions; (3) there were significant differences between CAPs and sham-exposed ApoE-/- mice in terms of cardiac function after the end of exposure period, as well as small differences in atherosclerotic plaque density, coronary artery disease, and cell density in the substantia nigra in the brain in the ApoE-/- mice; (4) there are suggestive indications of gene expression changes for genes associated with the control of circadian rhythm in the ApoE-/- LDLr-/- double knockout (DK) mice. These various CAPs-related effects on cardiac function and the development of histological evidence of increased risk of clinically significant disease at the end of exposures in animal models of atherosclerosis provide biological plausibility for the premature mortality associated with PM2.5 exposure in human subjects and provide suggestive evidence for neurogenic disease as well.

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

    OpenAIRE

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

    2013-01-01

    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 f...

  5. A common G10430A mutation (Gly 60 Ser) in the factor IX gene describes the presence of moderate and mild hemophilia B in the majority of the Gujarati population.

    Science.gov (United States)

    Quadros, Leera; Ghosh, Kanjaksha; Shetty, Shrimati

    2007-05-01

    Hemophilia B is an X-linked recessively inherited bleeding disorder afflicting humans across all socio-economic as well as racial groups. A wide range of mutations showing high heterogeneity has been reported in different populations. Thus, it has been difficult to adopt a cost-effective strategy for the genetic diagnosis of hemophilia B families. We report the presence of a common G10430A mutation in exon d of the factor IX gene, wherein the highly conserved Gly 60 residue of the first epidermal growth like domain was changed to Ser in 22 out of 22 moderately severe to mild hemophilia B patients originating from Gujarat. None of the eight Gujarati severe hemophilia B patients, 30 normal Gujarati men, and 20 moderately severe to mild hemophilia B patients belonging to other communities showed the presence of this mutation. This mutation occurred in the same haplotype background thereby suggesting a 'founder effect.' The direct detection of this G10430A mutation can be used for accurate carrier detection and prenatal diagnosis in mild to moderate factor-IX-deficient patients belonging to the Gujarat state of western India.

  6. Oxygen Availability for Porphyrin Biosynthesis Enzymes Determines the Production of Protoporphyrin IX (PpIX during Hypoxia.

    Directory of Open Access Journals (Sweden)

    Shimpei Otsuka

    Full Text Available 5-Aminolevulinic acid (ALA, a precursor of porphyrin, is specifically converted to the fluorescent substance protoporphyrin IX (PpIX in tumors to be used as a prodrug for photodynamic therapy and diagnosis. Hypoxia, a common feature of solid tumors, decreases the efficacy of ALA-based photodynamic therapy and diagnosis. This decrease results from the excretion of porphyrin precursor coproporphyrinogen III (CPgenIII, an intermediate in the biosynthesis of PpIX. However, the mechanism of CPgenIII excretion during hypoxia remains unclear. In this study, we revealed the importance of mitochondrial respiration for the production of PpIX during hypoxia. Porphyrin concentrations were estimated in human gastric cancer cell lines by HPLC. Expression levels of porphyrin biosynthesis genes were measured by qRT-PCR and immunoblotting. Blockage of porphyrin biosynthesis was an oxygen-dependent phenomenon resulting from decreased PpIX production in mitochondria under hypoxic conditions. PpIX production was increased by the inhibition of mitochondrial respiration complexes, which indicates that the enzymes of porphyrin biosynthesis compete with respiration complexes for molecular oxygen. Our results indicate that targeting the respiration complexes is a rationale for enhancing the effect of ALA-mediated treatment and diagnosis.

  7. B19 parvovirus DNA in solvent/detergent-treated anti-haemophilia concentrates.

    Science.gov (United States)

    Lefrère, J J; Mariotti, M; Thauvin, M

    1994-01-22

    A transfusional B19 parvovirus infection may have severe consequences in immunocompromised hosts. The presence of B19 DNA was investigated with a polymerase chain reaction (PCR) assay in 30 batches of solvent/detergent-treated clotting factor concentrates (12 batches of factor VIII, 16 batches of factor IX, 1 batch of factor VII, and 1 batch of PPSB). B19 DNA was detected in 6 (20%) batches, including 3 factor VIII and 3 factor IX concentrates. Because of the frequency of B19 DNA in batches of clotting factors, measures to prevent transfusional risk of B19 infection via these blood products are justified, especially in recipients immunocompromised by HIV infection.

  8. Breakpoint of a balanced translocation (X:14) (q27.1;q32.3) in a girl with severe hemophilia B maps proximal to the factor IX gene.

    Science.gov (United States)

    Di Paola, J; Goldman, T; Qian, Q; Patil, S R; Schutte, B C; Schute, B C

    2004-03-01

    Hemophilia B is an X-linked bleeding disorder caused by the deficiency of coagulation factor (F)IX, with an estimated prevalence of 1 in 30 000 male births. It is almost exclusively seen in males with rare exceptions. We report a girl who was diagnosed with severe (PAC DNA probe, RP6-88D7 (which contains the FIX gene) hybridized only on the normal chromosome X as well as onto the derivative 14. Using a PAC DNA probe, RP11-963P9 that is located proximal to the FIX gene, we obtained signals on the normal and derivative X and also on the derivative 14. We conclude that the breakpoint is located within the DNA sequence of this clone mapping proximal to the FIX gene. Since the FIX gene seems to be intact in the derivative 14, the breakpoint may affect an upstream regulatory sequence that subjects the gene to position effect variegation (PEV).

  9. Effect of IX dosing on polypropylene and PVDF membrane fouling control

    KAUST Repository

    Myat, Darli Theint

    2013-07-01

    The performance of ion exchange (IX) resin for organics removal from wastewater was assessed using advanced characterisation techniques for varying doses of IX. Organic characterisation using liquid chromatography with a photodiode array (PDA) and fluorescence spectroscopy (Method A), and UV254, organic carbon and organic nitrogen detectors (Method B), was undertaken on wastewater before and after magnetic IX treatment. Results showed partial removal of the biopolymer fraction at high IX doses. With increasing concentration of IX, evidence for nitrogen-containing compounds such as proteins and amino acids disappeared from the LC-OND chromatogram, complementary to the fluorescence response. A greater fluorescence response of tryptophan-like proteins (278nm/343nm) for low IX concentrations was consistent with aggregation of tryptophan-like compounds into larger aggregates, either by self-aggregation or with polysaccharides. Recycling of IX resin through multiple adsorption steps without regeneration maintained the high level of humics removal but there was no continued removal of biopolymer. Subsequent membrane filtration of the IX treated waters resulted in complex fouling trends. Filtration tests with either polypropylene (PP) or polyvinylidene fluoride (PVDF) membranes showed higher rates of initial fouling following treatment with high IX doses (10mL/L) compared to filtration of untreated water, while treatment with lower IX doses resulted in decreased fouling rates relative to the untreated water. However, at longer filtration times the rate of fouling of IX treated waters was lower than untreated water and the relative fouling rates corresponded to the amount of biopolymer material in the feed. It was proposed that the mode of fouling changed from pore constriction during the initial filtration period to filter cake build up at longer filtration times. The organic composition strongly influenced the rate of fouling during the initial filtration period due to

  10. Utilization evaluation of factor concentration and frequencyof bleeds among patients with haemophilia "A" and haemophilia "B" in northwest Iran

    Directory of Open Access Journals (Sweden)

    Roya Dolatkhah

    2013-12-01

    Full Text Available Background Haemophilia A and B are X-linked bleeding disorders which result in decreased blood levels of coagulants. According to some studies, Hemophilia Severity Score (HSS is higher in severe Haemophilia A(HA than in severe Haemophilia B(HB. Objectives The aim of this study was comparison of bleed frequency and utilization of factor concentrate between HA and HB patients. Materials/Patients and Methods This is a single institution retrospective study, and we gathered information from records of our Hemophilia Clinic .Our samples consisted of 176 Haemophilia A and 35 Haemophilia B severe and moderate deficient patients. All of our patients used on-demand treatment with plasma derived factor concentrates. Chi-Square , one sample T and Mann-Whitney U tests were used. All the calculations were performed with MedCalc Statistical Software 12.1.4 version. Results Overall admission rates for patients with Haemophilia A were 3.125/patient/year and for Haemophilia B were 0.77/patient/year (P<0.05.The amount of factor concentrates used by our HA patient was 3731500IU of FVIII (21201.704 IU/patient/year, and 611000 IU of Factor IX , by patients with hemophilia B(17457.142 IU/patient/year.The difference in the usage of factor concentrate was not statistically significant (P=0.57. Conclusion The data suggest that the two inherited coagulation disorders (Haemophilia A and Haemophilia B have a different severity of clinical phenotype. Our findings correlate with findings by some other similar studies that have been published recently.

  11. Apoptosis of THP-1 macrophages induced by protoporphyrin IX-mediated sonodynamic therapy

    Directory of Open Access Journals (Sweden)

    Guo S

    2013-06-01

    Full Text Available Shuyuan Guo,1* Xin Sun,1,2* Jiali Cheng,1 Haobo Xu,1 Juhua Dan,2 Jing Shen,3 Qi Zhou,4 Yun Zhang,1 Lingli Meng,1 Wenwu Cao,4,5 Ye Tian1,2 1Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, People's Republic of China; 2Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin, People's Republic of China; 3Division of Oncology, the Third Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China; 4Laboratory of Photo- and Sono-theranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, People's Republic of China; 5Department of Mathematics and Materials Research Institute, Pennsylvania State University, University Park, PA, USA *These authors contributed equally to this work Background: Sonodynamic therapy (SDT was developed as a localized ultrasound-activated cytotoxic therapy for cancer. The ability of SDT to destroy target tissues selectively is especially appealing for atherosclerotic plaque, in which selective accumulation of the sonosensitizer, protoporphyrin IX (PpIX, had been demonstrated. Here we investigate the effects of PpIX-mediated SDT on macrophages, which are the main culprit in progression of atherosclerosis. Methods and results: Cultured THP-1 derived macrophages were incubated with PpIX. Fluorescence microscopy showed that the intracellular PpIX concentration increased with the concentration of PpIX in the incubation medium. MTT assay demonstrated that SDT with PpIX significantly decreased cell viability, and this effect increased with duration of ultrasound exposure and PpIX concentration. PpIX-mediated SDT induced both apoptosis and necrosis, and the maximum apoptosis to necrosis ratio was obtained after SDT with 20 µg/mL PpIX and five minutes of sonication

  12. Investigating Factors that Affect Dissolved Oxygen Concentration in Water

    Science.gov (United States)

    Jantzen, Paul G.

    1978-01-01

    Describes activities that demonstrate the effects of factors such as wind velocity, water temperature, convection currents, intensity of light, rate of photosynthesis, atmospheric pressure, humidity, numbers of decomposers, presence of oxidizable ions, and respiration by plants and animals on the dissolved oxygen concentration in water. (MA)

  13. Variance of indoor radon concentration: Major influencing factors.

    Science.gov (United States)

    Yarmoshenko, I; Vasilyev, A; Malinovsky, G; Bossew, P; Žunić, Z S; Onischenko, A; Zhukovsky, M

    2016-01-15

    Variance of radon concentration in dwelling atmosphere is analysed with regard to geogenic and anthropogenic influencing factors. Analysis includes review of 81 national and regional indoor radon surveys with varying sampling pattern, sample size and duration of measurements and detailed consideration of two regional surveys (Sverdlovsk oblast, Russia and Niška Banja, Serbia). The analysis of the geometric standard deviation revealed that main factors influencing the dispersion of indoor radon concentration over the territory are as follows: area of territory, sample size, characteristics of measurements technique, the radon geogenic potential, building construction characteristics and living habits. As shown for Sverdlovsk oblast and Niška Banja town the dispersion as quantified by GSD is reduced by restricting to certain levels of control factors. Application of the developed approach to characterization of the world population radon exposure is discussed.

  14. Geochemical factors controlling free Cu ion concentrations in river water

    Science.gov (United States)

    Rozan, Tim F.; Benoit, Gaboury

    1999-10-01

    Copper speciation was determined monthly at seven sites on four rivers in southern New England to understand which geochemical factors control free metal ion concentrations in river water. Samples were conventionally filtered (stripping voltammetry (DPASV) was used to quantify natural organic complexation and cathodic stripping square wave voltammetry (CSSWV) to measure directly both Cu sulfide complexes and total EDTA concentrations. The results showed both dissolved organic matter (DOM) and sulfide complexation dominate Cu speciation and control the concentrations of free ion. Free Cu2+ was calculated to be in the subnanomolar range for the majority of the year. Only in the winter months, when concentrations of DOM and metal sulfides complexes were at a minimum were free metal ions directly measurable by DPASV at low nanomolar concentrations. The extent of sulfide complexation appears to be dominated by the size of headwater marshes (upstream sampling sites) and by the amount of sewage treatment plant effluent (downstream sites). DOM complexation was related to the organic matter composition and followed model organic ligands. Indirect evidence suggests variations in river water pH and Ca2+ (metal competition) has only a minor role in Cu complexation. Measured concentrations of total EDTA suggest this synthetic ligand can control Cu speciation in some highly developed watersheds; however, competition from Ni (and possibly Fe) limits the extent of this complexation.

  15. Topical glycerol monooleate/propylene glycol formulations enhance 5-aminolevulinic acid in vitro skin delivery and in vivo protophorphyrin IX accumulation in hairless mouse skin.

    Science.gov (United States)

    Steluti, Regilene; De Rosa, Fernanda Scarmato; Collett, John; Tedesco, Antônio Cláudio; Bentley, Maria Vitória Lopes Badra

    2005-08-01

    Photodynamic therapy (PDT), a potential therapy for cancer treatment, utilizes exogenously applied or endogenously formed photosensitizers, further activated by light in an appropriate wavelength and dose to induce cell death through free radical formation. 5-Aminolevulinic acid (5-ALA) is a pro-drug which can be converted to the effective photosensitizer, protoporphyrin IX (PpIX). However, the use of 5-ALA in PDT is limited by the low penetration capacity of this highly hydrophilic molecule into appropriate skin layers. In the present study, we propose to increase 5-ALA penetration by using formulations containing glycerol monooleate (GMO), an interesting and useful component of pharmaceutical formulations. Propylene glycol solutions containing different concentrations of GMO significantly increased the in vitro skin permeation/retention of 5-ALA in comparison to control solutions. In vivo studies also showed increased PpIX accumulation in mouse hairless skin, after the use of topical 5-ALA formulations containing GMO in a concentration-dependent manner. The results show that skin 5-ALA penetration and PpIX accumulation, important factors for the success of topical 5-ALA-PDT in skin cancer, are optimized by GMO/propylene glycol formulations.

  16. Photosensitizing effect of hematoporphyrin IX on immature stages of Ceratitis capitata (Diptera: Tephritidae).

    Science.gov (United States)

    Pujol-Lereis, Luciana Mercedes; Massaldi, Ana; Rabossi, Alejandro; Quesada-Allué, Luis Alberto

    2010-01-01

    Immature stages of Ceratitis capitata were tested as a model for hematoporphyrin IX (HP IX) phototoxicity. The lethal concentration 50 (LC(50)) of HP IX in the food was determined during postembryonic development until adult emergence as 0.173 mm (95% CI: 0.138-0.209). The corresponding HP IX LC(50) during the dispersal period alone was 0.536 mm (95% CI: 0.450-0.633). HP IX toxicity was compared against Phloxine B (PhB) (0.5 mm). HP IX elicited a mortality of 90.87%, which was mainly concentrated during prepupal and early pupal stages. PhB mortality was much lower (56.88%) and occurred mainly during the adult pharate stage. A direct correlation between light-dependent HP IX mortality, evidence of reactive oxygen species (ROS) and lipid peroxidation (conjugated dienes and thiobarbituric acid reactive substances) was established in C. capitata larvae. ROS were found to be very significant in both the brain and in the gut.

  17. Evaluating the displacement amplification factors of concentrically braced steel frames

    Science.gov (United States)

    Mahmoudi, Mussa; Zaree, Mahdi

    2013-12-01

    According to seismic design codes, nonlinear performance of structures is considered during strong earthquakes. Seismic design provisions estimate the maximum roof and story drifts occurring during major earthquakes by amplifying the drifts computed from elastic analysis at the prescribed seismic force level with a displacement amplification factor. The present study tries to evaluate the displacement amplification factors of conventional concentric braced frames (CBFs) and buckling restrained braced frames (BRBFs). As such, static nonlinear (pushover) analysis and nonlinear dynamic time history analysis have been performed on the model buildings with single and double bracing bays, and different stories and brace configurations (chevron V, invert V, and X bracing). It is observed that the displacement amplification factors for BRBFs are higher than that of CBFs. Also, the number of bracing bays and height of buildings have a profound effect on the displacement amplification factors. The evaluated ratios between displacement amplification factors and response modification factors are from 1 to 1.12 for CBFs and from 1 to 1.4 for BRBFs.

  18. Hemoglobin concentrations and associated factors in adolescentes from Recife, Brazil

    Directory of Open Access Journals (Sweden)

    Elisângela Barros Soares Mendonça

    2014-10-01

    Full Text Available OBJECTIVE: To estimate the prevalence of anemia and associated factors in adolescents from the city of Recife in Pernambuco state. METHODS: This is a cross-sectional study, involving a random sample of 256 adolescents of both genders, aged 13 to 18, whose hemoglobin concentrations were evaluated, along with their nutritional status and socioeconomic and demographic characteristics. RESULTS: The prevalence of inadequate hemoglobin concentrations was 10.2% [CI95%=6.7-14.5], reaching levels considered as mild anemia (9 g/dL 0.05, nor with socioeconomic or demographic characteristics (p>0.05. CONCLUSION: Although the prevalence of anemia was low and classified as a mild health problem, preventive nutrition education involving the dissemination of healthy eating habits in schools and encouraging the consumption of iron-rich foods are strongly recommended.

  19. Factors affecting pollutant concentrations in the near-road environment

    Science.gov (United States)

    Baldwin, Nichole; Gilani, Owais; Raja, Suresh; Batterman, Stuart; Ganguly, Rajiv; Hopke, Philip; Berrocal, Veronica; Robins, Thomas; Hoogterp, Sarah

    2015-08-01

    An improved understanding of traffic-related air pollutants is needed to estimate exposures and adverse health impacts in traffic corridors and near-road environments. In this study, concentrations of black carbon (BC), nitrogen oxides (NO, NO2, NOx), sulfur dioxide (SO2), and particulate matter (PM2.5, PM10, ultrafine particles, and accumulation mode particles, AMP) were measured using a mobile air pollutant laboratory along nine transects across major roads in Detroit, MI in winter 2012. Repeated measurements were taken during rush-hour periods at sites in residential neighborhoods located 50-500 m from both sides of the road. Concentration gradients attributable to on-road emissions were estimated by accounting for traffic volume and mix, wind speed, wind direction, and background concentrations. BC, NO, NOx, and UFP had the strongest gradients, and elevated concentrations of NOx, NO2, PM2.5 and PM10, as well as decreased particle size, were found at the 50 m sites compared to background levels. Exponential models incorporating effects of road size, wind speed, and up- and downwind distance explained from 31 to 53% of the variability in concentration gradients for BC, NO, NOx, UFP and particle size. The expected concentration increments 50 m from the study roads were 17.0 ppb for NO, 17.7 ppb for NOx, 2245 particles/cm3 for UFP, and 0.24 μg/m3 for BC, and the expected distance to decrease increments by half was 89-129 m in the downwind direction, and 14-20 m in the upwind direction. While accounting for portion of the temporal and spatial variability across transects and measurement periods, these results highlight the influence of road-to-road differences and other locally-varying factors important in urban and industrial settings. The study demonstrates a methodology to quantify near-road concentrations and influences on these concentrations while accounting for temporal and spatial variability, and it provides information useful for estimating exposures of

  20. [Two-photon excitation fluorescence of 5-ALA induced PpIX in DHL cells].

    Science.gov (United States)

    Huang, Zu-Fang; Chen, Rong; Li, Yong-Zeng; Chen, Guan-Nan; Chen, Xian-Ling; Feng, Shang-Yuan; Jia, Pei-Min

    2008-11-01

    Two-photon fluorescence microscopy is a novel imaging technique, which is primarily sensitive to a specimen's response coming from an in-focus plane, thus has low photo-bleaching and photo-damage to biological samples. 5-ALA induced production of PpIX in DHL cells was excited by 820 nm femtosecond laser; two-photon excitation fluorescence of single cell was obtained in Lambda mode of laser scanning confocal microscope. The specific fluorescence intensity of PpIX which accumulated in DHL cells was measured at 2, 4 and 10 mmol x L(-1) concentration of 5-ALA with different incubation time, which reflected the kinetics of 5-ALA accumulated in DHL cells. Accumulation of PpIX in DHL cells was a dynamic change process. Biphasic alterations of PpIX accumulation were noted: PpIX content enhanced with the increasing time and reached the maximal value around 3 h, however PpIX content decreased in the subsequent incubation time. Results indicate that two-photon fluorescence based on laser scanning microscope can be a useful technology for studying the kinetics of 5-ALA induced PpIX production in DHL cells and other leukemia cells.

  1. Decreased plasma brain-derived neurotrophic factor and vascular endothelial growth factor concentrations during military training.

    Directory of Open Access Journals (Sweden)

    Go Suzuki

    Full Text Available Decreased concentrations of plasma brain-derived neurotrophic factor (BDNF and serum BDNF have been proposed to be a state marker of depression and a biological indicator of loaded psychosocial stress. Stress evaluations of participants in military mission are critically important and appropriate objective biological parameters that evaluate stress are needed. In military circumstances, there are several problems to adopt plasma BDNF concentration as a stress biomarker. First, in addition to psychosocial stress, military missions inevitably involve physical exercise that increases plasma BDNF concentrations. Second, most participants in the mission do not have adequate quality or quantity of sleep, and sleep deprivation has also been reported to increase plasma BDNF concentration. We evaluated plasma BDNF concentrations in 52 participants on a 9-week military mission. The present study revealed that plasma BDNF concentration significantly decreased despite elevated serum enzymes that escaped from muscle and decreased quantity and quality of sleep, as detected by a wearable watch-type sensor. In addition, we observed a significant decrease in plasma vascular endothelial growth factor (VEGF during the mission. VEGF is also neurotrophic and its expression in the brain has been reported to be up-regulated by antidepressive treatments and down-regulated by stress. This is the first report of decreased plasma VEGF concentrations by stress. We conclude that decreased plasma concentrations of neurotrophins can be candidates for mental stress indicators in actual stressful environments that include physical exercise and limited sleep.

  2. Evaluation of ALA-induced PpIX as a photosensitizer for PDT in cats

    Science.gov (United States)

    Lucroy, Michael D.; Edwards, Benjamin F.; Peavy, George M.; Krasieva, Tatiana B.; Griffey, Stephen M.; Madewell, Bruce R.

    1998-07-01

    Given exogenously, ALA defeats intrinsic regulatory feedback mechanisms allowing intracellular accumulation of protoporphyrin IX (PpIX), a highly efficient photosensitizer. In vivo, PpIX synthesis in neoplastic mammary tissues averages 20-fold higher than in normal mammary tissues. PpIX is retained intracellularly, unlike perivascular localization of other photosensitizers, and it is then cleared quickly from the body. In vitro, ALA induced PpIX production in our laboratory in 6 cell lines tested, including an established feline kidney cell line and dermal fibroblasts from primary skin biopsy explant, resulting in photosensitization. Fluorescent microscopy confirmed PpIX production in skin adnexae following ALA administration in a normal cat. To evaluate toxicity, three cats were treated with a single i.v. dose of ALA (either 100, 200, of 400 mg/kg) and followed for 7 days. Cats receiving 100 or 200 mg/kg ALA i.v. had elevated liver enzymes and bilirubin within 24 hours. Histopathology revealed hydropic changes in the liver and renal fibrosis. The cat receiving 400 mg/kg ALA intravenously had cutaneous flush, bradycardia and apnea associated with ALA administration; within 24 hours the cat was lethargic, anorectic and icteric. ALT, AST and bilirubin concentrations had increased significantly. At necropsy the liver had a prominent lobular pattern; histopathology revealed severe periportal hepatitis and splenic necrosis. Systemically administered ALA induces PpIX production, but toxicity may preclude its clinical application in the cat. PpIX levels seem to be more time dependent than those dependent at these three ALA doses and they are well beyond the saturation point for adequate PpIX conversion. The literature is scant regarding toxicity associated with parenteral administration of ALA.

  3. Recombinant human insulin IX. Investigation of factors, influencing the folding of fusion protein-S-sulfonates, biotechnological precursors of human insulin.

    Science.gov (United States)

    Tikhonov, Roman V; Pechenov, Sergey E; Belacheu, Irina A; Yakimov, Sergey A; Klyushnichenko, Vadim E; Tunes, Heloisa; Thiemann, Josef E; Vilela, Luciano; Wulfson, Andrey N

    2002-11-01

    The peculiarities of molecular structures and the influence of reaction conditions on the folding efficiency of fusion proteins-biotechnological precursors of human insulin, expressed in Escherichia coli as inclusion bodies have been investigated. The fusion proteins contained proinsulin sequence with various leader peptides connected by an Arg residue to the insulin B-chain. The kind and the size of leader peptide do not have essential influence on folding efficiency. However, the efficiency of protein folding depends on the location of the (His)6 site, which is used for metal-chelating affinity chromatography. In our study the protein folding depends on the reaction medium composition (including additives), the presence of accompanied cell components, pH, temperature, concentrations of protein, and redox agents. A negative influence of nucleic acid and heavy metal ions on folding has been found. S-sulfonated fusion protein has proinsulin-like secondary structure (by CD-spectroscopy data) that is the key point for 95% efficient folding proceeding. Folded fusion proteins are transformed into insulin by enzymatic cleavage.

  4. Efficacy and safety of a recombinant factor IX (Bax326) in previously treated patients with severe or moderately severe haemophilia B undergoing surgical or other invasive procedures: a prospective, open-label, uncontrolled, multicentre, phase III study.

    Science.gov (United States)

    Windyga, J; Lissitchkov, T; Stasyshyn, O; Mamonov, V; Ghandehari, H; Chapman, M; Fritsch, S; Wong, W-Y; Pavlova, B G; Abbuehl, B E

    2014-09-01

    Haemostatic management of haemophilia B patients undergoing surgery is critical to patient safety. The aim of this ongoing prospective trial was to investigate the haemostatic efficacy and safety of a recombinant factor IX (rFIX) (Bax326) in previously treated subjects (12-65 years, without history of FIX inhibitors) with severe or moderately severe haemophilia B, undergoing surgical, dental or other invasive procedures. Haemostatic efficacy was assessed according to a predefined scale. Blood loss was compared to the average and maximum blood loss predicted preoperatively. Haemostatic FIX levels were achieved peri- and postoperatively in 100% of subjects (n = 14). Haemostasis was 'excellent' intraoperatively in all patients and postoperatively in those without a drain, and 'excellent' or 'good' at the time of drain removal and day of discharge in those with a drain employed. Following the initial dose, the mean FIX activity level rose from 6.55% to 107.58% for major surgeries and from 3.60% to 81.4% for minor surgeries. Actual vs. predicted blood loss matched predicted intraoperative blood loss but was equal to or higher than (but less than 150%) the maximum predicted postoperative blood loss reflecting the severity of procedure and FIX requirements. There were no related adverse events, severe allergic reactions or thrombotic events. There was no evidence that BAX326 increased the risk of inhibitor or binding antibody development to FIX. BAX326 was safe and effective for peri-operative management of 14 subjects with severe and moderately severe haemophilia B.

  5. Pharmacokinetics, efficacy and safety of BAX326, a novel recombinant factor IX: a prospective, controlled, multicentre phase I/III study in previously treated patients with severe (FIX level <1%) or moderately severe (FIX level ≤2%) haemophilia B.

    Science.gov (United States)

    Windyga, J; Lissitchkov, T; Stasyshyn, O; Mamonov, V; Rusen, L; Lamas, J L; Oh, M-S; Chapman, M; Fritsch, S; Pavlova, B G; Wong, W-Y; Abbuehl, B E

    2014-01-01

    BAX326 is a recombinant factor IX (rFIX; nonacog gamma) manufactured without the addition of any materials of human or animal origin, and with two viral inactivation steps (solvent/detergent treatment and 15 nm nanofiltration). The aim of this prospective trial was to investigate the pharmacokinetics, haemostatic efficacy and safety of BAX326 in previously treated patients aged 12-65 years with severe or moderately severe haemophilia B. BAX326 was safe and well tolerated in all 73 treated subjects; adverse events considered related to treatment (2.7% incidence, all non-serious) were transient and mild, and no hypersensitivity reactions, inhibitor formation or thrombotic events were observed. Pharmacokinetic (PK) equivalence (n = 28) between BAX326 and a licensed rFIX was confirmed in terms of the ratio of geometric mean AUC(0-72) h per dose. Twice-weekly prophylaxis [mean duration 6.2 (±0.7) months; 1.8 (±0.1) infusions per week, 49.5 (±4.8) IU kg(-1) per infusion] was effective in preventing bleeding episodes, with a significantly lower (79%, P < 0.001) annualized bleed rate (4.2) compared to an on-demand treatment in a historical control group (20.0); 24 of 56 subjects on prophylaxis (43%) did not bleed throughout the study observation period. Of 249 total acute bleeds, 211 (84.7%) were controlled with one to two infusions of BAX326. Haemostatic efficacy at resolution of bleed was rated excellent or good in 96.0% of all treated bleeding episodes. The results of this study indicate that BAX326 is safe and efficacious in treating bleeds and routine prophylaxis in patients aged 12 years and older with haemophilia B.

  6. Factors affecting plasma aluminum concentrations in nonexposed workers

    Energy Technology Data Exchange (ETDEWEB)

    House, R.A. (Department of Occupational and Environmental Health, St Michael' s Hospital, University of Toronto, Ontario (Canada))

    1992-10-01

    In this study, the distribution and determinants of plasma aluminum concentrations were examined in 71 office employees not occupationally exposed to aluminum. The samples were analyzed by Zeeman graphite furnace atomic absorption spectroscopy and were found to be log normally distributed. After using the International Federation of Clinical Chemistry (IFCC) recommended procedure for removal of likely aberrant values, the 95th percentile value was 198 nmol/L (90% CI:165-238); when those using antacids were also excluded, the 95th percentile value fell to 175 nmol/L (90% CI:147-208). Multiple regression analysis indicated that the factors most predictive of log plasma aluminum were the batch in which the sample was analyzed and the use of antacids containing aluminum. The statistical significance of the batch variable likely indicates the well-recognized problem of contamination in sampling and analyzing aluminum.35 references.

  7. Predicting DUI recidivism: blood alcohol concentration and driver record factors.

    Science.gov (United States)

    Marowitz, L A

    1998-07-01

    This study examined the relationship between blood alcohol concentration (BAC) at arrest, driving history and other demographic factors, and the 1-year post-arrest probability of recidivism for drunk driving (DUI) convictees. Complex and simple prediction models were developed. All models found a statistically significant cubic relationship between BAC and recidivism, reflecting a relatively high rate of recidivism at a BAC of 0.00%, decreasing to a minimum at ca 0.09% BAC, then increasing to another relatively high rate at a BAC of ca 0.29%, followed by a decline in recidivism to BAC levels of 0.35% and beyond. High rates of recidivism at high BACs suggest alcohol dependency, while high rates at low BACs suggest the involvement of other impairing substances. The rate of DUI recidivism for offenders who refused alcohol testing was the same as for aggregated BAC-tested offenders who had prior DUIs at the time of the arrest. The probability of DUI recidivism predicted by a simple model using BAC, prior 2-year traffic convictions, and offender level (first or repeat offender) could be used along with other factors by presentence investigators, judges or in administrative settings to determine appropriate sanctions, treatment or other remedial measures. The findings support the notion that first offenders with high BAC levels and prior 2-year traffic convictions are at as high a risk of recidivating as many repeat offenders, and might therefore benefit from similar sanctions and/or remedial treatment. The findings also support viewing DUI arrestees with very low BACs as probable drug users with relatively high probabilities of recidivating.

  8. Geological factors controlling radon hazardous concentration in groundwater

    Science.gov (United States)

    Przylibski, T. A.

    2009-04-01

    Radon waters are classified as waters containing more than 100 Bq/L of Rn-222. In many regions radon groundwaters are commonly used as a tap waters. Exploitation of radon groundwater without removing radon out of water in the intake may be hazardous for the consumers. Radon removing is relatively simple and cheap, and may be achieved trough the degassing of tapped water. The following factors are crucial for the genesis of radon (Rn-222) and changes in its concentration in groundwaters: the content of parent Ra-226 in the reservoir rock, the emanation coefficient of the reservoir rock, mixing of various groundwater components. Simplifying the geochemical characterisctics of Ra-226, one can say that the highest radium contents outside uranium deposits could be expected above all in crystalline rocks such as granites, ryolites and gneisses, and among sedimentary rocks - in fine-grained rocks - mudstones and clay rocks. Therefore the highest content of Rn-222 is characteristic of groundwaters flowing through the abovementioned rocks. What is very important for the genesis of groundwater dissolved Rn-222 is not only the total content of Ra-226 in the aquifer, but also the distribution of this isotope's atoms in relation to the surface of mineral grains (crystals) and crack surfaces. Only if Ra-226 atoms lie in the outer zone of grains (crystals), they can be the source of Rn-222 atoms released directly or indirectly into pores and fissures. If the pores and fissures are filled with free groundwater, then the radon dissolved in this water can migrate with it. Therefore particularly high Rn-222 concentration values can be expected in groundwaters circulating in zones of strongly cracked reservoir rocks, i.e. in the weathering zone, reaching the depth of several dozen meters below ground surface, as well as in zones of brittle tectonic deformations. The number of Rn-222 atoms formed in groundwater as a result of the decay of Ra-226 ion (Ra2+) dissolved in this water

  9. Factors Impeding Enzymatic Wheat Gluten Hydrolysis at High Solid Concentrations

    NARCIS (Netherlands)

    Hardt, N.A.; Janssen, A.E.M.; Boom, R.M.; Goot, van der A.J.

    2014-01-01

    Enzymatic wheat gluten hydrolysis at high solid concentrations is advantageous from an environmental and economic point of view. However, increased wheat gluten concentrations result in a concentration effect with a decreased hydrolysis rate at constant enzyme-to-substrate ratios and a decreased

  10. Quantum Supersymmetric Bianchi IX Cosmology

    CERN Document Server

    Damour, Thibault

    2014-01-01

    We study the quantum dynamics of a supersymmetric squashed three-sphere by dimensionally reducing to one timelike dimension the action of D=4 simple supergravity for a Bianchi IX cosmological model. After imposition of the diffeomorphism constraints, the wave function of the Universe becomes a spinor of Spin(8,4) depending on the three squashing parameters, which satisfies Dirac, and Klein-Gordon-like, wave equations describing the propagation of a quantum spinning particle reflecting off spin-dependent potential walls. The algebra of the susy constraints and of the Hamiltonian one is found to close. One finds that the quantum Hamiltonian is built from operators that generate a 64-dimensional representation of the maximally compact sub-algebra of the rank-3 hyperbolic Kac-Moody algebra AE3. The (quartic-in-fermions) squared-mass term entering the Klein-Gordon-like equation has several remarkable properties: 1)it commutes with all the other (Kac-Moody-related) building blocks of the Hamiltonian; 2)it is a quad...

  11. Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis

    Science.gov (United States)

    Kanick, Stephen Chad; Davis, Scott C.; Zhao, Yan; Hasan, Tayyaba; Maytin, Edward V.; Pogue, Brian W.; Chapman, M. Shane

    2014-01-01

    Abstract. Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for the background optical properties. Measurements in tissue phantoms showed accurate recovery of blood volume fraction and reduced scattering coefficient from WLS, and a linear response of PpIX fluorescence versus concentration down to 1.95 and 250 nM for blue and red excitations, respectively. A pilot clinical study of 19 patients receiving 1-h ALA incubation before treatment showed high intrinsic variance in PpIX fluorescence with a standard deviation/mean ratio of >0.9. PpIX fluorescence was significantly higher in patients reporting higher pain levels on a visual analog scale. These pilot data suggest that patient-specific PpIX quantitation may predict outcome response. PMID:24996661

  12. Radium concentration factors and their use in health and environmental risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Meinhold, A.F.; Hamilton, L.D.

    1991-01-01

    Radium is known to be taken up by aquatic animals, and tends to accumulate in bone, shell and exoskeleton. The most common approach to estimating the uptake of a radionuclide by aquatic animals for use in health and environmental risk assessments is the concentration factor method. The concentration factor method relates the concentration of a contaminant in an organism to the concentration in the surrounding water. Site specific data are not usually available, and generic, default values are often used in risk assessment studies. This paper describes the concentration factor method, summarizes some of the variables which may influence the concentration factor for radium, reviews reported concentration factors measured in marine environments and presents concentration factors derived from data collected in a study in coastal Louisiana. The use of generic default values for the concentration factor is also discussed.

  13. Radium concentration factors and their use in health and environmental risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Meinhold, A.F.; Hamilton, L.D.

    1991-12-31

    Radium is known to be taken up by aquatic animals, and tends to accumulate in bone, shell and exoskeleton. The most common approach to estimating the uptake of a radionuclide by aquatic animals for use in health and environmental risk assessments is the concentration factor method. The concentration factor method relates the concentration of a contaminant in an organism to the concentration in the surrounding water. Site specific data are not usually available, and generic, default values are often used in risk assessment studies. This paper describes the concentration factor method, summarizes some of the variables which may influence the concentration factor for radium, reviews reported concentration factors measured in marine environments and presents concentration factors derived from data collected in a study in coastal Louisiana. The use of generic default values for the concentration factor is also discussed.

  14. El Titulo IX y La Discriminacion por Sexo (Title IX and Sex Discrimination).

    Science.gov (United States)

    Office for Civil Rights (ED), Washington, DC.

    Title IX of the Education Amendments of 1972 protects people from discrimination based on sex in education programs or activities that receive Federal financial assistance. This brochure outlines the responsibilities of education programs and activities covered by Title IX, the responsibilities of the Office for Civil Rights (OCR) in enforcing…

  15. Modeling the Factors Impacting Pesticide Concentrations in Groundwater Wells.

    Science.gov (United States)

    Aisopou, Angeliki; Binning, Philip J; Albrechtsen, Hans-Jørgen; Bjerg, Poul L

    2015-01-01

    This study examines the effect of pumping, hydrogeology, and pesticide characteristics on pesticide concentrations in production wells using a reactive transport model in two conceptual hydrogeologic systems; a layered aquifer with and without a stream present. The pumping rate can significantly affect the pesticide breakthrough time and maximum concentration at the well. The effect of the pumping rate on the pesticide concentration depends on the hydrogeology of the aquifer; in a layered aquifer, a high pumping rate resulted in a considerably different breakthrough than a low pumping rate, while in an aquifer with a stream the effect of the pumping rate was insignificant. Pesticide application history and properties have also a great impact on the effect of the pumping rate on the concentration at the well. The findings of the study show that variable pumping rates can generate temporal variability in the concentration at the well, which helps understanding the results of groundwater monitoring programs. The results are used to provide guidance on the design of pumping and regulatory changes for the long-term supply of safe groundwater. The fate of selected pesticides is examined, for example, if the application of bentazone in a region with a layered aquifer stops today, the concentration at the well can continue to increase for 20 years if a low pumping rate is applied. This study concludes that because of the rapid response of the pesticide concentration at the drinking water well due to changes in pumping, wellhead management is important for managing pesticide concentrations.

  16. Modeling the Factors Impacting Pesticide Concentrations in Groundwater Wells

    DEFF Research Database (Denmark)

    Aisopou, Angeliki; Binning, Philip John; Albrechtsen, Hans-Jørgen

    2015-01-01

    variability in the concentration at the well, which helps understanding the results of groundwater monitoring programs. The results are used to provide guidance on the design of pumping and regulatory changes for the long-term supply of safe groundwater. The fate of selected pesticides is examined......, for example, if the application of bentazone in a region with a layered aquifer stops today, the concentration at the well can continue to increase for 20 years if a low pumping rate is applied. This study concludes that because of the rapid response of the pesticide concentration at the drinking water well......This study examines the effect of pumping, hydrogeology, and pesticide characteristics on pesticide concentrations in production wells using a reactive transport model in two conceptual hydrogeologic systems; a layered aquifer with and without a stream present. The pumping rate can significantly...

  17. Modeling the Factors Impacting Pesticide Concentrations in Groundwater Wells

    DEFF Research Database (Denmark)

    Aisopou, Angeliki; Binning, Philip John; Albrechtsen, Hans-Jørgen;

    2015-01-01

    This study examines the effect of pumping, hydrogeology, and pesticide characteristics on pesticide concentrations in production wells using a reactive transport model in two conceptual hydrogeologic systems; a layered aquifer with and without a stream present. The pumping rate can significantly...... affect the pesticide breakthrough time and maximum concentration at the well. The effect of the pumping rate on the pesticide concentration depends on the hydrogeology of the aquifer; in a layered aquifer, a high pumping rate resulted in a considerably different breakthrough than a low pumping rate......, while in an aquifer with a stream the effect of the pumping rate was insignificant. Pesticide application history and properties have also a great impact on the effect of the pumping rate on the concentration at the well. The findings of the study show that variable pumping rates can generate temporal...

  18. Concentration Variations of Growth Factors in Colostrum and Normal Milk of Sows

    Institute of Scientific and Technical Information of China (English)

    LI Yao; SHAN An-shan; FENG Zi-ke

    2004-01-01

    An experiment was conducted to determine the concentration variation of epidermal growth factors (EGF), include insulin-like growth factor - Ⅰ (IGF- I ), transforming growth factor-beta(TGF-β), and basic fibroblast growth factor (bFGF) in colostrum and normal milk of sows within 35 days after parturition. The results showed that the concentration of EGF, IGF- I , TGF-β, bFGF was significantly higher in colostrum than that in normal milk. The concentration of these growth factors in colostrum was significantly decreased with the stage lapse of lactation, and then they remained stable in normal milk. Parity had a slight effect on the concentration of these growth factors.

  19. Factors affecting the concentrations of heavy metals in precipitation of Tehran using factor analysis method

    Directory of Open Access Journals (Sweden)

    H Kamani

    2016-03-01

    Full Text Available Backgrounds and Objectives: Quantity of trace metals in the wet precipitation can illustrate the environmental pollution of different urban areas. Up to now, there is no study regarding the chemistry of wet precipitation in Tehran .The objectives of this study are: measurement of heavy metal concentrations and identification of the main factors affecting the heavy metal concentrations in wet precipitation using factor analysis method. Materials and Methods: This was a cross-sectional study in which measurements of heavy metals were performed in 53 wet precipitation samples collected from a central site of Tehran City, capital of Iran. The samples were collected during November to May in 2010, 2011 and 2012 on the roof of the student’s dormitory building of Tehran University of Medical Sciences and then the concentration of heavy metals in each sample was measured with ICP-MS. Results: pH ranged from 4.2 to 7.1 with a mean value of 5.1 indicating in acidic range. Result of EF calculations revealed that samples were not enriched with Fe and Cr but were enriched with Zn, Cd, Ni, Pb and Cu. Factor Component Analysis with Varimax normalized rotation showed Al, Fe and Cr are originated from crustal source and Zn, Cd, Ni, Pb and Cu are originated from anthropogenic sources.  Conclusion: EF and acidic pH values indicate Tehran is under the influence of extremely anthropogenic activities. Large number of vehicles and industrial activity in the city are undoubtedly responsible for the emission of a wide range of pollution.

  20. Quantum supersymmetric Bianchi IX cosmology

    Science.gov (United States)

    Damour, Thibault; Spindel, Philippe

    2014-11-01

    We study the quantum dynamics of a supersymmetric squashed three-sphere by dimensionally reducing (to one timelike dimension) the action of D =4 simple supergravity for a S U (2 ) -homogeneous (Bianchi IX) cosmological model. The quantization of the homogeneous gravitino field leads to a 64-dimensional fermionic Hilbert space. After imposition of the diffeomorphism constraints, the wave function of the Universe becomes a 64-component spinor of spin(8,4) depending on the three squashing parameters, which satisfies Dirac-like, and Klein-Gordon-like, wave equations describing the propagation of a "quantum spinning particle" reflecting off spin-dependent potential walls. The algebra of the supersymmetry constraints and of the Hamiltonian one is found to close. One finds that the quantum Hamiltonian is built from operators that generate a 64-dimensional representation of the (infinite-dimensional) maximally compact subalgebra of the rank-3 hyperbolic Kac-Moody algebra A E3 . The (quartic-in-fermions) squared-mass term μ^ 2 entering the Klein-Gordon-like equation has several remarkable properties: (i) it commutes with all the other (Kac-Moody-related) building blocks of the Hamiltonian; (ii) it is a quadratic function of the fermion number NF; and (iii) it is negative in most of the Hilbert space. The latter property leads to a possible quantum avoidance of the singularity ("cosmological bounce"), and suggests imposing the boundary condition that the wave function of the Universe vanish when the volume of space tends to zero (a type of boundary condition which looks like a final-state condition when considering the big crunch inside a black hole). The space of solutions is a mixture of "discrete-spectrum states" (parametrized by a few constant parameters, and known in explicit form) and of continuous-spectrum states (parametrized by arbitrary functions entering some initial-value problem). The predominantly negative values of the squared-mass term lead to a "bottle

  1. Lack of prognostic and predictive value of CA IX in radiotherapy of squamous cell carcinoma of the head and neck with known modifiable hypoxia: An evaluation of the DAHANCA 5 study

    DEFF Research Database (Denmark)

    Eriksen, Jesper Grau; Overgaard, Jens

    2007-01-01

    BACKGROUND AND PURPOSE: CA IX is suggested to be an endogenous marker of hypoxia in tumours like squamous cell carcinomas of the head and neck (HNSCC). The aim of the present study was to investigate whether CA IX served as a prognostic factor for outcome in a large population of HNSCC and if CA IX......+/-the hypoxic radiosensitizer nimorazole. CA IX was measured using immunohistochemistry and results were divided into four groups of CA IX expression: 30% of the tumour area with positive membrane staining. Locoregional control and disease-specific survival were used as endpoints...

  2. A new peptide ligand for targeting human carbonic anhydrase IX, identified through the phage display technology.

    Directory of Open Access Journals (Sweden)

    Vasileios Askoxylakis

    Full Text Available UNLABELLED: Carbonic anhydrase IX (CAIX is a transmembrane enzyme found to be overexpressed in various tumors and associated with tumor hypoxia. Ligands binding this target may be used to visualize hypoxia, tumor manifestation or treat tumors by endoradiotherapy. METHODS: Phage display was performed with a 12 amino acid phage display library by panning against a recombinant extracellular domain of human carbonic anhydrase IX. The identified peptide CaIX-P1 was chemically synthesized and tested in vitro on various cell lines and in vivo in Balb/c nu/nu mice carrying subcutaneously transplanted tumors. Binding, kinetic and competition studies were performed on the CAIX positive human renal cell carcinoma cell line SKRC 52, the CAIX negative human renal cell carcinoma cell line CaKi 2, the human colorectal carcinoma cell line HCT 116 and on human umbilical vein endothelial cells (HUVEC. Organ distribution studies were carried out in mice, carrying SKRC 52 tumors. RNA expression of CAIX in HCT 116 and HUVEC cells was investigated by quantitative real time PCR. RESULTS: In vitro binding experiments of (125I-labeled-CaIX-P1 revealed an increased uptake of the radioligand in the CAIX positive renal cell carcinoma cell line SKRC 52. Binding of the radioligand in the colorectal carcinoma cell line HCT 116 increased with increasing cell density and correlated with the mRNA expression of CAIX. Radioligand uptake was inhibited up to 90% by the unlabeled CaIX-P1 peptide, but not by the negative control peptide octreotide at the same concentration. No binding was demonstrated in CAIX negative CaKi 2 and HUVEC cells. Organ distribution studies revealed a higher accumulation in SKRC 52 tumors than in heart, spleen, liver, muscle, intestinum and brain, but a lower uptake compared to blood and kidney. CONCLUSIONS: These data indicate that CaIX-P1 is a promising candidate for the development of new ligands targeting human carbonic anhydrase IX.

  3. ADAMTS13 content in plasma-derived factor VIII/von Willebrand factor concentrates.

    Science.gov (United States)

    Peyvandi, Flora; Mannucci, Pier M; Valsecchi, Carla; Pontiggia, Silvia; Farina, Claudio; Retzios, Anastassios D

    2013-10-01

    Thrombotic thrombocytopenic purpura (TTP) is a microangiopathy syndrome caused by a congenital or acquired deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor (VWF) and thus prevents the formation of platelet-rich thrombi in the microcirculation. TTP can be fatal if not appropriately and timely treated with the infusion of fresh frozen plasma (FFP) or exchange plasmapheresis, that reverse the process of microangiopathy by removing anti-ADAMTS13 autoantibodies and replacing functional ADAMTS13. The treatment of TTP with FFP is not free from risks and must be administered in hospitals or clinics, owing to the substantial amount of plasma volume infused or exchanged and the frequent need of catheter application. Moreover, most FFPs are not subjected to treatments to remove or inactivate blood-borne infectious agents. A number of recent reports indicate that certain plasma-derived VWF-factor VIII (FVIII) concentrates are clinically effective in the treatment of congenital TTP. In this study, we measured ADAMTS13 levels in various plasma-derived VWF-FVIII concentrates, showing that Koate(®) -DVI (Grifols), contained relatively high amounts of ADAMTS13 and that Alphanate(®) (Grifols) was the closest other product in terms of protease content. Koate(®) -DVI contains, on average (five lots tested), 0.091 ± 0.007 Units of ADAMTS13 activity per IU of FVIII. On the basis of this analysis and other reports of VWF-FVIII concentrate utilization in congenital TTP, potential dosing, and future clinical developments are discussed.

  4. Factors influencing serum total tryptase concentrations in a general adult population

    DEFF Research Database (Denmark)

    Gonzalez-Quintela, Arturo; Vizcaino, Luis; Gude, Francisco;

    2010-01-01

    Serum tryptase measurements are increasingly being used in clinical practice. However, there is a paucity of studies focused on factors that influence tryptase concentrations. We investigated the relationships between total tryptase concentrations and age, gender, atopy, alcohol consumption, smok...

  5. Factors influencing serum total tryptase concentrations in a general adult population

    DEFF Research Database (Denmark)

    Gonzalez-Quintela, Arturo; Vizcaino, Luis; Gude, Francisco;

    2010-01-01

    Serum tryptase measurements are increasingly being used in clinical practice. However, there is a paucity of studies focused on factors that influence tryptase concentrations. We investigated the relationships between total tryptase concentrations and age, gender, atopy, alcohol consumption...

  6. The Future of Hemophilia Treatment: Longer-Acting Factor Concentrates versus Gene Therapy.

    Science.gov (United States)

    Giangrande, Paul

    2016-07-01

    Gene therapy is the only novel technology that currently offers the prospect of a lasting cure for hemophilia and freedom from the burden of repeated injections. Recent data from a handful of patients who have undergone gene therapy for hemophilia B are very encouraging with a sustained factor IX (FIX) level of 0.05 IU/mL maintained for over 4 years. While this level is above the current usual target trough levels, it falls well short of the level that patients on prophylaxis with longer-acting products can expect. Prophylaxis is also associated with high peak levels, which permits patients to maintain an active lifestyle. A major barrier to widespread adoption of gene therapy is a high seroprevalence of antibodies to adeno-associated virus (AAV) vectors in the general population. Young children would be the best candidates for gene therapy in view of much lower seroprevalence to AAV in infants. A stable level of FIX early in life would prevent the onset of joint bleeds and the development of arthropathy. The recent experience with apolipoprotein tiparvovec (Glybera; uniQure, Amsterdam, the Netherlands) indicates that gene therapy is unlikely to prove to be a cheap therapeutic option. It is also quite possible that other new technologies that do not require viral vectors (such as stem cell therapy) may overtake gene therapy during development and make it redundant. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  7. Factors affecting yearly variations of indoor radon concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Steck, D.J.; Baynes, S.A. [John`s Univ., Collegeville, MN (United States)

    1996-06-01

    Since indoor radon exposures take place over many years while radon measurement periods are shorter, we are studying the yearly variation of indoor radon concentrations in approximately 100 houses located throughout Minnesota. Most houses were initially measured for one or more years in the late 1980`s and for 5 consecutive years starting in 1990. Two houses have been monitored for 12 y. Each year, two alpha track detectors were placed on the two lowest livable levels. The year-to-year variations averaged about 35% (corrected for instrumental uncertainties) in both basements and first floors. The minimum observed variation was 5% and the maximum was 130%. Some homes have shown substantial variation associated with Structural modifications. While most homes show no obvious systematic trends, a few houses have shown temporal trends that may be associated with aging or climate. We are studying possible correlation between year-to-year radon variation, climatic variables (yearly-average and seasonal such as heating/cooling degree days, precipitation, soil moisture), and structural changes.

  8. Melanin-concentrating hormone (MCH: a new sleep factor?

    Directory of Open Access Journals (Sweden)

    Pablo eTorterolo

    2011-03-01

    Full Text Available Neurons that utilize the neuropeptide melanin-concentrating hormone (MCH as a neuromodulator are mainly located in the lateral hypothalamus and the incerto-hypothalamic area, and have widespread projections throughout the brain. While the biological functions of this neuropeptide are exerted in humans through two metabotropic receptors, the MCHR1 and MCHR2, only the MCHR1 is present in rodents. Recently, it has been shown that the MCHergic system is involved in the control of sleep. We can summarize the experimental findings as follows:1. The areas related to the control of sleep and wakefulness have an important density of MCHergic fibers and receptors.2. MCHergic neurons are active during sleep, especially during REM sleep.3. Genetically-modified animals without MCH have less REM sleep, notably under conditions of negative energy balance. 4. Systemically administered MCHR1 antagonists reduce sleep. 5. Intraventricular microinjection of MCH increases both slow wave sleep (SWS and REM sleep; however, the increment in REM sleep is more pronounced.6. Microinjection of MCH into the dorsal raphe nucleus increases REM sleep time. REM seep is inhibited by immunoneutralization of MCH within this nucleus.7. Microinjection of MCH in the nucleus pontis oralis of the cat enhances REM sleep time and reduces REM sleep latency.All these data strongly suggest that MCH has a potent role in the promotion of sleep. Although both SWS and REM sleep are facilitated by MCH, REM sleep seems to be more sensitive to MCH modulation.

  9. Homoclinic Chaos in Axisymmetric Bianchi-IX cosmological models with an "ad hoc" quantum potential

    OpenAIRE

    Corrêa, G. C.; Stuchi, T. J.; Jorás, S. E.

    2010-01-01

    In this work we study the dynamics of the axisymmetric Bianchi IX cosmological model with a term of quantum potential added. As it is well known this class of Bianchi IX models are homogeneous and anisotropic with two scale factors, $A(t)$ and $B(t)$, derived from the solution of Einstein's equation for General Relativity. The model we use in this work has a cosmological constant and the matter content is dust. To this model we add a quantum-inspired potential that is intended to represent sh...

  10. Carbonic anhydrase IX, a hypoxia-induced catalytic component of the pH regulating machinery in tumors.

    Science.gov (United States)

    Sedlakova, Olga; Svastova, Eliska; Takacova, Martina; Kopacek, Juraj; Pastorek, Jaromir; Pastorekova, Silvia

    2014-01-08

    Acidic tissue microenvironment contributes to tumor progression via multiple effects including the activation of angiogenic factors and proteases, reduced cell-cell adhesion, increased migration and invasion, etc. In addition, intratumoral acidosis can influence the uptake of anticancer drugs and modulate the response of tumors to conventional therapy. Acidification of the tumor microenvironment often develops due to hypoxia-triggered oncogenic metabolism, which leads to the extensive production of lactate, protons, and carbon dioxide. In order to avoid intracellular accumulation of the acidic metabolic products, which is incompatible with the survival and proliferation, tumor cells activate molecular machinery that regulates pH by driving transmembrane inside-out and outside-in ion fluxes. Carbonic anhydrase IX (CA IX) is a hypoxia-induced catalytic component of the bicarbonate import arm of this machinery. Through its catalytic activity, CA IX directly participates in many acidosis-induced features of tumor phenotype as demonstrated by manipulating its expression and/or by in vitro mutagenesis. CA IX can function as a survival factor protecting tumor cells from hypoxia and acidosis, as a pro-migratory factor facilitating cell movement and invasion, as a signaling molecule transducing extracellular signals to intracellular pathways (including major signaling and metabolic cascades) and converting intracellular signals to extracellular effects on adhesion, proteolysis, and other processes. These functional implications of CA IX in cancer are supported by numerous clinical studies demonstrating the association of CA IX with various clinical correlates and markers of aggressive tumor behavior. Although our understanding of the many faces of CA IX is still incomplete, existing knowledge supports the view that CA IX is a biologically and clinically relevant molecule, exploitable in anticancer strategies aimed at targeting adaptive responses to hypoxia and/or acidosis.

  11. The Broadband Spectral Variability of Holmberg IX X-1

    CERN Document Server

    Walton, D J; Harrison, F A; Middleton, M J; Fabian, A C; Bachetti, M; Barret, D; Miller, J M; Ptak, A; Rana, V; Stern, D; Tao, L

    2016-01-01

    We present the results from four new broadband X-ray observations of the extreme ultraluminous X-ray source Holmberg IX X-1 ($L_{\\rm{X}} > 10^{40}$ erg s$^{-1}$), performed by the $Suzaku$ and $NuSTAR$ observatories in coordination. Combined with the two prior observations coordinating $XMM$-$Newton$, $Suzaku$ and $NuSTAR$, we now have broadband observations of this remarkable source from six separate epochs. Two of these new observations probe lower fluxes than seen previously, allowing us to extend our knowledge of the broadband spectral variability exhibited by Holmberg IX X-1. The broadband spectra are well fit by two thermal blackbody components, which dominate the emission below 10 keV, as well as a steep ($\\Gamma \\sim 3.5$) powerlaw tail which dominates above $\\sim$15 keV. Remarkably, while the 0.3-10.0 keV flux varies by a factor of $\\sim$3 between all these epochs, the 15-40 keV flux varies by only $\\sim$20%. Although the spectral variability is strongest in the $\\sim$1-10 keV band, the broadband var...

  12. In vivo wide-field multispectral dosimeter for use in ALA-PpIX based photodynamic therapy of skin

    Science.gov (United States)

    LaRochelle, Ethan P. M.; Davis, Scott C.; de Souza, Ana Luiza Ribeiro; Pogue, Brian W.

    2017-02-01

    Photodynamic therapy (PDT) for Actinic Kertoses (AK) using aminoluvelinic acid (ALA) is an FDA-approved treatment, which is generally effective, yet response rates vary. The origin of the variability is not well characterized, but may be related to inter-patient variability in the production of protoporphyrin IX (PpIX). While fiber-based point probe systems provide a method for measuring PpIX production, these measurements have demonstrated large spatial and inter-operator variability. Thus, in an effort to improve patient-specific dosimetry and treatment it is important to develop a robust system that accounts for spatial variability and reduces the chance of operator errors. To address this need, a wide-field multispectral imaging system was developed that is capable of quantifying maps of PpIX in both liquid phantoms and in vivo experiments, focusing on high sensitivity light signals. The system uses both red and blue excitation to elicit a fluorescent response at varying skin depths. A ten-position filter wheel with bandpass filters ranging from 635nm to 710nm are used to capture images along the emission band. A linear least-square spectral fitting algorithm provides the ability to decouple background autofluorescence from PpIX fluorescence, which has improved the system sensitivity by an order of magnitude, detecting nanomolar PpIX concentrations in liquid phantoms in the presence of 2% whole blood and 2% intralipid.

  13. VOCs in industrial, urban and suburban neighborhoods—Part 2: Factors affecting indoor and outdoor concentrations

    Science.gov (United States)

    Jia, Chunrong; Batterman, Stuart; Godwin, Christopher

    Many microenvironmental and behavioral factors can affect concentrations of and exposures to volatile organic compounds (VOCs). Identifying these determinants is important to understand exposures and risks, and also to design policies and strategies that minimize concentrations. This study is aimed at determining factors associated with VOC concentrations found indoors in residences and outdoors in ambient air. It utilizes results from a comprehensive field study in which 98 VOCs were measured both inside and outside of 159 residences in three communities in southeast Michigan, USA. Additional measurements included indoor CO 2 concentrations, temperature, relative humidity, building and neighborhood characteristics, and occupant activities, assessed using a questionnaire and comprehensive walkthrough investigation. Factors potentially affecting concentrations were identified using bivariate and multivariate analyses. Outdoors, seasonal and community effects were observed. Indoors, seasonal effects were limited to the urban and industrial communities, largely due to changes in ambient levels. Elevated indoor VOC concentrations were associated with eight sources or activities: the presence of an attached garage; recent renovations; older residences; indoor smoking; less frequent window or door opening; higher CO 2 concentrations; and lower ventilation rates. VOC levels were uninfluenced by building materials (wood vs. brick), flooring type (carpeting vs. wood), stove type (gas or electric), number of occupants, air freshener use, and hobbies involving arts and crafts. Factor analyses identified up to five factors for the ambient VOC measurements, and up to 10 factors for the indoor measurements, which further helped to explain the variability of concentrations and associations between VOCs.

  14. [Estimation of average traffic emission factor based on synchronized incremental traffic flow and air pollutant concentration].

    Science.gov (United States)

    Li, Run-Kui; Zhao, Tong; Li, Zhi-Peng; Ding, Wen-Jun; Cui, Xiao-Yong; Xu, Qun; Song, Xian-Feng

    2014-04-01

    On-road vehicle emissions have become the main source of urban air pollution and attracted broad attentions. Vehicle emission factor is a basic parameter to reflect the status of vehicle emissions, but the measured emission factor is difficult to obtain, and the simulated emission factor is not localized in China. Based on the synchronized increments of traffic flow and concentration of air pollutants in the morning rush hour period, while meteorological condition and background air pollution concentration retain relatively stable, the relationship between the increase of traffic and the increase of air pollution concentration close to a road is established. Infinite line source Gaussian dispersion model was transformed for the inversion of average vehicle emission factors. A case study was conducted on a main road in Beijing. Traffic flow, meteorological data and carbon monoxide (CO) concentration were collected to estimate average vehicle emission factors of CO. The results were compared with simulated emission factors of COPERT4 model. Results showed that the average emission factors estimated by the proposed approach and COPERT4 in August were 2.0 g x km(-1) and 1.2 g x km(-1), respectively, and in December were 5.5 g x km(-1) and 5.2 g x km(-1), respectively. The emission factors from the proposed approach and COPERT4 showed close values and similar seasonal trends. The proposed method for average emission factor estimation eliminates the disturbance of background concentrations and potentially provides real-time access to vehicle fleet emission factors.

  15. Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion.

    Science.gov (United States)

    Feghhi, Shirin; Munday, Adam D; Tooley, Wes W; Rajsekar, Shreya; Fura, Adriane M; Kulman, John D; López, Jose A; Sniadecki, Nathan J

    2016-08-09

    Platelets bind to exposed vascular matrix at a wound site through a highly specialized surface receptor, glycoprotein (GP) Ib-IX-V complex, which recognizes von Willebrand factor (VWF) in the matrix. GPIb-IX-V is a catch bond for it becomes more stable as force is applied to it. After attaching to the wound site, platelets generate cytoskeletal forces to compact and reinforce the hemostatic plug. Here, we evaluated the role of the GPIb-IX-V complex in the transmission of cytoskeletal forces. We used arrays of flexible, silicone nanoposts to measure the contractility of individual platelets on VWF. We found that a significant proportion of cytoskeletal forces were transmitted to VWF through GPIb-IX-V, an unexpected finding given the widely held notion that platelet forces are transmitted exclusively through its integrins. In particular, we found that the interaction between GPIbα and the A1 domain of VWF mediates this force transmission. We also demonstrate that the binding interaction between GPIbα and filamin A is involved in force transmission. Furthermore, our studies suggest that cytoskeletal forces acting through GPIbα are involved in maintaining platelet adhesion when external forces are absent. Thus, the GPIb-IX-V/VWF bond is able to transmit force, and uses this force to strengthen the bond through a catch-bond mechanism. This finding expands our understanding of how platelets attach to sites of vascular injury, describing a new, to the best of our knowledge, mechanism in which the catch bonds of GPIb-IX-V/VWF can be supported by internal forces produced by cytoskeletal tension.

  16. Carbonic anhydrase IX as a specific biomarker for clear cell renal cell carcinoma: comparative study of Western blot and immunohistochemistry and implications for diagnosis.

    Science.gov (United States)

    Giménez-Bachs, José M; Salinas-Sánchez, Antonio S; Serrano-Oviedo, Leticia; Nam-Cha, Syong H; Rubio-Del Campo, Antonio; Sánchez-Prieto, Ricardo

    2012-10-01

    This study aimed to evaluate the usefulness of carbonic anhydrase IX (CA-IX) expression in clear cell renal cell carcinoma (CCRCC) using two different techniques to detect protein expression. An experimental, cross-sectional, analytical study was conducted to analyse proteins in renal tumour and healthy tissue specimens from 38 consecutive patients who underwent nephrectomy for renal cancer. CA-IX protein expression was measured by immunohistochemistry and Western blot analysis and quantified. Statistical analysis was performed with the positive and negative specific agreements and kappa coefficient. The sensitivity and specificity of both techniques were assessed. Statistical tests were conducted to analyse the association between CA-IX expression quantitation and normal prognosis factors (TNM stage and Fuhrman nuclear grade), only in CCRCC. The mean patient age was 65 years, 78.9% of patients were men and 57.9% of tumours were CCRCC. CA-IX protein expression was positive in 63.2% of tumours by immunohistochemistry and in 60.5% by Western blot. Both techniques detected CA-IX expression only in CCRCC and unclassifiable tumours. High concordance indices were observed for CCRCC diagnosis. Western blot and immunohistochemistry had a sensitivity of 95.5% and 100%, respectively; the specificity was 100% in both techniques. CA-IX expression quantitation did not correlate with tumour stage or Fuhrman nuclear grade. Immunochemistry and Western blot techniques can be used to detect abnormal CA-IX protein expression in CCRCC and to support morphology-based diagnostic techniques.

  17. Carbonic anhydrase IX is a marker of hypoxia and correlates with higher Gleason scores and ISUP grading in prostate cancer.

    Science.gov (United States)

    Ambrosio, Maria Raffaella; Di Serio, Claudia; Danza, Giovanna; Rocca, Bruno Jim; Ginori, Alessandro; Prudovsky, Igor; Marchionni, Niccolò; Del Vecchio, Maria Teresa; Tarantini, Francesca

    2016-05-25

    Carbonic anhydrase IX is a member of α-carbonic anhydrases that is preferentially expressed in solid tumors. It enables bicarbonate transport across the plasma membrane, neutralizing intracellular pH and conferring to cancer cells a survival advantage in hypoxic/acidic microenvironments. Overexpression of carbonic anhydrase IX in cancer tissues is regulated by hypoxia inducible factor 1α - mediated transcription and the enzyme is considered a marker of tumor hypoxia and poor outcome. The role of carbonic anhydrase IX in prostate cancer has not been fully clarified and controversy has arisen on whether this enzyme is overexpressed in hypoxic prostate cancer tissues. We analyzed the expression of carbonic anhydrase IX and hypoxia inducible factor 1α in two prostate cancer cell lines, LNCaP and PC-3, and in 110 cancer biopsies, by western blotting and immunocyto/histochemistry. In LNCaP and PC-3 cells, carbonic anhydrase IX was mostly cytoplasmic/nuclear, with very limited membrane localization. Nuclear staining became stronger under hypoxia. When we analyzed carbonic anhydrase IX expression in human prostate cancer biopsies, we found that protein staining positively correlated with hypoxia inducible factor 1α and with Gleason pattern and score, as well as with the novel grading system proposed by the International Society of Urological Pathology for prostate cancer. Once more, carbonic anhydrase IX was mainly cytoplasmic in low grade carcinomas, whereas in high grade tumors was strongly expressed in the nucleus of the neoplastic cell. An association between carbonic anhydrase IX expression level and the main clinic-pathological features involved in prostate cancer aggressiveness was identified. There was a statistically significant association between carbonic anhydrase IX and hypoxia inducible factor 1α in prostate cancer tissues, that identifies the enzyme as a reliable marker of tumor hypoxia. In addition, carbonic anhydrase IX expression positively

  18. Atomistic evaluation of the stress concentration factor of graphene sheets having circular holes

    Science.gov (United States)

    Jalali, S. K.; Beigrezaee, M. J.; Pugno, N. M.

    2017-09-01

    Stress concentration factor concept has been developed for single-layered graphene sheets (SLGSs) with circular holes through an atomistic point of view by the application of molecular structural mechanics (MSM) approach. In this approach the response of SLGSs against unidirectional tensile loading is matched to the response of a frame-like macro structure containing beam elements by making an equivalence between strain energies of beam elements in MSM and potential energies of chemical bonds of SLGSs. Both chirality and size effects are considered and the atomistic evaluation of stress concentration factor is performed for different sizes of circular holes. Also, molecular dynamics simulations are implemented to verify the existence and location of the predicted stress concentration. The results reveal that size effects and the diameters of circular holes have a significant influence on the stress concentration factor of SLGSs and armchair SLGSs show a larger value of stress concentration than zigzag ones.

  19. Parametric Equation of Stress Concentration Factor for Circular X-Joints Under Axial Loads

    Institute of Scientific and Technical Information of China (English)

    QU Shu-ying; ZHANG Guo-dong; ZHANG Bao-feng; WANG Xin-jian

    2007-01-01

    In engineering practice,tubular X-joints have been widely used in offshore structures.The fatigue failure of tubular X-joints in offshore engineering is mainly caused by axial tensile stress.In this study,the stress concentration factor distribution along the weld toe in the hot spot stress region for tubular X-joints subject to axial loads have been analyzed by use of finite element method.Through numerical analysis,it has been found that the peak stress concentration factor is located at the saddle position.Thereafter,80 models have been analyzed,and the effect of the geometric parameters of a tubular X-joint on the stress concentration factor has been investigated.Based on the experimental values of the numerical stress concentration factor,a parametric equation to calculate the stress concentration factor of tubular X-joints has been proposed.The accuracy of this equation has been verified against the requirement of the Fatigue Guidance Review Panel,and the proposed equation is found capable of producing reasonably accurate stress concentration factor values for tubular X-joints subject to axial loads.

  20. Evaluation of factors important in modeling plasma concentrations of tetracycline hydrochloride administered in water in swine.

    Science.gov (United States)

    Mason, Sharon E; Almond, Glen W; Riviere, Jim E; Baynes, Ronald E

    2012-10-01

    To model the plasma tetracycline concentrations in swine (Sus scrofa domestica) treated with medication administered in water and determine the factors that contribute to the most accurate predictions of measured plasma drug concentrations. Plasma tetracycline concentrations measured in blood samples from 3 populations of swine. Data from previous studies provided plasma tetracycline concentrations that were measured in blood samples collected from 1 swine population at 0, 4, 8, 12, 24, 32, 48, 56, 72, 80, 96, and 104 hours and from 2 swine populations at 0, 12, 24, 48, and 72 hours hours during administration of tetracycline hydrochloride dissolved in water. A 1-compartment pharmacostatistical model was used to analyze 5 potential covariate schemes and determine factors most important in predicting the plasma concentrations of tetracycline in swine. 2 models most accurately predicted the tetracycline plasma concentrations in the 3 populations of swine. Factors of importance were body weight or age of pig, ambient temperature, concentration of tetracycline in water, and water use per unit of time. The factors found to be of importance, combined with knowledge of the individual pharmacokinetic and chemical properties of medications currently approved for administration in water, may be useful in more prudent administration of approved medications administered to swine. Factors found to be important in pharmacostatistical models may allow prediction of plasma concentrations of tetracycline or other commonly used medications administered in water. The ability to predict in vivo concentrations of medication in a population of food animals can be combined with bacterial minimum inhibitory concentrations to decrease the risk of developing antimicrobial resistance.

  1. Bianchi IX Cosmologies and the Golden Ratio

    CERN Document Server

    Bryant, M S

    2016-01-01

    Solutions to the Einstein equations for Bianchi IX cosmologies are examined through the use of Ellis MacCallum Wainwright (expansion-normalized) variables. Using an iterative map derived from the Einstein equations one can construct an infinite number of periodic solutions. The simplest periodic solutions consist of 3-cycles. It is shown that for 3-cycles the time series of the logarithms of the expansion-normalized spatial curvature components vs normalized time (which is runs backwards towards the initial singularity), generates a set of self-similar golden rectangles. In addition the golden ratio appears in other aspects of the same time series representation.

  2. Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25(OHD concentrations in healthy women

    Directory of Open Access Journals (Sweden)

    Heffernan Mary E

    2008-07-01

    Full Text Available Abstract Background Circulating 25 hydroxyvitamin D (25 (OHD, an accurate measure of vitamin D status, is markedly greater in individuals with increased exposure to ultraviolet B (UVB light via sunlight or the use of artificial UV light. Aside from the known relationship between vitamin D and bone, vitamin D has also been implicated in immune function and inflammation. Furthermore, a mass of evidence is accumulating that vitamin D deficiency could lead to immune malfunction. Our overall objective was to study the relationship between vitamin D status (as determined by serum 25(OH D concentrations and inflammatory markers in healthy women. Methods This observational study included 69 healthy women, age 25–82 years. Women with high UVB exposure and women with minimal UVB exposure were specifically recruited to obtain a wide-range of serum 25(OHD concentrations. Health, sun exposure and habitual dietary intake information were obtained from all subjects. Body composition was determined by dual-energy-x-ray absorptiometry. A fasting blood sample was collected in the morning and analyzed for serum 25(OHD, parathyroid hormone (iPTH, estradiol (E2, cortisol, and inflammatory markers [tumor necrosis factor -alpha (TNF-α, interleukin-6 and -10 (IL-6, IL-10, and C-reactive protein (CRP]. Results Women with regular UVB exposure (Hi-D had serum 25(OHD concentrations that were significantly higher (p p Conclusion Serum 25(OHD status is inversely related to TNF-α concentrations in healthy women, which may in part explain this vitamin's role in the prevention and treatment of inflammatory diseases. Results gleaned from this investigation also support the need to re-examine the biological basis for determining optimal vitamin D status.

  3. HTLV-III seropositivity in European haemophiliacs exposed to Factor VIII concentrate imported from the USA.

    Science.gov (United States)

    Melbye, M; Froebel, K S; Madhok, R; Biggar, R J; Sarin, P S; Stenbjerg, S; Lowe, G D; Forbes, C D; Goedert, J J; Gallo, R C

    1984-12-22

    77 Scottish haemophiliacs and 22 Danish haemophiliacs were serologically tested for antibodies to human T-cell leukaemia virus III (HTLV-III). Since 1979 the Scottish patients had been treated largely with factor VIII concentrate produced in Scotland, whereas all but 2 of the Danish patients had received both locally prepared concentrate and commercial concentrate made from US donor material. 15.6% of Scottish and 59.1% of Danish haemophiliacs were antibody positive (p less than 0.001). None of 11 haemophiliacs not treated in the period 1979-84 was seropositive. 2 (6.7%) of 30 subjects who had been treated with locally produced concentrate only were antibody positive, compared with 23 (39.7%) of 58 subjects who had been treated with commercial concentrate. Among 52 users of both commercially and locally produced factor VIII concentrate, seropositivity was directly correlated with the consumption of commercial concentrate (p less than 0.001) but not locally produced material. These data indicate that European haemophiliacs were exposed to HTLV-III via some factor VIII concentrates obtained from the USA.

  4. Quantitative fluorescence using 5-aminolevulinic acid–induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery

    Science.gov (United States)

    Valdés, Pablo A.; Jacobs, Valerie; Harris, Brent T.; Wilson, Brian C.; Leblond, Frederic; Paulsen, Keith D.; Roberts, David W.

    2015-01-01

    OBJECT Previous studies in high-grade gliomas (HGGs) have indicated that protoporphyrin IX (PpIX) accumulates in higher concentrations in tumor tissue, and, when used to guide surgery, it has enabled improved resection leading to increased progression-free survival. Despite the benefits of complete resection and the advances in fluorescence-guided surgery, few studies have investigated the use of PpIX in low-grade gliomas (LGGs). Here, the authors describe their initial experience with 5-aminolevulinic acid (ALA)–induced PpIX fluorescence in a series of patients with LGG. METHODS Twelve patients with presumed LGGs underwent resection of their tumors after receiving 20 μg/kg of ALA approximately 3 hours prior to surgery under an institutional review board–approved protocol. Intraoperative assessments of the resulting PpIX emissions using both qualitative, visible fluorescence and quantitative measurements of PpIX concentration were obtained from tissue locations that were subsequently biopsied and evaluated histopathologically. Mixed models for random effects and receiver operating characteristic curve analysis for diagnostic performance were performed on the fluorescence data relative to the gold-standard histopathology. RESULTS Five of the 12 LGGs (1 ganglioglioma, 1 oligoastrocytoma, 1 pleomorphic xanthoastrocytoma, 1 oligodendroglioma, and 1 ependymoma) demonstrated at least 1 instance of visible fluorescence during surgery. Visible fluorescence evaluated on a specimen-by-specimen basis yielded a diagnostic accuracy of 38.0% (cutoff threshold: visible fluorescence score ≥ 1, area under the curve = 0.514). Quantitative fluorescence yielded a diagnostic accuracy of 67% (for a cutoff threshold of the concentration of PpIX [CPpIX] > 0.0056 μg/ml, area under the curve = 0.66). The authors found that 45% (9/20) of nonvisibly fluorescent tumor specimens, which would have otherwise gone undetected, accumulated diagnostically significant levels of CPpIX that were

  5. Ares I-X Ground Diagnostic Prototype

    Science.gov (United States)

    Schwabacher, Mark A.; Martin, Rodney Alexander; Waterman, Robert D.; Oostdyk, Rebecca Lynn; Ossenfort, John P.; Matthews, Bryan

    2010-01-01

    The automation of pre-launch diagnostics for launch vehicles offers three potential benefits: improving safety, reducing cost, and reducing launch delays. The Ares I-X Ground Diagnostic Prototype demonstrated anomaly detection, fault detection, fault isolation, and diagnostics for the Ares I-X first-stage Thrust Vector Control and for the associated ground hydraulics while the vehicle was in the Vehicle Assembly Building at Kennedy Space Center (KSC) and while it was on the launch pad. The prototype combines three existing tools. The first tool, TEAMS (Testability Engineering and Maintenance System), is a model-based tool from Qualtech Systems Inc. for fault isolation and diagnostics. The second tool, SHINE (Spacecraft Health Inference Engine), is a rule-based expert system that was developed at the NASA Jet Propulsion Laboratory. We developed SHINE rules for fault detection and mode identification, and used the outputs of SHINE as inputs to TEAMS. The third tool, IMS (Inductive Monitoring System), is an anomaly detection tool that was developed at NASA Ames Research Center. The three tools were integrated and deployed to KSC, where they were interfaced with live data. This paper describes how the prototype performed during the period of time before the launch, including accuracy and computer resource usage. The paper concludes with some of the lessons that we learned from the experience of developing and deploying the prototype.

  6. Ares I-X Ground Diagnostic Prototype

    Science.gov (United States)

    Schwabacher, Mark; Martin, Rodney; Waterman, Robert; Oostdyk, Rebecca; Ossenfort, John; Matthews, Bryan

    2010-01-01

    Automating prelaunch diagnostics for launch vehicles offers three potential benefits. First, it potentially improves safety by detecting faults that might otherwise have been missed so that they can be corrected before launch. Second, it potentially reduces launch delays by more quickly diagnosing the cause of anomalies that occur during prelaunch processing. Reducing launch delays will be critical to the success of NASA's planned future missions that require in-orbit rendezvous. Third, it potentially reduces costs by reducing both launch delays and the number of people needed to monitor the prelaunch process. NASA is currently developing the Ares I launch vehicle to bring the Orion capsule and its crew of four astronauts to low-earth orbit on their way to the moon. Ares I-X will be the first unmanned test flight of Ares I. It is scheduled to launch on October 27, 2009. The Ares I-X Ground Diagnostic Prototype is a prototype ground diagnostic system that will provide anomaly detection, fault detection, fault isolation, and diagnostics for the Ares I-X first-stage thrust vector control (TVC) and for the associated ground hydraulics while it is in the Vehicle Assembly Building (VAB) at John F. Kennedy Space Center (KSC) and on the launch pad. It will serve as a prototype for a future operational ground diagnostic system for Ares I. The prototype combines three existing diagnostic tools. The first tool, TEAMS (Testability Engineering and Maintenance System), is a model-based tool that is commercially produced by Qualtech Systems, Inc. It uses a qualitative model of failure propagation to perform fault isolation and diagnostics. We adapted an existing TEAMS model of the TVC to use for diagnostics and developed a TEAMS model of the ground hydraulics. The second tool, Spacecraft Health Inference Engine (SHINE), is a rule-based expert system developed at the NASA Jet Propulsion Laboratory. We developed SHINE rules for fault detection and mode identification. The prototype

  7. Pretreatment to enhance protoporphyrin IX accumulation in photodynamic therapy.

    NARCIS (Netherlands)

    Gerritsen, M.J.P.; Smits, T.; Kleinpenning, M.M.; Kerkhof, P.C.M. van de; Erp, P.E.J. van

    2009-01-01

    The response rates of photodynamic therapy (PDT) vary widely. Limited uptake of topically applied 5-aminolaevulinic acid (ALA), or its methyl ester (MAL), and suboptimal production of protoporphyrin IX (PpIX) may account for these differences. Recently, we demonstrated that hyperkeratosis is an impo

  8. ARES I-X USS Fracture Analysis Loads Spectra Development

    Science.gov (United States)

    Larsen, Curtis; Mackey, Alden

    2008-01-01

    This report describes the development of a set of bounding load spectra for the ARES I-X launch vehicle. These load spectra are used in the determination of the critical initial flaw size (CIFS) of the welds in the ARES I-X upper stage simulator (USS).

  9. Changing Paradigm of Hemophilia Management: Extended Half-Life Factor Concentrates and Gene Therapy.

    Science.gov (United States)

    Kumar, Riten; Dunn, Amy; Carcao, Manuel

    2016-02-01

    Management of hemophilia has evolved significantly in the last century-from recognition of the causative mechanism in the 1950s to commercially available clotting factor concentrates in the 1960s. Availability of lyophilized concentrates in the 1970s set the stage for home-based therapy, followed by introduction of virally attenuated plasma-derived, and then recombinant factor concentrates in the 1980s and 1990s, respectively. The subsequent years saw a paradigm shift in treatment goals from on-demand therapy to prophylactic factor replacement starting at an early age, to prevent hemarthrosis becoming the standard of care for patients with severe hemophilia. In the developed world, the increasing use of home-based prophylactic regimens has significantly improved the quality of life, and life expectancy of patients with severe hemophilia. Seminal developments in the past 5 years, including the commercial availability of extended half-life factor concentrates and the publication of successful results of gene therapy for patients with hemophilia B, promise to further revolutionize hemophilia care over the next few decades. In this review, we summarize the evolution of management for hemophilia, with a focus on extended half-life factor concentrates and gene therapy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  10. INVESTIGATION ON THE RESPONSE FACTORS OF CONCENTRATION DETECTORS WITHIN SEC PROCESS

    Institute of Scientific and Technical Information of China (English)

    Cheng-guo Liu; Hong-feng Xie; Zhi-liu Wang; Hu Yang; Rong-shi Cheng

    2011-01-01

    The response factors of refractive index (RI) and ultraviolet (UV) detectors of size exclusion chromatography (SEC) defined as the ratio of area of output signal to the mass of injected sample are studied and analyzed by using five narrowly distributed polystyrene (PS) standard samples with known molar masses. It is found that the individual response factor for a given sample varies with the concentration of the injected solution within a limited range bounded by an upper and a lower limiting response factor values. This variation reveals the conformational change of the polymer chains with the concentration of the injected solution. The dynamic contact concentrations Cs of the PS samples derived from the response factor data are in good accordance with those reported earlier by other methods. The physical meanings of the signals of the two detectors are further analyzed and theoretically formulated. The solvation of the polymer chain and the conformation changes play an important role in these detecting systems. Both of the solvation number of the structural repeating unit and the extra embedded solvent due to cluster forming in higher concentrations could be deduced from the variation of response factor with the concentration of the injected solution.

  11. SHAPE EFFECT OF ANNULAR CONCENTRATOR IN ULTRASONIC SYSTEM ON AMPLIFICATION FACTOR OF VIBRATIONS AMPLITUDE

    Directory of Open Access Journals (Sweden)

    D. A. Stepanenko

    2016-01-01

    Full Text Available The paper contains a theoretical underpinning on creation of ultrasonic vibration concentrators based on annular elastic elements with non-circular (ellipse-like eccentric shape of internal contour. Shape of internal contour in polar coordinates is described by Fourier series relative to angular coordinate that consists of a constant term and first and second harmonics. An effect of geometric parameters of the concentrator on amplification factor and natural vibration frequencies has been investigated with the help of a finite element method. The paper reveals the possibility to control an amplification factor of annular concentrators while varying eccentricity of internal contour and mean value of cross-section thickness. The amplification factor satisfies a condition K < N, where N is thickness ratio of amplifier input and output sections, and it is decreasing with increase of vibration mode order. The similar condition has been satisfied for conical bar concentrator with the difference that in the case of bar concentrators an amplification is ensured due to variation of diameter and N will represent ratio of diameters. It has been proved that modification of internal contour shape makes it possible to carry out a wide-band tuning of natural frequencies of concentrator vibrations without alteration of its overall dimensions and substantial change of amplification factor, which is important for frequency matching of the concentrator and ultrasonic vibratory system. Advantages of the proposed concentrators include simplicity of design and manufacturing, small overall dimensions, possibility for natural frequency tuning by means of static load variation. The developed concentrators can find their application in ultrasonic devices and instruments for technological and medical purposes.

  12. The variation characteristics and effect factors of surface ozone concentration in the Taklimakan Desert hinterland

    Institute of Scientific and Technical Information of China (English)

    XinChun Liu; YuTing Zhong; Qing He; YanMei Peng; XingHua Yang; Ali Mamtimin; Wen Huo

    2014-01-01

    Based on automatic continuous surface ozone concentration observation data from June 10, 2010 to March 20, 2012 in the Taklimakan Desert hinterland, combined with corresponding meteorological data, the temporal, seasonal and daily variation characteristics of surface ozone concentrations under different weather conditions were analyzed. At the same time, the main fac-tors affecting ozone variation are discussed. Results show that:(1) Daily variation of ozone concentration was characterized by one obvious peak, with gentle changes during the night and dramatic changes during the day. The lowest concentration was at 09:00 and the highest was at 18:00. Compared to urban areas, there was a slight time delay. (2) Ozone concentration variation had a weekend effect phenomenon. Weekly variation of ozone concentration decreased from Monday to Wednesday with the lowest in Wednesday, and increased after Thursday with the highest in Sunday. (3) The highest monthly average concentration was 89.6μg/m3 in June 2010, and the lowest was 32.0μg/m3 in January 2012. Ozone concentration reduced month by month from June to December in 2010. (4) Ozone concentration in spring and summer was higher than in autumn and winter. The variation trend agreed with those in other large and medium-sized cities. (5) Under four different types of weather, daily ozone concentration var-ied most dramatically in sunny days, followed by slight variation in rain days, and varied gently in cloudy days. Ozone concentra-tion varied inconspicuously before a sandstorm appearance, and dropped rapidly at the onset of a sandstorm. (6) Daily variation of radiation was also characterized by a single peak, and the variation was significantly earlier than ozone concentration variation. Sun radiation intensity had a direct influence on the photochemical reaction speed, leading to variation of ozone concentration. (7) Daily average ozone concentration in dust weather was higher than in slight rain and clear days. The

  13. Correction factor for real-time determination of wood dust mass concentration by photometric method

    Directory of Open Access Journals (Sweden)

    Ankica Čavlović

    2009-03-01

    Full Text Available Samples of wood dust were collected in the working environment of wood machining processes for the purpose of determining correction factors for measuring mass concentration of wood dust by photometric method. According to the NIOSH 0600 Norm and NIOSH Manual of Analytical Methods for photometric measurement, correction factor must be determined before measuring mass concentration of different types of dust. The correction factor is defined as the ratio of mass concentration obtained by the gravimetric method and mass concentration obtained by the photometric method. The correction factor should be determined because of the influence of particle size distribution, density, particle shape and refractive index on values obtained by the photometric method. The aim of the research was to investigate the possibility of using photometric method for the determination of mass concentration of inhalable fraction of airborne wood dust. Sampling was conducted in several woodworking plants during the machining of wet and dry beech-wood, wet and dry oak-wood, wet fir-wood and particleboard. There is a significant correlation between the results obtained by the photometric method and values obtained by the gravimetric method (R2=0.88 and this is the base for using the photometric method in determining mass concentration of airborne wood dust. According to the results of this research, correction factors must be determined and used for measuring mass concentration of inhalable wood dust during the machining of different wood species and wood with different moisture content. The best corresponding results of photometric and gravimetric methods are obtained for the samples collected during machining of wet fir-wood (k=1. The largest correction factor should be used in determining workers exposure to wood dust during machining of dry oak-wood (k=4.4 and particleboard (k=4.5. Only the results of 8-hour measurements of mass concentration by gravimetric methods can

  14. Factors affecting the concentration of outdoor particles indoors (COPI): Identification of data needs and existing data

    Energy Technology Data Exchange (ETDEWEB)

    Thatcher, Tracy L.; McKone, Thomas E.; Fisk, William J.; Sohn, Michael D.; Delp, Woody W.; Riley, William J.; Sextro, Richard G.

    2001-12-01

    The process of characterizing human exposure to particulate matter requires information on both particle concentrations in microenvironments and the time-specific activity budgets of individuals among these microenvironments. Because the average amount of time spent indoors by individuals in the US is estimated to be greater than 75%, accurate characterization of particle concentrations indoors is critical to exposure assessments for the US population. In addition, it is estimated that indoor particle concentrations depend strongly on outdoor concentrations. The spatial and temporal variations of indoor particle concentrations as well as the factors that affect these variations are important to health scientists. For them, knowledge of the factors that control the relationship of indoor particle concentrations to outdoor levels is particularly important. In this report, we identify and evaluate sources of data for those factors that affect the transport to and concentration of outdoor particles in the indoor environment. Concentrations of particles indoors depend upon the fraction of outdoor particles that penetrate through the building shell or are transported via the air handling (HVAC) system, the generation of particles by indoor sources, and the loss mechanisms that occur indoors, such as deposition. To address these issues, we (i) identify and assemble relevant information including the behavior of particles during air leakage, HVAC operations, and particle filtration; (ii) review and evaluate the assembled information to distinguish data that are directly relevant to specific estimates of particle transport from those that are only indirectly useful and (iii) provide a synthesis of the currently available information on building air-leakage parameters and their effect on indoor particle matter concentrations.

  15. Hierarchical modeling of indoor radon concentration: how much do geology and building factors matter?

    Science.gov (United States)

    Borgoni, Riccardo; De Francesco, Davide; De Bartolo, Daniela; Tzavidis, Nikos

    2014-12-01

    Radon is a natural gas known to be the main contributor to natural background radiation exposure and only second to smoking as major leading cause of lung cancer. The main concern is in indoor environments where the gas tends to accumulate and can reach high concentrations. The primary contributor of this gas into the building is from the soil although architectonic characteristics, such as building materials, can largely affect concentration values. Understanding the factors affecting the concentration in dwellings and workplaces is important both in prevention, when the construction of a new building is being planned, and in mitigation when the amount of Radon detected inside a building is too high. In this paper we investigate how several factors, such as geologic typologies of the soil and a range of building characteristics, impact on indoor concentration focusing, in particular, on how concentration changes as a function of the floor level. Adopting a mixed effects model to account for the hierarchical nature of the data, we also quantify the extent to which such measurable factors manage to explain the variability of indoor radon concentration.

  16. Immunological abnormalities in haemophilia: are they caused by American factor VIII concentrate?

    Science.gov (United States)

    Froebel, K S; Madhok, R; Forbes, C D; Lennie, S E; Lowe, G D; Sturrock, R D

    1983-10-15

    Scottish patients with haemophilia, most of whom had received no American factor VIII concentrate for over two years, were found to have immunological abnormalities similar to those in their American counterparts--that is, a reduced proportion of T helper cells, an increased proportion of T suppressor cells, and a reduced response to concanavilin A. Factor VIII from both the United States and Scotland severely inhibited the in vitro lymphocyte response to mitogens in patients and controls. The American and Scottish concentrates could not be distinguished in terms of either patient usage or their effect in vitro. These results argue against a disease vector specific to American blood products.

  17. Multicenter study of posaconazole therapeutic drug monitoring: exposure-response relationship and factors affecting concentration.

    Science.gov (United States)

    Dolton, Michael J; Ray, John E; Chen, Sharon C-A; Ng, Kingsley; Pont, Lisa; McLachlan, Andrew J

    2012-11-01

    Posaconazole has an important role in the prophylaxis and salvage treatment of invasive fungal infections (IFIs), although poor and variable bioavailability remains an important clinical concern. Therapeutic drug monitoring of posaconazole concentrations has remained contentious, with the use of relatively small patient cohorts in previous studies hindering the assessment of exposure-response relationships. This multicenter retrospective study aimed to investigate relationships between posaconazole concentration and clinical outcomes and adverse events and to assess clinical factors and drug interactions that may affect posaconazole concentrations. Medical records were reviewed for patients who received posaconazole and had ≥1 concentration measured at six hospitals in Australia. Data from 86 patients with 541 posaconazole concentrations were included in the study. Among 72 patients taking posaconazole for prophylaxis against IFIs, 12 patients (17%) developed a breakthrough fungal infection; median posaconazole concentrations were significantly lower than in those who did not develop fungal infection (median [range], 289 [50 to 471] ng/ml versus 485 [0 to 2,035] ng/ml; P posaconazole concentration was a significant predictor of breakthrough fungal infection via binary logistic regression (P posaconazole exposure, including coadministration with proton pump inhibitors, metoclopramide, phenytoin or rifampin, and the H(2) antagonist ranitidine (P posaconazole exposure (P posaconazole concentrations are common and are associated with breakthrough fungal infection, supporting the utility of monitoring posaconazole concentrations to ensure optimal systemic exposure.

  18. Anemia as a factor that elevates plasma brain natriuretic peptide concentration in apparently healthy subjects.

    Science.gov (United States)

    Matsumoto, Mika; Tsujino, Takeshi; Naito, Yoshiro; Lee-Kawabata, Masaaki; Ezumi, Akira; Yamamoto, Kazuhiro; Mano, Toshiaki; Masuyama, Tohru

    2008-09-01

    Plasma brain natriuretic peptide (BNP) is widely used as a biomarker of heart failure (HF); however, its concentration is often found to be high even in apparently healthy subjects and little is known about which factors contribute to physiological change in plasma BNP concentration in subjects without HF. We examined the effects of gender, age, and anemia on plasma BNP concentration in apparently healthy subjects. The study population consisted of 1036 healthy subjects who underwent an annual health examination at their company in 2005. There were 874 women, ranging in age from 30 to 63 years (mean, 41 years). Plasma BNP concentration was abnormal (> 18.4 pg/mL) in 292 subjects. The incidence was significantly higher in women than in men (31% versus 14%, P < 0.01). Mean plasma BNP concentration was higher in women than in men. The difference in plasma BNP concentration was associated with the difference in blood hemoglobin and age. Logarithmically transformed BNP concentration correlated inversely with blood hemoglobin (r = -0.30, P < 0.01 for all; r = -0.21, P < 0.01 for women; r = -0.20, P < 0.01 for men). By multiple regression analysis, logarithmically transformed BNP concentration correlated with hemoglobin, age, and gender. In conclusion, anemia is likely a critical determinant that elevates plasma BNP concentration in apparently healthy subjects.

  19. Arsenic concentrations, related environmental factors, and the predicted probability of elevated arsenic in groundwater in Pennsylvania

    Science.gov (United States)

    Gross, Eliza L.; Low, Dennis J.

    2013-01-01

    Analytical results for arsenic in water samples from 5,023 wells obtained during 1969–2007 across Pennsylvania were compiled and related to other associated groundwater-quality and environmental factors and used to predict the probability of elevated arsenic concentrations, defined as greater than or equal to 4.0 micrograms per liter (µg/L), in groundwater. Arsenic concentrations of 4.0 µg/L or greater (elevated concentrations) were detected in 18 percent of samples across Pennsylvania; 8 percent of samples had concentrations that equaled or exceeded the U.S. Environmental Protection Agency’s drinking-water maximum contaminant level of 10.0 µg/L. The highest arsenic concentration was 490.0 µg/L.

  20. Factors influencing measurement of serum iron concentration in dogs: diurnal variation and hyperferritinemia.

    Science.gov (United States)

    Chikazawa, Seishiro; Hori, Yasutomo; Kanai, Kazutaka; Ito, Naoyuki; Hoshi, Fumio; Orino, Koichi; Watanabe, Kiyotaka; Higuchi, Seiichi

    2013-12-30

    We evaluated diurnal variation and hyperferritinemia as factors that influence the values of serum iron concentration in dogs, using the International Committee for Standardization in Hematology (ICSH) colorimetric method. Serum iron levels were significantly higher in the morning than in the evening in 6 clinically healthy beagle dogs, and the maximum decrease in serum iron concentration was 47.3%. Moreover, the change in serum iron concentrations in 22 clinical canine cases with various serum ferritin levels was evaluated by immunoprecipitation of ferritin. The rate of decline in the serum iron concentrations positively correlated with serum ferritin levels (r=0.48, P=0.024). These results show that it is necessary to consider the sampling time and serum ferritin level for accurate interpretation of serum iron concentrations in dogs.

  1. [Spatiotemporal distribution of negative air ion concentration in urban area and related affecting factors: a review].

    Science.gov (United States)

    Huang, Xiang-Hua; Wang, Jian; Zeng, Hong-Da; Chen, Guang-Shui; Zhong, Xian-Fang

    2013-06-01

    Negative air ion (NAI) concentration is an important indicator comprehensively reflecting air quality, and has significance to human beings living environment. This paper summarized the spatiotemporal distribution features of urban NAI concentration, and discussed the causes of these features based on the characteristics of the environmental factors in urban area and their effects on the physical and chemical processes of NAI. The temporal distribution of NAI concentration is mainly controlled by the periodic variation of solar radiation, while the spatial distribution of NAI concentration along the urban-rural gradient is mainly affected by the urban aerosol distribution, underlying surface characters, and urban heat island effect. The high NAI concentration in urban green area is related to the vegetation life activities and soil radiation, while the higher NAI concentration near the water environment is attributed to the water molecules that participate in the generation of NAI through a variety of ways. The other environmental factors can also affect the generation, life span, component, translocation, and distribution of NAI to some extent. To increase the urban green space and atmospheric humidity and to maintain the soil natural attributes of underlying surface could be the effective ways to increase the urban NAI concentration and improve the urban air quality.

  2. Ares I-X Flight Test Philosophy

    Science.gov (United States)

    Davis, S. R.; Tuma, M. L.; Heitzman, K.

    2007-01-01

    In response to the Vision for Space Exploration, the National Aeronautics and Space Administration (NASA) has defined a new space exploration architecture to return humans to the Moon and prepare for human exploration of Mars. One of the first new developments will be the Ares I Crew Launch Vehicle (CLV), which will carry the Orion Crew Exploration Vehicle (CEV), into Low Earth Orbit (LEO) to support International Space Station (ISS) missions and, later, support lunar missions. As part of Ares I development, NASA will perform a series of Ares I flight tests. The tests will provide data that will inform the engineering and design process and verify the flight hardware and software. The data gained from the flight tests will be used to certify the new Ares/Orion vehicle for human space flight. The primary objectives of this first flight test (Ares I-X) are the following: Demonstrate control of a dynamically similar integrated Ares CLV/Orion CEV using Ares CLV ascent control algorithms; Perform an in-flight separation/staging event between an Ares I-similar First Stage and a representative Upper Stage; Demonstrate assembly and recovery of a new Ares CLV-like First Stage element at Kennedy Space Center (KSC); Demonstrate First Stage separation sequencing, and quantify First Stage atmospheric entry dynamics and parachute performance; and Characterize the magnitude of the integrated vehicle roll torque throughout the First Stage (powered) flight. This paper will provide an overview of the Ares I-X flight test process and details of the individual flight tests.

  3. ALA-induced PpIX fluorescence in epileptogenic tissue

    Science.gov (United States)

    Kleen, Jonathan K.; Valdes, Pablo A.; Harris, Brent T.; Holmes, Gregory L.; Paulsen, Keith D.; Roberts, David W.

    2011-03-01

    Astrogliotic tissue displays markedly increased levels of ALA-induced PpIX fluorescence, making it useful for fluorescence-guided resection in glioma surgery. In patients with temporal lobe epilepsy (TLE) and corresponding animal models, there are areas of astrogliosis that often co-localize with the epileptic focus, which can be resected to eliminate seizures in the majority of treated patients. If this epileptogenic tissue can exhibit PpIX fluorescence that is sufficiently localized, it could potentially help identify margins in epilepsy surgery. We tested the hypothesis that ALA-induced PpIX fluorescence could visually accentuate epileptogenic tissue, using an established animal model of chronic TLE. An acute dose of pilocarpine was used to induce chronic seizure activity in a rat. This rat and a normal control were given ALA, euthanized, and brains examined post-mortem for PpIX fluorescence and neuropathology. Preliminary evidence indicates increased PpIX fluorescence in areas associated with chronic epileptic changes and seizure generation in TLE, including the hippocampus and parahippocampal areas. In addition, strong PpIX fluorescence was clearly observed in layer II of the piriform cortex, a region known for epileptic reorganization and involvement in the generation of seizures in animal studies. We are further investigating whether ALA-induced PpIX fluorescence can consistently identify epileptogenic zones, which could warrant the extension of this technique to clinical studies for use as an adjuvant guidance technology in the resection of epileptic tissue.

  4. Circulating concentrations of insulin-like growth factor-1 in dogs with naturally occurring mitral regurgitation

    DEFF Research Database (Denmark)

    Pedersen, Henrik Duelund; Falk, Bo Torkel; Häggström, Jens;

    2005-01-01

    Insulin-like growth factor-1 (IGF-1), which mediates most effects of growth hormone, has effects on cardiac mass and function, and plays an important role in the regulation of vascular tone. In humans, an inverse relationship between degree of heart failure (HF) and circulating IGF-1 concentrations...

  5. Folate intake, lifestyle factors, and homocysteine concentrations in younger and older women

    DEFF Research Database (Denmark)

    Rasmussen, Lone Banke; Ovesen, L.; Bulow, I.

    2000-01-01

    Background: An elevated total homocysteine (tHcy) concentration is considered to be an independent risk factor for cardiovascular diseases and has also been associated with an increased risk of neural tube defects. Objective: The objective of this study was to investigate folate intake, folate...

  6. Cross-system comparison of factors influencing chlorophyll-a concentration in Oregon estuaries

    Science.gov (United States)

    Water column chlorophyll-a (chla) is a proxy for phytoplankton biomass and is often used as a biological response indicator of eutrophication. Although watershed nutrient loading may influence chla concentration in estuaries, factors such as freshwater inflow, residence time, and...

  7. Physical limitations and fundamental factors affecting performance of liquid crystal tunable lenses with concentric electrode rings.

    Science.gov (United States)

    Li, Liwei; Bryant, Doug; van Heugten, Tony; Bos, Philip J

    2013-03-20

    A comprehensive analysis of fundamental factors and their effects on the performance of liquid crystal (LC)-based lenses is given. The analysis adopts numerical LC director and electric field simulation, as well as scalar diffraction theory for calculating the lens performance considering different variable factors. A high-efficiency LC lens with concentric electrode rings is fabricated for verifying and enriching the analysis. The measurement results are in close agreement with the analysis, and a summary of key factors is given with their quantitative contributions to the efficiency.

  8. Factors Affecting 25-Hydroxyvitamin D Concentration in Response to Vitamin D Supplementation

    Directory of Open Access Journals (Sweden)

    Hajar Mazahery

    2015-06-01

    Full Text Available Sun exposure is the main source of vitamin D. Due to many lifestyle risk factors vitamin D deficiency/insufficiency is becoming a worldwide health problem. Low 25(OHD concentration is associated with adverse musculoskeletal and non-musculoskeletal health outcomes. Vitamin D supplementation is currently the best approach to treat deficiency and to maintain adequacy. In response to a given dose of vitamin D, the effect on 25(OHD concentration differs between individuals, and it is imperative that factors affecting this response be identified. For this review, a comprehensive literature search was conducted to identify those factors and to explore their significance in relation to circulating 25(OHD response to vitamin D supplementation. The effect of several demographic/biological factors such as baseline 25(OHD, aging, body mass index(BMI/body fat percentage, ethnicity, calcium intake, genetics, oestrogen use, dietary fat content and composition, and some diseases and medications has been addressed. Furthermore, strategies employed by researchers or health care providers (type, dose and duration of vitamin D supplementation and environment (season are other contributing factors. With the exception of baseline 25(OHD, BMI/body fat percentage, dose and type of vitamin D, the relative importance of other factors and the mechanisms by which these factors may affect the response remains to be determined.

  9. Plasma-derived versus recombinant factor concentrates in PUPs: a never ending debate?

    Science.gov (United States)

    Berntorp, Erik

    2017-01-31

    Inhibitor development in haemophilia is a serious complication to treatment with factor concentrates. Since the advent of more pure products, especially developed using recombinant DNA technology, some studies have shown an increased incidence of inhibitors in previously untreated patients (PUPs) receiving recombinant products whereas plasma-derived concentrates sometimes have been claimed to have a protective role, probably due to the content of von Willebrand factor (VWF). In fact, experiments indicate that the VWF may block uptake of factor VIII into macrophages for further processing to the immune system. Also, a competition between VWF and inhibitor binding to the C2 domain of factor VIII has been suggested. Recently, large cohort and surveillance studies have created a vigorous debate about the role of product class for inhibitor development as results have been conflicting. The only randomised prospective study, the SIPPET study, was published in 2016, and substantiated previous reports claiming that plasma derived concentrates give less inhibitors in patients with severe haemophilia A, previously not exposed to factor VIII. The debate will continue.

  10. IBM PC/IX operating system evaluation plan

    Science.gov (United States)

    Dominick, Wayne D. (Editor); Granier, Martin; Hall, Philip P.; Triantafyllopoulos, Spiros

    1984-01-01

    An evaluation plan for the IBM PC/IX Operating System designed for IBM PC/XT computers is discussed. The evaluation plan covers the areas of performance measurement and evaluation, software facilities available, man-machine interface considerations, networking, and the suitability of PC/IX as a development environment within the University of Southwestern Louisiana NASA PC Research and Development project. In order to compare and evaluate the PC/IX system, comparisons with other available UNIX-based systems are also included.

  11. Leaf litter nitrogen concentration as related to climatic factors in Eurasian forests

    DEFF Research Database (Denmark)

    Liu, Chunjiang; Berg, Bjørn; Kutsch, Werner

    2006-01-01

    The aim of this study is to determine the patterns of nitrogen (N) concentrations in leaf litter of forest trees as functions of climatic factors, annual average temperature (Temp, °C) and annual precipitation (Precip, dm) and of forest type (coniferous vs. broadleaf, deciduous vs. evergreen, Pinus......, etc.). Location: The review was conducted using data from studies across the Eurasian continent. Methods: Leaf litter N concentration was compiled from 204 sets of published data (81 sets from coniferous and 123 from broadleaf forests in Eurasia). We explored the relationships between leaf litter N...... concentration and Temp and Precip by means of regression analysis. Leaf litter data from N2-fixing species were excluded from the analysis. Results: Over the Eurasian continent, leaf litter N concentration increased with increasing Temp and Precip within functional groups such as conifers, broadleaf, deciduous...

  12. Landscape factors and hydrology influence mercury concentrations in wading birds breeding in the Florida Everglades, USA.

    Science.gov (United States)

    Herring, Garth; Eagles-Smith, Collin A; Ackerman, Joshua T; Gawlik, Dale E; Beerens, James M

    2013-08-01

    The hydrology of wetland ecosystems is a key driver of both mercury (Hg) methylation and waterbird foraging ecology, and hence may play a fundamental role in waterbird exposure and risk to Hg contamination. However, few studies have investigated hydrological factors that influence waterbird Hg exposure. We examined how several landscape-level hydrological variables influenced Hg concentrations in great egret and white ibis adults and chicks in the Florida Everglades. The great egret is a visual "exploiter" species that tolerates lower prey densities and is less sensitive to hydrological conditions than is the white ibis, which is a tactile "searcher" species that pursues higher prey densities in shallow water. Mercury concentrations in adult great egrets were most influenced by the spatial region that they occupied in the Everglades (higher in the southern region); whereas the number of days a site was dry during the previous dry season was the most important factor influencing Hg concentrations in adult ibis (Hg concentrations increased with the number of days dry). In contrast, Hg concentrations in egret chicks were most influenced by calendar date (increasing with date), whereas Hg concentrations in ibis chicks were most influenced by chick age, region, and water recession rate (Hg concentrations decreased with age, were higher in the southern regions, and increased with positive water recession rates). Our results indicate that both recent (preceding two weeks) hydrological conditions, and those of the prior year, influence Hg concentrations in wading birds. Further, these results suggest that Hg exposure in wading birds is driven by complex relationships between wading bird behavior and life stage, landscape hydrologic patterns, and biogeochemical processes. Published by Elsevier B.V.

  13. Rotating night shift work, sleep quality, selected lifestyle factors and prolactin concentration in nurses and midwives.

    Science.gov (United States)

    Bukowska, Agnieszka; Sobala, Wojciech; Peplonska, Beata

    2015-04-01

    The pattern of secretion of many hormones, including prolactin, is dependent on the circadian rhythm. Night shift work involves exposure to artificial light at night and sleep deficiency, which in turn can affect prolactin synthesis. The aim of this study was to evaluate a possible association between night shift work characteristics, sleep quality, lifestyle factors and prolactin concentration, using data from a cross-sectional study of nurses and midwives. A cross-sectional study was conducted among 327 nurses and midwives currently working on rotating night shifts, and 330 nurses and midwives working during the day (aged 40-60 years) (388 premenopausal and 269 postmenopausal). Information about night shift work characteristics, lifestyle, reproductive factors, sleep pattern and other covariates was collected through a face-to-face interview, and from a one-week work and sleep diary completed by the subjects. Weight and height were measured. Prolactin concentration was measured in the morning blood sample using the electrochemiluminesence immunoassay method. Associations were analyzed using linear regression models adjusted for important confounders. Analyses were carried out separately in pre- and postmenopausal women. None of the night shift work or sleep characteristics was significantly associated with prolactin concentration. Prolactin concentration was significantly (p prolactin among premenopausal women, but inversely among postmenopausal. Age was related to prolactin among postmenopausal women only. Our study indicates that rotating night shift work is not associated with prolactin concentration. Smoking, parity, time of blood collection and age among postmenopausal women were significant determinants of prolactin.

  14. INFLUENCE OF HEXAVALENT CHROMIUM INITIAL CONCENTRATION ON RETARDATION FACTOR AND CONTAMINANT VELOCITY IN A SOIL MEDIA

    Directory of Open Access Journals (Sweden)

    K. SHIVA PRASHANTH KUMAR

    2016-02-01

    Full Text Available Sources of soil and ground water contamination are many and include many folds of accidental spills and leaks of toxic and hazardous chemicals. Preparation of ground water contamination model needs good understanding of the behavior of contaminant transport through soil media for predicting the level of contamination of ground water in the near future at the intended site conditions. Sorption is a natural process; due to its presence, the contaminant can move slowly as compared to the ground water and hence the effects of sorption must be taken into consideration while predicting the travel time of the contaminant to reach the ground water sources. This paper discusses the results of column test studies carried out in the laboratory under controlled conditions about the spreading of contaminant (Hexavalent chromium, Cr (VI through the clay mixed red soil at two different initial concentrations (800 mg/L and 4200 mg/L. The variations of the contaminant flow velocity and retardation factor for two different initial concentrations of contaminant were brought out and discussed. The contaminant flow velocity drastically coming down for a relative concentration of 0 to 0.2 and beyond this range, the contaminant flow velocity value is decreasing in a slow rate for both the lower and higher initial contaminant concentrations tested. At the lower relative concentration, the higher retardation factor was observed and it may be due to slowly filling the available sorption sites in the soil column.

  15. Metabolic syndrome, alcohol consumption and genetic factors are associated with serum uric acid concentration.

    Directory of Open Access Journals (Sweden)

    Blanka Stibůrková

    Full Text Available OBJECTIVE: Uric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals. METHODS: The cohort consisted of 589 healthy subjects aged 18-65 years. We studied the associations between the serum uric acid concentration and the following: (i demographic, anthropometric and other variables previously reported to be associated with serum uric acid concentrations; (ii the presence of metabolic syndrome and the levels of metabolic syndrome components; and (iii selected genetic variants of the MTHFR (c.665C>T, c.1286A>C, SLC2A9 (c.844G>A, c.881G>A and ABCG2 genes (c.421C>A. A backward model selection procedure was used to build two multiple linear regression models; in the second model, the number of metabolic syndrome criteria that were met replaced the metabolic syndrome-related variables. RESULTS: The models had coefficients of determination of 0.59 and 0.53. The serum uric acid concentration strongly correlated with conventional determinants including male sex, and with metabolic syndrome-related variables. In the simplified second model, the serum uric acid concentration positively correlated with the number of metabolic syndrome criteria that were met, and this model retained the explanatory power of the first model. Moderate wine drinking did not increase serum uric acid concentrations, and the urate transporter ABCG2, unlike MTHFR, was a genetic determinant of serum uric acid concentrations. CONCLUSION: Metabolic syndrome, moderate wine drinking and the c.421C>A variant in the ABCG gene are independently associated with the serum uric acid concentration. Our model indicates that uric acid should be clinically monitored in persons with metabolic syndrome.

  16. Comparative study of two routes of administration of 5-aminolevulinic acid (oral and intratumoral via) and their effect on the accumulation of PpIX in tissues in murine model of breast cancer

    Science.gov (United States)

    González-Agüero, G.; Ramón-Gallegos, E.

    2012-10-01

    Protoporphyrin IX (PpIX) is a photosensitizer synthesized from 5-aminolevulinic acid (ALA) that has been used in photodynamic therapy (PDT) as a promising treatment for many types of cancer. In this work it was quantified the accumulation of PpIX in tumors and in different tissues of female mice (nu/nu) inoculated with breast cancer cells. Two routes of administration of ALA: gastric probe and intratumoral injection were used to find optimum time of accumulation and the via that induce the higher quantity of PpIX to improve the efficiency of PDT. The results show that the accumulation of PpIX using the intratumoral via is two times bigger than the oral via in tumors at 8 h of treatment. The concentrations obtained in the different tissues are not physiologically significant.

  17. Protoporphyrin IX in the skin measured noninvasively predicts photosensitivity in patients with erythropoietic protoporphyria

    DEFF Research Database (Denmark)

    Heerfordt, I M; Wulf, H C

    2016-01-01

    BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare genetic disease that causes severe sensitivity to visible light as a result of protoporphyrin IX (PpIX) accumulation in the skin. OBJECTIVES: To establish a noninvasive method to measure PpIX in the skin of patients with EPP...... and to investigate how skin PpIX relates to erythrocyte PpIX and photosensitivity. METHODS: Skin PpIX was measured in 25 patients with EPP by calculating the difference in PpIX fluorescence before and after complete photobleaching of PpIX using controlled illumination. The patients reported symptoms during...... the illumination and skin erythema was measured before and after illumination. Confirmation of the presence of PpIX was obtained in seven patients by measuring the in vivo fluorescence emission spectrum. This method was used to examine skin PpIX during the hours after an illumination in seven patients. RESULTS: We...

  18. Bianchi-IX string cosmological model in Lyra geometry

    Indian Academy of Sciences (India)

    F Rahaman; S Chakraborty; N Begum; M Hossain; M Kalam

    2003-06-01

    A class of cosmological solutions of massive strings for the Bianchi-IX space-time are obtained within the framework of Lyra geometry. Various physical and kinematical properties of the models are discussed.

  19. The decrease of serum vascular endothelial growth factor concentration in patients with pregnancy induced hypertension

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objectives:To detect the concentration of serum vascular endothelial growth factor (VEGF) in patients with pregnancy induced hypertension (PIH) as well as to explore the role of VEGF in the pathogenesis of PIH.Methods:Serum VEGF concentrations in 23 healthy nonpregnant women (normal group),30 normal pregnant women (control group) and 37 women with PIH (PIH group) were measured by sandwich enzyme-linked immunoadsorbent assay (ELISA).Results:Serum concentrations of VEGF in control group were significantly higher (149.39±27.15ng/L) than those in normal group (11.98±3.99ng/L) (P<0.001),peaking in the second trimester of pregnancy (183.84±49.02ng/L) and decreasing in the third trimester (118.37±34.29ng/L).Serum VEGF concentrations (64.45±24.33ng/L) in PIH group were significantly lower than those in normal late pregnancy women of control group (118.37±34.29ng/L) (P<0.01).There was a trend that serum VEGF concentrations in PIH group decreased with the severity of PIH (P<0.05).Conclusion:The serum VEGF concentration in PIH women are significantly decreased,which suggests that VEGF may play an important role in the pathogenic mechanism of PIH.

  20. 硬汉 现代ix45

    Institute of Scientific and Technical Information of China (English)

    TNT

    2012-01-01

    在纽约车展亮相的现代圣达菲虽然采用了ix45的全新家族命名,但是在美国市场上还依旧傈留着Santa Fe的名字,预计年内在北京现代三工厂投产后也将采用ix45这一命名。

  1. Induced Protoporphyrin IX Accumulation by the δ-Aminolevulinic Acid in Bacteria and its Potential Use in the Photodynamic Therapy

    Science.gov (United States)

    Brígido-Aparicio, Cyntiha; Ramón-Gallegos, Eva; Arenas-Huertero, Francisco Jesús; Uribe-Hernández, Raúl

    2008-08-01

    The increasing incident of resistant strains to antibiotic has encouraged the search of new antibacterial treatments, such as the photodynamic therapy. In recent years, photodynamic therapy has demonstrated being a good technology for the treatment of recurrent bacteria infection. PDT presents a hopeful approach to eliminate Gram positive and negative bacteria in immunological compromised patients. This therapy uses a laser in combination with a photosensibilizer in presence of intracellular molecular oxygen. The process generates an effect of phototoxicity in bacterial cells. The aim of this work was to determine the in vitro conditions to accumulate PpIX in effective concentrations in Staphylococcus aureus ATCC25923 and Streptococcus pyogenes, which are responsible of human cutaneous diseases. A cellular suspension of both strains was prepared in TSB to obtain growth in Log-phase, then, the suspensions were adjusted to a final concentration of 2.61×108 cells/mL. The strains were exposed to increasing concentrations from 0 to 160μg/mL of δ-ALA in order to determinate the concentration that induces the biggest accumulation of PpIX. PpIX was measured using the Piomelli method modified for bacteria. The concentration selected was 40 mg/mL of ALA. It was found that in basal concentration of δ-ALA (0 μg/mL) both strains accumulated similar amount of PpIX. In concentrations of 5 mg/mL of δ-ALA it was observed a significant (p<0.001) increment in PpIX concentration. Finally it was realized a kinetic to determinate the optimal accumulation over the time at 0, 5, 10, 15 and 30 min, and 1, 2, 4, 8, 16 and 32 h. It was found that the ideal time for PDT application, in both strains, was 24 h because in smaller times there was not statistically significant difference. The S. aureus ATCC25923 accumulated significantly the biggest concentration of PpIX with regard to S. pyogenes. In conclusion, it was found that the optimal conditions to apply PDT will be to expose both

  2. Imaging shear stress distribution and evaluating the stress concentration factor of the human eye

    Science.gov (United States)

    Joseph Antony, S.

    2015-03-01

    Healthy eyes are vital for a better quality of human life. Historically, for man-made materials, scientists and engineers use stress concentration factors to characterise the effects of structural non-homogeneities on their mechanical strength. However, such information is scarce for the human eye. Here we present the shear stress distribution profiles of a healthy human cornea surface in vivo using photo-stress analysis tomography, which is a non-intrusive and non-X-ray based method. The corneal birefringent retardation measured here is comparable to that of previous studies. Using this, we derive eye stress concentration factors and the directional alignment of major principal stress on the surface of the cornea. Similar to thermometers being used for monitoring the general health in humans, this report provides a foundation to characterise the shear stress carrying capacity of the cornea, and a potential bench mark for validating theoretical modelling of stresses in the human eye in future.

  3. Hair mercury concentrations and associated factors in an electronic waste recycling area, Guiyu, China

    Energy Technology Data Exchange (ETDEWEB)

    Ni, Wenqing [Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong (China); Chen, Yaowen [Central Laboratory of Shantou University, Shantou 515063, Guangdong (China); Huang, Yue; Wang, Xiaoling [Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong (China); Zhang, Gairong [Central Laboratory of Shantou University, Shantou 515063, Guangdong (China); Luo, Jiayi [Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong (China); Wu, Kusheng, E-mail: kswu@stu.edu.cn [Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong (China)

    2014-01-15

    Objective: Toxic heavy metals are released to the environment constantly from unregulated electronic waste (e-waste) recycling in Guiyu, China, and thus may contribute to the elevation of mercury (Hg) and other heavy metals levels in human hair. We aimed to investigate concentrations of mercury in hair from Guiyu and potential risk factors and compared them with those from a control area where no e-waste processing occurs. Methods: A total of 285 human hair samples were collected from three villages (including Beilin, Xianma, and Huamei) of Guiyu (n=205) and the control area, Jinping district of Shantou city (n=80). All the volunteers were administered a questionnaire regarding socio-demographic characteristics and other possible factors contributed to hair mercury concentration. Hair mercury concentration was analyzed by hydride generation atomic fluorescence spectrometry (AFS). Results: Our results suggested that hair mercury concentrations in volunteers of Guiyu (median, 0.99; range, 0.18–3.98 μg/g) were significantly higher than those of Jinping (median, 0.59; range, 0.12–1.63 μg/g). We also observed a higher over-limit ratio (>1 μg/g according to USEPA) in Guiyu than in Jinping (48.29% vs. 11.25%, P<0.001). Logistic regression model showed that the variables of living house also served as an e-waste workshop, work related to e-waste, family income, time of residence in Guiyu, the distance between home and waste incineration, and fish intake were associated with hair mercury concentration. After multiple stepwise regression analysis, in the Guiyu samples, hair mercury concentration was found positively associated with the time residence in Guiyu (β=0.299, P<0.001), and frequency of shellfish intake (β=0.184, P=0.016); and negatively associated with the distance between home and waste incineration (β=−0.190, P=0.015) and whether house also served as e-waste workshop (β=−0.278, P=0.001). Conclusions: This study investigated human mercury exposure

  4. Silicon concentrator cells in a two-stage photovoltaic system with a concentration factor of 300x

    Energy Technology Data Exchange (ETDEWEB)

    Mohr, A.

    2005-06-15

    In this work a rear contacted silicon concentrator cell was developed for an application in a two stage concentrator photovoltaic system. This system was developed at Fraunhofer ISE some years ago. The innovation of this one-axis tracked system is that it enables a high geometrical concentration of 300x in combination with a high optical efficiency (around 78%) and a large acceptance angle of {+-}23.5 all year through. For this, the system uses a parabolic mirror (40.4x) and a three dimensional second stage consisting of compound parabolic concentrators (CPCs, 7.7x). For the concentrator concept and particularly for an easy cell integration, the rear line contacted concentrator (RLCC) cells with a maximum efficiency of 25% were developed and a hybrid mounting concept for the RLCC cells is presented. The optical performance of different CPC materials was tested and analysed in this work. Finally, small modules consisting of six series interconnected RLCC cells and six CPCs were integrated into the concentrator system and tested outdoor. A system efficiency of 16.2% was reached at around 800 W/m2 direct irradiance under realistic outdoor conditions. (orig.)

  5. Protoporphyrin IX Content Correlates with Activity of Photobleaching Herbicides

    Science.gov (United States)

    Becerril, Jose M.; Duke, Stephen O.

    1989-01-01

    Several laboratories have demonstrated recently that photobleaching herbicides such as acifluorfen and oxadiazon cause accumulation of protoporphyrin IX (PPIX), a photodynamic pigment capable of herbicidal activity. We investigated, in acifluorfen-treated tissues, the in vivo stability of PPIX, the kinetics of accumulation, and the correlation between concentration of PPIX and herbicidal damage. During a 20 hour dark period, PPIX levels rose from barely detectable concentrations to 1 to 2 nanomoles per 50 cucumber (Cucumis sativus L.) cotyledon discs treated with 10 micromolar acifluorfen. When placed in 500 micromoles per square meter per second PAR, PPIX levels decayed logarithmically, with an initial half-life of about 2.5 hours. PPIX levels at each time after exposure to light correlated positively with the cellular damage that occurred during the following 1 hour in both green and yellow (tentoxin-treated) cucumber cotyledon tissues. PPIX levels in discs incubated for 20 hours in darkness correlated positively with the acifluorfen concentration in which they were incubated. In cucumber, the level of herbicidal damage caused by several p-nitrodiphenyl other herbicides, a p-chlorodiphenylether herbicide, and oxadiazon correlated positively with the amount of PPIX induced to accumulate by each of the herbicide treatments. Similar results were obtained with acifluorfen-treated pigweed and velvetleaf primary leaf tissues. In cucumber, PPIX levels increased within 15 and 30 minutes after exposure of discs to 10 micromolar acifluorfen in the dark and light, respectively. These data strengthen the view that PPIX is responsible for all or a major part of the photobleaching activity of acifluorfen and related herbicides. PMID:16666869

  6. Serum selenium concentration is associated with metabolic factors in the elderly: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Huang Hui-Ying

    2010-05-01

    Full Text Available Abstract Background Selenium is an essential micronutrient known for its antioxidant function. However, the association of serum selenium with lipid profiles and fasting glucose are inconsistent in populations with average intake of selenium. Furthermore, there were few studies conducted specifically for the elderly. This study examined the relationship of serum selenium concentration with serum lipids and fasting glucose in the Taiwanese elderly population. Methods This was a cross-sectional study of 200 males and females aged 65-85 years (mean 71.5 ± 4.6 years from Taipei, Taiwan. Serum selenium was measured by inductively coupled plasma-mass spectrometer. The association between serum selenium and metabolic factors was examined using a multivariate linear regression analysis after controlling several confounders. Results The mean serum selenium concentration was 1.14 μmol/L, without significant difference between sexes. Total cholesterol, triglycerides, and LDL cholesterol increased significantly with serum selenium concentration (P P P P Conclusions Total cholesterol, triglycerides, and LDL cholesterol, and fasting serum glucose concentrations increased significantly with serum selenium concentration in the Taiwanese elderly. The underlying mechanism warrants further research.

  7. Environmental Factors and Seasonality Affect the Concentration of Rotundone in Vitis vinifera L. cv. Shiraz Wine

    Science.gov (United States)

    Zhang, Pangzhen; Howell, Kate; Krstic, Mark; Herderich, Markus; Barlow, Edward William R.; Fuentes, Sigfredo

    2015-01-01

    Rotundone is a sesquiterpene that gives grapes and wine a desirable ‘peppery’ aroma. Previous research has reported that growing grapevines in a cool climate is an important factor that drives rotundone accumulation in grape berries and wine. This study used historical data sets to investigate which weather parameters are mostly influencing rotundone concentration in grape berries and wine. For this purpose, wines produced from 15 vintages from the same Shiraz vineyard (The Old Block, Mount Langi Ghiran, Victoria, Australia) were analysed for rotundone concentration and compared to comprehensive weather data and minimal temperature information. Degree hours were obtained by interpolating available temperature information from the vineyard site using a simple piecewise cubic hermite interpolating polynomial method (PCHIP). Results showed that the highest concentrations of rotundone were consistently found in wines from cool and wet seasons. The Principal Component Analysis (PCA) showed that the concentration of rotundone in wine was negatively correlated with daily solar exposure and grape bunch zone temperature, and positively correlated with vineyard water balance. Finally, models were constructed based on the Gompertz function to describe the dynamics of rotundone concentration in berries through the ripening process according to phenological and thermal times. This characterisation is an important step forward to potentially predict the final quality of the resultant wines based on the evolution of specific compounds in berries according to critical environmental and micrometeorological variables. The modelling techniques described in this paper were able to describe the behaviour of rotundone concentration based on seasonal weather conditions and grapevine phenological stages, and could be potentially used to predict the final rotundone concentration early in future growing seasons. This could enable the adoption of precision irrigation and canopy

  8. PARTICULATE MATTER CONCENTRATION AND EMISSION FACTOR IN THREE DIFFERENT LAYING HEN HOUSING SYSTEMS

    Directory of Open Access Journals (Sweden)

    Annamaria Costa

    2009-09-01

    Full Text Available The aim of this study was to evaluate PM10 concentration in three different laying hens houses (traditional battery cages with aerated open manure storage, aviary system and vertical tiered cages with manure belts with forced air drying and to evaluate particulate matter emission into atmosphere during one year of observation. Internal and external temperature and relative humidity, ventilation rate, PM10 concentration have been continuously monitored in order to evaluate particulate matter concentration changes during the day and the season and to define PM10 emission factors. PM10 concentration was corrected by gravimetric technique to lower measurements error. In the aviary system house, TSP and fine particulate matter (particles smaller than 2.5 micron concentration was measured. Average yearly PM10 concentration was remarkably higher in the aviary system house with 0.215 mg m-3 vs 108 mg m-3 for the ventilated belt house and vs 0.094 mg m-3 for the traditional battery cages house. In the Aviary system housing, TSP concentration was 0.444 mg m-3 and PM2.5 was 0.032 mg m-3, highlighting the existence of a severe working environment for men and animals. Recorded values for PM10 emission were 0.433 mg h-1 hen-1 for battery cages housing type, 0.081 mg h-1 hen-1 for ventilated belt cages house, values lower than those available in literature, while the aviary system housing type showed the highest PM10 emission (1.230 mg h-1 hen-1 with appreciable peaks during the morning, together with the increased animal activity and daily farmer operations, as feed administration, cleaning and droppings removal.

  9. Environmental Factors and Seasonality Affect the Concentration of Rotundone in Vitis vinifera L. cv. Shiraz Wine.

    Science.gov (United States)

    Zhang, Pangzhen; Howell, Kate; Krstic, Mark; Herderich, Markus; Barlow, Edward William R; Fuentes, Sigfredo

    2015-01-01

    Rotundone is a sesquiterpene that gives grapes and wine a desirable 'peppery' aroma. Previous research has reported that growing grapevines in a cool climate is an important factor that drives rotundone accumulation in grape berries and wine. This study used historical data sets to investigate which weather parameters are mostly influencing rotundone concentration in grape berries and wine. For this purpose, wines produced from 15 vintages from the same Shiraz vineyard (The Old Block, Mount Langi Ghiran, Victoria, Australia) were analysed for rotundone concentration and compared to comprehensive weather data and minimal temperature information. Degree hours were obtained by interpolating available temperature information from the vineyard site using a simple piecewise cubic hermite interpolating polynomial method (PCHIP). Results showed that the highest concentrations of rotundone were consistently found in wines from cool and wet seasons. The Principal Component Analysis (PCA) showed that the concentration of rotundone in wine was negatively correlated with daily solar exposure and grape bunch zone temperature, and positively correlated with vineyard water balance. Finally, models were constructed based on the Gompertz function to describe the dynamics of rotundone concentration in berries through the ripening process according to phenological and thermal times. This characterisation is an important step forward to potentially predict the final quality of the resultant wines based on the evolution of specific compounds in berries according to critical environmental and micrometeorological variables. The modelling techniques described in this paper were able to describe the behaviour of rotundone concentration based on seasonal weather conditions and grapevine phenological stages, and could be potentially used to predict the final rotundone concentration early in future growing seasons. This could enable the adoption of precision irrigation and canopy management

  10. Environmental Factors and Seasonality Affect the Concentration of Rotundone in Vitis vinifera L. cv. Shiraz Wine.

    Directory of Open Access Journals (Sweden)

    Pangzhen Zhang

    Full Text Available Rotundone is a sesquiterpene that gives grapes and wine a desirable 'peppery' aroma. Previous research has reported that growing grapevines in a cool climate is an important factor that drives rotundone accumulation in grape berries and wine. This study used historical data sets to investigate which weather parameters are mostly influencing rotundone concentration in grape berries and wine. For this purpose, wines produced from 15 vintages from the same Shiraz vineyard (The Old Block, Mount Langi Ghiran, Victoria, Australia were analysed for rotundone concentration and compared to comprehensive weather data and minimal temperature information. Degree hours were obtained by interpolating available temperature information from the vineyard site using a simple piecewise cubic hermite interpolating polynomial method (PCHIP. Results showed that the highest concentrations of rotundone were consistently found in wines from cool and wet seasons. The Principal Component Analysis (PCA showed that the concentration of rotundone in wine was negatively correlated with daily solar exposure and grape bunch zone temperature, and positively correlated with vineyard water balance. Finally, models were constructed based on the Gompertz function to describe the dynamics of rotundone concentration in berries through the ripening process according to phenological and thermal times. This characterisation is an important step forward to potentially predict the final quality of the resultant wines based on the evolution of specific compounds in berries according to critical environmental and micrometeorological variables. The modelling techniques described in this paper were able to describe the behaviour of rotundone concentration based on seasonal weather conditions and grapevine phenological stages, and could be potentially used to predict the final rotundone concentration early in future growing seasons. This could enable the adoption of precision irrigation and

  11. Hair mercury concentrations and associated factors in an electronic waste recycling area, Guiyu, China.

    Science.gov (United States)

    Ni, Wenqing; Chen, Yaowen; Huang, Yue; Wang, Xiaoling; Zhang, Gairong; Luo, Jiayi; Wu, Kusheng

    2014-01-01

    Toxic heavy metals are released to the environment constantly from unregulated electronic waste (e-waste) recycling in Guiyu, China, and thus may contribute to the elevation of mercury (Hg) and other heavy metals levels in human hair. We aimed to investigate concentrations of mercury in hair from Guiyu and potential risk factors and compared them with those from a control area where no e-waste processing occurs. A total of 285 human hair samples were collected from three villages (including Beilin, Xianma, and Huamei) of Guiyu (n=205) and the control area, Jinping district of Shantou city (n=80). All the volunteers were administered a questionnaire regarding socio-demographic characteristics and other possible factors contributed to hair mercury concentration. Hair mercury concentration was analyzed by hydride generation atomic fluorescence spectrometry (AFS). Our results suggested that hair mercury concentrations in volunteers of Guiyu (median, 0.99; range, 0.18-3.98μg/g) were significantly higher than those of Jinping (median, 0.59; range, 0.12-1.63μg/g). We also observed a higher over-limit ratio (>1μg/g according to USEPA) in Guiyu than in Jinping (48.29% vs. 11.25%, P<0.001). Logistic regression model showed that the variables of living house also served as an e-waste workshop, work related to e-waste, family income, time of residence in Guiyu, the distance between home and waste incineration, and fish intake were associated with hair mercury concentration. After multiple stepwise regression analysis, in the Guiyu samples, hair mercury concentration was found positively associated with the time residence in Guiyu (β=0.299, P<0.001), and frequency of shellfish intake (β=0.184, P=0.016); and negatively associated with the distance between home and waste incineration (β=-0.190, P=0.015) and whether house also served as e-waste workshop (β=-0.278, P=0.001). This study investigated human mercury exposure and suggested elevated hair mercury concentrations in

  12. [Implant fixation strength and osseointegration following systemic administration of recombinant factor XIII and factor XIII concentrate. Animal experiment with implant fixation strength and osseointegration of porous surface implants].

    Science.gov (United States)

    Kienapfel, H; Wilke, A; Dörner, P; Jürgensen, R; Prinz, H; Hettel, A; Swain, R; Griss, P

    1995-01-01

    30 cylindrical commercially pure titanium fiber porous coated Ti6A14V implants were inserted press-fit into the proximal humeral portion of 30 sheep humeri to determine the systemic effect of recombinant factor XIII and placenta-derived factor XIII concentrate on bone ingrowth and on strength of fixation. For both the recombinant factor XIII and the factor XIII concentrate group the volume fraction of bone ingrowth and the strength of fixation was higher when compared with the control specimens. However the difference was only significant for the factor XIII concentrate group.

  13. Various Oscillation Patterns of Serum Fibroblast Growth Factor 21 Concentrations in Healthy Volunteers

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    Sang Ah Lee

    2012-02-01

    Full Text Available BackgroundFibroblast growth factor 21 (FGF21 was originally identified as a paroxysm proliferator activated receptor-α target gene product and is a hormone involved in metabolic regulation. The purpose of this study was to investigate the diurnal variation of serum FGF21 concentration in obese and non-obese healthy volunteers.MethodsBlood samples were collected from five non-obese (body mass index [BMI] ≤23 kg/m2 and five obese (BMI ≥25 kg/m2 healthy young men every 30 to 60 minutes over 24 hours. Serum FGF21 concentrations were determined by radioimmunoassay. Anthropometric parameters, glucose, free fatty acid, insulin, leptin, and cortisol concentrations were also measured.ResultsThe serum FGF21 concentrations displayed various individual oscillation patterns. The oscillation frequency ranged between 6 and 12 times per day. The average duration of oscillation was 2.52 hours (range, 1.9 to 3.0 hours. The peaks and troughs of FGF21 oscillation showed no circadian rhythm. However, the oscillation frequency had a diurnal variation and was lower during the light-off period than during the light-on period (2.4 vs. 7.3 times, P<0.001. There was no difference in the total frequency or duration of oscillations between non-obese and obese subjects, but obese individuals had increased numbers of larger oscillations (amplitude ≥0.19 ng/mL.ConclusionVarious oscillation patterns in serum FGF21 concentration were observed, and reduced oscillation frequencies were seen during sleep. The oscillation patterns of serum FGF21 concentration suggest that FGF21 may be secreted into systemic circulation in a pulsatile manner. Obesity appeared to affect the amplitude of oscillations of serum FGF21.

  14. Factors affecting Escherichia coli concentrations at Lake Erie public bathing beaches

    Science.gov (United States)

    Francy, Donna S.; Darner, Robert A.

    1998-01-01

    The environmental and water-quality factors that affect concentrations of Escherichia coli (E. coli) in water and sediment were investigated at three public bathing beachesEdgewater Park, Villa Angela, and Sims Parkin the Cleveland, Ohio metropolitan area. This study was done to aid in the determination of safe recreational use and to help water- resource managers assess more quickly and accurately the degradation of recreational water quality. Water and lake-bottom sediments were collected and ancillary environmental data were compiled for 41 days from May through September 1997. Water samples were analyzed for E. coli concentrations, suspended sediment concentrations, and turbidity. Lake- bottom sediment samples from the beach area were analyzed for E. coli concentrations and percent dry weight. Concentrations of E. coli were higher and more variable at Sims Park than at Villa Angela or Edgewater Park; concentrations were lowest at Edgewater Park. Time-series plots showed that short-term storage (less than one week) of E. coli in lake-bottom sediments may have occurred, although no evidence for long-term storage was found during the sampling period. E. coli concentrations in water were found to increase with increasing wave height, but the resuspension of E. coli from lake-bottom sediments by wave action could not be adequately assessed; higherwave heights were often associated with the discharge of sewage containing E. coli during or after a rainfall and wastewater-treatment plant overflow. Multiple linear regression (MLR) was used to develop models to predict recreational water quality at the in water. The related variables included turbidity, antecedent rainfall, antecedent weighted rainfall, volumes of wastewater-treatment plant overflows and metered outfalls (composed of storm-water runoff and combined-sewer overflows), a resuspension index, and wave heights. For the beaches in this study, wind speed, wind direction, water temperature, and the prswimmers

  15. Total flavonoid concentrations of bryophytes from Tianmu Mountain, Zhejiang Province (China): Phylogeny and ecological factors

    Science.gov (United States)

    Cao, Jianguo; Dai, Xiling; Xiao, Jianbo; Wu, Yuhuan; Wang, Quanxi

    2017-01-01

    The flavonoids in bryophytes may have great significance in phylogeny and metabolism research. However, to date there has been little research on bryophyte metabolites, especially flavonoids. To redress this somewhat, we determined flavonoid concentrations of bryophytes from Tianmu Mountain through a colorimetric assay and considered the factors influencing the results. This is the first time that the flavonoid contents of bryophytes have been examined in detail. The results revealed a range of total flavonoid concentrations in 90 samples collected from Tianmu Mountain from 1.8 to 22.3 mg/g (w/w). The total flavonoid contents of liverworts were generally higher than those of mosses; acrocarpous mosses had generally higher values than that of pleurocarpous mosses. The total flavonoid contents of bryophytes growing at lower light levels were general higher than those growing in full-sun. The total flavonoid contents of epiphytic bryophytes were highest, while those of aquatic bryophytes were the lowest. Total flavonoid contents of species growing at low-latitudes were much higher than those at high-latitude individuals. In conclusion, total flavonoid contents of bryophytes have some connection with plant phylogeny; more flavonoids might be contained in relatively primitive bryophytes. Meanwhile, the effects of ecological factors on total flavonoid contents of bryophytes exist; light and habitat (especially tree habitat and river habitat) might be representative factor. PMID:28263997

  16. Total flavonoid concentrations of bryophytes from Tianmu Mountain, Zhejiang Province (China): Phylogeny and ecological factors.

    Science.gov (United States)

    Wang, Xin; Cao, Jianguo; Dai, Xiling; Xiao, Jianbo; Wu, Yuhuan; Wang, Quanxi

    2017-01-01

    The flavonoids in bryophytes may have great significance in phylogeny and metabolism research. However, to date there has been little research on bryophyte metabolites, especially flavonoids. To redress this somewhat, we determined flavonoid concentrations of bryophytes from Tianmu Mountain through a colorimetric assay and considered the factors influencing the results. This is the first time that the flavonoid contents of bryophytes have been examined in detail. The results revealed a range of total flavonoid concentrations in 90 samples collected from Tianmu Mountain from 1.8 to 22.3 mg/g (w/w). The total flavonoid contents of liverworts were generally higher than those of mosses; acrocarpous mosses had generally higher values than that of pleurocarpous mosses. The total flavonoid contents of bryophytes growing at lower light levels were general higher than those growing in full-sun. The total flavonoid contents of epiphytic bryophytes were highest, while those of aquatic bryophytes were the lowest. Total flavonoid contents of species growing at low-latitudes were much higher than those at high-latitude individuals. In conclusion, total flavonoid contents of bryophytes have some connection with plant phylogeny; more flavonoids might be contained in relatively primitive bryophytes. Meanwhile, the effects of ecological factors on total flavonoid contents of bryophytes exist; light and habitat (especially tree habitat and river habitat) might be representative factor.

  17. Low dialysate potassium concentration: an overrated risk factor for cardiac arrhythmia?

    Science.gov (United States)

    Abuelo, J Gary

    2015-01-01

    Serum potassium concentrations rise with dietary potassium intake between dialysis sessions and are often at hyperkalemic levels by the next session. Conversely, potassium concentrations fall during each hemodialysis, and sometimes reach hypokalemic levels by the end. Low potassium dialysate, which rapidly decreases serum potassium and often brings it to hypokalemic levels, is almost universally considered a risk factor for life-threatening arrhythmias. While there is little doubt about the threat of lethal arrhythmias due to hyperkalemia, convincing evidence for the danger of low potassium dialysate and rapid or excess potassium removal has not been forthcoming. The original report of more frequent ventricular ectopy in early dialysis that was improved by reducing potassium removal has received very little confirmation from subsequent studies. Furthermore, the occurrence of ventricular ectopy during dialysis does not appear to predict mortality. Studies relating sudden deaths to low potassium dialysate are countered by studies with more thorough adjustment for markers of poor health. Dialysate potassium concentrations affect the excursions of serum potassium levels above or below the normal range, and have the potential to influence dialysis safety. Controlled studies of different dialysate potassium concentration and their effect on mortality and cardiac arrests have not been done. Until these results become available, I propose interim guidelines for the setting of dialysate potassium levels that may better balance risks and benefits.

  18. Plasma concentrations of blood coagulation factor VII measured by immunochemical and amidolytic methods

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Gram, J; Jespersen, J

    2000-01-01

    plasma, in cold activated plasma and in FVII deficient plasma. There was a positive correlation (r=0.96) between FVII:Ag and FVII:Am with slightly but significantly higher values for FVII:Ag (FVII:Ag= 106 U/ml and FVII:Am=100 U/ml; p ...Ever since the coagulant activity of blood coagulation factor VII (FVII:C) was identified as a risk indicator of cardiac death, a large number of studies have measured FVII protein concentrations in plasma. FVII protein concentrations are either measured immunologically with an ELISA method (FVII......:Ag) or estimated with an amidolytic method (FVII:Am). We have investigated whether FVII:Am is a valuable alternative to FVII:Ag. FVII:Ag and FVII:Am were measured in 147 plasma samples from blood donors, patients on oral anticoagulant therapy, postmenopausal women on hormone replacement therapy, in postprandial...

  19. Subinhibitory concentrations of perilla oil affect the expression of secreted virulence factor genes in Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Jiazhang Qiu

    Full Text Available BACKGROUND: The pathogenicity of staphylococcus aureus is dependent largely upon its ability to secrete a number of virulence factors, therefore, anti-virulence strategy to combat S. aureus-mediated infections is now gaining great interest. It is widely recognized that some plant essential oils could affect the production of staphylococcal exotoxins when used at subinhibitory concentrations. Perilla [Perilla frutescens (L. Britton], a natural medicine found in eastern Asia, is primarily used as both a medicinal and culinary herb. Its essential oil (perilla oil has been previously demonstrated to be active against S. aureus. However, there are no data on the influence of perilla oil on the production of S. aureus exotoxins. METHODOLOGY/PRINCIPAL FINDINGS: A broth microdilution method was used to determine the minimum inhibitory concentrations (MICs of perilla oil against S. aureus strains. Hemolysis, tumour necrosis factor (TNF release, Western blot, and real-time RT-PCR assays were performed to evaluate the effects of subinhibitory concentrations of perilla oil on exotoxins production in S. aureus. The data presented here show that perilla oil dose-dependently decreased the production of α-toxin, enterotoxins A and B (the major staphylococcal enterotoxins, and toxic shock syndrome toxin 1 (TSST-1 in both methicillin-sensitive S. aureus (MSSA and methicillin-resistant S. aureus (MRSA. CONCLUSIONS/SIGNIFICANCE: The production of α-toxin, SEA, SEB, and TSST-1 in S. aureus was decreased by perilla oil. These data suggest that perilla oil may be useful for the treatment of S. aureus infections when used in combination with β-lactam antibiotics, which can increase exotoxins production by S. aureus at subinhibitory concentrations. Furthermore, perilla oil could be rationally applied in food systems as a novel food preservative both to inhibit the growth of S. aureus and to repress the production of exotoxins, particularly staphylococcal enterotoxins.

  20. BTEX in indoor air of waterpipe cafés: Levels and factors influencing their concentrations.

    Science.gov (United States)

    Hazrati, Sadegh; Rostami, Roohollah; Fazlzadeh, Mehdi

    2015-08-15

    BTEX (benzene, toluene, ethylbenzene and xylene) concentrations, factors affecting their levels, and the exposure risks related to these compounds were studied in waterpipe (Ghalyun/Hookah) cafés of Ardabil city in Islamic Republic of Iran. 81 waterpipe cafés from different districts of Ardabil city were selected and their ambient air was monitored for BTEX compounds. Air samples were taken from standing breathing zone of employees, ~150 cm above the ground level, and were analyzed using GC-FID. In each case, the types of smoked tobacco (regular, fruit flavored), types of ventilation systems (natural/artificial), and the floor level at which the café was located were investigated. A high mean concentration of 4.96±2.63 mg/m(3) corresponding to long term exposure to benzene-related cancer risk of 4314×10(-6) was estimated. The levels of the remaining compounds were lower than the national guideline limits, but their hazard quotients (HQ) for long term exposure to ethylbenzene (1.15) and xylene (17.32) exceeded the HQ unit value. Total hazard indices (HI) of 63.23 were obtained for non-cancer risks. Type of the smoked tobacco was the most important factor influencing BTEX concentrations in the cafés. BTEX concentrations in indoor ambient air of Ardabil waterpipe cafés were noticeably high, and therefore may pose important risks for human health on both short and long term exposures. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Folate intake, lifestyle factors, and homocysteine concentrations in younger and older women

    DEFF Research Database (Denmark)

    Rasmussen, Lone Banke; Ovesen, L.; Bulow, I.

    2000-01-01

    Background: An elevated total homocysteine (tHcy) concentration is considered to be an independent risk factor for cardiovascular diseases and has also been associated with an increased risk of neural tube defects. Objective: The objective of this study was to investigate folate intake, folate...... linear regression analyses. Smoking status, coffee consumption, systolic blood pressure, and body mass index were positively associated and estrogen replacement therapy and tea consumption were inversely associated with log tHcy in some of the models. Conclusions: According to the criteria used, between...

  2. Factoring the brain signatures of anesthesia concentration and level of arousal across individuals

    Science.gov (United States)

    Barttfeld, Pablo; Bekinschtein, Tristan A.; Salles, Alejo; Stamatakis, Emmanuel A.; Adapa, Ram; Menon, David K.; Sigman, Mariano

    2015-01-01

    Combining resting-state functional magnetic resonance imaging (fMRI) connectivity and behavioral analysis during sedation, we factored out general effects of the anesthetic drug propofol and a specific index of conscious report, participants’ level of responsiveness. The factorial analysis shows that increasing concentration of propofol in blood specifically decreases the connectivity strength of fronto-parietal cortical loops. In contrast, loss of responsiveness is indexed by a functional disconnection between the thalamus and the frontal cortex, balanced by an increase in connectivity strength of the thalamus to the occipital and temporal regions of the cortex. PMID:26509121

  3. Therapeutic Potential of Adipose-Derived Therapeutic Factor Concentrate for Treating Critical Limb Ischemia.

    Science.gov (United States)

    Procházka, Václav; Jurčíková, Jana; Laššák, Ondrej; Vítková, Kateřina; Pavliska, Lubomír; Porubová, Ludmila; Buszman, Piotr P; Krauze, Agata; Fernandez, Carlos; Jalůvka, František; Špačková, Iveta; Lochman, Ivo; Jana, Dvořáčková; Merfeld-Clauss, Stephanie; March, Keith L; Traktuev, Dmitry O; Johnstone, Brian H

    2016-01-01

    Transplantation of adipose-derived stem cells (ADSCs) is an emerging therapeutic option for addressing intractable diseases such as critical limb ischemia (CLI). Evidence suggests that therapeutic effects of ADSCs are primarily mediated through paracrine mechanisms rather than transdifferentiation. These secreted factors can be captured in conditioned medium (CM) and concentrated to prepare a therapeutic factor concentrate (TFC) composed of a cocktail of beneficial growth factors and cytokines that individually and in combination demonstrate disease-modifying effects. The ability of a TFC to promote reperfusion in a rabbit model of CLI was evaluated. A total of 27 adult female rabbits underwent surgery to induce ischemia in the left hindlimb. An additional five rabbits served as sham controls. One week after surgery, the ischemic limbs received intramuscular injections of either (1) placebo (control medium), (2) a low dose of TFC, or (3) a high dose of TFC. Limb perfusion was serially assessed with a Doppler probe. Blood samples were analyzed for growth factors and cytokines. Tissue was harvested postmortem on day 35 and assessed for capillary density by immunohistochemistry. At 1 month after treatment, tissue perfusion in ischemic limbs treated with a high dose of TFC was almost double (p < 0.05) that of the placebo group [58.8 ± 23 relative perfusion units (RPU) vs. 30.7 ± 13.6 RPU; mean ± SD]. This effect was correlated with greater capillary density in the affected tissues and with transiently higher serum levels of the angiogenic and prosurvival factors vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). The conclusions from this study are that a single bolus administration of TFC demonstrated robust effects for promoting tissue reperfusion in a rabbit model of CLI and that a possible mechanism of revascularization was promotion of angiogenesis by TFC. Results of this study demonstrate that TFC represents a potent

  4. Iron and obesity status-associated insulin resistance influence circulating fibroblast-growth factor-23 concentrations.

    Directory of Open Access Journals (Sweden)

    José Manuel Fernández-Real

    Full Text Available Fibroblast growth factor 23 (FGF-23 is known to be produced by the bone and linked to metabolic risk. We aimed to explore circulating FGF-23 in association with fatness and insulin sensitivity, atherosclerosis and bone mineral density (BMD. Circulating intact FGF-23 (iFGF-23 and C-terminal (CtFGF-23 concentrations (ELISA were measured in 133 middle aged men from the general population in association with insulin sensitivity (Cohort 1; and in association with fat mass and bone mineral density (DEXA and atherosclerosis (intima media thickness, IMT in 78 subjects (52 women with a wide range of adiposity (Cohort 2. Circulating iFGF-23 was also measured before and after weight loss. In all subjects as a whole, serum intact and C-terminal concentrations were linearly and positively associated with BMI. In cohort 1, both serum iFGF-23 and CtFGF-23 concentrations increased with insulin resistance. Serum creatinine contributed to iFGF-23 variance, while serum ferritin and insulin sensitivity (but not BMI, age or serum creatinine contributed to 17% of CtFGF-23 variance. In cohort 2, CtFGF-23 levels were higher in women vs. men, and increased with BMI, fat mass, fasting and post-load serum glucose, insulin, HOMA-IR and PTH, being negatively associated with circulating vitamin D and ferritin levels. The associations of CtFGF-23 with bone density in the radius, lumbar spine and carotid IMT were no longer significant after controlling for BMI. Weight loss led to decreased iFGF-23 concentrations. In summary, the associations of circulating FGF-23 concentration with parameters of glucose metabolism, bone density and atherosclerosis are dependent on iron and obesity status-associated insulin resistance.

  5. Cystatin C and lactoferrin concentrations in biological fluids as possible prognostic factors in eye tumor development

    Directory of Open Access Journals (Sweden)

    Mariya A. Dikovskaya

    2013-08-01

    Full Text Available Objectives. To investigate the possible role of cystatin C in eye biological fluids locally and in serum and lactoferrin revealing anti-tumor activity in eye tumor development. Background. The increased number of eye tumors was registered recently not only in the countries with high insolation, but also in the northern countries including Russia (11 cases per million of population. Search for new biological markers is important for diagnosis and prognosis in eye tumors. Cystatin C, an endogenous inhibitor of cysteine proteases, plays an important protective role in several tumors. Lactoferrin was shown to express anti-tumor and antiviral activities. It was hypothesized that cystatin C and lactoferrin could serve as possible biomarkers in the diagnosis of malignant and benign eye tumors. Study design. A total of 54 patients with choroidal melanoma and benign eye tumors were examined (part of them undergoing surgical treatment. Serum, tear fluid and intraocular fluid samples obtained from the anterior chamber of eyes in patients with choroidal melanoma were studied. Methods. Cystatin C concentration in serum and eye biological fluids was measured by commercial ELISA kits for human (BioVendor, Czechia; lactoferrin concentration – by Lactoferrin-strip D 4106 ELISA test systems (Vector-BEST, Novosibirsk Region, Russia. Results. Cystatin C concentration in serum of healthy persons was significantly higher as compared to tear and intraocular fluids. In patients with choroidal melanoma, increased cystatin C concentration was similar in tear fluid of both the eyes. Lactoferrin level in tear fluid of healthy persons was significantly higher than its serum level. Significantly increased lactoferrin concentration in tear fluid was noted in patients with benign and malignant eye tumors. Conclusion. Increased level of cystatin C in tear fluid seems to be a possible diagnostic factor in the eye tumors studied. However, it does not allow us to differentiate

  6. The Structure of Carbonic Anhydrase IX Is Adapted for Low-pH Catalysis

    OpenAIRE

    Mahon, Brian P.; Bhatt, Avni; Socorro, Lilien; Driscoll, Jenna M.; Okoh, Cynthia; Lomelino, Carrie L.; Mboge, Mam Y.; Kurian, Justin J.; Tu, Chingkuang; Agbandje-McKenna, Mavis; Frost, Susan C; McKenna, Robert

    2016-01-01

    Human carbonic anhydrase IX (hCA IX) expression in many cancers is associated with hypoxic tumors and poor patient outcome. Inhibitors of hCA IX have been used as anticancer agents with some entering Phase I clinical trials. hCA IX is transmembrane protein whose catalytic domain faces the extracellular tumor milieu, which is typically associated with an acidic microenvironment. Here, we show that the catalytic domain of hCA IX (hCA IX-c) exhibits the necessary biochemical and biophysical prop...

  7. Factors affecting paddy soil arsenic concentration in Bangladesh: prediction and uncertainty of geostatistical risk mapping.

    Science.gov (United States)

    Ahmed, Zia U; Panaullah, Golam M; DeGloria, Stephen D; Duxbury, John M

    2011-12-15

    Knowledge of the spatial correlation of soil arsenic (As) concentrations with environmental variables is needed to assess the nature and extent of the risk of As contamination from irrigation water in Bangladesh. We analyzed 263 paired groundwater and paddy soil samples covering highland (HL) and medium highland-1 (MHL-1) land types for geostatistical mapping of soil As and delineation of As contaminated areas in Tala Upazilla, Satkhira district. We also collected 74 non-rice soil samples to assess the baseline concentration of soil As for this area. The mean soil As concentrations (mg/kg) for different land types under rice and non-rice crops were: rice-MHL-1 (21.2)>rice-HL (14.1)>non-rice-MHL-1 (11.9)>non-rice-HL (7.2). Multiple regression analyses showed that irrigation water As, Fe, land elevation and years of tubewell operation are the important factors affecting the concentrations of As in HL paddy soils. Only years of tubewell operation affected As concentration in the MHL-1 paddy soils. Quantitatively similar increases in soil As above the estimated baseline-As concentration were observed for rice soils on HL and MHL-1 after 6-8 years of groundwater irrigation, implying strong retention of As added in irrigation water in both land types. Application of single geostatistical methods with secondary variables such as regression kriging (RK) and ordinary co-kriging (OCK) gave little improvement in prediction of soil As over ordinary kriging (OK). Comparing single prediction methods, kriging within strata (KWS), the combination of RK for HL and OCK for MHL-1, gave more accurate soil As predictions and showed the lowest misclassification of declaring a location "contaminated" with respect to 14.8 mg As/kg, the highest value obtained for the baseline soil As concentration. Prediction of soil As buildup over time indicated that 75% or the soils cropped to rice would contain at least 30 mg/L As by the year 2020. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Kinetics and subcellular localization of 5-ALA-induced PpIX in DHL cells via two-photon excitation fluorescence microscopy.

    Science.gov (United States)

    Chen, Rong; Huang, Zufang; Chen, Guannan; Li, Yongzeng; Chen, Xianlian; Chen, Jianxin; Zeng, Haishan

    2008-04-01

    Two-photon excitation fluorescence (TPEF) microscopy was used to measure the 5-aminolevulinic acid (5-ALA)-induced PpIX fluorescence in follicular lymphoma DHL cells. Kinetics of 5-ALA-induced PpIX accumulation in DHL cells under various 5-ALA concentrations was studied. We found that during the course of continuous incubation with 5-ALA, the relationship between the DHL cell fluorescence signal and the incubation time showed a biphasic variation. Initially the PpIX signal increased with the incubation time and reached the maximal value at about 3 h, and then it decreased with time during the subsequent incubation period. By labeling the 5-ALA incubated DHL cells with different organelle-specific fluorescence probes: Rhodamine 123 (for mitochondria), DioC6(3) (for endoplasmic reticulum) and LysoTracker Green (for lysosomes) respectively, we found that 5-ALA-induced PpIX was primarily localized in endoplasmic reticulum and mitochondria; its concentration in the lysosome was much lower. The results suggested that 5-ALA could potentially be an effective photosensitizer in photodynamic purging of DHL cells. Two-photon excitation fluorescence microscope is a useful tool for studying 5-ALA-induced PpIX subcellular localization.

  9. Radiocaesium activity concentrations in macrofungi from Galicia (NW Spain): Influence of environmental and genetic factors.

    Science.gov (United States)

    García, M A; Alonso, J; Melgar, M J

    2015-05-01

    Radiocaesium ((137)Cs) is an artificial radionuclide that can be captured from the soil through the mycelium of fungi. However, in Spain there are few data on its presence in edible mushrooms. (137)Cs activity concentrations were determined using 54 samples of wild and cultivated mushrooms and 18 samples of soil, all of them collected in Galicia (NW Spain) during 2010. Samples were analyzed by gamma spectroscopy with a High-Purity Germanium (HPGe) detector. The average activity concentration of (137)Cs in wild mushrooms was 249.2Bqkg(-1) dry weight (dw) and about 24.9Bqkg(-1) fresh weight (fw). Genetic factors (species) influenced the uptake of (137)Cs, highlighting Hydnum repandum as the greatest accumulator of all wild species (1016.4Bqkg(-1) dw), while cultivated species showed much lower levels (1.6Bqkg(-1) fw). Accumulation was also favored by fungal mycorrhizal ecology, whose mycelium was distributed in contaminated soil horizons. The mean levels detected in soils were 14Bqkg(-1) fw. Although some species behaved as bioexclusors of radiocaesium, the transfer factors (TF) suggest that mushrooms preferentially bioaccumulate (137)Cs. No sample reached the limit of 600Bqkg(-1) fw (about 6000Bqkg(-1) dw) indicated in the European legislation. In conclusion, the consumption of mushrooms harvested from the investigated areas poses no toxicological risk to human health due to radiocaesium.

  10. Factors Influencing the Concentration of Certain Liposoluble Components in Cow and Goat Milk: A Review

    Directory of Open Access Journals (Sweden)

    Anamaria COZMA

    2014-09-01

    Full Text Available Milk fat contains a large number of fatty acids (FA and other liposoluble components that exhibit various effects on human health. The present article reviews some of the factors affecting FA, vitamin A and cholesterol concentrations in milk from dairy cow and goat. Milk fat composition is linked to many factors, both intrinsic (animal species, breed, lactation stage and extrinsic (environmental. The effect of animal species on milk fat composition is important, as reflected by higher concentrations of short- and medium-chain FA, vitamin A and cholesterol in goat than in cow milk. In a given ruminant species, the effects linked to breed are significant but limited and they can only be achieved over long periods of time. The lactation stage has an important effect on milk FA composition, mainly linked to body fat mobilisation in early lactation, but it only lasts a few weeks each year. Furthermore, changes in feeding have a marked influence on milk fat composition. Changing the forages in the diet of ruminants, pasture in particular, or supplementing lipids to the diet, represent an efficient mean to modify milk fat composition by decreasing saturated FA and cholesterol, and increasing cis-9,trans-11-CLA and vitamin A. Nutrition therefore constitutes a natural strategy to rapidly modulate milk FA, vitamin A and cholesterol composition, with the overall aim of improving the long-term health of consumers.

  11. Risk factors for a low linezolid trough plasma concentration in acute infections.

    Science.gov (United States)

    Morata, Laura; Cuesta, Marta; Rojas, Jhon F; Rodriguez, Sebastian; Brunet, Merce; Casals, Gregori; Cobos, Nazareth; Hernandez, Cristina; Martínez, José A; Mensa, Josep; Soriano, Alex

    2013-04-01

    Linezolid is an antibiotic with time-dependent activity, and both the percentage of time that plasma concentrations exceed the MIC and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC24/MIC ratio) are associated with clinical response. The aim of this study was to analyze the linezolid trough plasma concentration (C(min)) and to determine factors associated with a C(min) 80 ml/min, in intensive care unit (ICU) patients, and in patients with an infection due to Staphylococcus aureus. The independent predictors of C(min) 80 ml/min (odds ratio [OR], 10; 95% confidence interval [CI], 2.732 to 37.037; P = 0.001) and infection due to S. aureus (OR, 5.906; 95% CI, 1.651 to 21.126; P = 0.006). A linezolid C(min) of 80 ml/min and in infections due to S. aureus. In patients with severe sepsis, a loading dose or continuous infusion and drug monitoring could improve the pharmacodynamic parameters associated with linezolid efficacy.

  12. Overexpression of a NAC transcription factor delays leaf senescence and increases grain nitrogen concentration in wheat.

    Science.gov (United States)

    Zhao, D; Derkx, A P; Liu, D-C; Buchner, P; Hawkesford, M J

    2015-07-01

    Increasing the duration of leaf photosynthesis during grain filling using slow-senescing functional stay-green phenotypes is a possible route for increasing grain yields in wheat (Triticum aestivum L.). However, delayed senescence may negatively affect nutrient remobilisation and hence reduce grain protein concentrations and grain quality. A novel NAC1-type transcription factor (hereafter TaNAC-S) was identified in wheat, with gene expression located primarily in leaf/sheath tissues, which decreased during post-anthesis leaf senescence. Expression of TaNAC-S in the second leaf correlated with delayed senescence in two doubled-haploid lines of an Avalon × Cadenza population (lines 112 and 181), which were distinct for leaf senescence. Transgenic wheat plants overexpressing TaNAC-S resulted in delayed leaf senescence (stay-green phenotype). Grain yield, aboveground biomass, harvest index and total grain N content were unaffected, but NAC over-expressing lines had higher grain N concentrations at similar grain yields compared to non-transgenic controls. These results indicate that TaNAC-S is a negative regulator of leaf senescence, and that delayed leaf senescence may lead not only to increased grain yields but also to increased grain protein concentrations.

  13. Spatial and temporal variations in concentration factors in NW European seas - secondary use of monitoring data

    Energy Technology Data Exchange (ETDEWEB)

    Kershaw, P.J.; Mcmahon, C.A.; Rudjord, A.L.; Smedley, C.; Nawakowski, C.; Leonard, K.S. [Centre for Environment, Fisheries and Aquaculture Science (CEFAS), Lowestoft (United Kingdom)

    2004-07-01

    This paper presents new data on concentration factors (CFs: concentration kg-1 biota/concentration l-1 seawater) for several marine species-radionuclide pairs, in three regions: coastal waters of Ireland, eastern Irish Sea, coastal waters of Norway. The CFs were estimated using data from long-term monitoring programmes, obtained for radiological protection purposes. The practical constraints of using such data sources are discussed. CFs were obtained for Mytilus edulis (mussels), Nephrops norvegicus (Norway lobster/Dublin Bay prawn/scampi), Pleuronectes platessa (plaice), Cancer pagurus (edible crab), Littorina littoria (winkles) and Fucus vesiculosus, for one or more of the following radionuclides: {sup 99}Tc, {sup 137}Cs, {sup 239,240}Pu and {sup 241}Am. In general, there was a relatively high degree of variability in the values obtained, and it was not possible to discern systematic regional or time-dependent differences. However, for two datasets in the eastern Irish Sea ({sup 137}Cs in winkles and crabs) there was a statistically-significant increase in the CF over the 40 year monitoring period. In several cases the range of values obtained exceeded the range recommended by the IAEA. In 2002, the average {sup 99}Tc CF for F. vesiculosus from the eastern Irish Sea coastline was 26, significantly lower than the IAEA recommended valve (1 x 10{sup 3} - 1 x 10{sup 5}).The results are discussed in relation to the influence of contemporaneous discharges and the possible impact of re-mobilised radionuclides. (author)

  14. Factors influencing the crystallisation of highly concentrated water-in-oil emulsions: A DSC study

    Directory of Open Access Journals (Sweden)

    Irina Masalova

    2012-03-01

    Full Text Available Highly concentrated emulsions are used in a variety of applications, including the cosmetics, food and liquid explosives industries. The stability of these highly concentrated water-in-oil emulsions was studied by differential scanning calorimetry. Crystallisation of the emulsions was initiated by exposing the emulsions to a low temperature. The effects of surfactant type, electrolyte concentration and electrolyte composition in the aqueous phase on emulsion crystallisation temperature were studied. Surfactant type affected the emulsion crystallisation temperature in the following order: PIBSA-MEA=PIBSA-UREA < PIBSA-MEA/SMO < PIBSA-IMIDE < SMO. These results are in the same sequence as results obtained for the stability of these emulsions in aging studies, that is, PIBSA-MEA was the most stable with age and SMO was the least. The effect of the surfactant type on emulsion crystallisation can probably be attributed to the differing strengths of the surfactant–electrolyte interactions, which result in different molecular packing geometry and differing mobility of the surfactant lipophilic portion at the interface. These results enhance our understanding of the factors that affect the stability of explosive emulsions.

  15. Risk Factors for a Low Linezolid Trough Plasma Concentration in Acute Infections

    Science.gov (United States)

    Morata, Laura; Cuesta, Marta; Rojas, Jhon F.; Rodriguez, Sebastian; Brunet, Merce; Casals, Gregori; Cobos, Nazareth; Hernandez, Cristina; Martínez, José A.; Mensa, Josep

    2013-01-01

    Linezolid is an antibiotic with time-dependent activity, and both the percentage of time that plasma concentrations exceed the MIC and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC24/MIC ratio) are associated with clinical response. The aim of this study was to analyze the linezolid trough plasma concentration (Cmin) and to determine factors associated with a Cmin 80 ml/min, in intensive care unit (ICU) patients, and in patients with an infection due to Staphylococcus aureus. The independent predictors of Cmin 80 ml/min (odds ratio [OR], 10; 95% confidence interval [CI], 2.732 to 37.037; P = 0.001) and infection due to S. aureus (OR, 5.906; 95% CI, 1.651 to 21.126; P = 0.006). A linezolid Cmin of 80 ml/min and in infections due to S. aureus. In patients with severe sepsis, a loading dose or continuous infusion and drug monitoring could improve the pharmacodynamic parameters associated with linezolid efficacy. PMID:23403416

  16. Factors influencing relationships between personal and ambient concentrations of gaseous and particulate pollutants.

    Science.gov (United States)

    Brown, Kathleen Ward; Sarnat, Jeremy A; Suh, Helen H; Coull, Brent A; Koutrakis, Petros

    2009-06-01

    Previous exposure studies have shown considerable inter-subject variability in personal-ambient associations. This paper investigates exposure factors that may be responsible for inter-subject variability in these personal-ambient associations. The personal and ambient data used in this paper were collected as part of a personal exposure study conducted in Boston, MA, during 1999-2000. This study was one of a group of personal exposure panel studies funded by the U.S. Environmental Protection Agency's National Exposure Research Laboratory to address areas of exposure assessment warranting further study, particularly associations between personal exposures and ambient concentrations of particulate matter and gaseous co-pollutants. Twenty-four-hour integrated personal, home indoor, home outdoor and ambient sulfate, elemental carbon (EC), PM(2.5), ozone (O(3)), nitrogen dioxide (NO(2)) and sulfur dioxide were measured simultaneously each day. Fifteen homes in the Boston area were measured for 7 days during winter and summer. A previous paper explored the associations between personal-indoor, personal-outdoor, personal-ambient, indoor-outdoor, indoor-ambient and outdoor-ambient PM(2.5), sulfate and EC concentrations. For the current paper, factors that may affect personal exposures were investigated, while controlling for ambient concentrations. The data were analyzed using mixed effects regression models. Overall personal-ambient associations were strong for sulfate during winter (ppersonal-ambient mixed model slope for PM(2.5) during winter but was not significant at p=0.10. Personal exposures to most pollutants, with the exception of NO(2), increased with ventilation and time spent outdoors. An opposite pattern was found for NO(2) likely due to gas stoves. Personal exposures to PM(2.5) and to traffic-related pollutants, EC and NO(2), were higher for those individuals living close to a major road. Both personal and indoor sulfate and PM(2.5) concentrations were

  17. Plasma triacylglycerol and coagulation factor concentrations predict the anticoagulant effect of dietary fish oil in overweight subjects

    DEFF Research Database (Denmark)

    Vanschoonbeek, Kristof; Feijge, Marion A H; Saris, Wim H M;

    2007-01-01

    determined partly the interindividual variation in thrombin generation, of which prothrombin and triacylglycerol concentrations were the main determinants. In both healthy subjects and diabetes patients, high triacylglycerol concentrations (>1.69 mmol/L) at baseline were closely linked to a strong fish oil......-induced lowering of triacylglycerol and coagulation factor V, VII, and X concentrations, and thrombin generation. We conclude that high fasting triacylglycerol concentrations predict high procoagulant activity and a lowering of thrombin potential with dietary fish oil....

  18. Tramadol Induced QTc-Interval Prolongation: Prevalence, Clinical Factors and Correlation to Plasma Concentrations.

    Science.gov (United States)

    Keller, Guillermo A; Etchegoyen, María C V; Fernandez, Nicolás; Olivera, Nancy M; Quiroga, Patricia N; Belloso, Waldo H; Diez, Roberto A; Di Girolamo, Guillermo

    2016-01-01

    In recent years, several cases of torsade de pointes have been associated with many opioids. However, to present no cases have been reported with tramadol. To evaluate the effect of tramadol on QT-interval in the clinical setting. Medical history and comorbidities predisposing to QT interval prolongation were registered for patients requiring medical assistance that involved tramadol administration. Ionograms and ECGs were performed at baseline and intratreatment; QT interval was analyzed after correction with Bazzet, Fridericia, Framinghan and Hogdes formula. 115 patients were studied (50.4% males) All patients had received tramadol 150-400 mg/day during 3.0-5.0 days at the moment of intratreatment control. Plasma concentrations of tramadol were 201-1613 ng/mL. Intratreatment electrocardiographic control, as mean ± SD (range), showed QTcB 372±32 (305 to 433), QTcFri 356±37 (281 to 429), QTcFra 363±33 (299 to 429), QTcH 362±30 (304 to 427), ΔQTcB 26±40 (-73 to 110), ΔQTcFri 24±48 (-97 to 121), ΔQTcFra 22±42 (-81 to 109) and .QTcH 22±38 (-68 to 110) ms. QTc interval presents high correlation with plasma tramadol concentrations (for .QTc, R>0.77). Renal failure was associated with a relative risk for ΔQTc > 30 ms of 1.90 (IC95% 1.31-2.74) and for ΔQTc > 60 ms of 4.74 (IC95% 2.57-8.74). No patient had evidence of arrhythmia during the present study. Tramadol produces QTc interval prolongation in good correlation with plasma drug concentrations; renal failure is a risk factor for higher concentration and QT prolongation by tramadol.

  19. Factors affecting biotic mercury concentrations and biomagnification through lake food webs in the Canadian high Arctic

    Energy Technology Data Exchange (ETDEWEB)

    Lescord, Gretchen L., E-mail: glescord@gmail.com [University of New Brunswick/Canadian Rivers Institute, 100 Tucker Park Rd, Saint John, NB E2L 4A6 (Canada); Kidd, Karen A. [University of New Brunswick/Canadian Rivers Institute, 100 Tucker Park Rd, Saint John, NB E2L 4A6 (Canada); Kirk, Jane L. [Environment Canada, Aquatic Contaminants Research Division, 867 Lakeshore Rd, Burlington, ON L7S 1A1 (Canada); O' Driscoll, Nelson J. [Acadia University, 15 University Ave, Wolfville, NS B4P 2R6 (Canada); Wang, Xiaowa; Muir, Derek C.G. [Environment Canada, Aquatic Contaminants Research Division, 867 Lakeshore Rd, Burlington, ON L7S 1A1 (Canada)

    2015-03-15

    In temperate regions of Canada, mercury (Hg) concentrations in biota and the magnitude of Hg biomagnification through food webs vary between neighboring lakes and are related to water chemistry variables and physical lake features. However, few studies have examined factors affecting the variable Hg concentrations in landlocked Arctic char (Salvelinus alpinus) or the biomagnification of Hg through their food webs. We estimated the food web structure of six high Arctic lakes near Resolute Bay, Nunavut, Canada, using stable carbon (δ{sup 13}C) and nitrogen (δ{sup 15}N) isotopes and measured Hg (total Hg (THg) in char, the only fish species, and methylmercury (MeHg) in chironomids and zooplankton) concentrations in biota collected in 2010 and 2011. Across lakes, δ{sup 13}C showed that benthic carbon (chironomids) was the dominant food source for char. Regression models of log Hg versus δ{sup 15}N (of char and benthic invertebrates) showed positive and significant slopes, indicting Hg biomagnification in all lakes, and higher slopes in some lakes than others. However, no principal components (PC) generated using all water chemistry data and physical characteristics of the lakes predicted the different slopes. The PC dominated by aqueous ions was a negative predictor of MeHg concentrations in chironomids, suggesting that water chemistry affects Hg bioavailability and MeHg concentrations in these lower-trophic-level organisms. Furthermore, regression intercepts were predicted by the PCs dominated by catchment area, aqueous ions, and MeHg. Weaker relationships were also found between THg in small char or MeHg in pelagic invertebrates and the PCs dominated by catchment area, and aqueous nitrate and MeHg. Results from these high Arctic lakes suggest that Hg biomagnification differs between systems and that their physical and chemical characteristics affect Hg concentrations in lower-trophic-level biota. - Highlights: • Mercury (Hg) in Arctic char and invertebrates

  20. Detection limits of 405 nm and 633 nm excited PpIX fluorescence for brain tumor detection during stereotactic biopsy

    Science.gov (United States)

    Markwardt, Niklas; Götz, Marcus; Haj-Hosseini, Neda; Hollnburger, Bastian; Sroka, Ronald; Stepp, Herbert; Zelenkov, Petr; Rühm, Adrian

    2016-04-01

    5-aminolevulinic-acid-(5-ALA)-induced protoporphyrin IX (PpIX) fluorescence may be used to improve stereotactic brain tumor biopsies. In this study, the sensitivity of PpIX-based tumor detection has been investigated for two potential excitation wavelengths (405 nm, 633 nm). Using a 200 μm fiber in contact with semi-infinite optical phantoms containing ink and Lipovenös, PpIX detection limits of 4.0 nM and 200 nM (relating to 1 mW excitation power) were determined for 405 nm and 633 nm excitation, respectively. Hence, typical PpIX concentrations in glioblastomas of a few μM should be well detectable with both wavelengths. Additionally, blood layers of selected thicknesses were placed between fiber and phantom. Red excitation was shown to be considerably less affected by blood interference: A 50 μm blood layer, for instance, blocked the 405- nm-excited fluorescence completely, but reduced the 633-nm-excited signal by less than 50%. Ray tracing simulations demonstrated that - without blood layer - the sensitivity advantage of 405 nm rises for decreasing fluorescent volume from 50-fold to a maximum of 100-fold. However, at a tumor volume of 1 mm3, which is a typical biopsy sample size, the 633-nm-excited fluorescence signal is only reduced by about 10%. Further simulations revealed that with increasing fiber-tumor distance, the signal drops faster for 405 nm. This reduces the risk of detecting tumor tissue outside the needle's coverage, but diminishes the overlap between optically and mechanically sampled volumes. While 405 nm generally offers a higher sensitivity, 633 nm is more sensitive to distant tumors and considerably superior in case of blood-covered tumor tissue.

  1. MILK WITH INCREASED CONCENTRATION OF MELATONIN PACKAGING FACTORS ON CONSUMER PURCHASE INTENTION

    Directory of Open Access Journals (Sweden)

    Maria Patricia Milagres

    2014-02-01

    Full Text Available The conjoint analysis of factors was used employed to develop a label for the packaging of milk with increased concentration of melatonin. Three factors were selected with three or two levels for the assembly of packaging: packaging design (“blue design with stars and pouring milk”, “white without drawing” and “blue stars with and without drawing”, name (“milk night “and” melatonin “ and informative text about getting natural melatonin by night milking, and the benefits of this compound (“with” and “without”. Twelve packaging designs were created based on a complete factorial arrangement. The designs were presented to 144 consumers who were asked to assess purchase intent of each package. For the joint analysis of factors, the ideal product or more likely to purchase for the most consumers would be blue with stars and packaging design of milk pouring, named milk night and in the presence of informational text, demonstrating that consumers like a package that brings the product and that contains information described. Therefore, the packaging has a major influence on consumer choice and can contribute positively or negatively to the acceptance of food.

  2. Correction factors for determination of annual average radon concentration in dwellings of Poland resulting from seasonal variability of indoor radon

    Energy Technology Data Exchange (ETDEWEB)

    Kozak, K., E-mail: Krzysztof.Kozak@ifj.edu.pl [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Krakow (Poland); Mazur, J. [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Krakow (Poland); KozLowska, B. [University of Silesia, Bankowa 12, 40-007 Katowice (Poland); Karpinska, M. [Medical University of Bialystok, Jana Kilinskiego 1, 15-089 BiaLystok (Poland); Przylibski, T.A. [WrocLaw University of Technology, Wybrzeze S. Wyspianskiego 27, 50-370 WrocLaw (Poland); Mamont-Ciesla, K. [Central Laboratory for Radiological Protection, Konwaliowa 7, 03-194 Warszawa (Poland); Grzadziel, D. [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Krakow (Poland); Stawarz, O. [Central Laboratory for Radiological Protection, Konwaliowa 7, 03-194 Warszawa (Poland); Wysocka, M. [Central Mining Institute, Plac Gwarkow1, 40-166 Katowice (Poland); Dorda, J. [University of Silesia, Bankowa 12, 40-007 Katowice (Poland); Zebrowski, A. [WrocLaw University of Technology, Wybrzeze S. Wyspianskiego 27, 50-370 WrocLaw (Poland); Olszewski, J. [Nofer Institute of Occupational Medicine, Sw.Teresy od Dzieciatka Jezus 8, 91-348 lodz (Poland); Hovhannisyan, H. [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Krakow (Poland); Dohojda, M. [Institute of Building Technology (ITB), Filtrowa 1, 00-611 Warszawa (Poland); KapaLa, J. [Medical University of Bialystok, Jana Kilinskiego 1, 15-089 BiaLystok (Poland); Chmielewska, I. [Central Mining Institute, Plac Gwarkow1, 40-166 Katowice (Poland); KLos, B. [University of Silesia, Bankowa 12, 40-007 Katowice (Poland); Jankowski, J. [Nofer Institute of Occupational Medicine, Sw.Teresy od Dzieciatka Jezus 8, 91-348 lodz (Poland); Mnich, S. [Medical University of Bialystok, Jana Kilinskiego 1, 15-089 BiaLystok (Poland); KoLodziej, R. [Central Mining Institute, Plac Gwarkow1, 40-166 Katowice (Poland)

    2011-10-15

    The method for the calculation of correction factors is presented, which can be used for the assessment of the mean annual radon concentration on the basis of 1-month or 3-month indoor measurements. Annual radon concentration is an essential value for the determination of the annual dose due to radon inhalation. The measurements have been carried out in 132 houses in Poland over a period of one year. The passive method of track detectors with CR-39 foil was applied. Four thermal-precipitation regions in Poland were established and correction factors were calculated for each region, separately for houses with and without basements. - Highlights: > Using radon concentration results in houses we calculated the correction factors. > Factors were calculated for each month, 2 house types in different regions in Poland. > They enable the evaluation of average annual radon concentration in the house. > Annual average radon concentration basing on 1 or 3 months detector exposure.

  3. Three versus four-factor prothrombin complex concentrates for "factor-based" resuscitation in a porcine hemorrhagic shock model.

    Science.gov (United States)

    Moe, Donald Michael; Lallemand, Michael Scott; McClellan, John Mason; Smith, Joshua Porter; Marko, Shannon T; Eckert, Matthew J; Martin, Matthew J

    2017-07-12

    Bleeding is a leading cause of preventable death following severe injury. Prothrombin complex concentrates (PCC) treat inborn coagulation disorders and reverse oral anticoagulants, but are proposed for use in "factor-based" resuscitation strategies. Few studies exist for this indication in acidosis, or that compare 3-factor (3PCC) versus 4-factor (4PCC) products. We aimed to assess and compare their safety and efficacy in a porcine model of severe hemorrhagic shock and coagulopathy. Twenty-five adult Yorkshire swine underwent 35% volume hemorrhage, ischemia-reperfusion injury, and protocolized crystalloid resuscitation. Seventeen animals were randomized at 4 hours following model creation to receive a 45-IU/kg dose of either 3PCC or 4PCC. An additional 8 animals received autologous plasma transfusion prior to 4PCC to better characterize response to PCC. Individual factor levels were drawn at 4 and 6 hours. The model created significant acidosis with mean pH 7.21 and lactate of 9.6 mmol/L. Following PCC, 66.7% of 3PCC animals and 25% of 4PCC animals (regardless of plasma administration) developed consumptive coagulopathy. The animals that developed consumptive coagulopathy had manifested the "lethal triad" with lower temperatures (36.3 vs. 37.8°C), increased acidosis (pH 7.14 vs. 7.27, base excess -12.1 vs. -6.5 mEq/L), and worse coagulopathy (prothrombin time 17.1 vs. 14.6 seconds, fibrinogen 87.9 vs. 124.1 mg/dL) (all pfactors with transient improvement of prothrombin time, but there was significant depletion of fibrinogen and platelets with no lasting improvement of coagulopathy. PCC failed to correct coagulopathy and was associated with fibrinogen and platelet depletion. Of greater concern, PCC administration resulted in consumptive coagulopathy in the more severely ill animals. The incidence of consumptive coagulopathy was markedly increased with 3PCC versus 4PCC, and these products should be used with caution in this setting. II, therapeutic.

  4. 20. IX saab Briti Nõukogus avatud uste päevade raames...

    Index Scriptorium Estoniae

    2005-01-01

    21. IX tutvustab kunstiteadlane Anneli Porri kunstnik Tracey Eminist valmistatud portreefilmi ja teisi Briti Nõukogu raamatukogus leiduvaid Briti kaasaegset kunsti käsitlevaid dokumentaalfilme. Tallinna Kunstihoones kuni 18. IX Briti kaasaegset abstraktsionismi tutvustav näitus "Supernoova"

  5. Formaldehyde concentration and its influencing factors in residential homes after decoration at Hangzhou, China

    Institute of Scientific and Technical Information of China (English)

    Min Guo; Xiaoqiang Pei; Feifei Mo; Jianlei Liu; Xueyou Shen

    2013-01-01

    Air pollution surveys of formaldehyde (HCHO) were conducted in 2324 rooms decorated within one year in 2007-2009 in Hangzhou,China.The mean HCHO concentration (CHCHO) was 0.107 + 0.095 mg/m3,and 38.9% of samples exceeded the Chinese National Standard GB 50325-2010.Over the past 3 years,the CHCHO decreased with time (p < 0.05).Relationships of potential factors to indoor CHCHO were also evaluated.CHCHO was related to temperature (T),relative humidity (RH),time duration of the windows and doors being closed before sampling (DC),time duration from the end of decoration to sampling (DR) and source characteristics (d).A model to relate indoor CHCHO to these five factors (T,RH,DC,DR,d) was established based on 298 samples (R2 =0.87).Various factors contributed to Cacao in the following order:T,43.7%; d,31.0%; DC,10.2%; DR,8.0%; RH,7.0%; specifically,meteorological conditions (i.e.,RH plus T) accounted for 50.7%.The coefficient of T and RH,RTH,was proposed to describe their combined influence on HCHO emission,which also had a linear relationship (R2 =0.9387) with HCHO release in a simulation chamber test.In addition,experiments confirm that it is a synergistic action as T and RH accelerate the release of HCHO,and that is a significant factor influencing indoor HCHO pollution.These achievements could lead to reference values of measures for the efficient reduction of indoor HCHO pollution.

  6. Factors controlling spatial variability of DOC concentrations in soil solution at European level

    Science.gov (United States)

    Camino Serrano, Marta; Janssens, Ivan; Luyssaert, Sebastiaan; Gielen, Bert; Guenet, Bertrand; De Vos, Bruno; Ciais, Philippe

    2013-04-01

    The lateral transport of dissolved organic carbon (DOC) is an important and not well-understood process linking terrestrial and aquatic ecosystems. Up to day very few Earth System Models (ESMs) represent explicitly this process despite its crucial role in the global carbon cycle. However, to be able to integrate DOC leaching in ESMs, more accurate information is needed in order to better understand and predict DOC dynamics. DOC concentrations mainly vary by geographical location, soil and vegetation types, topography, season and climate. Within this framework, a database was designed to compile data on DOC in soil solution at different depths in different ecosystems around the world, with special focus on European sites. The database contains information on 349 sites, with 304 being forest, gathered from published literature and datasets accessible on the internet. A substantial dataset was provided by International Co-operative Programme on Assessment and Monitoring of Air Pollution Effects on Forests (ICP Forests). The database also includes other meta-data related to the sites, such as land cover, soil properties, climate, annual water balance and other soil solution parameters. The analysis of the database has been focused on: 1) the study of the environmental and physical factors that are acting as drivers of DOC concentrations changes in soil solution across sites at European level , and 2) the DOC distribution through the soil profile and how this varies with different vegetation types and soil properties. The preliminary results show that variables related to biological processes (Dry weight of the organic layer, for example) are the most important in explaining the spatial distribution of the DOC concentration in soil solution at the European scale. However, the interactions between variables are complex and we will need further analysis in order to draw more robust conclusions. With regards to the vertical profile of DOC, we found that there is a

  7. A note on the modal kurtosis and the concentration factor in reverberation rooms

    DEFF Research Database (Denmark)

    Jacobsen, Finn

    2012-01-01

    by the concentration factor, which is usually assumed to be 2. However, because of the stronger direct sound field at the source position, it is obviously very difficult to measure this quantity directly under steady-state conditions. A related parameter of crucial importance for the ensemble statistics of responses......The effect known as “weak Anderson localization,” “coherent backscattering,” or “enhanced back-scattering” is a physical phenomenon that occurs in random systems, e.g., disordered media and linear wave systems, including reverberation rooms: The mean square response is increased at the drive point....... In a reverberation room, this means that one can expect an increase of the reverberant sound field at the position of the source that generates the sound field. This affects the sound power output of the source and is therefore of practical concern. The relative increase of reverberant energy is described...

  8. Effects of Optical Loss Factors on Heliostat Field Layout for Beam-Down Solar Concentrating Systems

    Science.gov (United States)

    Utamura, Motoaki; Takamatsu, Tadahiko; Yuasa, Minoru; Kajita, Rina; Yamamoto, Takashi

    A methodology to give an optimal layout of a group of heliostats has been developed for beam-down concentrating solar tower systems. Given the maximum solar power together with optical parameters, the method determines an optimal configuration of a heliostat field around a tower. Various optical losses such as cosine factor, shadowing and blocking at heliostats are considered in the calculation. Furthermore, spillage at the receiver is taken into account due to the spread of light caused by the effects of a finite solar disk, flat facet and various stochastic errors in optical hardware and control. It is found the effect of spillage becomes significant at heliostats from the tower at the distance farther than four times of upper focus height of the reflector when receiver diameter is one fifteenth of the height and dominates the configuration of the optimal heliostat layout.

  9. Determination of Stress Concentration factor in Linearly Elastic Structures with Different Stress-Raisers Using FEM

    Directory of Open Access Journals (Sweden)

    Dheeraj Gunwant

    2016-02-01

    Full Text Available Stress concentration is the localization of stress around stress raisers. Sudden changes in the geometry of structures give rise to stress values that are higher than those obtained by elementary equations of solid mechanics. Therefore the evaluation of stress state at such locations needs specialized techniques such as Finite Element Method (FEM.The finite element method is a numerical procedure that can be used to obtain solution to a large variety of engineering problems such as structural, thermal, heat transfer, electromagnetism and fluid flow. In the present investigation, focus has been kept on the finite element modeling and determination of stress concentration factor (SCF in linearly elastic structures with different stress-raisers such as circular and elliptical holes and double semicircular notch at different locations in a finite plate. The results obtained from FEM are compared with those obtained by analytical relations as given in literature. A commercially available finite element solver ANSYS has been used for the modeling and analysis in the investigation. Throughout the investigation, plane82, which is an eight node two-dimensional element is used for the discretization.

  10. Relation between Poaceae pollen concentrations and meteorological factors during 2000–2010 in Timisoara, Romania

    Directory of Open Access Journals (Sweden)

    Nicoleta Ianovici

    2015-12-01

    Full Text Available This paper presents the results of Poaceae pollen seasons from 2000–2010 in Timisoara, Romania. Airborne Poaceae pollen concentrations was high. An increasing trend in the annual totals was observed. The longest pollen season was recorded in the year 2000. The period in which the Poaceae pollen count exceeded the threshold value of 30 grains/m3 lasted from 9 to 46 days. The present study analyzed the dynamics of pollen seasons in relation to meteorological factors. On the basis of Spearman’s correlation test, the strongest positive correlation was found between the Poaceae pollen counts and temperature; and sunshine hours. Daily average relative humidity, atmospheric pressure and precipitation had a negative effect. A multiple regression analysis was applied to determine how much of the total variance in Poaceae pollen counts can be explained by meteorological parameters. The coefficient of determination ranged from 0.245 to 0.460. Our data illustrate the contrasting effects of temperature, wind, relative humidity and rainfall on the concentration of pollen in the air. The optimum conditions for Poaceae pollen release occur during late spring and early summer. The Poaceae pollen remains one of the major aeroallergens in Timisoara area.

  11. Fluorometric quantification of protoporphyrin IX in biological skin samples from in vitro penetration/permeation studies

    Directory of Open Access Journals (Sweden)

    Fábia Cristina Rossetti

    2010-12-01

    Full Text Available A fluorometric analytical method was developed for quantification of protoporphyrin IX (PpIX in skin samples and receptor phase solution after in vitro cutaneous penetration/permeation studies. Analytical conditions used were: excitation and emission wavelengths: 400 nm and 632 nm; bandwidth: 0.5 nm; excitation and emission slits: 10/10. PpIX was recovered from two different layers of skin, the stratum corneum (SC and the epidermis plus dermis ([E+D], by vortex homogenization, probe and bath sonication, using DMSO as an extraction solvent. The detection and quantification limits were 0.002 and 0.005 μg/mL, respectively. The assay was linear from 0.005 - 0.5 μg/mL. The within-day and between-day assay precision and accuracy in DMSO and receptor phase solution were each studied at the two concentration levels 0.04 and 0.2 μg/mL, and 0.01 and 0.08 μg/mL, respectively. The coefficients of variation and deviation from the theoretical values were lower than 5%. The skin recovery of PpIX from SC and [E+D] layers using two different concentrations (0.5 and 1.0 μg/mL were all above 90.0%. The method described has potential application to in vitro penetration/permeation studies of PpIX using porcine skin as a biological membrane model.Um método analítico por espectrofluorimetria foi desenvolvido para quantificar a protoporfirina IX (Pp IX em amostras de pele e fase receptora após a realização de testes in vitro de penetração/permeação cutâneas. As condições analíticas utilizadas foram: comprimentos de onda de excitação e emissão: 400 nm e 632 nm; largura de banda: 0,5 nm; fendas de excitação e emissão: 10/10. A PpIX foi extraída de amostras de estrato córneo (EC e da epiderme sem estrato córneo + derme ([E+D] através da agitação em vórtex e sonicação por haste e banho, utilizando-se o DMSO como solvente extrator. O limite de detecção e quantificação foram, respectivamente, de 0,002 e 0,005 μg/mL. O método mostrou

  12. 40 CFR Appendix Ix to Part 264 - Ground-Water Monitoring List

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Ground-Water Monitoring List IX... Pt. 264, App. IX Appendix IX to Part 264—Ground-Water Monitoring List Ground-Water Monitoring List... species in the ground water that contain this element are included. 3 CAS index names are those used in...

  13. 46 CFR 57.02-2 - Adoption of section IX of the ASME Code.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Adoption of section IX of the ASME Code. 57.02-2 Section... AND BRAZING General Requirements § 57.02-2 Adoption of section IX of the ASME Code. (a) The... accordance with section IX of the ASME (American Society of Mechanical Engineers) Code, as limited,...

  14. Updating Environmental Media Concentration Limits and Uncertainty factors in the ERICA Tool

    Energy Technology Data Exchange (ETDEWEB)

    Brown, J.E.; Hosseini, A. [Norwegian Radiation Protection Authority, P.O. Box 55, N-1332 Oesteraas (Norway); Alfonso, B.; Avila, R. [Facilia AB, S-167 51 Bromma (Sweden); Beresford, N.A. [Centre for Ecology and Hydrology, CEH-Lancaster, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LA 1 4AP (United Kingdom); Copplestone, D. [Dept. Biological and Environmental Sciences, University of Stirling, Stirling, FK9 4LA (United Kingdom)

    2014-07-01

    Tiered approaches have become a standard means of structuring information in the process of conducting environmental risk assessments. For cases involving the assessment of impacts on wildlife from ionising radiation, the ERICA integrated approach and its supporting software (The ERICA Tool) provides such a structure, splitting the system into two generic screening tiers and a third site-specific tier. The first Tier is very simple, based around Environmental Media Concentration Limits, EMCLs, and requires minimal input from the assessor. The second Tier, although still a screening tier, calculates dose rates and requires more detailed input from the assessor allowing for scrutiny and editing of default parameters in the process. A key element of Tier 2 involves the application of Uncertainty Factors, UFs. Such factors reflect our knowledge concerning probability distribution functions and provide a way of incorporating conservatism into the assessment by considering high percentile values in underlying parameters. Following its launch in 2007, there have been significant developments regarding certain components of the ERICA integrated approach. Most notably, an extended international collation of concentration ratio data has precipitated the need to update parameter values in the Tools databases. In addition, more considered guidance has been developed with regards to filling knowledge gaps in the absence of transfer data. Furthermore, the efficacy of the methods used in assigning probability distribution functions has been questioned leading to an acknowledgement from the developers that the methods were not described in enough detail nor were the justifications for applying the selected approach provided in a convincing way. This has implications for the EMCL values which are derived probabilistically using parameters including concentration ratios. Furthermore, there are implications for UF derivation that relies upon a robust consideration of underlying

  15. Optical properties of Ge-rich G e1 -xS ix alloys: Compositional dependence of the lowest direct and indirect gaps

    Science.gov (United States)

    Xu, Chi; Gallagher, J. D.; Senaratne, C. L.; Menéndez, J.; Kouvetakis, J.

    2016-03-01

    Ge-rich G e1 -xS ix alloys have been investigated using spectroscopic ellipsometry and photoluminescence at room temperature. Special emphasis was placed on the compositional dependence of the lowest-energy interband transitions. For x ≤0.05 , a compositional range of particular interest for modern applications, we find E0=0.799 (1 ) +3.214 (45 ) x +0.080 (44 ) x2 (in eV) for the lowest direct gap. The compositional dependence of the indirect gap is obtained from photoluminescence as Eind=0.659 (4 ) +1.18 (17 ) x (in eV). We find no significant discrepancies between these results and the extrapolations from measurements at higher Si concentrations. Such discrepancies had been suggested by recent work on G e1 -xS ix films on Si. Accurate knowledge of the interband transition energies is an important requirement for the design of devices incorporating Ge-rich G e1 -xS ix alloys and for the understanding of more complex systems, such as ternary G e1 -x -yS ixS ny alloys, in terms of its binary constituents.

  16. Correlation of maternal factors and hemoglobin concentration during pregnancy Shiraz 2006

    Directory of Open Access Journals (Sweden)

    Marzieh Akbarzadeh

    2009-12-01

    Full Text Available Background: Anemia in pregnancy is a serious condition, contributing to maternal mortality, morbidity and fetal morbidity and its prevalence varies between 35-100% in developing countries. This investigation is conducted to survey the correlation of maternal factors and the changes in hemoglobin in pregnant women. Method: In this study, 108 healthy pregnant women with gestational age of 10 to 14 weeks, chosen by cluster random sampling were included. The women were followed in three visits: at the end of the first, second and third trimester. In addition, correlation of Hb concentration with maternal factors including BMI, age parity, hyperemesis, gestational age, pregnancy interval and weight gain was investigated. Results: There was no significant correlation between BMI, parity, pregnancy interval, severe nausea and vomiting and also maternal age with hemoglobin level during pregnancy. Moreover, Multiple regression models showed that adequate maternal weight gain (P<0.009 and high hemoglobin (p<0.0001 in the first trimester were positive predictors and late iron supplementation was negative predictor of hemoglobin in pregnancy (P<0.006. Conclusion: Our data demonstrated that adequate maternal weight gain, high hemoglobin in the first trimester and also late iron supplementation could be as predictors in clinical settings in this query.

  17. The influence of selected factors and sport results of endurance horses on their saliva cortisol concentration.

    Science.gov (United States)

    Janczarek, I; Bereznowski, A; Strzelec, K

    2013-01-01

    The aim of the study was to define the influence of the selected factors (gender, age, transportation time, riding distance and air temperature during the ride) on the cortisol secretion and finding a correlation between the hormone level and the horses' sport results (veterinary parameters and the ride route parameters). The research was performed on 38 Arabian pure breed horses taking part in the endurance rides. The cortisol level was measured with enzyme-immunological method in saliva samples, taken four times from each horse. In order to verify the differences between the mean results the repeated measures design was applied. The significance of the differences between the mean values was determined by the Tukey test. To evaluate the interrelations between the analysed attributes Pearson's correlation analysis was applied. The cortisol level at rest was not affected by any of the analysed factors. In case of other results, the most significant influence (P cortisol level was noted in mares, horses running the longest distances and at the highest temperatures. A significant increase in the cortisol level was noted when the ride distance was longer. There were no clear correlation between the adrenal cortex activity and the veterinary parameters at different riding speed. High cortisol concentration can negatively affect the heart rate (HR) by increasing it, but it can simultaneously stimulate the body to fight dehydration.

  18. Factors influencing serum concentrations of IgD in the adult population: an observational study in Spain.

    Science.gov (United States)

    Carballo, Iago; Rabuñal, Noelia; Alvela, Lucía; Pérez, Luis-Fernando; Vidal, Carmen; Alonso, Manuela; Sopeña, Bernardo; Gude, Francisco; Gonzalez-Quintela, Arturo

    2017-01-27

    Immunoglobulin D (IgD) is the least studied of immunoglobulin classes. This study sought to investigate the potential relationship between demographic, metabolic, lifestyle and immunologic factors, and serum IgD concentrations in a general adult population. We measured serum IgD concentrations by means of a commercial turbidimetric assay in 413 individuals (median age, 55 years; 45% males), randomly selected from the adult population of a Spanish municipality. Serum IgD concentrations displayed considerable variation in the population, ranging from undetectable (immune disease after a median 11.4 years of follow-up. In conclusion, serum IgD concentrations in adults show a wide variation in the population and may be influenced by common factors, particularly age and smoking habit. These factors should be taken into account when defining reference ranges for serum IgD concentrations. This article is protected by copyright. All rights reserved.

  19. Methods of producing protoporphyrin IX and bacterial mutants therefor

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jizhong; Qiu, Dongru; He, Zhili; Xie, Ming

    2016-03-01

    The presently disclosed inventive concepts are directed in certain embodiments to a method of producing protoporphyrin IX by (1) cultivating a strain of Shewanella bacteria in a culture medium under conditions suitable for growth thereof, and (2) recovering the protoporphyrin IX from the culture medium. The strain of Shewanella bacteria comprises at least one mutant hemH gene which is incapable of normal expression, thereby causing an accumulation of protoporphyrin IX. In certain embodiments of the method, the strain of Shewanella bacteria is a strain of S. loihica, and more specifically may be S. loihica PV-4. In certain embodiments, the mutant hemH gene of the strain of Shewanella bacteria may be a mutant of shew_2229 and/or of shew_1140. In other embodiments, the presently disclosed inventive concepts are directed to mutant strains of Shewanella bacteria having at least one mutant hemH gene which is incapable of normal expression, thereby causing an accumulation of protoporphyrin IX during cultivation of the bacteria. In certain embodiments the strain of Shewanella bacteria is a strain of S. loihica, and more specifically may be S. loihica PV-4. In certain embodiments, the mutant hemH gene of the strain of Shewanella bacteria may be a mutant of shew_2229 and/or shew_1140.

  20. Spectroscopy of Ferric Heme and Protoporphyrin IX Ions In Vacuo

    DEFF Research Database (Denmark)

    Wyer, Jean; Nielsen, Steen Brøndsted

    2013-01-01

    This chapter deals with gas-phase spectroscopy of protoporphyrin IX and heme ions, two important biochromophores in nature. These ions strongly absorb blue and green light, which accounts for e.g. the red colour of blood. We present absorption spectra of four-coordinate ferric heme cations at room...

  1. Bianchi type IX string cosmological model in general relativity

    Indian Academy of Sciences (India)

    Raj Bali; Shuchi Dave

    2001-04-01

    We have investigated Bianchi type IX string cosmological models in general relativity. To get a determinate solution, we have assumed a condition ρ= i.e. rest energy density for a cloud of strings is equal to the string tension density. The various physical and geometrical aspects of the models are also discussed.

  2. IX : An OS for datacenter applications with aggressive networking requirements

    CERN Document Server

    CERN. Geneva

    2014-01-01

    The conventional wisdom is that aggressive networking requirements, such as high packet rates for small messages and microsecond-scale tail latency, are best addressed outside the kernel, in a user-level networking stack. We present IX, a dataplane operating system designed to support low-latency, high-throughput and high-connection count applications.  Like classic operating systems such as Linux, IX provides strong protection guarantees to the networking stack.  However, and unlike classic operating systems, IX is designed for the ground up to support applications with aggressive networking requirements on dense multi-core platforms with 10GbE and 40GbE Ethernet NICs.  IX outperforms Linux by an order of magnitude on micro benchmarks, and by up to 3.6x when running an unmodified memcached, a popular key-value store. The presentation is based on the joint work with Adam Belay, George Prekas, Ana Klimovic, Sam Grossman and Christos Kozyrakis, published at OSDI 2014; Best P...

  3. A Model Program for Statewide Title IX Capacity Building.

    Science.gov (United States)

    Berard, Barbara K.; Huppertz, Nancy

    This manual is intended to increase awareness of Title IX and related equity issues at the local school district level by providing materials and resources to specialists in school districts. The manual: (1) describes a model traveling equity resource display; and (2) provides instructions, agendas, and participant materials for a two-day training…

  4. Secondary Athletic Administrators' Perceptions of Title IX Policy Changes

    Science.gov (United States)

    Dahl, Gabriel Grawe

    2012-01-01

    The purpose of this study was to investigate North Dakota's Normal Competitive Region (NDNCR) high school athletic administrators' perceptions of 2010 Title IX policy changes respective to their athletic programs. Quantitative and qualitative data were collected to investigate the perceptions. Quantitatively, perception data were gathered from a…

  5. 23. IX korraldab Vaala galerii kunstioksjoni "Väliseesti eri"

    Index Scriptorium Estoniae

    2004-01-01

    Oksjonil on esindatud Eerik Haamer, Jaan Grünberg, Arno Vihalemm, Eduard Wiiralt, Ruth Tulving, Endel Kõks, Harald Jürissaar, Otto Paas, Ville Tops, Otto Puusta. Töödega saab tutvuda alates 18. IX, traditsiooniline sügisoksjon toimub 18. XI

  6. Alates 24. IX on Rotermanni soolalao suures saalis...

    Index Scriptorium Estoniae

    2005-01-01

    Arhitektuurifoto näitus "Urbanistlik antoloogia: Stockholmi portreed". Eksponeeritud 15 rootsi fotograafi tööd alates 1860. aastatest kuni tänapäevani. Näituse kuraator Lars Westberg. 23. IX pidas rootsi fotograaf ja näituse idee autor Bruno Ehrs loengu kunstist pildistada arhitektuuri ja inimesi linnamaastikul

  7. Gender Equity in Intercollegiate Athletics: Determinants of Title IX Compliance

    Science.gov (United States)

    Anderson, Deborah J.; Cheslock, John Jesse; Ehrenberg, Ronald G.

    2006-01-01

    Using new data on intercollegiate athletes, this article shows that recent improvement in Title IX compliance among NCAA Division I institutions was previously overestimated, and provides the first estimates of compliance in Divisions II and III. In addition, regression analyses investigate how institutional characteristics relate to the extent of…

  8. Ares I-X Malfunction Turn Range Safety Analysis

    Science.gov (United States)

    Beaty, J. R.

    2011-01-01

    Ares I-X was the designation given to the flight test version of the Ares I rocket which was developed by NASA (also known as the Crew Launch Vehicle (CLV) component of the Constellation Program). The Ares I-X flight test vehicle achieved a successful flight test on October 28, 2009, from Pad LC-39B at Kennedy Space Center, Florida (KSC). As part of the flight plan approval for the test vehicle, a range safety malfunction turn analysis was performed to support the risk assessment and vehicle destruct criteria development processes. Several vehicle failure scenarios were identified which could have caused the vehicle trajectory to deviate from its normal flight path. The effects of these failures were evaluated with an Ares I-X 6 degrees-of-freedom (6-DOF) digital simulation, using the Program to Optimize Simulated Trajectories Version II (POST2) simulation tool. The Ares I-X simulation analysis provided output files containing vehicle trajectory state information. These were used by other risk assessment and vehicle debris trajectory simulation tools to determine the risk to personnel and facilities in the vicinity of the launch area at KSC, and to develop the vehicle destruct criteria used by the flight test range safety officer in the event of a flight test anomaly of the vehicle. The simulation analysis approach used for this study is described, including descriptions of the failure modes which were considered and the underlying assumptions and ground rules of the study.

  9. Driving factors of aerosol concentration changes in the foothills of Central Himalayas

    Science.gov (United States)

    Kivekäs, Niku; Hooda, Rakesh; Hyvärinen, Antti-Pekka; Collaud-Coen, Martine; O'Connor, Ewan; Pietikäinen, Joni-Pekka; Backman, John; Vakkari, Ville; Lihavainen, Heikki

    2017-04-01

    Because of their short residence time in the atmosphere and uneven sources, the concentration, composition and properties of aerosol particles at a given location vary strongly depending on the air mass history and atmospheric mixing properties. Therefore detailed analysis is needed before a representative picture of the amount or composition of aerosol particles can be obtained. In this study we have analyzed 10 years (2005 - 2014) of aerosol data from Mukteshwar, a high-altitude site at 2180 m elevation in the foothills of Central Himalayas. The site is located on a mountain ridge with valleys on both sides. On larger scale the area consists of is low (peaks 1500 - 2500 m) mountains between the Gangetic Plains (100-200 m) and the actual Himalayas (peaks 6000 - 8000 m). The site is located in monsoon climate with most of the annual precipitation falling during the monsoon months (July and August). The data includes a variety of physical and optical properties of aerosols. We have analyzed the data for diurnal, weekly, and annual cycles, and for inter-annual variability and trends. We have also tried to identify the driving factors behind these changes. There were clear diurnal cycles in aerosol particle concentrations during all seasons apart for monsoon. All external aerosol parameters showed 1.5 - 2 times higher values during afternoon than during night time. This was linked to the diurnal pattern of turbulent mixing layer height, bringing polluted air from the valleys to the site. The timing of the pattern was consistent with increased turbulence, increased water vapor concentration in the air and change of wind direction at the site. The aerosol internal properties did not show a clear diurnal cycle. There were some weak indications of a weekday-weekend cycle during some months for some aerosol parameters, but no consistent patterns were found. The seasonal cycles of all external aerosol parameters were very clear. Every year the monsoon rains removed most of

  10. 24. The transcription factors and the relevant signaling pathways activated by low concentration MNNG

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Aims: To explore the transcription factors and related signal transduction pathways activated in the alkylating agents N-methyl-N'-nitro-N-nitrosoguanindine (MNNG) exposed cells which may involved in the mechanism of MNNG induced changes of gene expression, especially the elevation of DNA polymerase β expression and also the consequence of JNK kinase activation which were reported previously in this lab. Methods: Clontech Mercury pathway profiling system containing 8 different vectors in which a specific response element is located upstream from the SEAP-reporter gene were employed to detect the transcription factor activation in Vero cells treated with 0.2 μmol/L MNNG for 2 hours. Thoroughly, CREB phosphorylation, protein kinase A (PKA) and the cellular cAMP content were also assayed with PhosphoPlus CREB (ser-133) antibody kit, protein kinase assay kit and cAMP RIA kit respectively. Results: Among 8 different response elements, the expression of the reporter gene governed by the transcription factors CREB (cAMP response element binding protein), AP1 (activator protein 1), NF-κB (nuclear factor κ B) were elevated by 1.3, 1.4 and 1.3 times higber than control respectively. The level of activated CREB by Ser-133 phosphorylation was 2.08 times higher than control in cells treated with MNNG for 60 min, as measured by immunoblotting. The activity of CREB upstream kinase protein kinase A (PKA), which can phosphorylate CREB on ser-133 was also activated, and the activation peaked at 60 min (11.03±2.80 arbitrary units vs 0.86±0.43 of control). Also, cAMP levels were significantly raised after 60-minute-treatment, 1.52 times higher vs those in solvent control. Conclusion: In addition of previously reported JNK activation, we show here that low concentration alkylating agent MNNG can also activate the cAMP-PKA and NF-κB pathway. These in consequence induce the activation of transcription factors APl, CREB and NF-κB, which may related to the MNNG induced changes in

  11. Factors associated with serum fetuin-A concentrations after long-term use of different phosphate binders in hemodialysis patients

    National Research Council Canada - National Science Library

    Lin, Hsin-Hung; Liou, Hung-Hsiang; Wu, Ming-Shiou; Huang, Chiu-Ching

    2016-01-01

    Fetuin-A is known as a circulating inhibitor of vascular calcification. Factors associated with serum fetuin-A concentrations after long-term use of different phosphate binders in hemodialysis patients is still uncertain...

  12. Cardiometabolic risk factors are associated with high urinary enterolactone concentration, independent of urinary enterodiol concentration and dietary fiber intake in adults.

    Science.gov (United States)

    Frankenfeld, Cara L

    2014-09-01

    The study objective was to evaluate independent and interactive associations of dietary fiber intake and high urinary enterolignans with cardiometabolic risk factors. The analysis included 2260 adults (≥20 y of age) from the 2003-2010 NHANES. Logistic regression models were used to evaluate obesity and clinically defined cardiometabolic risk factors in relation to dietary fiber intake and urinary enterolignan concentrations. Three sets of models were created: 1) independent associations, 2) mutually adjusted associations, and 3) interactions. Models were adjusted for age, gender, race/ethnicity, education, smoking status, and energy intake. High concentrations were considered to be above the 90th percentile of urinary enterolignan concentrations. Increasing dietary fiber intake was associated with high blood pressure (P = 0.02) and low serum HDL cholesterol (P-trend = 0.03). High urinary enterodiol concentration was not associated with obesity or cardiometabolic risk factors. High urinary enterolactone concentration was inversely associated with obesity (OR: 0.44; 95% CI: 0.29, 0.66), abdominal obesity (OR: 0.58; 95% CI: 0.39, 0.87), high serum C-reactive protein (CRP; OR: 0.52; 95% CI: 0.37, 0.74), high serum triglycerides (OR: 0.39; 95% CI: 0.23, 0.61), low serum HDL cholesterol (OR: 0.37; 95% CI: 0.23, 0.61), and metabolic syndrome (OR: 0.47; 95% CI: 0.30, 0.74). In mutually adjusted models, enterolactone associations observed in independent models remained similar, but associations for dietary fiber intake were attenuated, with the exception of blood pressure. In interaction models, there were 2 significant interactions: between high urinary enterodiol concentration and dietary fiber intake for high serum CRP (P = 0.04) and high plasma glucose (P = 0.04). Overall, being in the highest 10% of urinary enterolactone concentration was associated with cardiometabolic risk factors, independent of dietary fiber intake and enterodiol concentration. Future studies are

  13. Inhibition of hepatitis C virus replication by chalepin and pseudane IX isolated from Ruta angustifolia leaves.

    Science.gov (United States)

    Wahyuni, Tutik Sri; Widyawaruyanti, Aty; Lusida, Maria Inge; Fuad, Achmad; Soetjipto; Fuchino, Hiroyuki; Kawahara, Nobuo; Hayashi, Yoshitake; Aoki, Chie; Hotta, Hak

    2014-12-01

    Hepatitis C virus (HCV) infection is highly prevalent among global populations, with an estimated number of infected patients being 170 million. Approximately 70-80% of patients acutely infected with HCV will progress to chronic liver disease, such as liver cirrhosis and hepatocellular carcinoma, which is a substantial cause of morbidity and mortality worldwide. New therapies for HCV infection have been developed, however, the therapeutic efficacies still need to be improved. Medicinal plants are promising sources for antivirals against HCV. A variety of plants have been tested and proven to be beneficial as antiviral drug candidates against HCV. In this study, we examined extracts, their subfractions and isolated compounds of Ruta angustifolia leaves for antiviral activities against HCV in cell culture. We isolated six compounds, chalepin, scopoletin, γ-fagarine, arborinine, kokusaginine and pseudane IX. Among them, chalepin and pseudane IX showed strong anti-HCV activities with 50% inhibitory concentration (IC₅₀) of 1.7 ± 0.5 and 1.4 ± 0.2 μg/ml, respectively, without apparent cytotoxicity. Their anti-HCV activities were stronger than that of ribavirin (2.8 ± 0.4 μg/ml), which has been widely used for the treatment of HCV infection. Mode-of-action analyses revealed that chalepin and pseudane IX inhibited HCV at the post-entry step and decreased the levels of HCV RNA replication and viral protein synthesis. We also observed that arborinine, kokusaginine and γ-fagarine possessed moderate levels of anti-HCV activities with IC₅₀ values being 6.4 ± 0.7, 6.4 ± 1.6 and 20.4 ± 0.4 μg/ml, respectively, whereas scopoletin did not exert significant anti-HCV activities at 30 μg/ml.

  14. Genetic damage induced by CrO3 can be reduced by low doses of Protoporphyrin-IX in somatic cells of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Luz M. Vidal E.

    2014-01-01

    Full Text Available Several epidemiological studies have reported the relation between chromium exposure (used in different industrial processes and cancer risk. Evidence indicates that the hexavalent form is mutagenic and carcinogenic. Chemoprevention has emerged as a good strategy for reducing the risk from exposure to heavy metals. There is evidence that some tetrapyrrols such as protoporphyrin IX (PP-IX, a porphyrin without a metal center and which is a precursor of hemoglobin and cytochrome, acts as an antioxidant modulating the induction of antioxidant enzymes. The present study was performed to evaluate their antimutagenic potential of PP-IX against genetic damage induced by chromium trioxide (CrO3. The wing spot test was used. Groups of 48 h-old larvae were pretreated for 24 h with 0, 0.69, 6.9, or 69 mM of PP-IX, after which groups of larvae were fed 0.025–2.5 mM CrO3 solution in Drosophila instant medium. The results indicated that the lower PP-IX concentration (0.69 mM significantly reduced the genetic damage induced by all CrO3 concentrations tested. In contrast, 6.9 and 69 mM only inhibited the damage induced by CrO3 2.5 mM. Absence of an inhibitor effect of PP-IX against 20 Gy gamma rays suggested that this porphyrin acted primarily by forming complexes with chromium at low doses, inactivating its genotoxic action rather than capturing or inactivating the reactive oxygen species generated by the chromium.

  15. Genetic damage induced by CrO3 can be reduced by low doses of Protoporphyrin-IX in somatic cells of Drosophila melanogaster.

    Science.gov (United States)

    Vidal E, Luz M; Pimentel P, Emilio; Cruces M, M Patricia; Sánchez M, Juan C

    2014-01-01

    Several epidemiological studies have reported the relation between chromium exposure (used in different industrial processes) and cancer risk. Evidence indicates that the hexavalent form is mutagenic and carcinogenic. Chemoprevention has emerged as a good strategy for reducing the risk from exposure to heavy metals. There is evidence that some tetrapyrrols such as protoporphyrin IX (PP-IX), a porphyrin without a metal center and which is a precursor of hemoglobin and cytochrome, acts as an antioxidant modulating the induction of antioxidant enzymes. The present study was performed to evaluate their antimutagenic potential of PP-IX against genetic damage induced by chromium trioxide (CrO3). The wing spot test was used. Groups of 48 h-old larvae were pretreated for 24 h with 0, 0.69, 6.9, or 69 mM of PP-IX, after which groups of larvae were fed 0.025-2.5 mM CrO3 solution in Drosophila instant medium. The results indicated that the lower PP-IX concentration (0.69 mM) significantly reduced the genetic damage induced by all CrO3 concentrations tested. In contrast, 6.9 and 69 mM only inhibited the damage induced by CrO3 2.5 mM. Absence of an inhibitor effect of PP-IX against 20 Gy gamma rays suggested that this porphyrin acted primarily by forming complexes with chromium at low doses, inactivating its genotoxic action rather than capturing or inactivating the reactive oxygen species generated by the chromium.

  16. A low serum bicarbonate concentration as a risk factor for mortality in peritoneal dialysis patients.

    Directory of Open Access Journals (Sweden)

    Tae Ik Chang

    Full Text Available BACKGROUND AND AIM: Metabolic acidosis is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, this relationship has not yet been determined in peritoneal dialysis (PD patients. METHODS: This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum bicarbonate (TA-Bic levels, we aimed to investigate whether a low serum bicarbonate concentration can predict mortality in these patients. RESULTS: Among the baseline parameters, serum bicarbonate level was positively associated with hemoglobin level and residual glomerular filtration rate (GFR, while it was negatively associated with albumin, C-reactive protein (CRP levels, peritoneal Kt/V urea, and normalized protein catabolic rate (nPCR in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. After adjustment for age, diabetes, coronary artery disease, serum albumin, ferritin, CRP, residual GFR, peritoneal Kt/V urea, nPCR, and percentage of lean body mass, TA-Bic level was associated with a significantly decreased risk of mortality (HR per 1 mEq/L increase, 0.83; 95% CI, 0.76-0.91; p < 0.001. In addition, compared to patients with a TA-Bic level of 24-26 mEq/L, those with a TA-Bic level < 22 and between 22-24 mEq/L conferred a 13.10- and 2.13-fold increased risk of death, respectively. CONCLUSIONS: This study showed that a low serum bicarbonate concentration is an independent risk factor for mortality in PD patients. This relationship between low bicarbonate levels and adverse outcome could be related to enhanced inflammation and a more rapid loss of RRF associated with metabolic acidosis. Large randomized clinical trials to correct acidosis are warranted to confirm our findings.

  17. Analysis and modelling of the factors controlling seed oil concentration in sunflower: a review

    Directory of Open Access Journals (Sweden)

    Andrianasolo Fety Nambinina

    2016-03-01

    Full Text Available Sunflower appears as a potentially highly competitive crop, thanks to the diversification of its market and the richness of its oil. However, seed oil concentration (OC – a commercial criterion for crushing industry – is subjected to genotypic and environmental effects that make it sometimes hardly predictable. It is assumed that more understanding of oil physiology combined with the use of crop models should permit to improve prediction and management of grain quality for various end-users. Main effects of temperature, water, nitrogen, plant density and fungal diseases were reviewed in this paper. Current generic and specific crop models which simulate oil concentration were found to be empirical and to lack of proper evaluation processes. Recently two modeling approaches integrating ecophysiological knowledge were developed by Andrianasolo (2014, Statistical and dynamic modelling of sunflower (Helianthus annuus L. grain composition as a function of agronomic and environmental factors, Ph.D. Thesis, INP Toulouse: (i a statistical approach relating OC to a range of explanatory variables (potential OC, temperature, water and nitrogen stress indices, intercepted radiation, plant density which resulted in prediction quality from 1.9 to 2.5 oil points depending on the nature of the models; (ii a dynamic approach, based on “source-sink” relationships involving leaves, stems, receptacles (as sources and hulls, proteins and oil (as sinks and using priority rules for carbon and nitrogen allocation. The latter model reproduced dynamic patterns of all source and sink components faithfully, but tended to overestimate OC. A better description of photosynthesis and nitrogen uptake, as well as genotypic parameters is expected to improve its performance.

  18. Correction factors for estimating potassium concentrations in samples with in vitro hemolysis: a detriment to patient safety.

    Science.gov (United States)

    Mansour, Mai M H; Azzazy, Hassan M E; Kazmierczak, Steven C

    2009-06-01

    Correction factors have been proposed for estimating true potassium concentrations in blood samples with evidence of in vitro hemolysis. We used 2 different models of true (ie, nonsimulated) in vitro hemolysis to evaluate the clinical utility of correction factors for estimating potassium concentrations in samples with evidence of in vitro hemolysis. Potassium correction factors were derived using 2 different models. In model 1, potassium and plasma hemoglobin were measured with the Hitachi 747 analyzer in 132 paired blood samples, with each pair consisting of 1 sample with evidence of hemolysis and 1 without, collected during the same phlebotomy procedure. The change in measured potassium concentration was plotted versus the change in plasma hemoglobin concentration for each pair of samples. In model 2, the potassium levels of 142 784 blood samples and the corresponding hemolytic index values were measured with the Beckman LX20 analyzer. Potassium concentrations at the 10th, 25th, 50th, 75th, and 90th percentiles were calculated for each hemolysis index category. From our 2 models, we derived correction factors expressing an increase in potassium concentration of 0.51 and 0.40 mEq/L for every increase in plasma hemoglobin concentration of 0.1 g/dL. These correction factors are much higher than those reported in studies that simulated in vitro hemolysis by freeze-thaw lysis or osmotic disruption of whole blood. Use of correction factors for estimating the true potassium concentration in samples with evidence of in vitro hemolysis is not recommended. Derivation of correction factors by using samples with nonsimulated in vitro hemolysis suggests that the actual increase in potassium in hemolyzed samples is much higher than that reported in previous studies that produced hemolysis with artificial means.

  19. MO-FG-BRA-07: Theranostic Gadolinium-Based AGuIX Nanoparticles for MRI-Guided Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Detappe, A [Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical, Boston, MA (United States); Institut Lumiere-Matiere, Villeurbanne (France); Nano-H, St-Quentin Fallavier (France); Rottmann, J; Kunjachan, S; Berbeco, R [Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical, Boston, MA (United States); Tillement, O [Institut Lumiere-Matiere, Villeurbanne (France)

    2015-06-15

    Purpose: AGuIX are gadolinium-based nanoparticles, initially developed for MRI, that have a potential role in radiation therapy as a radiosensitizer. Our goal is to demonstrate that these nanoparticles can both be used as an MRI contrast agent, as well as to obtain local dose enhancement in a pancreatic tumor when delivered in combination with an external beam irradiation. Methods: We performed in vitro cell uptake and radiosensitization studies of a pancreatic cancer cell line in a low energy (220kVp) beam, a standard clinical 6MV beam (STD) and a flattening filter free clinical 6MV beam (FFF). After injection of 40mM of nanoparticles, a biodistribution study was performed in vivo on mice with subcutaneous xenograft pancreatic tumors. In vivo radiation therapy studies were performed at the time point of maximum tumor uptake. Results: The concentration of AGuIX nanoparticles in Panc-1 pancreatic cancer cells, determined in vitro by MRI and ICPMS, peaks after 30 minutes with 0.3% of the initial concentration (5mg/g). Clonogenic assays show a significant effect (p<0.05) when the AGuIX are coupled with MV photon irradiation (DEF20%=1.31). Similar AGuIX tumor uptake is found in vivo by both MRI and ICPMS 30 minutes after intravenous injection. For long term survival studies, the choice of the radiation dose is determined with 5 control groups (3mice/group) irradiated with 0, 5, 10, 15, and 20Gy. Afterwards, 4 groups (8mice/group) are used to evaluate the effect of the nanoparticles. A Logrank test is performed as a statistical test to evaluate the effect of the nanoparticles. Conclusion: The combination of the MRI contrast and radiosensitization properties of gadolinium nanoparticles reveals a strong potential for usage with MRI-guided radiation therapy.

  20. Effect of warfarin on the kinetics of the vitamin K-dependent clotting factors in rats.

    Science.gov (United States)

    Vainieri, H; Wingard, L B

    1977-05-01

    The objectives of this study were to compare the time course of activities and rates of synthesis of activities for the separate clotting factors II, VII, IX, and X and to relate the rate of synthesis of activity of each factor to the plasma concentration of warfarin in individual rats after acute and chronic dosing with warfarin. Sequences of blood samples were obtained from each rat for 50 to 70 hours after an acute dose of warfarin or for 120 hours after a chronic loading dose plus 12-hour maintenance doses of warfarin and assayed for factor activities and warfarin concentration. The half-lives for degradation of factor activities ranged from 2.6 to 9.0 hours for the four factors. During periods of changing warfarin concentration (acute dosing) factor VII and X activities and rates of synthesis of activity showed large rapid changes, while factors II and IX responded more slowly. As the warfarin concentration diminished, the factor X rate of synthesis of activity appeared to exceed predrug values in all rats. During chronic dosing with warfarin the factor II activity and rate of synthesis of activity was depressed the most. The percent depression of the rate of synthesis of activity for each factor was related linearly to the logarithm of the plasma concentration of warfarin for the range 0 to 80% depression with acute dosing. However, this relationship was not suitable to explain the apparent overshoot in factor X rate of synthesis of activity.

  1. Utilization of internal standard response factors to estimate the concentration of organic compounds leached from pharmaceutical packaging systems and application of such estimated concentrations to safety assessment.

    Science.gov (United States)

    Jenke, Dennis; Odufu, Alex

    2012-03-01

    Substances from packaging systems that are leached into packaged medical products may have a safety impact on patients to whom such medical products are administered. The potential safety impact depends on the identity and concentration of the leached substances. The concentration above which a leachable must be identified in order to assess its safety impact is frequently estimated using an internal standard to "calibrate" the analytical response of a chromatographic system. Such an estimate is accurate to the extent that the responses of the internal standard and leachables are similar. To establish the accuracy of the internal standard approach, a database of gas chromatography-flame ionization detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS) responses was generated for thirty-eight leachables and eight internal standard candidates. Although the FID and MS responses of many of the leachables and internal standards fell within a narrow band, acidic and basic compounds produced responses that were discernibly different from those of neutral analytes. While most of the internal standards were suited for concentration estimation, three of the candidates, dimethylphthalate, triphenylphosphate and 4,4-dibromobiphenyl, produced the smallest mean error in estimated concentration for the analytes examined. As the FID and MS responses were linear, internal standards could be used to estimate leachables concentrations even when the difference in leachable versus internal standard concentrations was as great as a factor of 25. A multiplier may be appropriate to adjust an estimated concentration to its greatest possible value, and it is this value that is used to convert an estimated Analytical Evaluation Threshold (AET) into a working or final AET.

  2. The Development of the Ares I-X Flight Test

    Science.gov (United States)

    Ess, Robert H.

    2008-01-01

    The National Aeronautics and Space Administration (NASA) Constellation Program (CxP) has identified a series of tests to provide insight into the design and development of the Ares I Crew Launch Vehicle (CLV) and the Orion Crew Exploration Vehicle (CEV). Ares I-X was created as the first suborbital development flight test to help meet CxP objectives. The Ares I-X flight vehicle is an early operational model of Ares, with specific emphasis on Ares I and ground operation characteristics necessary to meet Ares I-X flight test objectives. Ares I-X will encompass the design and construction of an entire system that includes the Flight Test Vehicle (FTV) and associated operations. The FTV will be a test model based on the Ares I design. Select design features will be incorporated in the FTV design to emulate the operation of the CLV in order to meet the flight test objectives. The operations infrastructure and processes will be customized for Ares I-X, while still providing data to inform the developers of the launch processing system for Ares/Orion. The FTV is comprised of multiple elements and components that will be developed at different locations. The components will be delivered to the launch/assembly site, Kennedy Space Center (KSC), for assembly of the elements and components into an integrated, flight-ready, launch vehicle. The FTV will fly a prescribed trajectory in order to obtain the necessary data to meet the objectives. Ares I-X will not be commanded or controlled from the ground during flight, but the FTV will be equipped with telemetry systems, a data recording capability and a flight termination system (FTS). The in-flight part of the test includes a trajectory to simulate maximum dynamic pressure during flight and perform a stage separation representative of the CLV. The in-flight test also includes separation of the Upper Stage Simulator (USS) from the First Stage and recovery of the First Stage. The data retrieved from the flight test will be analyzed

  3. Factors influencing pre-race serum concentration of total carbon dioxide in Thoroughbred horses racing in California.

    Science.gov (United States)

    Cohen, N D; Stanley, S D; Arthur, R M; Wang, N

    2006-11-01

    Many racing jurisdictions monitor pre-race serum concentration of total carbon dioxide (TCO2) among racing horses. To our knowledge, factors influencing concentration of TCO2 among horses participating in racing have not been systematically evaluated and reported. To determine if characteristics of horses and racing conditions routinely recorded were significantly associated with pre-race concentration of TCO2, while accounting for and estimating effects of trainer and horse. Pre-race serum TCO2 concentrations from 5028 starts made by 2,349 horses trained by 287 trainers at 2 racetracks in California during 2005 were examined. Data regarding characteristics of starters and race conditions obtained from a commercial database were recorded for each start. Data were analysed using mixed-effects, with TCO2 concentration as the dependent variable, and trainer and horse nested within trainer as random effects. Sex, class and distance of race, frusemide administration and cloudy weather conditions were significantly (Prace TCO2 concentration. Horses that finished in the top 3 positions had values that were slightly (0.2 mmol/) but significantly (Phorses not finishing in the top 3. There were significant effects of trainer on pre-race TCO2 concentration. A variety of factors may influence pre-race TCO2 concentration in horses. Horses with better performance tend to have higher pre-race TCO2 concentrations. TCO2 concentration is associated with improved performance although the magnitude of effect was quite small. Regulatory programmes based on monitoring should consider the influence of other factors on TCO2 concentration.

  4. Arabidopsis Lectin Receptor Kinases LecRK-IX.1 and LecRK-IX.2 Are Functional Analogs in Regulating Phytophthora Resistance and Plant Cell Death.

    Science.gov (United States)

    Wang, Yan; Cordewener, Jan H G; America, Antoine H P; Shan, Weixing; Bouwmeester, Klaas; Govers, Francine

    2015-09-01

    L-type lectin receptor kinases (LecRK) are potential immune receptors. Here, we characterized two closely-related Arabidopsis LecRK, LecRK-IX.1 and LecRK-IX.2, of which T-DNA insertion mutants showed compromised resistance to Phytophthora brassicae and Phytophthora capsici, with double mutants showing additive susceptibility. Overexpression of LecRK-IX.1 or LecRK-IX.2 in Arabidopsis and transient expression in Nicotiana benthamiana increased Phytophthora resistance but also induced cell death. Phytophthora resistance required both the lectin domain and kinase activity, but for cell death, the lectin domain was not needed. Silencing of the two closely related mitogen-activated protein kinase genes NbSIPK and NbNTF4 in N. benthamiana completely abolished LecRK-IX.1-induced cell death but not Phytophthora resistance. Liquid chromatography-mass spectrometry analysis of protein complexes coimmunoprecipitated in planta with LecRK-IX.1 or LecRK-IX.2 as bait, resulted in the identification of the N. benthamiana ABC transporter NbPDR1 as a potential interactor of both LecRK. The closest homolog of NbPDR1 in Arabidopsis is ABCG40, and coimmunoprecipitation experiments showed that ABCG40 associates with LecRK-IX.1 and LecRK-IX.2 in planta. Similar to the LecRK mutants, ABCG40 mutants showed compromised Phytophthora resistance. This study shows that LecRK-IX.1 and LecRK-IX.2 are Phytophthora resistance components that function independent of each other and independent of the cell-death phenotype. They both interact with the same ABC transporter, suggesting that they exploit similar signal transduction pathways.

  5. Structural and functional probing of PorZ, an essential bacterial surface component of the type-IX secretion system of human oral-microbiomic Porphyromonas gingivalis

    DEFF Research Database (Denmark)

    Lasica, Anna M; Goulas, Theodoros; Mizgalska, Danuta;

    2016-01-01

    Porphyromonas gingivalis is a member of the human oral microbiome abundant in dysbiosis and implicated in the pathogenesis of periodontal (gum) disease. It employs a newly described type-IX secretion system (T9SS) for secretion of virulence factors. Cargo proteins destined for secretion through T...

  6. Use of linear regression models to determine influence factors on the concentration levels of radon in occupied houses

    Science.gov (United States)

    Buermeyer, Jonas; Gundlach, Matthias; Grund, Anna-Lisa; Grimm, Volker; Spizyn, Alexander; Breckow, Joachim

    2016-09-01

    This work is part of the analysis of the effects of constructional energy-saving measures to radon concentration levels in dwellings performed on behalf of the German Federal Office for Radiation Protection. In parallel to radon measurements for five buildings, both meteorological data outside the buildings and the indoor climate factors were recorded. In order to access effects of inhabited buildings, the amount of carbon dioxide (CO2) was measured. For a statistical linear regression model, the data of one object was chosen as an example. Three dummy variables were extracted from the process of the CO2 concentration to provide information on the usage and ventilation of the room. The analysis revealed a highly autoregressive model for the radon concentration with additional influence by the natural environmental factors. The autoregression implies a strong dependency on a radon source since it reflects a backward dependency in time. At this point of the investigation, it cannot be determined whether the influence by outside factors affects the source of radon or the habitant’s ventilation behavior resulting in variation of the occurring concentration levels. In any case, the regression analysis might provide further information that would help to distinguish these effects. In the next step, the influence factors will be weighted according to their impact on the concentration levels. This might lead to a model that enables the prediction of radon concentration levels based on the measurement of CO2 in combination with environmental parameters, as well as the development of advices for ventilation.

  7. ALA-PpIX variability quantitatively imaged in A431 epidermoid tumors using in vivo ultrasound fluorescence tomography and ex vivo assay

    Science.gov (United States)

    DSouza, Alisha V.; Flynn, Brendan P.; Gunn, Jason R.; Samkoe, Kimberley S.; Anand, Sanjay; Maytin, Edward V.; Hasan, Tayyaba; Pogue, Brian W.

    2014-03-01

    Treatment monitoring of Aminolevunilic-acid (ALA) - Photodynamic Therapy (PDT) of basal-cell carcinoma (BCC) calls for superficial and subsurface imaging techniques. While superficial imagers exist for this purpose, their ability to assess PpIX levels in thick lesions is poor; additionally few treatment centers have the capability to measure ALA-induced PpIX production. An area of active research is to improve treatments to deeper and nodular BCCs, because treatment is least effective in these. The goal of this work was to understand the logistics and technical capabilities to quantify PpIX at depths over 1mm, using a novel hybrid ultrasound-guided, fiber-based fluorescence molecular spectroscopictomography system. This system utilizes a 633nm excitation laser and detection using filtered spectrometers. Source and detection fibers are collinear so that their imaging plane matches that of ultrasound transducer. Validation with phantoms and tumor-simulating fluorescent inclusions in mice showed sensitivity to fluorophore concentrations as low as 0.025μg/ml at 4mm depth from surface, as presented in previous years. Image-guided quantification of ALA-induced PpIX production was completed in subcutaneous xenograft epidermoid cancer tumor model A431 in nude mice. A total of 32 animals were imaged in-vivo, using several time points, including pre-ALA, 4-hours post-ALA, and 24-hours post-ALA administration. On average, PpIX production in tumors increased by over 10-fold, 4-hours post-ALA. Statistical analysis of PpIX fluorescence showed significant difference among all groups; p<0.05. Results were validated by exvivo imaging of resected tumors. Details of imaging, analysis and results will be presented to illustrate variability and the potential for imaging these values at depth.

  8. Impact of low concentration factor microfiltration on milk component recovery and Cheddar cheese yield.

    Science.gov (United States)

    Neocleous, M; Barbano, D M; Rudan, M A

    2002-10-01

    The effect of microfiltration (MF) on the composition of Cheddar cheese, fat, crude protein (CP), calcium, total solids recovery, and Cheddar cheese yield efficiency (i.e., composition adjusted yield divided by theoretical yield) was determined. Raw skim milk was microfiltered twofold using a 0.1-microm ceramic membrane at 50 degrees C. Four vats of cheese were made in one day using milk at lx, 1.26x, 1.51x, and 1.82x concentration factor (CF). An appropriate amount of cream was added to achieve a constant casein (CN)-to-fat ratio across treatments. Cheese manufacture was repeated on four different days using a randomized complete block design. The composition of the cheese was affected by MF. Moisture content of the cheese decreased with increasing MF CF. Standardization of milk to a constant CN-to-fat ratio did not eliminate the effect of MF on cheese moisture content. Fat recovery in cheese was not changed by MF. Separation of cream prior to MF, followed by the recombination of skim or MF retentate with cream resulted in lower fat recovery in cheese for control and all treatments and higher fat loss in whey when compared to previous yield experiments, when control Cheddar cheese was made from unseparated milk. Crude protein, calcium, and total solids recovery in cheese increased with increasing MF CF, due to partial removal of these components prior to cheese making. Calcium and calcium as a percentage of protein increased in the cheese, suggesting an increase in calcium retention in the cheese with increasing CF. While the actual and composition adjusted cheese yields increased with increasing MF CF, as expected, there was no effect of MF CF on cheese yield efficiency.

  9. Star formation rate in Holmberg IX dwarf galaxy

    Directory of Open Access Journals (Sweden)

    Anđelić M.M.

    2011-01-01

    Full Text Available In this paper we use previously determined Hα fluxes for dwarf galaxy Holmberg IX (Arbutina et al. 2009 to calculate star formation rate (SFR in this galaxy. We discuss possible contaminations of Hα flux and, for the first time, we take into account optical emission from supernova remnants (SNRs as a possible source of contamination of Hα flux. Derived SFR for Holmberg IX is 3:4 x 10-4M.yr-1. Our value is lower then in previous studies, due to luminous shock-heated source M&H 9-10, possible hypernova remnant, which we excluded from the total Hα flux in our calculation of SFR.

  10. Ares I-X Best Estimated Trajectory Analysis and Results

    Science.gov (United States)

    Karlgaard, Christopher D.; Beck, Roger E.; Starr, Brett R.; Derry, Stephen D.; Brandon, Jay; Olds, Aaron D.

    2011-01-01

    The Ares I-X trajectory reconstruction produced best estimated trajectories of the flight test vehicle ascent through stage separation, and of the first and upper stage entries after separation. The trajectory reconstruction process combines on-board, ground-based, and atmospheric measurements to produce the trajectory estimates. The Ares I-X vehicle had a number of on-board and ground based sensors that were available, including inertial measurement units, radar, air-data, and weather balloons. However, due to problems with calibrations and/or data, not all of the sensor data were used. The trajectory estimate was generated using an Iterative Extended Kalman Filter algorithm, which is an industry standard processing algorithm for filtering and estimation applications. This paper describes the methodology and results of the trajectory reconstruction process, including flight data preprocessing and input uncertainties, trajectory estimation algorithms, output transformations, and comparisons with preflight predictions.

  11. Bianchi-IX, Darboux-Halphen and Chazy-Ramanujan

    CERN Document Server

    Chanda, Sumanto; Roychowdhury, Raju

    2015-01-01

    Bianchi-IX four metrics are $SU(2)$ invariant solutions of vacuum Einstein equation, for which the connection-wise self-dual case describes the Euler Top, while the curvature-wise self-dual case yields the Ricci flat classical Darboux-Halphen system. It is possible to see such a solution exhibiting Ricci flow. The classical Darboux-Halphen system is a special case of the generalized one that arises from a reduction of the self-dual Yang-Mills equation and the solutions to the related homogeneous quadratic differential equations provide the desired metric. A few integrable and near-integrable dynamical systems related to the Darboux-Halphen system and occur in the study of Bianchi IX gravitational instanton have been listed as well. We explore in details whether self-duality implies integrability.

  12. Loop quantum cosmology of Bianchi type IX models

    CERN Document Server

    Wilson-Ewing, Edward

    2010-01-01

    The loop quantum cosmology "improved dynamics" of the Bianchi type IX model are studied. The action of the Hamiltonian constraint operator is obtained via techniques developed for the Bianchi type I and type II models, no new input is required. It is shown that the big bang and big crunch singularities are resolved by quantum gravity effects. We also present the effective equations which provide modifications to the classical equations of motion due to quantum geometry effects.

  13. Loop quantum cosmology of Bianchi type IX models

    Science.gov (United States)

    Wilson-Ewing, Edward

    2010-08-01

    The loop quantum cosmology “improved dynamics” of the Bianchi type IX model are studied. The action of the Hamiltonian constraint operator is obtained via techniques developed for the Bianchi type I and type II models, no new input is required. It is shown that the big bang and big crunch singularities are resolved by quantum gravity effects. We also present effective equations which provide quantum geometry corrections to the classical equations of motion.

  14. Effects of maternal smoking and exposure to methylmercury on brain-derived neurotrophic factor concentrations in umbilical cord serum

    DEFF Research Database (Denmark)

    Spulber, Stefan; Rantamäki, Tomi; Nikkilä, Outi;

    2010-01-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin essential for neuronal survival and differentiation. We examined the concentration of BDNF in cord serum from newborns exposed to methylmercury (MeHg) and polychlorinated biphenyls (PCB) in utero by maternal consumption of whale meat....... The cohort consisted of 395 singleton births (206 boys and 189 girls), gestational age ranging from 38 to 42 weeks. Serum BDNF was measured by sandwich ELISA. Maternal smoking habits and other relevant factors were obtained by interviewing the mothers. The exposure to MeHg was estimated from Hg...... concentrations in cord blood, whereas exposure to PCB was estimated based on maternal serum concentrations. Only MeHg exposure affected the serum BDNF, which decreased in a concentration-dependent manner in girls born to nonsmoking mothers. Maternal smoking significantly increased BNDF in girls but not in boys...

  15. Loop quantum cosmology of Bianchi IX: effective dynamics

    Science.gov (United States)

    Corichi, Alejandro; Montoya, Edison

    2017-03-01

    We study solutions to the effective equations for the Bianchi IX class of spacetimes within loop quantum cosmology (LQC). We consider Bianchi IX models whose matter content is a massless scalar field, by numerically solving the loop quantum cosmology effective equations, with and without inverse triad corrections. The solutions are classified using certain geometrically motivated classical observables. We show that both effective theories—with lapse N  =  V and N  =  1—resolve the big bang singularity and reproduce the classical dynamics far from the bounce. Moreover, due to the positive spatial curvature, there is an infinite number of bounces and recollapses. We study the limit of large field momentum and show that both effective theories reproduce the same dynamics, thus recovering general relativity. We implement a procedure to identify amongst the Bianchi IX solutions, those that behave like k  =  0,1 FLRW as well as Bianchi I, II, and VII0 models. The effective solutions exhibit Bianchi I phases with Bianchi II transitions and also Bianchi VII0 phases, which had not been studied before. We comment on the possible implications of these results for a quantum modification to the classical BKL behaviour.

  16. Loop quantum cosmology of Bianchi IX: Effective dynamics

    CERN Document Server

    Corichi, Alejandro

    2015-01-01

    We study numerically the solutions to the effective equations of Bianchi IX spacetimes within Loop Quantum Cosmology. We consider Bianchi IX models with and without inverse triad corrections whose matter content is a scalar field without mass. The solutions are classified using the classical observables. We show that both effective theories --with lapse N=V and N=1-- solve the big bang singularity and reproduce the classical dynamics far from the bounce. Moreover, due to the spatial compactness, there is an infinity number of bounces and recollapses. We study the limit of large volume and show that both effective theories reproduce the same dynamics, thus recovering general relativity. We implement a procedure to identify amongst the Bianchi IX solutions, those that behave like k=0,1 FLRW as well as Bianchi I, II, and VII_0 models. The effective solutions exhibit Bianchi I phases with Bianchi II transitions and also Bianchi VII_0 phases, which had not been studied before, at the quantum nor effective level. W...

  17. Black Carbon Concentrations and Diesel Vehicle Emission Factors Derived from Coefficient of Haze Measurements in California: 1967-2003

    Energy Technology Data Exchange (ETDEWEB)

    Tast, CynthiaL; Kirchstetter, Thomas W.; Aguiar, Jeffery; Tonse, Shaheen; Novakov, T.; Fairley, David

    2007-11-09

    We have derived ambient black carbon (BC) concentrations and estimated emission factors for on-road diesel vehicles from archived Coefficient of Haze (COH) data that was routinely collected beginning in 1967 at 11 locations in the San Francisco Bay Area. COH values are a measure of the attenuation of light by particles collected on a white filter, and available data indicate they are proportional to BC concentrations measured using the conventional aethalometer. Monthly averaged BC concentrations are up to five times greater in winter than summer, and, consequently, so is the population?s exposure to BC. The seasonal cycle in BC concentrations is similar for all Bay Area sites, most likely due to area-wide decreased pollutant dispersion during wintertime. A strong weekly cycle is also evident, with weekend concentrations significantly lower than weekday concentrations, consistent with decreased diesel traffic volume on weekends. The weekly cycle suggests that, in the Bay Area, diesel vehicle emissions are the dominant source of BC aerosol. Despite the continuous increase in diesel fuel consumption in California, annual Bay Area average BC concentrations decreased by a factor of ~;;3 from the late 1960s to the early 2000s. Based on estimated annual BC concentrations, on-road diesel fuel consumption, and recent measurements of on-road diesel vehicle BC emissions, diesel BC emission factors decreased by an order of magnitude over the study period. Reductions in the BC emission factor reflect improved engine technology, emission controls and changes in diesel fuel composition. A new BC monitoring network is needed to continue tracking ambient BC trends because the network of COH monitors has recently been retired.

  18. Optimization and characterization of the endogenous production of protoporphyrin IX in a yeast model

    Science.gov (United States)

    Joniová, Jaroslava; Gerelli, Emmanuel; Zellweger, Matthieu; Wagnières, Georges

    2016-12-01

    The availability of reproducible, convenient, and inexpensive model organisms able to generate predictable levels of endogenous porphyrins, including protoporphyrin IX (PpIX), is essential in photomedicine research. Saccharomyces cerevisiae produces endogenous PpIX and was used as a model organism for this study with the aim to maximize endogenous PpIX fluorescence intensity. It was found that PpIX fluorescence was significantly enhanced by administration of 5-aminolevulinic acid (ALA) and 2,2‧-bipyridyl. Fluorescence intensity and spectroscopy of PpIX produced endogenously were measured in diluted yeast solutions under various conditions. The optimal protocol was: 5 μM ALA and 1 mM 2,2‧-bipyridyl administered synchronously at 32°C. After 3 h, PpIX in yeast demonstrated similar steady-state and time-resolved spectroscopy as that of PpIX in DMSO. Moreover, under hypoxic conditions, the reciprocal lifetime of PpIX delayed fluorescence measured in real time was correlated to the partial pressure of oxygen (pO2) measured concomitantly with a commercially available pO2 probe. These data show that yeast can, in optimal conditions, reproducibly generate PpIX. This is of interest in various fields such as photodiagnosis, photodynamic therapy, and photobiomodulation. Use of this model organism focuses on essential mechanisms, without the complexity of a multicellular organism.

  19. Aluminum Enhances Growth and Sugar Concentration, Alters Macronutrient Status and Regulates the Expression of NAC Transcription Factors in Rice

    Science.gov (United States)

    Moreno-Alvarado, Marcos; García-Morales, Soledad; Trejo-Téllez, Libia Iris; Hidalgo-Contreras, Juan Valente; Gómez-Merino, Fernando Carlos

    2017-01-01

    Aluminum (Al) is a beneficial element for some plant species, especially when used at low concentrations. Though some transcription factors are induced by exposure to this element, no data indicate that Al regulates the expression of NAC genes in rice. In this study we tested the effect of applying 200 μM Al on growth, chlorophyll, amino acids, sugars, macronutrient concentration and regulation of NAC transcription factors gene expression in 24-day-old plants of four rice (Oryza sativa ssp. indica) cultivars: Cotaxtla, Tres Ríos, Huimanguillo and Temporalero, grown hydroponically under greenhouse conditions. Twenty days after treatment, we observed that Al enhanced growth in the four cultivars studied. On average, plants grown in the presence of Al produced 140% more root dry biomass and were 30% taller than control plants. Cotaxtla and Temporalero showed double the root length, while Huimanguillo and Cotaxtla had three times more root fresh biomass and 2.5 times more root dry biomass. Huimanguillo plants showed 1.5 times more shoot height, while Cotaxtla had almost double the root dry biomass. With the exception of Tres Ríos, the rest of the cultivars had almost double the chlorophyll concentration when treated with Al, whereas amino acid and proline concentrations were not affected by Al. Sugar concentration was also increased in plants treated with Al, almost 11-fold in comparison to the control. Furthermore, we observed a synergic response of Al application on P and K concentration in roots, and on Mg concentration in shoots. Twenty-four hours after Al treatment, NAC transcription factors gene expression was measured in roots by quantitative RT-PCR. Of the 57 NAC transcription factors genes primer-pairs tested, we could distinguish that 44% (25 genes) showed different expression patterns among rice cultivars, with most of the genes induced in Cotaxtla and Temporalero plants. Of the 25 transcription factors up-regulated, those showing differential expression

  20. Correction factors for determination of annual average radon concentration in dwellings of Poland resulting from seasonal variability of indoor radon.

    Science.gov (United States)

    Kozak, K; Mazur, J; Kozłowska, B; Karpińska, M; Przylibski, T A; Mamont-Cieśla, K; Grządziel, D; Stawarz, O; Wysocka, M; Dorda, J; Zebrowski, A; Olszewski, J; Hovhannisyan, H; Dohojda, M; Kapała, J; Chmielewska, I; Kłos, B; Jankowski, J; Mnich, S; Kołodziej, R

    2011-10-01

    The method for the calculation of correction factors is presented, which can be used for the assessment of the mean annual radon concentration on the basis of 1-month or 3-month indoor measurements. Annual radon concentration is an essential value for the determination of the annual dose due to radon inhalation. The measurements have been carried out in 132 houses in Poland over a period of one year. The passive method of track detectors with CR-39 foil was applied. Four thermal-precipitation regions in Poland were established and correction factors were calculated for each region, separately for houses with and without basements.

  1. Reduced serum concentrations of nerve growth factor, but not brain-derived neurotrophic factor, in chronic cannabis abusers.

    Science.gov (United States)

    Angelucci, Francesco; Ricci, Valerio; Spalletta, Gianfranco; Pomponi, Massimiliano; Tonioni, Federico; Caltagirone, Carlo; Bria, Pietro

    2008-12-01

    Chronic cannabis use produces effects within the central nervous system (CNS) which include deficits in learning and attention tasks and decreased brain volume. Neurotrophins, in particular nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), are proteins that serve as survival factors for CNS neurons. Deficits in the production and utilization of these proteins can lead to CNS dysfunctions including those associated with cannabis abuse. In this study we measured by enzyme-linked immunosorbent assay (ELISA) the NGF and BDNF serum levels in two groups of subjects: cannabis-dependent patients and healthy subjects. We found that NGF serum levels were significantly reduced in cannabis abusers as compared to healthy subjects. These findings indicate that NGF may have a role in the central action of cannabis and potentially in the neurotoxicity induced by this drug. These data also suggest that chronic cannabis consumption may be a risk factor for developing psychosis among drug users.

  2. [The concentration of growth factors in patients with inherent and acquired shortenings of limbs bones].

    Science.gov (United States)

    Strogov, M V; Luneva, S N; Novikov, K I

    2013-04-01

    The article deals with the results of study of level of growth factors in blood serum of patients with inherent and post-traumatic shortenings of limbs' bones. The detection in blood serum the level of epidermal growth factor insulin-like growth factor I and angiopoetins is proposed to monitor in given patients the reparative bone formation.

  3. Rheology and influence factor of low-concentration Konjac gum solutions

    Institute of Scientific and Technical Information of China (English)

    王元兰; 李忠海; 魏玉

    2008-01-01

    Rheological properties of low-concentration Konjac gum and impacts of concentration,shearing rate,pH value and stirring time on its viscosity were studied.The results show that the viscosity of low-concentration Konjac gum increases with the increase of its concentration.The solution presents pseudo-plasticity fluid,which shows the characters of shear thinning as follows:first,its viscosity decreases gradually as the temperature increases,and then increases with the increase of temperature.The viscosity decreases sharply at both acid and alkaline conditions,indicating that it is influenced apparently by pH value.And the viscosity of low-concentration Konjac gum is also impacted by the stirring time.

  4. Air exchanges and indoor carbon dioxide concentration in Australian pig buildings: Effect of housing and management factors

    DEFF Research Database (Denmark)

    Banhazi, T. M.; Stott, P.; Rutley, D.

    2011-01-01

    factors on the concentrations of carbon dioxide (CO(2)) and air exchange rates in 160 representative Australian pig buildings. CO(2) concentrations were measured, air changes per hour (ACH) were estimated using a CO(2) balance method, and structural and management parameters were recorded. The mean CO(2......(2) concentration. Air exchange rates were primarily affected by the type of ventilation, inlet height, stocking density, and building width and height. In conclusion, the equable Australian climate has allowed the construction of cheaper pig buildings, which provide an adequate environment for pig...

  5. Factors that can interfere with virus concentration from wastewater when using zeta plus 60S filter membranes

    Directory of Open Access Journals (Sweden)

    Queiroz APS

    2000-01-01

    Full Text Available Zeta plus filter membranes (ZP60S have been shown to be efficient for rotavirus concentration from wastewater and for the reduction of cytotoxicity for cell cultures. Recently a variability in both properties was observed. In view of the low costs and the high virus recovery rates obtained in the past, we re-evaluated the application of ZP60S filter membranes for virus concentration from environmental samples. Some factors that could interfere with the concentration strategy using ZP60S were also considered and assessed including the type of water to be filtered and the possible release of toxic substances from the membrane matrix during filtration.

  6. Investigation of the spatiotemporal variation and influencing factors on fine particulate matter and carbon monoxide concentrations near a road intersection

    Science.gov (United States)

    Wang, Zhanyong; Lu, Qing-Chang; He, Hong-Di; Wang, Dongsheng; Gao, Ya; Peng, Zhong-Ren

    2017-03-01

    The minute-scale variations of fine particulate matter (PM2.5) and carbon monoxide (CO) concentrations near a road intersection in Shanghai, China were investigated to identify the influencing factors at three traffic periods. Measurement results demonstrate a synchronous variation of pollutant concentrations at the roadside and setbacks, and the average concentration of PM2.5 at the roadside is 7% (44% for CO) higher than that of setbacks within 500 m of the intersection. The pollution level at traffic peak periods is found to be higher than that of off-peak periods, and the morning peak period is found to be the most polluted due to a large amount of diesel vehicles and unfavorable dispersion conditions. Partial least square regressions were constructed for influencing factors and setback pollutant concentrations, and results indicate that meteorological factors are the most significant, followed by setback distance from the intersection and traffic factors. CO is found to be sensitive to distance from the traffic source and vehicle type, and highly dependent on local traffic conditions, whereas PM2.5 originates more from other sources and background levels. These findings demonstrate the importance of localized factors in understanding spatiotemporal patterns of air pollution at intersections, and support decision makers in roadside pollution management and control.

  7. Investigation of the spatiotemporal variation and influencing factors on fine particulate matter and carbon monoxide concentrations near a road intersection

    Science.gov (United States)

    Wang, Zhanyong; Lu, Qing-Chang; He, Hong-Di; Wang, Dongsheng; Gao, Ya; Peng, Zhong-Ren

    2016-05-01

    The minute-scale variations of fine particulate matter (PM2.5) and carbon monoxide (CO) concentrations near a road intersection in Shanghai, China were investigated to identify the influencing factors at three traffic periods. Measurement results demonstrate a synchronous variation of pollutant concentrations at the roadside and setbacks, and the average concentration of PM2.5 at the roadside is 7% (44% for CO) higher than that of setbacks within 500 m of the intersection. The pollution level at traffic peak periods is found to be higher than that of off-peak periods, and the morning peak period is found to be the most polluted due to a large amount of diesel vehicles and unfavorable dispersion conditions. Partial least square regressions were constructed for influencing factors and setback pollutant concentrations, and results indicate that meteorological factors are the most significant, followed by setback distance from the intersection and traffic factors. CO is found to be sensitive to distance from the traffic source and vehicle type, and highly dependent on local traffic conditions, whereas PM2.5 originates more from other sources and background levels. These findings demonstrate the importance of localized factors in understanding spatiotemporal patterns of air pollution at intersections, and support decision makers in roadside pollution management and control.

  8. Plasma butyrylcholinesterase concentrations in psittacine birds: reference values, factors of variation, and association with feather-damaging behavior.

    Science.gov (United States)

    Grosset, Claire; Bougerol, Christian; Sanchez-Migallon Guzman, David

    2014-03-01

    Butyrylcholinesterase is a glycoprotein enzyme used in the diagnosis of toxicosis by cholinesterase-inhibitor agents like organophosphates and carbamates. In animals, butyrylcholinesterase concentrations have been shown to vary depending on numerous factors such as age, sex, diet, and season of sampling. To establish reference values of plasma butyrylcholinesterase concentrations in common psittacine species, plasma butyrylcholinesterase concentrations were measured in 1942 companion psittacine birds. The birds were classified by age, sex, season, health status, and the presence of feather-damaging behavior. A significant difference was observed among species, with eclectus parrots (Eclectus roratus) having the lowest and African grey parrots (Psittacus erithacus) having the highest reference values. Plasma butyrylcholinesterase concentrations varied by age, health status, and season but not by sex. Concentrations were significantly higher during autumn and spring than during winter and summer, and significantly lower in healthy birds than in sick birds. No significant association between butyrylcholinesterase concentrations and feather-damaging behavior could be established except in lovebirds (Agapornis species). Further research is needed to better understand the effect of nutritional and hormonal factors on butyrylcholinesterase concentrations in psittacine birds and its possible effect on bird cognition.

  9. Polymer and Concentrator Photovoltaic Technologies - Energy Return Factors and Area Efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Loefgren, Birger; Gustaf Zettergren

    2006-12-20

    Market diffusion of flat plate crystalline silicon photovoltaic (PV) technology has been induced by economical support schemes and has lead to reduced cost per produced kWh electricity. For further market penetration of the PV technology, a continued reduction of production cost is required. Two alternative approaches to achieve this are using less expensive materials or changing the active materials. The technologies of concentrator PV (CPV) systems and polymer PV (PPV) devices represent these two strategies. The potential energy performance of these technologies is studied in terms of the process primary energy requirements for manufacturing, how many times this energy is paid back during its lifetime and as the required land area for electricity generation. The study is an energy analysis incorporating the inherent uncertainties in technology development. Uncertainties are identified in data acquisition, in design choices, as induced by development and improvement, in performance and by different application scenarios. The future technology alternatives are defined in different ways for CPV and PPV. CPV parameters are derived from existing products and ideas for improvements and PPV parameters from the directions of research. This study shows that the invested energy in future CPV and PPV is potentially paid back up to about 90 and 170 times, respectively, under Arizona (CPV) and average European (PPV) solar irradiation conditions. However the result is highly dependent on configuration, inventory data and device performance. Thus, for certain design alternatives, data and performance, PPV production energy is far from paid back during its lifetime. For CPV the energy return factor is decreased to about 13 in the least beneficial case. Area efficiency is studied as the land area requirements for producing a net output electricity of 1 MWh during 25 years. With device efficiencies from 1 to 5 per cent and lifetimes from 1 to 5 years a PPV device requires from 2

  10. Human von Willebrand factor/factor VIII concentrates in the management of pediatric patients with von Willebrand disease/hemophilia A

    OpenAIRE

    Castaman G; Linari S

    2016-01-01

    Giancarlo Castaman, Silvia Linari Department of Oncology, Center for Bleeding Disorders, Careggi University Hospital, Florence, ItalyAbstract: Several plasma-derived intermediate and high-purity concentrates containing von Willebrand factor (VWF) and factor VIII (FVIII) are currently available. The main role of these products in the management of pediatric the population is represented by the replacement therapy in patients with severe or intermediate forms of von Willebrand disease, in whom ...

  11. Indoor carbonyl compounds in an academic building in Beijing, China: concentrations and influencing factors

    Institute of Scientific and Technical Information of China (English)

    Chuanjia JIANG; Pengyi ZHANG

    2012-01-01

    Carbonyl compounds in indoor air are of great concern for their adverse health effects. Between February and May, 2009, concentrations of 13 carbonyl compounds were measured in an academic building in Beijing, China. Total concentration of the detected carbonyls ranged from 20.7 to 189.1 I.tg.m3, and among them acetone and formaldehyde were the most abundant, with mean concentrations of 26.4 and 22.6gg.m-3, respectively. Average indoor concentrations of other carbonyls were below I 0 gg. m~3. Principal component analysis identified a combined effect of common indoor carbonyl sources and ventilation on indoor carbonyl levels. Diurnal variations of the carbonyl compounds were investigated in one office room, and carbonyl concentrations tended to be lower in the daytime than at night, due to enhanced ventilation. Average concentrations of carbonyl compounds in the office room were generally higher in early May than in late February, indicating the influence of temperature. Carbo- nyl source emission rates from both the room and human occupants were estimated during two lectures, based on one-compartment mass balance model. The influence of human occupants on indoor carbonyl concentrations varies with environmental conditions, and may become signifi- cant in the case of a large human occupancy.

  12. Is there an effect of folic acid supplementation on the coagulation factors and C-reactive protein concentrations in subjects with atherosclerosis risk factors

    Directory of Open Access Journals (Sweden)

    Artur Mierzecki

    2012-10-01

    Full Text Available Introduction:Folic acid (FA may delay the formation of atherosclerotic lesions. Increased plasma levels of von Willebrand factor (VWF are observed in cardiovascular disease, which leads to higher risk of thrombosis. Fibrinogen (Fb is a well-documented risk factor of cardiovascular disease. The aim of this study was to analyze the effect of FA supplementation on the Fb, VWF and C-reactive protein (CRP plasma concentrations in subjects with atherosclerosis risk factors.Material/Methods:The study enrolled 124 Caucasian individuals (60 M, 64 F with atherosclerosis risk factors – family history of premature ischaemic stroke, arterial hypertension, dyslipidaemia, overweight and obesity, cigarette smoking and low physical activity. The participants were asked to take FA in the low dose of 0.4 mg/24 h for three months.Results:After FA supplementation a significant reduction of the VWF concentrations in females (76.6 vs 72.3�20p=0.028 and in males (75.5 vs 66.9�20p=0.001 was observed. Among women and men with dyslipidaemia concentrations of VWF decreased after FA supplementation (76.8�0vs 69.6�20p=0.003 and 76.7�0vs 67.8�20p=0.001 respectively. Among females and males with BMI ≥25 kg/m2 concentrations of VWF decreased only in men (77.6�0vs 66.5�20p=0.001. In female and male smokers supplementation of FA decreased VWF concentrations (82.5�0vs 74.4�20p=0.012 and 76.6�0vs 69.5�20p=0.036 respectively.Discussion:The results of our study suggest that there is an effect of FA supplementation on VWF concentrations in subjects with atherosclerosis risk factors

  13. Agents described in the Molecular Imaging and Contrast Agent Database for imaging carbonic anhydrase IX expression.

    Science.gov (United States)

    Sneddon, Deborah; Poulsen, Sally-Ann

    2014-10-01

    Carbonic anhydrase IX (CA IX) is selectively expressed in a range of hypoxic tumours and is a validated endogenous hypoxia marker with prognostic significance; hence, CA IX is of great interest as a molecular imaging target in oncology. In this review, we present an overview of the different imaging agents and imaging modalities that have been applied for the in vivo detection of CA IX. The imaging agents reviewed are all entries in the Molecular Imaging and Contrast Agent Database (MICAD) and comprise antibody, antibody fragments and small molecule imaging agents. The effectiveness of these agents for imaging CA IX in vivo gave variable performance; however, a number of agents proved very capable. As molecular imaging has become indispensable in current medical practice we anticipate that the clinical significance of CA IX will see continued development and improvements in imaging agents for targeting this enzyme.

  14. Adenovirus protein IX sequesters host-cell promyelocytic leukaemia protein and contributes to efficient viral proliferation.

    Science.gov (United States)

    Rosa-Calatrava, Manuel; Puvion-Dutilleul, Francine; Lutz, Pierre; Dreyer, Dominique; de Thé, Hugues; Chatton, Bruno; Kedinger, Claude

    2003-10-01

    The product of adenovirus type 5 (Ad5) gene IX, protein IX (pIX), is a multifunctional protein that stabilizes the viral capsid and has transcriptional activity. We show that pIX also contributes to the Ad5-induced reorganization of the host-cell nuclear ultrastructure: pIX induces the formation of specific and dynamic nuclear inclusions, and the host promyelocytic leukaemia (PML) protein, which is the main structural organizer of PML bodies, is stably relocated and confined within the pIX-induced inclusions late in infection. Our results suggest that Ad5 has evolved a unique strategy that leads to the sustained neutralization of PML bodies throughout infection, thereby ensuring optimal viral proliferation.

  15. Factors influencing arsenic concentrations and species in mangrove surface sediments from south-east NSW, Australia.

    Science.gov (United States)

    Hettiarachchi, S R; Maher, W A; Krikowa, F; Ubrihien, R

    2017-02-01

    Arsenic concentrations and speciation of 55 mangrove surface sediment samples from the south-eastern coast of NSW, Australia, have been measured. Arsenic concentrations were in the range 1.6-8.6 μg/g dry mass. All arsenic concentration values were well below 20 μg/g, the ANZEC/ARMCANZ interim sediment quality guideline-low trigger value. The bulk sediment pH was 6.0-7.3 and Eh -80 to -260 mV. The sediments contained variable silt-clay (2-30 % w/w), iron (668-12721 μg/g), manganese (1-115 μg/g), sulphur (70-18400 μg/g) and carbon (5-90 mg/g) concentrations. Arsenic concentrations correlated with silt and clay content, iron and manganese concentrations, indicating silt-clay particles covered and coated with iron and manganese (oxy) hydroxides scavenged arsenic. Arsenic extracted with 0.5 M phosphoric acid (68-95 %) was present only as inorganic arsenic (55-91 %), indicating that other arsenic species such as arsenobetaine derived from marine animal tissues rapidly degrade in sediments. The unextractable arsenic was correlated with increases in organic carbon, iron and manganese content. In conclusion, the cycling of arsenic in mangrove sediments is essentially the cycling of inorganic arsenic and primarily controlled by the redox cycling of carbon, sulphur, iron and manganese.

  16. Inclusion of the Förster-rate orientation factor into the theory of concentration self-quenching by statistical traps

    NARCIS (Netherlands)

    Knoester, J.; Himbergen, J.E. Van

    1987-01-01

    The incorporation is studied of the orientation factor occurring in the complete Förster rate of incoherent energy transfer, into the theory of concentration self-quenching by statistical pairs of luminescent molecules. Within Burshtein’s theory of hopping transport, exact results for the steady

  17. Increasing Polymer Solar Cell Fill Factor by Trap-Filling with F4-TCNQ at Parts Per Thousand Concentration.

    Science.gov (United States)

    Yan, Han; Manion, Joseph G; Yuan, Mingjian; García de Arquer, F Pelayo; McKeown, George R; Beaupré, Serge; Leclerc, Mario; Sargent, Edward H; Seferos, Dwight S

    2016-08-01

    Intrinsic traps in organic semiconductors can be eliminated by trap-filling with F4-TCNQ. Photovoltaic tests show that devices with F4-TCNQ at parts per thousand concentration outperform control devices due to an improved fill factor. Further studies confirm the trap-filling pathway and demonstrate the general nature of this finding.

  18. Mortality in vitamin K antagonist-related intracerebral bleeding treated with plasma or 4-factor prothrombin complex concentrate

    NARCIS (Netherlands)

    Majeed, Ammar; Meijer, Karina; Larrazabal, Ramiro; Arnberg, Fabian; Luijckx, Gert J.; Roberts, Robin S.; Schulman, Sam

    2014-01-01

    Prothrombin complex concentrates (PCC) can rapidly normalise prolonged prothrombin time, induced by vitamin K antagonists (VKA). We conducted a multicentre retrospective study to investigate whether reversal of VKA coagulopathy with 4-factor PCC improves the survival of patients with VKA-related int

  19. A simple relationship between the sunlight concentration factor and the thermal conductance in a class of photothermal engines

    Energy Technology Data Exchange (ETDEWEB)

    Rocha-Martinez, J.A.; Navarrete-Gonzalez, T.D. [Area de Fisica, Dept. de Ciencias Basicas, Universidad Autonoma Metropolitana Azcapotzalco, Mexico (Mexico); Angulo-Brown, F. [Departaamento de Fisica, Escuela Superior de Fisica y Matematicas, Instituto Politecnico Nacional, Mexico (Mexico)

    1998-07-21

    In this brief paper we present an addendum to a recently published analysis of a photothermal engine model. Here, we numerically demonstrate that the design parameters, the sunlight concentration factor and the thermal conductances of materials employed as thermal conductors are linked by a simple relationship, if one wishes to obtain the maximization of the power output of the photothermal engine. (author)

  20. MYStIX First Results: Spatial Structures of Massive Young Stellar Clusters

    CERN Document Server

    Kuhn, Michael A; Feigelson, Eric D; Getman, Konstantin V; Broos, Patrick S; Townsley, Leisa K; Povich, Matthew S; Naylor, Tim; King, Robert R; Busk, Heather A; Luhman, Kevin L

    2012-01-01

    Observations of the spatial distributions of young stars in star-forming regions can be linked to the theory of clustered star formation using spatial statistical methods. The MYStIX project provides rich samples of young stars from the nearest high-mass star-forming regions. Maps of stellar surface density reveal diverse structure and subclustering. Young stellar clusters and subclusters are fit with isothermal spheres and ellipsoids using the Bayesian Information Criterion to estimate the number of subclusters. Clustering is also investigated using Cartwright and Whitworth's Q statistic and the inhomogeneous two-point correlation function. Mass segregation is detected in several cases, in both centrally concentrated and fractally structured star clusters, but a few clusters are not mass segregated.

  1. Ventilation scheme, room location and meteorological factors influence indoor birch pollen concentrations

    Science.gov (United States)

    Jochner, Susanne; Matiu, Michael; Michaelis, Rico; Menzel, Annette

    2017-04-01

    Allergenic pollen, often in co-occurrence with air pollutants from traffic and industries aggravating its pollen allergenicity, constitutes a major health risk for the urban population during the pollen season. Airborne pollen concentrations are traditionally monitored with fixed pollen traps mounted >10 m above ground on flat roof tops. However, the personal exposure of allergic people mostly depends on their main residences and the local emission patterns. Consequently, the assessment of indoor pollen is essential for human health since people stay most of the day inside buildings. In our study, hourly indoor birch pollen concentrations were measured on eight days in April 2015 with portable pollen traps in five rooms of a university building at Freising, Germany. A traditional pollen trap on the roof of the building provided the background birch pollen concentration which was compared to the respective outdoor values right in front of the rooms. The office and lab rooms were characterised by different aspects and window ventilation schemes. Meteorological data were equally measured at a nearby climate station and directly in front of the windows. The observed flowering phenology of 56 birch trees in the nearer surrounding partly explained daily peaks in airborne pollen concentrations. As expected, outdoor pollen concentrations were larger than indoor concentrations: Mean indoor/outdoor (I/O) ratio was highest (0.75) in a south oriented room with fully opened window and additional mechanical ventilation, followed by two rooms with fully opened windows orientated to the west and north (0.35, 0.12) and lowest in east oriented neighbouring rooms with tilted window (0.19) and with windows only opened for short ventilation (0.07). The latter two rooms even had a birch tree directly flowering in front of the façade. Hourly I/O ratios depended on meteorology and increased with outside temperature and wind speed oriented perpendicular to the window opening. As also

  2. Examination of the influence of environmental factors in contaminant vapor concentration attenuation factor with U.S. EPA’s vapor intrusion database

    Science.gov (United States)

    Yao, Yijun; Shen, Rui; Pennell, Kelly G.; Suuberg, Eric M.

    2013-01-01

    Those charged with the responsibility of estimating the risk posed by vapor intrusion (VI) processes have often looked to information contained in the U.S. Environmental Protection Agency (EPA)’s VI database for insight. Indoor air concentration attenuation factors have always been a key focus of this database, but the roles of different environmental factors in these attenuation processes are still unclear. This study aims to examine the influences of these factors in the context of the information in the VI database. The database shows that the attenuation factors vary over many orders of magnitude, and that no simple statistical fluctuation around any typical mean value exists. Thus far, no simple explanation of this phenomenon has been presented. This paper examines various possible contributing factors to the enormous range of observed values, looking at which ones can plausibly contribute to explaining them. PMID:23252837

  3. The NC2 domain of type IX collagen determines the chain register of the triple helix.

    Science.gov (United States)

    Boudko, Sergei P; Bächinger, Hans Peter

    2012-12-28

    Precise mapping and unraveling the mechanism of interaction or degradation of a certain type of collagen triple helix requires the generation of short and stable collagenous fragments. This is a great challenge especially for hetero-trimeric collagens, where chain composition and register (stagger) are important factors. No system has been reported that can be efficiently used to generate a natural collagenous fragment with exact chain composition and desired chain register. The NC2 domain (only 35-50 residues) of FACIT collagens is a potent trimerization domain. In the case of type IX collagen it provides the efficient selection and hetero-trimerization of three distinct chains. The ability of the NC2 domain to determine the chain register of the triple helix is studied. We generated three possible sequence combinations (α1α1α2, α1α2α1, α2α1α1) of a type I collagen fragment (the binding region for the von Willebrand factor A3 domain) attached to the NC2 domain. In addition, two control combinations were produced that constitute homo-trimers of (α1)(3) or (α2)(3). For the hetero-trimeric constructs, α1α1α2 demonstrated a higher melting temperature than the other two. Binding experiments with the von Willebrand factor A3 domain revealed the homo-trimer of (α1)(3) as the strongest binding construct, whereas the homo-trimer of (α2)(3) showed no binding. For hetero-trimers, α1α1α2 was found to be the strongest binding construct. Differences in thermal stability and binding to the A3 domain unambiguously demonstrate that the NC2 domain of type IX collagen determines not only the chain composition but also the chain register of the adjacent triple helix.

  4. Evaluation of PpIX formation in Cervical Intraepithelial Neoplasia I (CIN) using widefield fluorescence images

    Science.gov (United States)

    Carbinatto, Fernanda M.; Inada, Natalia M.; Fortunato, Thereza C.; Lombardi, Welington; da Silva, Eduardo V.; Vollet Filho, José D.; Kurachi, Cristina; Pratavieira, Sebastião.; Bagnato, Vanderlei S.

    2016-03-01

    Optical techniques has been described as auxiliary technology for screening of neoplasia because shows the potential for tissues differentiation in real-time and it is a noninvasive detection and safe. However, only endogenous fluorophores presents the lesion may be insufficient and needed of the administration of the fluorophores synthesized, such as, precursor molecule of protoporphyrin IX (PpIX) induced by 5- aminolevulinic acid and your derivatives. Topical application of methylaminolevulinate (MAL), induces formation of the endogenous photosensitizer, PpIX in tissues where carcinogenesis has begun. The PpIX tend to accumulate in premalignant and malignant tissues and the illumination with light with appropriate wavelength beginning to excitation of PpIX fluorescence, which helps to localize PpIX-rich areas and identify potentially malignant tissues. The aim of the study is to evaluate the production of PpIX in the cervix with CIN I through of the fluorescence images captured after 1 hour of cream application. It was possible to visualize PpIX fluorescence in cervix and it was possible to observe the selectivity in fluorescence in squamous-columnar junction, which a pre-cancerous condition (CIN) and usually is localized. Through the image processing it was possible to quantify the increase of red fluorescence. For the CIN I the increase of red fluorescence was approximately of 4 times indicating a good PpIX formation.

  5. The spectroscopy analyses of PpIX by ultrasound irradiation and its sonotoxicity in vitro.

    Science.gov (United States)

    Wang, Pan; Wang, Xiaobing; Zhang, Kun; Gao, Kaili; Song, Ming; Liu, Quanhong

    2013-07-01

    Protoporphyrin IX (PpIX) has been used as a sensitizer in photodynamic therapy (PDT) as well as in sonodynamic therapy (SDT). The photo-bleaching of PpIX has been well investigated in many experimental systems and some photo-products have also been identified in PDT. But until now, little information has been reported about the sono-damage of PpIX in SDT. So, the present study was to investigate changes of PpIX properties before and after different ultrasound treatment, and the potential interactions between PpIX, ultrasound and the irradiated cells. In cell-free system, the absorption and fluorescence spectra of PpIX in different solutions were measured by ultraviolet spectrometer and fluorescence spectrophotometer, respectively. The terephthalic acid dosimetry was applied to evaluate the efficiency of ultrasound cavitation by monitoring hydroxyl radical (OH) production on the thermolysis of H2O in the ultrasound field. In in vitro study, confocal microscopy was applied to detect the sub-cellular localization of PpIX in S180 cells before and after ultrasound exposure. Flow cytometry was used to detect the reactive oxygen species (ROS) generation during PpIX-SDT. MTT assay was performed to evaluate the cell viability of S180 cells after SDT treatment with or without ROS scavengers. The results show that PpIX displayed different spectral patterns in different solutions. PpIX was decomposed by ultrasound exposure as measured by the decreased absorption and fluorescence peak values in RPMI-1640 medium. In addition, the decomposition of PpIX was found to be simultaneously accompanied by OH production with increasing output power from ultrasound generator. PpIX at 1μg/ml significantly enhanced the ultrasound induced cavitation as measured by OH generation, and which was greatly eliminated by NaN3, histidine, mannitol, EDTA and catalase, but not by SOD. The in vitro study indicates more PpIX entered into S180 cells after ultrasound exposure. And, the extra-cellular PpIX

  6. Saccharin: a lead compound for structure-based drug design of carbonic anhydrase IX inhibitors.

    Science.gov (United States)

    Mahon, Brian P; Hendon, Alex M; Driscoll, Jenna M; Rankin, Gregory M; Poulsen, Sally-Ann; Supuran, Claudiu T; McKenna, Robert

    2015-02-15

    Carbonic anhydrase IX (CA IX) is a key modulator of aggressive tumor behavior and a prognostic marker and target for several cancers. Saccharin (SAC) based compounds may provide an avenue to overcome CA isoform specificity, as they display both nanomolar affinity and preferential binding, for CA IX compared to CA II (>50-fold for SAC and >1000-fold when SAC is conjugated to a carbohydrate moiety). The X-ray crystal structures of SAC and a SAC-carbohydrate conjugate bound to a CA IX-mimic are presented and compared to CA II. The structures provide substantial new insight into the mechanism of SAC selective CA isoform inhibition.

  7. Enhanced cellular uptake of protoporphyrine IX/linolenic acid-conjugated spherical nanohybrids for photodynamic therapy.

    Science.gov (United States)

    Lee, Hye-In; Kim, Young-Jin

    2016-06-01

    Protoporphyrin IX (PpIX) has wide applications in photodynamic diagnosis and photodynamic therapy (PDT) in many human diseases. However, poor water solubility and cancer cell localization limit its direct application for PDT. We improved the water-solubility and cellular internalization of PpIX to enhance PDT efficacy by developing biocompatible PpIX/linolenic acid-conjugated polyhedral oligomeric silsesquioxane (PPLA) nanohybrids. The resulting PPLA nanohybrids exhibited a quasi-spherical shape with a size of gastric cancer cells. These results imply that the PPLA nanohybrid system may be applicable in PDT.

  8. Determination of effect factor for effective parameter on saccharification of lignocellulosic material by concentrated acid

    Science.gov (United States)

    Aghili, Sina; Nodeh, Ali Arasteh

    2015-12-01

    Tamarisk usage as a new group of lignocelluloses material to produce fermentable sugars in bio ethanol process was studied. The overall aim of this work was to establish the optimum condition for acid hydrolysis of this new material and a mathematical model predicting glucose release as a function of operation variable. Sulfuric acid concentration in the range of 20 to 60%(w/w), process temperature between 60 to 95oC, hydrolysis time from 120 to 240 min and solid content 5,10,15%(w/w) were used as hydrolysis conditions. HPLC was used to analysis of the product. This analysis indicated that glucose was the main fermentable sugar and was increase with time, temperature and solid content and acid concentration was a parabola influence in glucose production. The process was modeled by a quadratic equation. Curve study and model were found that 42% acid concentration, 15 % solid content and 90oC were optimum condition.

  9. The influence of meteorological factors and biomass burning on surface ozone concentrations at Tanah Rata, Malaysia

    Science.gov (United States)

    Toh, Ying Ying; Lim, Sze Fook; von Glasow, Roland

    2013-05-01

    The surface ozone concentrations at the Tanah Rata regional Global Atmosphere Watch (GAW) station, Malaysia (4°28‧N, 101°23‧E, 1545 m above Mean Sea Level (MSL)) from June 2006 to August 2008 were analyzed in this study. Overall the ozone mixing ratios are very low; the seasonal variations show the highest mixing ratios during the Southwest monsoon (average 19.1 ppb) and lowest mixing ratios during the spring intermonsoon (average 14.2 ppb). The diurnal variation of ozone is characterised by an afternoon maximum and night time minimum. The meteorological conditions that favour the formation of high ozone levels at this site are low relative humidity, high temperature and minimum rainfall. The average ozone concentration is lower during precipitation days compared to non-precipitation days. The hourly averaged ozone concentrations show significant correlations with temperature and relative humidity during the Northeast monsoon and spring intermonsoon. The highest concentrations are observed when the wind is blowing from the west. We found an anticorrelation between the atmospheric pressure tide and ozone concentrations. The ozone mixing ratios do not exceed the recommended Malaysia Air Quality Guidelines for 1-h and 8-h averages. Five day backward trajectories on two high ozone episodes in 07 August 2006 (40.0 ppb) and 24 February 2008 (45.7 ppb) are computed using the HYbrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model to investigate the origin of the pollutants and influence of regional transport. The high ozone episode during 07 August 2006 (burning season during southwest monsoon) is mainly attributed to regional transport from biomass burning in Sumatra, whereas favourable meteorological conditions (i.e. low relative humidity, high temperature and solar radiation, zero rainfall) and long range transport from Indo-China have elevated the ozone concentrations during 24 February 2008.

  10. Elevated platelet-derived growth factor-BB concentrations in premature neonates who develop chronic lung disease

    Directory of Open Access Journals (Sweden)

    Adcock Kim G

    2004-06-01

    Full Text Available Abstract Background Chronic lung disease (CLD in the preterm newborn is associated with inflammation and fibrosis. Platelet-derived growth factor-BB (PDGF-BB, a potent chemotactic growth factor, may mediate the fibrotic component of CLD. The objectives of this study were to determine if tracheal aspirate (TA concentrations of PDGF-BB increase the first 2 weeks of life in premature neonates undergoing mechanical ventilation for respiratory distress syndrome (RDS, its relationship to the development of CLD, pulmonary hemorrhage (PH and its relationship to airway colonization with Ureaplasma urealyticum (Uu. Methods Infants with a birth weight less than 1500 grams who required mechanical ventilation for RDS were enrolled into this study with parental consent. Tracheal aspirates were collected daily during clinically indicated suctioning. Uu cultures were performed on TA collected in the first week of life. TA supernatants were assayed for PDGF-BB and secretory component of IgA concentrations using ELISA techniques. Results Fifty premature neonates were enrolled into the study. Twenty-eight infants were oxygen dependent at 28 days of life and 16 infants were oxygen dependent at 36 weeks postconceptual age. PDGF-BB concentrations peaked between 4 and 6 days of life. Maximum PDGF-BB concentrations were significantly higher in infants who developed CLD or died from respiratory failure. PH was associated with increased risk of CLD and was associated with higher PDGF-BB concentrations. There was no correlation between maximum PDGF-BB concentrations and Uu isolation from the airway. Conclusions PDGF-BB concentrations increase in TAs of infants who undergo mechanical ventilation for RDS during the first 2 weeks of life and maximal concentrations are greater in those infants who subsequently develop CLD. Elevation in lung PDGF-BB may play a role in the development of CLD.

  11. Modelling nutrient concentration to determine the environmental factors influencing grass quality

    CSIR Research Space (South Africa)

    Dudeni-Tlhone, N

    2010-10-01

    Full Text Available This paper uses the spatial and the least squares (Analysis of Covariance-ANCOVA) regression methods to evaluate the important environmental factors in estimating quality grass for grazing (based on the nitrogen (N) content in grass...

  12. What Environmental Factors Impact the Concentration of Microcystin in an Inland Reservoir?

    Science.gov (United States)

    Cyanobacteria are naturally occurring phytoplankton in aquatic environments. Increased nutrient inputs and temperatures, among others, have been identified as contributing factors in the proliferation of harmful algal blooms (HABs). CyanoHABs potentially produce toxic compounds ...

  13. Lignin extraction--reassessment of the severity factor with respect to hydroxide concentration.

    Science.gov (United States)

    Lee, Roland A; Berberi, Veronique; Labranche, Joey; Lavoie, Jean-Michel

    2014-10-01

    Steam processes have often been associated with a severity factor, correlating the cooking temperature, time and catalyst used in the process. Although equations for treatments with and without acid catalyst have been suggested, there is so far no simple equation allowing a precise estimation of the amount of lignin extracted from lignocellulosic biomass. In this work, a new version of the severity factor equation is proposed. This has been shown to correlate effectively to the amount of lignin extracted from various types of lignocellulosic materials and different extraction methods. The resulting severity factor is robust with potential to be utilized both for acid and base-catalyzed extraction of lignin. Finally, the proposed correlation between the severity factor and extracted lignin under base conditions has been correlated with empirical data to validate the entire model and especially under mild condition where lesser information was available from open literature. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Multicenter Study of Posaconazole Therapeutic Drug Monitoring: Exposure-Response Relationship and Factors Affecting Concentration

    OpenAIRE

    Dolton, Michael J; Ray, John E.; Chen, Sharon C.-A.; Ng, Kingsley; Pont, Lisa; McLachlan, Andrew J

    2012-01-01

    Posaconazole has an important role in the prophylaxis and salvage treatment of invasive fungal infections (IFIs), although poor and variable bioavailability remains an important clinical concern. Therapeutic drug monitoring of posaconazole concentrations has remained contentious, with the use of relatively small patient cohorts in previous studies hindering the assessment of exposure-response relationships. This multicenter retrospective study aimed to investigate relationships between posaco...

  15. Factors affecting the indoor concentrations of carbonaceous aerosols of outdoor origin

    Energy Technology Data Exchange (ETDEWEB)

    Lunden, Melissa M.; Kirchstetter, Thomas W.; Thatcher, Tracy L.; Hering, Susanne V.; Brown, Nancy J.

    2007-06-25

    A field study was conducted in an unoccupied single story residence in Clovis, California to provide data to address issues important to assess the indoor exposure to particles of outdoor origin. Measurements of black and organic carbonaceous aerosols were performed using a variety of methods, resulting in both near real-time measurements as well as integrated filter based measurements. Comparisons of the different measurement methods show that it is crucial to account for gas phase adsorption artifacts when measuring organic carbon (OC). Measured concentrations affected by the emissions of organic compounds sorbed to indoor surfaces imply a higher degree of infiltration of outdoor organic carbon aerosols into the indoor environment for our unoccupied house. Analysis of the indoor and outdoor data for black carbon (BC) aerosols show that, on average, the indoor concentration of black carbon aerosols behaves in a similar manner to sulfate aerosols. In contrast, organic carbon aerosols are subject to chemical transformations indoors that, for our unoccupied home, resulted in lower indoor OC concentrations than would be expected by physical loss mechanisms alone. These results show that gas to particle partitioning of organic compounds, as well as gas to surface interactions within the residence, are an important process governing the indoor concentration to OC aerosols of outdoor origin.

  16. Inhibition of hypoxia-inducible carbonic anhydrase-IX enhances hexokinase Ⅱ inhibitor-induced hepatocellular carcinoma cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Su-jong YU; Hyo-suk LEE; Jung-hwan YOON; Jeong-hoon LEE; Sun-jung MYUNG; Eun-sun JANG; Min-sun KWAK; Eun-ju CHO; Ja-june JANG; Yoon-jun KIM

    2011-01-01

    Aim: The hypoxic condition within large or infiltrative hypovascular tumors produces intracellular acidification, which could activate many signaling pathways and augment cancer cell growth and invasion. Carbonic anhydrase-Ⅸ (CA-Ⅸ) is an enzyme lowering pH. This study is to examine whether hypoxia induces CA-Ⅸ in hepatocellular carcinoma (HCC) cells, and to evaluate its clinical implication in HCC patients.Methods: Human HCC cell lines (Huh-7 and HepG2 cells) were used, and cell growth was assessed using MTS assay. CA-IX expression and apoptotic/kinase signaling were evaluated using immunoblotting. The cells were transfected with CA-Ⅸ-specific siRNA, or treated with its inhibitor 4-(2-aminoethyl) benzenesulfonamide (CAI#1), and/or the hexokinase Ⅱ inhibitor, 3-bromopyruvate (3-BP). A clinic pathological analysis of 69 patients who underwent an HCC resection was performed using a tissue array.Results: Incubation of HCC cells under hypoxia (1% 02, 5% C02, 94% N2) for 36 h significantly increased CA-IX expression level. CAI#1(400 μmol/L) or CA-IX siRNA (100 μmol/L) did not influence HCC cell growth and induce apoptosis. However, CAI#1 or CA-IX siRNA at these concentrations enhanced the apoptosis induced by 3-BP (100 μmol/L). This enhancement was attributed to increased ER stress and JNK activation, as compared with 3-BP alone. Furthermore, a clinic pathological analysis of 69 HCC patients revealed that tumor CA-Ⅸ intensity was inversely related to E-cadherin intensity.Conclusion: Inhibition of hypoxia-induced CA-Ⅸ enhances hexokinase Ⅱ inhibitor-induced HCC apoptosis. Furthermore, CA-IX expres sion profiles may have prognostic implications in HCC patients. Thus, the inhibition of CA-Ⅸ, in combination with a hexokinase Ⅱ inhibitor, may be therapeutically useful in patients with HCCs that are aggressively growing in a hypoxic environment.

  17. The effects of meteorological factors on airborne fungal spore concentration in two areas differing in urbanisation level

    Science.gov (United States)

    Oliveira, M.; Ribeiro, H.; Delgado, J. L.; Abreu, I.

    2009-01-01

    Although fungal spores are an ever-present component of the atmosphere throughout the year, their concentration oscillates widely. This work aims to establish correlations between fungal spore concentrations in Porto and Amares and meteorological data. The seasonal distribution of fungal spores was studied continuously (2005-2007) using volumetric spore traps. To determine the effect of meteorological factors (temperature, relative humidity and rainfall) on spore concentration, the Spearman rank correlation test was used. In both locations, the most abundant fungal spores were Cladosporium, Agaricus, Agrocybe, Alternaria and Aspergillus/Penicillium, the highest concentrations being found during summer and autumn. In the present study, with the exception of Coprinus and Pleospora, spore concentrations were higher in the rural area than in the urban location. Among the selected spore types, spring-autumn spores ( Coprinus, Didymella, Leptosphaeria and Pleospora) exhibited negative correlations with temperature and positive correlations both with relative humidity and rainfall level. On the contrary, late spring-early summer (Smuts) and summer spores ( Alternaria, Cladosporium, Epicoccum, Ganoderma, Stemphylium and Ustilago) exhibited positive correlations with temperature and negative correlations both with relative humidity and rainfall level. Rust, a frequent spore type during summer, had a positive correlation with temperature. Aspergillus/Penicillium, showed no correlation with the meteorological factors analysed. This knowledge can be useful for agriculture, allowing more efficient and reliable application of pesticides, and for human health, by improving the diagnosis and treatment of respiratory allergic disease.

  18. Symbolic Dynamics, Modular Curves, and Bianchi IX Cosmologies

    OpenAIRE

    Manin, Yuri I.; Marcolli, Matilde

    2015-01-01

    It is well known that the so called Bianchi IX spacetimes with SO(3)-symmetry in a neighbourhood of the Big Bang exhibit a chaotic behaviour of typical trajectories in the backward movement of time. This behaviour (Mixmaster Model of the Universe) can be encoded by the shift of two-sided continued fractions. Exactly the same shift encodes the sequences of intersections of hyperbolic geodesics with purely imaginary axis in the upper complex half-plane, that is geodesic flow on an appropriate m...

  19. Aportes de "una empresa docente" a la IX CIAM

    OpenAIRE

    Gómez, Pedro; Carulla, Cristina; De Castro, Mauricio; Fernández, Felipe; Gómez, Cristina; Mesa, Vilma María; Perry, Patricia; Valero, Paola

    1995-01-01

    Este volumen contiene los aportes del grupo de investigadores de "una empresa docente" a la IX Conferencia Interamericana de Educación Matemática, realizada en Santiago de Chile en agosto de 1995. Los artículos que se incluyen representan parcialmente los intereses y las realizaciones de este centro de investigación de la Universidad de los Andes durante los últimos años. Los primeros dos capítulos, La potenciación del sistema de educación matemática en Colombia y La interdisciplinareidad ...

  20. Concentrations and Soil-To-Plant Transfer Factor of Selenium in Soil and Plant Species from an Arid Area

    Science.gov (United States)

    Sakizadeh, Mohamad; Mehrabi Sharafabadi, Fatemeh; Shayegan, Eshagh; Ghorbani, Hadi

    2016-10-01

    The concentration of selenium in 97 plants related to seven different species and the associated soil samples was considered in an arid area in the central part of Iran. The mean of Se in the soil samples varied from 0.17 to 0.43 mgkg-1 which is within the worldwide range. There was a highly significant correlation (r=0.688, pfruit) were higher than stem/stalk implying the facile translocation of this element in the considered plant species. The higher than one bio concentration factors (BCFs) of selenium for the chives, spindle tree and wheat is indicative of high phytoremediation potential for these plants.

  1. Factors that influence the membrane area of a multistage microfiltration process required to produce a micellar casein concentrate.

    Science.gov (United States)

    Hurt, Emily E; Barbano, David M

    2015-04-01

    The objective of the work reported in this paper was to develop a theoretical model to determine the effect of type of microfiltration (MF)-process feed, number of stages, and flux on the minimization of the MF membrane area required to produce a 95% serum protein-reduced micellar casein concentrate. The MF feed, number of stages, and flux were all factors that had an effect on the MF membrane area and should be taken into consideration when designing a MF system to produce a 95% serum protein-reduced micellar casein concentrate. Feeding the MF process with a diluted ultrafiltration retentate (DUR) diluted to the protein concentration of skim milk, as opposed to skim milk, reduced the required membrane area by 36% for a 5-stage process. When DUR was the MF feed, feed protein concentration, which depended on the number of MF stages, was optimized. The DUR protein concentration that minimized the required MF membrane area was 2.47, 3.85, 4.77, and 5.41% for a 2-, 3-, 4-, or 5-stage MF process, respectively. For a 5-stage process, increasing the protein concentration of the feed from 3.2 to 5.4% decreased the required MF membrane area by 10%. It was also found that as the number of stages increased from 2 to 5, the required MF membrane area decreased by 39%, when the MF feed was DUR at the optimal feed protein concentration. Finally, increasing the flux from 50 to 60 kg/m(2) per hour decreased the required MF membrane area by 17% when the MF feed was DUR at the optimal MF feed protein concentration. Overall, using DUR as a feed for MF could reduce the amount of MF membrane area required to make a 95% serum protein-reduced micellar casein concentrate.

  2. A comparative study of friction factor correlations for high concentrate slurry flow in smooth pipes

    Directory of Open Access Journals (Sweden)

    Assefa K. M.

    2015-03-01

    Full Text Available A number of correlations for friction factor determinations in smooth pipes have been proposed in the past decades. The accuracy and applicability of these friction factor formulas should be examined. Based on this notion the paper is designed to provide a comparative study of friction factor correlations in smooth pipes for all flow regimes of Bingham fluids. Nine models were chosen. The comparisons of the selected equations with the existing experimental results, which are available in the literature, were expressed through MARE, MRE+, MRE-, RMSE, Ѳ, and S. The statistical comparisons were also carried out using MSC and AIC. The analyses show that the Wilson-Thomas (1985 and Morrison (2013 models are best fit models to the experimental data for the Reynolds number up to 40000. Within this range, both models can be used alternately. But beyond this Re value the discrepancy of the Wilson-Thomas model is higher than the Morrison model. In view of the fact that the Morrison model requires fewer calculations and parameters as well as a single equation is used to compute the friction factor for all flow regimes, it is the authors’ advice to use this model for friction factor estimation for the flow of Bingham fluids in smooth pipes as an alternative to the Moody chart and other implicit formulae.

  3. The driving factors of electro-convective instability in concentration polarization

    CERN Document Server

    Rubinstein, Isaak

    2016-01-01

    Ionic current through a charge-selective interface in a binary electrolyte is a basic element of many electrochemical engineering and microfluidic processes. Such current passage is diffusion-limited: it induces a decrease of electrolyte concentration towards the interface (concentration polarization, CP), expressed in the saturation of current upon increasing voltage at some value (limiting current, LC). With further increase of voltage, this saturation breaks down (overlimiting conductance, OLC). In open systems OLC is mediated by a microscale vortical flow which develops as a result of electroconvective instability (ECI) of quiescent CP near LC. Electroconvection (EC) is a flow driven by the electric force acting either upon the space charge of the interfacial EDL (electroosmosis, EO) or the residual space charge of the quasielectroneutral bulk (bulk EC). There are two types of EO, the equilibrium and the nonequilibrium one. The former relates to the action of the tangential electric field upon the space c...

  4. Switching clotting factor concentrates: considerations in estimating the risk of immunogenicity.

    Science.gov (United States)

    Matino, D; Lillicrap, D; Astermark, J; Dolan, G; Kessler, C; Lambert, T; Makris, M; O'Donnell, J; Pipe, S; Santagostino, E; Saint-Remy, J-M; Schramm, W; Iorio, A

    2014-03-01

    The development of neutralizing antibodies to factor VIII (FVIII) is the most serious complication of therapy for haemophilia A. There is now excellent documentation that a large number of both genetic and environmental factors contribute to the risk of FVIII inhibitor incidence. One of the environmental factors that has been proposed as an influence on this complication is the occurrence of FVIII product switching. There are only a small number of clinical studies that have addressed this question, and thus, the amount of objective information available to assess this association is limited. In this review, in addition to summarizing past evidence pertinent to this subject, we present the results of a complementary strategy, a Delphi analysis, to add to the considerations of product switching and FVIII immunogenicity. With the imminent arrival in the clinic of several new FVIII products, the haemophilia community must be prepared to collect prospectively controlled data to better address this important management issue.

  5. Indoor formaldehyde concentrations in urban China: Preliminary study of some important influencing factors.

    Science.gov (United States)

    Huang, Shaodan; Wei, Wenjuan; Weschler, Louise B; Salthammer, Tunga; Kan, Haidong; Bu, Zhongming; Zhang, Yinping

    2017-07-15

    The Huai River and Qingling Mountain divide (H-Q) divide China into north and south with respect to public policies for building construction and operation practises. China's building energy efficiency standard mandates that air exchange rates be 0.5h(-1) north of the H-Q divide and 1h(-1) south of the divide. China's heating policy allows space heating systems only north of the H-Q divide. Consequently, indoor temperature and humidity differ considerably between north and south. A theoretical model using indoor temperature, humidity, and air change rate was developed to predict indoor formaldehyde concentrations. Data for 39 cities were obtained from 42 studies. There was good agreement between the literature and modelling in a theoretical reference room. The United States Environmental Protection Agency (U.S.EPA) model was applied to estimate cancer risk from formaldehyde exposure indoors. The median indoor formaldehyde concentration for renovation ever from 2002 to 2015 in Chinese cities was 125μg/m(3), which is higher than the WHO threshold, 100μg/m(3). The median indoor formaldehyde concentrations in the north were higher than in the south (0.5 times higher for dwellings renovated within the past year and 0.2 times higher for renovation ever), driven by the much higher northern winter concentrations (40-1320%). The U.S.EPA model predicts that the lifetime formaldehyde related cancer risk for people living north of the H-Q divide is 1.2 times greater than for people living south. This can be partly explained by greater indoor exposure to formaldehyde for Chinese living north of the H-Q divide.

  6. Factors affecting the association between ambient concentrations and personal exposures to particles and gases.

    Science.gov (United States)

    Sarnat, Stefanie Ebelt; Coull, Brent A; Schwartz, Joel; Gold, Diane R; Suh, Helen H

    2006-05-01

    Results from air pollution exposure assessment studies suggest that ambient fine particles [particulate matter with aerodynamic diameterpersonal exposures. For particles, the strength of the personal-ambient association can differ by particle component and level of home ventilation. For gases, however, such as ozone (O3), nitrogen dioxide (NO2), and sulfur dioxide (SO2), the impact of home ventilation on personal-ambient associations is untested. We measured 24-hr personal exposures and corresponding ambient concentrations to PM2.5, sulfate (SO2-(4)), elemental carbon, O3, NO2, and SO2 for 10 nonsmoking older adults in Steubenville, Ohio. We found strong associations between ambient particle concentrations and corresponding personal exposures. In contrast, although significant, most associations between ambient gases and their corresponding exposures had low slopes and R2 values; the personal-ambient NO2 association in the fall season was moderate. For both particles and gases, personal-ambient associations were highest for individuals spending most of their time in high- compared with low-ventilated environments. Cross-pollutant models indicated that ambient particle concentrations were much better surrogates for exposure to particles than to gases. With the exception of ambient NO2 in the fall, which showed moderate associations with personal exposures, ambient gases were poor proxies for both gas and particle exposures. In combination, our results suggest that a) ventilation may be an important modifier of the magnitude of effect in time-series health studies, and b) results from time-series health studies based on 24-hr ambient concentrations are more readily interpretable for particles than for gases.

  7. Chemical factors affecting the interpretation of blood cyanide concentrations in fire victims.

    Science.gov (United States)

    Moriya, Fumio; Hashimoto, Yoshiaki

    2003-03-01

    The purpose of this study was to examine the effects of methemoglobinemia caused by fire gases on blood cyanide concentrations in fire victims. Twenty-two fire victims with postmortem intervals of 8-48 h were involved. Blood cyanide concentrations at the time of death (C(0)) were estimated using the formula: C(0)=Ce(0.046 t) (C=blood cyanide concentration detected at autopsy, 0.046=first-order rate constant of cyanide disappearing from blood in corpses, and t=postmortem interval). Total (free and combined with cyanide) methemoglobin (MetHb) content was used to estimate the maximum capacity of MetHb for combining cyanide. Blood cyanide concentrations at the time of death were very high (5.32-6.47 mg/l) in five victims. Three showed high saturation (54.7-63.0%) of carboxyhemoglobin (CO-Hb) and elevated total MetHb contents (2.6-5.0%). MetHb at these levels is capable of scavenging up to 8.6-11.4 mg/l of blood cyanide. Thus, blood cyanide might have been completely combined with MetHb at the time of their death. In the remaining two victims, CO-Hb saturation was not high (30.9 and 37.9%) and no free MetHb was detected. As a result they may have exhibited severe toxic effects of cyanide at the time of their death. Our results indicate that MetHb contents and CO-Hb saturation should be determined to evaluate the toxic effects of cyanide in fire victims.

  8. Improvement of health risk factors after reduction of VOC concentrations in industrial and urban areas.

    Science.gov (United States)

    Lerner, Jorge Esteban Colman; Kohajda, Tibor; Aguilar, Myriam Elisabeth; Massolo, Laura Andrea; Sánchez, Erica Yanina; Porta, Atilio Andrés; Opitz, Philipp; Wichmann, Gunnar; Herbarth, Olf; Mueller, Andrea

    2014-01-01

    After reductions of fugitive and diffuse emissions by an industrial complex, a follow-up study was performed to determine the time variability of volatile organic compounds (VOCs) and the lifetime cancer risk (LCR). Passive samplers (3 M monitors) were placed outdoors (n = 179) and indoors (n = 75) in industrial, urban, and control areas for 4 weeks. Twenty-five compounds including n-alkanes, cycloalkanes, aromatics, chlorinated hydrocarbons, and terpenes were determined by GC/MS. The results show a significant decrease of all VOCs, especially in the industrial area and to a lesser extent in the urban area. The median outdoor concentration of benzene in the industrial area declined compared to the former study, around 85% and about 50% in the urban area, which in the past was strongly influenced by industrial emissions. Other carcinogenic compounds like styrene and tetrachloroethylene were reduced to approximately 60%. VOC concentrations in control areas remained nearly unchanged. According to the determined BTEX ratios and interspecies correlations, in contrast to the previous study, traffic was identified as the main emission source in the urban and control areas and showed an increased influence in the industrial area. The LCR, calculated for benzene, styrene, and tetrachloroethylene, shows a decrease of one order of magnitude in accordance to the decreased total VOC concentrations and is now acceptable according to values proposed by the World Health Organization.

  9. Evaluation of correlating factors between {sup 238}U concentration measured in fine and course atmospheric particles

    Energy Technology Data Exchange (ETDEWEB)

    Peixoto, Claudia Marques; Jacomino, Vanusa Maria Feliciano; Barreto, Alberto Avelar; Dias, Vagner Silva, E-mail: cmp@cdtn.b, E-mail: vmfj@cdtn.b, E-mail: aab@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Dias, Fabiana Ferrari, E-mail: fdias@cnen.gov.b [Brazilian Nuclear Energy Commission (CNEN-/MG), Pocos de Caldas, MG (Brazil). Lab. de Pocos de Caldas (LAPOC)

    2009-07-01

    Air quality is ever more important in function of the enormous proportion of human actions that have affected the environment over the last two centuries. Particulate material is one among many pollutants that can cause great risk to human health and the environment. It can be classified as: Total Suspended Particles (TSP), defined simply as particles with less than 50 mum aerodynamic diameter (one group of these particles can be inhaled and may cause health problems, while others may unfavorably affect the population's quality of life, interfering in environmental conditions and impairing normal community activities); and Inhalable Particles (PM{sub 10}), defined as those particles with less than 10 mum aerodynamic diameter. These particles penetrate the respiratory system and can reach pulmonary alveoli due to their small size, causing serious health damage. The Nuclear Technology Development Center (CDTN) has monitored air quality around its installations since 2000. CDTN's Environmental Monitoring Program (EMP) includes monitoring radioactivity levels contained in atmospheric TSP. In order to optimize its program, CDTN is carrying out a study to estimate the correlation between concentrations of particulate material measured in TSP and those measured in PM{sub 10}, PI{sub 2.5} and PI{sub 1}, as well as determination of activity concentration for each controlled radionuclide in all parts. The objective of this study is to present preliminary results and report {sup 238}U activity concentration results. (author)

  10. Factors affecting ice crystal purity during freeze concentration process for urine treatment

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Freeze concentration has great potential in treating wastewaters containing soluble pollutions. It is important for freeze concentration process to produce ice crystals with large size and high purity. In this work raw urines of 4660-7914 mg/L in COD,512.71-872.41 mg/L in NH3-N and 22600-28800μs/cm in e lectric conductivity were studied. Urines were frozen by a digital refrigerated circulator bath. Ice crystals were purified by ice-water steep and vacuum filtration. The COD,NH3-N,and electric conductivity levels of the melted ices were measured to reflect ice crystal purity. Effects of coolant temperature, ice crystal shape, initial solution temperature, solution concentration, ice seeding, re-crystallization process and crystallization time on ice crystal purity were analyzed. The results show that an appropriate coolant temperature, suspended ice crystals,an initial solution temperature of about 6 C, introduction of seed ice, addition of re-crystallization process. And crystallization time of less than 30 min are in favor of producing ice crystals with hith purity.Under such conditions, more than 99 percent of inorganic salts, COD and NH3-N sources in raw urine could be removed.

  11. Optimization of a novel peptide ligand targeting human carbonic anhydrase IX.

    Directory of Open Access Journals (Sweden)

    Shoaib Rana

    Full Text Available BACKGROUND: Carbonic anhydrase IX (CA IX is a hypoxia-regulated transmembrane protein over-expressed in various types of human cancer. Recently, a new peptide with affinity for human carbonic anhydrase IX (CaIX-P1 was identified using the phage display technology. Aim of the present study is to characterize the binding site in the sequence of CaIX-P1, in order to optimize the binding and metabolic properties and use it for targeting purposes. METHODOLOGY/PRINCIPAL FINDINGS: Various fragments of CaIX-P1 were synthesized on solid support using Fmoc chemistry. Alanine scanning was performed for identification of the amino acids crucial for target binding. Derivatives with increased binding affinity were radiolabeled and in vitro studies were carried out on the CA IX positive human renal cell carcinoma cell line SKRC 52 and the CA IX negative human pancreatic carcinoma cell line BxPC3. Metabolic stability was investigated in cell culture medium and human serum. Organ distribution and planar scintigraphy studies were performed in Balb/c nu/nu mice carrying subcutaneously transplanted SKRC 52 tumors. The results of our studies clearly identified amino acids that are important for target binding. Among various fragments and derivatives the ligand CaIX-P1-4-10 (NHVPLSPy was found to possess increased binding potential in SKRC 52 cells, whereas no binding capacity for BxPC3 cells was observed. Binding of radiolabeled CaIX-P1-4-10 on CA IX positive cells could be inhibited by both the unlabeled and the native CaIX-P1 peptide but not by control peptides. Stability experiments indicated the degradation site in the sequence of CaIX-P1-4-10. Biodistribution studies showed a higher in vivo accumulation in the tumor than in most healthy tissues. CONCLUSIONS: Our data reveal modifications in the sequence of the CA IX affine ligand CaIX-P1 that might be favorable for improvement of target affinity and metabolic stability, which are necessary prior to the use of

  12. Inhibition of carbonic anhydrase isoforms I, II, IX and XII with novel Schiff bases: identification of selective inhibitors for the tumor-associated isoforms over the cytosolic ones.

    Science.gov (United States)

    Sarikaya, Busra; Ceruso, Mariangela; Carta, Fabrizio; Supuran, Claudiu T

    2014-11-01

    A series of new Schiff bases was obtained from sulfanilamide, 3-fluorosulfanilamide or 4-(2-aminoethyl)-benzenesulfonamide and aromatic/heterocyclic aldehydes incorporating both hydrophobic and hydrophilic moieties. The obtained sulfonamides were investigated as inhibitors of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic CA I and II, as well as the transmembrane, tumor-associated CA IX and XII. Most derivatives were medium potency or weak hCA I/II inhibitors, but several of them showed nanomolar affinity for CA IX and/or XII, making them an interesting example of isoform-selective compounds. The nature of the aryl/hetaryl moiety present in the initial aldehyde was the main factor influencing potency and isoform selectivity. The best and most CA IX-selective compounds incorporated moieties such as 4-methylthiophenyl, 4-cyanophenyl-, 4-(2-pyridyl)-phenyl and the 4-aminoethylbenzenesulfonamide scaffold. The best hCA XII inhibitors, also showing selectivity for this isoform, incorporated 2-methoxy-4-nitrophenyl-, 2,3,5,6-tetrafluorophenyl and 4-(2-pyridyl)-phenyl functionalities and were also derivatives of 4-aminoethylbenzenesulfonamide. The sulfanilamide and 3-fluorosulfanilamide derived Schiff bases were less active compared to the corresponding 4-aminoethyl-benzenesulfonamide derivatives. As hCA IX/XII selective inhibition is attractive for obtaining antitumor agents/diagnostic tools with a new mechanism of action, compounds of the type described here may be considered interesting preclinical candidates.

  13. Reconstituting factor concentrates: Defining Evidence of Coaching Non-Experts (DEVICE) in haemophilia--a prospective randomized feasibility study.

    Science.gov (United States)

    Bidlingmaier, C; Kurnik, K; Hölscher, G; Kappler, M

    2007-09-01

    The introduction of new needleless devices as demanded by the US Department of Labor Occupational Safety and Health Administration (OSHA) has caused problems with the reconstitution of antihaemophilic factor in emergency situations. Our aim therefore was to evaluate the feasibility of a needleless device for reconstitution of antihaemophilic factor for non-haemophilia experts and to define evidence of the need for coaching these physicians via providing two additional photographs illustrating the two key points of the factor reconstitution process. Twenty-eight physicians of a tertiary care university children's hospital were randomized into two groups, either with no further explanation of the reconstitution device or with two additional photographs, showing the two key steps of the procedure. Reconstitution of dummy-factor concentrate was video-taped and evaluated by a blinded helper. Main outcome measure was the successful reconstitution of dummy-factor concentrate and procedure failure respectively. Of the group without explanation of the reconstitution device, only two of 14 physicians were able to reconstitute the dummy-factor concentrate. Of the group receiving two photographs, nine of 14 completed the task successfully (P = 0.0068). The needleless device is not self explaining to non-haemophilia physicians involved in emergency services. Coaching via short to the point instructions as provided by simple visual educational material therefore is crucial to enable these physicians to resolve the expensive emergency drug quickly and correctly. Companies concerned with the production of any devices to dissolve drugs, especially for treatment of rare diseases as haemophilia, therefore should take measures to simplify therapy.

  14. Dabigatran and its reversal with recombinant factor VIIa and prothrombin complex concentrate

    DEFF Research Database (Denmark)

    Sølbeck, Sacha; Nilsson, Caroline U; Engström, Martin

    2014-01-01

    different Sonoclot cuvettes: Glassbead, kaolin and tissue factor (diluted) activated. RESULTS: The Sonoclot detected in vitro-induced anticoagulation due to dabigatran with the glassbead- and kaolin-activated cuvettes. There was no reversing effect of PCC, probably due to the presence of heparin in the PCC...

  15. Effect of GFR on plasma N-terminal connective tissue growth factor (CTGF) concentrations.

    NARCIS (Netherlands)

    Gerritsen, K.G.; Abrahams, A.C.; Peters, H.P.E.; Nguyen, T.Q.; Koeners, M.P.; Hoedt, C.H. den; Dendooven, A.; Dorpel, M.A. van den; Blankestijn, P.J.; Wetzels, J.F.M.; Joles, J.A.; Goldschmeding, R.; Kok, R.J.

    2012-01-01

    BACKGROUND: Connective tissue growth factor (CTGF) has a key role in the pathogenesis of renal and cardiac fibrosis. Its amino-terminal fragment (N-CTGF), the predominant form of CTGF detected in plasma, has a molecular weight in the middle molecular range (18 kDa). However, it is unknown whether N-

  16. Host-related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans

    NARCIS (Netherlands)

    Bohn, Torsten; Desmarchelier, Charles; Dragsted, Lars O.; Nielsen, Charlotte S.; Stahl, Wilhelm; Rühl, Ralph; Keijer, Jaap; Borel, Patrick

    2017-01-01

    Carotenoid dietary intake and their endogenous levels have been associated with a decreased risk of several chronic diseases. There are indications that carotenoid bioavailability depends, in addition to the food matrix, on host factors. These include diseases (e.g. colitis), life-style habits (e

  17. Diminished concentrations of insulin-like growth factor I in cystic fibrosis

    DEFF Research Database (Denmark)

    Laursen, Erik; Juul, A; Lanng, S

    1995-01-01

    Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data on ...

  18. Ecological optimization of a family of n-Müser engines for an arbitrary value of the solar concentration factor

    Science.gov (United States)

    Ramírez-Moreno, M. A.; Angulo-Brown, F.

    2017-03-01

    In a recent paper (Ramírez-Moreno, González-Hernández and Angulo-Brown, 2016) it was discussed the thermodynamic performance of a family of n-Müser engines under the so-called ecological optimization criterion for finite-time heat engines. In this reference it was shown that a 4-Müser engine accomplishes the best performance in comparison with any other n-Müser engine with n ≠ 4. However, this result was obtained for Müser engines operating under the condition of C =Cmax; that is, maximum solar concentration factor. In the present paper we show that the result previously described is also valid for arbitrary values of the concentration factor C.

  19. Concentration factors of radionuclides and trace metals in Mytilus galloprovincialis in an estuarine ecosystem - North Aegean Sea - Greece

    Energy Technology Data Exchange (ETDEWEB)

    Florou, H.; Catsiki, A.B.; Papaefthymiou, H.; Chaloulou, Ch. [NCSR Demokritos, INT-RP, Environmental Radioactivity Lab., Athens (Greece)

    2004-07-01

    Mussels are worldwide recognized as pollution bio-indicator organisms (Mussel watch program of CIESM) because they accumulate pollutants in their tissues at elevated levels in terms of biological availability in the marine environment. In the present study, the levels of {sup 137}Cs, Cr, Cu, Mn and Zn were measured in Mytilus galloprovincialis caught from Thermaikos gulf in North Aegean Sea Greece. The samples were collected seasonally from two aqua-cultures during the period 2000 2003. Measured and published concentrations of the above elements in seawater were used for the evaluation of concentration factors by applying a linear and a non-linear regression analysis. The variation in between the two stations and the seasonal evolution of bioaccumulation of the examined elements was also investigated. Some data on the concentrations of the measured elements in sediments from the area considered were evaluated as for determining the pollution conditions of the organism habitat. (author)

  20. IX Draconis - a curious ER UMa-type dwarf nova

    CERN Document Server

    Otulakowska-Hypka, M; de Miguel, E; Rutkowski, A; Koff, R; B\\kakowska, K

    2012-01-01

    We report results of an extensive world-wide observing campaign devoted to a very active dwarf nova star - IX Draconis. We investigated photometric behaviour of the system to derive its basic outburst properties and understand peculiarities of IX Dra as well as other active cataclysmic variables, in particular dwarf novae of the ER Uma-type. In order to measure fundamental parameters of the system, we carried out analyses of the light curve, O-C diagram, and power spectra. During over two months of observations we detected two superoutbursts and several normal outbursts. The V magnitude of the star varied in the range 14.6 - 18.2 mag. Superoutbursts occur regularly with the supercycle length of 58.5+/-0.5 d. When analysing data over the past 20 years, we found that the supercycle length is increasing at a rate of P_dot = 1.8 * 10^{-3}. Normal outbursts appear to be irregular, with typical occurrence times in the range 3.1 - 4.1 d. We detected a double-peaked structure of superhumps during superoutburst, with ...

  1. Ares I-X Upper Stage Simulator Residual Stress Analysis

    Science.gov (United States)

    Raju, Ivatury S.; Brust, Frederick W.; Phillips, Dawn R.; Cheston, Derrick

    2008-01-01

    The structural analyses described in the present report were performed in support of the NASA Engineering and Safety Center (NESC) Critical Initial Flaw Size (CIFS) assessment for the Ares I-X Upper Stage Simulator (USS) common shell segment. An independent assessment was conducted to determine the critical initial flaw size (CIFS) for the flange-to-skin weld in the Ares I-X Upper Stage Simulator (USS). The Ares system of space launch vehicles is the US National Aeronautics and Space Administration s plan for replacement of the aging space shuttle. The new Ares space launch system is somewhat of a combination of the space shuttle system and the Saturn launch vehicles used prior to the shuttle. Here, a series of weld analyses are performed to determine the residual stresses in a critical region of the USS. Weld residual stresses both increase constraint and mean stress thereby having an important effect on fatigue and fracture life. The results of this effort served as one of the critical load inputs required to perform a CIFS assessment of the same segment.

  2. Symbolic Dynamics, Modular Curves, and Bianchi IX Cosmologies

    CERN Document Server

    Manin, Yuri

    2015-01-01

    It is well known that the so called Bianchi IX spacetimes with SO(3)-symmetry in a neighbourhood of the Big Bang exhibit a chaotic behaviour of typical trajectories in the backward movement of time. This behaviour (Mixmaster Model of the Universe) can be encoded by the shift of two-sided continued fractions. Exactly the same shift encodes the sequences of intersections of hyperbolic geodesics with purely imaginary axis in the upper complex half-plane, that is geodesic flow on an appropriate modular surface. A physical interpretation of this coincidence was suggested in arXiv:1402.2158: namely, that Mixmaster chaos is an approximate description of the passage from a hot quantum Universe at the Big Bang moment to the cooling classical Universe. Here we discuss and elaborate this suggestion, looking at the Mixmaster Model from the perspective of the second class of Bianchi IX spacetimes: those with SU(2)-symmetry (self-dual Einstein metrics). We also extend it to the more general context related to Painleve' VI ...

  3. Atomic Data and Spectral Line Intensities for Ca IX

    Science.gov (United States)

    Landi, E.; Bhatia, A. K.

    2012-01-01

    Electron impact collision strengths, energy levels, oscillator strengths and spontaneous radiative decay rates are calculated for Ca IX. We include in the calculations the 33 lowest configurations in the n = 3, 4, 5 complexes, corresponding to 283 fine structure levels in the 3l3l ', 3l4l'' and 3l4l''' configurations, where l,l' = s, p, d, l '' = s, p, d, f and l''' = s, p, d, f, g. Collision strengths are calculated at five incident energies for all transitions: 5.8, 13.6, 24.2, 38.6 and 57.9 Ry above the threshold of each transition. An additional energy, very close to the transition threshold, has been added, whose value is between 0.0055 Ry and 0.23 Ry depending on the levels involved. Calculations have been carried out using the Flexible Atomic Code and the distorted wave approximation. Excitation rate coefficients are calculated as a function of electron temperature by assuming a Maxwellian electron velocity distribution. Using the excitation rate coefficients and the radiative transition rates calculated in the present work, statistical equilibrium equations for level populations are solved at electron densities covering the 10(exp 8)-10(exp 14)/cubic cm range and at an electron temperature of log T(sub e)(K)=5.8, corresponding to the maximum abundance of Ca IX. Spectral line intensities are calculated, and their diagnostic relevance is discussed.

  4. Localization of type II collagen, long form alpha 1(IX) collagen, and short form alpha 1(IX) collagen transcripts in the developing chick notochord and axial skeleton.

    Science.gov (United States)

    Swiderski, R E; Solursh, M

    1992-06-01

    In this study we compare, by in situ hybridization, the spatial and temporal expression patterns of transcripts of avian type II collagen and the long and short forms of the (alpha 1) chain of type IX collagen during the development of the notochord and axial skeleton. We observed type II collagen and short form type IX collagen transcripts in the developing (stage 25-28) nonchondrogenic notochord. Conversely, long form type IX transcripts were not detectable in the notochord or perinotochordal sheath. Interestingly, all three transcripts colocalized in the developing chondrogenic vertebrae of the axial skeleton as well as in the chondrocranium and Meckel's cartilage. The expression of the short form of type IX collagen in these regions was more restricted than that of the long form. This report provides additional support for a complex regulatory pathway of cartilage marker gene expression in chondrogenic vs. nonchondrogenic tissues during avian embryogenesis.

  5. Dietary zinc affects concentrations of insulin, insulin-like growth factor-I and growth hormone in lambs

    Energy Technology Data Exchange (ETDEWEB)

    Droke, E.A.; Spears, J.W.; Armstrong, J.D. (North Carolina State Univ., Raleigh, NC (United States))

    1991-03-15

    Glucose tolerance and concentrations of insulin, growth hormone (GH) and insulin-like growth factor-I (IGF-I) were evaluated in lambs deficient, marginal or adequate in zinc (Zn). Lambs were fed a semipurified diet that contained either 3.7, 8.7, or 43.7 mg Zn/kg. Zinc deficiency resulted in lower serum insulin levels 1 h after feeding while levels in marginal lambs were not different from that of adequate lambs. Dietary Zn did not affect plasma glucose post feeding. One h after IV glucose administration plasma glucose concentrations were lower in deficient lambs compared to adequate lambs; marginal lambs had intermediate glucose levels. Concentration of GH before and after feeding or glucose challenge were not affected by Zn status; however, serum IGF-I was lower in deficient than in marginal or adequate lambs. A GH releasing factor (GRF) analog was given to evaluate the release of GH. Serum GH in response to GRF challenge was higher in deficient lambs and tended to be higher in marginal lambs when compared to adequate lambs. Impaired growth observed with Zn deficiency may be mediated in part by its effect on insulin, GH and IGF-I concentrations.

  6. Worldwide estimation of river concentrations of any chemical originating from sewage-treatment plants using dilution factors.

    Science.gov (United States)

    Keller, Virginie D J; Williams, Richard J; Lofthouse, Caryn; Johnson, Andrew C

    2014-02-01

    Dilution factors are a critical component in estimating concentrations of so-called "down-the-drain" chemicals (e.g., pharmaceuticals) in rivers. The present study estimated the temporal and spatial variability of dilution factors around the world using geographically referenced data sets at 0.5° × 0.5° resolution. Domestic wastewater effluents were derived from national per capita domestic water use estimates and gridded population. Monthly and annual river flows were estimated by accumulating runoff estimates using topographically derived flow directions. National statistics, including the median and interquartile range, were generated to quantify dilution factors. Spatial variability of the dilution factor was found to be considerable; for example, there are 4 orders of magnitude in annual median dilution factor between Canada and Morocco. Temporal variability within a country can also be substantial; in India, there are up to 9 orders of magnitude between median monthly dilution factors. These national statistics provide a global picture of the temporal and spatial variability of dilution factors and, hence, of the potential exposure to down-the-drain chemicals. The present methodology has potential for a wide international community (including decision makers and pharmaceutical companies) to assess relative exposure to down-the-drain chemicals released by human pollution in rivers and, thus, target areas of potentially high risk.

  7. Revisiting spontaneous silver nanoparticles formation: a factor influencing the determination of minimum inhibitory concentration values?

    Directory of Open Access Journals (Sweden)

    Karolína M. Šišková

    2015-06-01

    Full Text Available The present study gives evidence that silver nanoparticles (AgNPs are spontaneously formed from Ag+ ions in Mueller-Hinton broth, which is frequently used as a standard cultivation medium for many types of bacteria. Silver ions often serve as a reference in the determination of minimum inhibitory concentration (MIC values of engineered AgNPs. It is thus a question if the MIC values determined for engineered AgNPs are not influenced by the presence of spontaneously formed AgNPs. Furthermore, as shown here, the addition of augmented concentrations of selected amino acids, namely glutamic acid and glutamine, can change the growth and characteristic features of spontaneously formed AgNPs. For the sake of a direct comparison, the influence of the two selected amino acids on characteristics and MIC values determination of engineered AgNPs has been also investigated. The determined MIC values of all investigated systems (i.e., with and without the presence of engineered AgNPs and their mutual comparison demonstrated that MIC values are slightly influenced by the actual composition of a cultivation medium for bacterial growth. On the other hand, the actual composition of a cultivation medium is crucial for the final characteristics of AgNPs. The changes in characteristic features of spontaneously formed as well as engineered AgNPs are most probably induced by the covalent bonding of amino acids to AgNPs surface which is proven by vibrational spectroscopic techniques.

  8. The effect of meteorological factors on airborne Betula pollen concentrations in Lublin (Poland).

    Science.gov (United States)

    Piotrowska, Krystyna; Kubik-Komar, Agnieszka

    2012-12-01

    The present study investigated the pattern of the birch atmospheric pollen seasons in Lublin in the period 2001-2010. Pollen monitoring was conducted using a Lanzoni VPPS 2000 sampler. The atmospheric pollen seasons were determined with the 98% method. Regression analysis was used to determine correlations between meteorological conditions and the pattern of the birch pollen season. On average, the birch pollen season started on 12 April, ended on 13 May, and lasted 32 days. The peak value and the Seasonal Pollen Index showed the greatest variation in particular years. All the seasons were right-skewed. During the study years, a trend was found towards earlier occurrence of the seasonal peak. Regression equations were developed for the following parameters of the atmospheric pollen season: start, duration, peak value and average pollen concentration during the season. The obtained model fit was at a level of 64-81%. Statistical analysis shows that minimum temperature of February and March and total rainfall in June in the year preceding pollen release have the greatest effect on the birch atmospheric pollen season in Lublin. Low temperatures in February promote the occurrence of high pollen concentrations.

  9. A study on surveillance of environmental factors affecting the variation of indoor radon concentration

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Shin Ae; Kim, Ok Ja; Lee, Mi Kyeong; Cho, Eun Ok; Choi, Yun Sun; Choi, Jin Kyeong; Park, Seon Hye; Han, Hyeon Sun [Hankook Research, Seoul (Korea, Republic of)

    2000-03-15

    Before the main survey, a preliminary survey was carried out to decide the most suitable type of a radon detector the most appropriate places to install such a radon detector. To this end, three types of detectors were set up in 108 locations, approximately 3% of 3,000 to measure the radon levels, and 102 detectors(94%) were collected. As a result of the preliminary survey, Radtrack was chosen as a radon detector for the main survey, and bedrooms on the first floor of houses and the first floor of public buildings were decided to be the places for the first installment of detectors. It is most desirable to survey the radon concentrations in all houses nationwide. Considering the survey period and budgets, however, 3,000 spots were targeted for the main survey at the recommendation of the Korea Institute of Nuclear Safety in charge of this study. As it is important to maintain the same panels for a year to measure the radon concentrations at 3,000 locations, a total of 3,237 panels, 10% more than the target sample number, were surveyed considering the possible loss of panels during the survey period. The first radon detector was installed in each of 3,237 spots in December 1999, and collected three months later in March 2000, followed by the installment of the second detector.

  10. The bioconcentration and bioaccumulation factors for molybdenum in the aquatic environment from natural environmental concentrations up to the toxicity boundary

    Energy Technology Data Exchange (ETDEWEB)

    Regoli, Lidia, E-mail: dagobert.heijerick@arche-consulting.be [IMOA, 4 Heathfield Terrace, Chiswick, London, W4 4JE (United Kingdom); Van Tilborg, Wim [VTBC Beekhuizenseweg 46, 6881Al Plaats, Velp (Netherlands); Heijerick, Dagobert [ARCHE Consulting, Stapelplein 70 box 104, 9000 Gent (Belgium); Stubblefield, William [Oregon State University, Department of Environmental and Molecular Toxicology, 421 Weniger Hall, Corvallis, OR 97331 (United States); Carey, Sandra [IMOA, 4 Heathfield Terrace, Chiswick, London, W4 4JE (United Kingdom)

    2012-10-01

    In a regulatory context, bioaccumulation or bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. In this paper, literature data on the bioaccumulation of molybdenum in the aquatic organisms are reviewed and assessed for relevance and reliability. The data available in the literature were generated at exposure concentrations below those recommended in the REACH registration dossiers for molybdenum compounds i.e. PNEC{sub freshwater} 12.7 mg Mo/L. To address possible environmental concerns at regulatorily-relevant molybdenum concentrations, both a field study and a laboratory study were conducted. In the field study, whole body and organ-specific molybdenum levels were evaluated in fish (eel, stickleback, perch, carp bream, roach) held in the discharge water collector tanks of a molybdenum processing plant, containing a mean measured molybdenum level of 1.03 mg Mo/L. In the laboratory study, rainbow trout were exposed to two different nominal molybdenum levels (1.0 and 12.7 mg Mo/L), for 60 days followed by a 60-day depuration period. Whole body concentrations in rainbow trout during the exposure period were between < 0.20 and 0.53 mg Mo/L. Muscle tissue molybdenum concentrations in fish taken from both experiments remained below 0.2 mg/kg dry wt. These studies show an inverse relationship between exposure concentration and bioconcentration or bioaccumulation factor for molybdenum. In aquatic organisms, and in fish in particular, internal molybdenum concentrations are maintained in the presence of variation in external molybdenum concentrations. These observations must be considered when evaluating potential risks associated with the bioconcentration and/or bioaccumulation of molybdenum in the aquatic environment. -- Highlights: Black-Right-Pointing-Pointer Addressing environmental concerns at regulatory-relevant molybdenum concentrations. Black-Right-Pointing-Pointer Inverse

  11. A Place on the Team: The Triumph and Tragedy of Title IX

    Science.gov (United States)

    Suggs, Welch

    2006-01-01

    "A Place on the Team" is the inside story of how Title IX revolutionized American sports. The federal law guaranteeing women's rights in education, Title IX opened gymnasiums and playing fields to millions of young women previously locked out. Journalist Welch Suggs chronicles both the law's successes and failures-the exciting…

  12. Modelling topical photodynamic therapy treatment including the continuous production of Protoporphyrin IX

    Science.gov (United States)

    Campbell, C. L.; Brown, C. T. A.; Wood, K.; Moseley, H.

    2016-11-01

    Most existing theoretical models of photodynamic therapy (PDT) assume a uniform initial distribution of the photosensitive molecule, Protoporphyrin IX (PpIX). This is an adequate assumption when the prodrug is systematically administered; however for topical PDT this is no longer a valid assumption. Topical application and subsequent diffusion of the prodrug results in an inhomogeneous distribution of PpIX, especially after short incubation times, prior to light illumination. In this work a theoretical simulation of PDT where the PpIX distribution depends on the incubation time and the treatment modality is described. Three steps of the PpIX production are considered. The first is the distribution of the topically applied prodrug, the second in the conversion from the prodrug to PpIX and the third is the light distribution which affects the PpIX distribution through photobleaching. The light distribution is modelled using a Monte Carlo radiation transfer model and indicates treatment depths of around 2 mm during daylight PDT and approximately 3 mm during conventional PDT. The results suggest that treatment depths are not only limited by the light penetration but also by the PpIX distribution.

  13. 75 FR 18245 - Public Federal Regulatory Enforcement Fairness Hearing Region IX Regulatory Fairness Board

    Science.gov (United States)

    2010-04-09

    ... ADMINISTRATION Public Federal Regulatory Enforcement Fairness Hearing Region IX Regulatory Fairness Board.... Small Business Administration (SBA) Region IX Regulatory Fairness Board and the SBA Office of the National Ombudsman will hold a National Regulatory Fairness Hearing on Monday, April 26, 2010, at 1:30 p.m...

  14. Not Second-Class: Title IX, Equity, and Girls' High School Sports

    Science.gov (United States)

    Stader, David L.; Surface, Jeanne L.

    2014-01-01

    Title IX is designed to protect students from discrimination based on sex in any educational institution that receives financial assistance. This article focuses on Title IX as it applies to high school athletic programs by considering the trial of a high school district in California. A federal court found considerable inequalities between boys…

  15. "What Do I Think about Title IX?" Voices from a University Community

    Science.gov (United States)

    Paule-Koba, Amanda L.; Harris, Othello; Freysinger, Valeria J.

    2013-01-01

    Despite the apparent benefits of Title IX, the implementation of the law remains controversial, and there are divergent beliefs regarding its impact on collegiate sport. The purpose of this study was to examine how members of a university community, whose intercollegiate sport programs have changed, perceive and make sense of Title IX and the…

  16. Reduced serum concentrations of brain-derived neurotrophic factor (BDNF) in transsexual Brazilian men.

    Science.gov (United States)

    Fontanari, Anna Martha Vaitses; Costa, Angelo Brandelli; Aguiar, Bianca; Tusset, Cíntia; Andreazza, Tahiana; Schneider, Maiko; da Rosa, Eduarda Dias; Soll, Bianca Machado Borba; Schwarz, Karine; da Silva, Dhiordan Cardoso; Borba, André Oliveira; Mueller, Andressa; Massuda, Raffael; Lobato, Maria Inês Rodrigues

    2016-09-06

    Serum BDNF levels are significantly decreased in transsexual Brazilian women when compared to cis-sexual men. Since transsexual men are also exposed to chronic social stress and have a high prevalence of associated psychopathologies, it is plausible to inquire if BDNF serum levels are altered in transsexual men as well. Therefore, our objective was to evaluate differences in BDNF serum level of transsexual men when compared to cis-sexual men and women. Our sample comprises 27 transsexual men, 31 cis-sexual women and 30 cis-sexual men recruited between 2011 and 2015. We observed that BDNF serum concentration is decreased in transsexual men comparing to cis-sexual men and women. Cross-sex hormone treatment, chronic social stress or long-term gender dysphoria (GD) could explain the variation found in BDNF serum levels.

  17. Increased brain-derived neurotrophic factor (BDNF) protein concentrations in mice lacking brain serotonin.

    Science.gov (United States)

    Kronenberg, Golo; Mosienko, Valentina; Gertz, Karen; Alenina, Natalia; Hellweg, Rainer; Klempin, Friederike

    2016-04-01

    The interplay between BDNF signaling and the serotonergic system remains incompletely understood. Using a highly sensitive enzyme-linked immunosorbent assay, we studied BDNF concentrations in hippocampus and cortex of two mouse models of altered serotonin signaling: tryptophan hydroxylase (Tph)2-deficient (Tph2 (-/-)) mice lacking brain serotonin and serotonin transporter (SERT)-deficient (SERT(-/-)) mice lacking serotonin re-uptake. Surprisingly, hippocampal BDNF was significantly elevated in Tph2 (-/-) mice, whereas no significant changes were observed in SERT(-/-) mice. Furthermore, BDNF levels were increased in the prefrontal cortex of Tph2 (-/-) but not of SERT(-/-) mice. Our results emphasize the interaction between serotonin signaling and BDNF. Complete lack of brain serotonin induces BDNF expression.

  18. Evaluating the roles of biotransformation, spatial concentration differences, organism home range, and field sampling design on trophic magnification factors.

    Science.gov (United States)

    Kim, Jaeshin; Gobas, Frank A P C; Arnot, Jon A; Powell, David E; Seston, Rita M; Woodburn, Kent B

    2016-05-01

    Trophic magnification factors (TMFs) are field-based measurements of the bioaccumulation behavior of chemicals in food-webs. TMFs can provide valuable insights into the bioaccumulation behavior of chemicals. However, bioaccumulation metrics such as TMF may be subject to considerable uncertainty as a consequence of systematic bias and the influence of confounding variables. This study seeks to investigate the role of systematic bias resulting from spatially-variable concentrations in water and sediments and biotransformation rates on the determination of TMF. For this purpose, a multibox food-web bioaccumulation model was developed to account for spatial concentration differences and movement of organisms on chemical concentrations in aquatic biota and TMFs. Model calculated and reported field TMFs showed good agreement for persistent polychlorinated biphenyl (PCB) congeners and biotransformable phthalate esters (PEs) in a marine aquatic food-web. Model testing showed no systematic bias and good precision in the estimation of the TMF for PCB congeners but an apparent underestimation of model calculated TMFs, relative to reported field TMFs, for PEs. A model sensitivity analysis showed that sampling designs that ignore the presence of concentration gradients may cause systematically biased and misleading TMF values. The model demonstrates that field TMFs are most sensitive to concentration gradients and species migration patterns for substances that are subject to a low degree of biomagnification or trophic dilution. The model is useful in anticipating the effect of spatial concentration gradients on the determination of the TMF; guiding species collection strategies in TMF studies; and interpretation of the results of field bioaccumulation studies in study locations where spatial differences in chemical concentration exist.

  19. Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX.

    Science.gov (United States)

    Assunção-Miranda, I; Cruz-Oliveira, C; Neris, R L S; Figueiredo, C M; Pereira, L P S; Rodrigues, D; Araujo, D F F; Da Poian, A T; Bozza, M T

    2016-03-01

    To investigate the effect of heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX (CoPPIX and SnPPIX), macrocyclic structures composed by a tetrapyrrole ring with a central metallic ion, on Dengue Virus (DENV) and Yellow Fever Virus (YFV) infection. Treatment of HepG2 cells with heme, CoPPIX and SnPPIX after DENV infection reduced infectious particles without affecting viral RNA contents in infected cells. The reduction of viral load occurs only with the direct contact of DENV with porphyrins, suggesting a direct effect on viral particles. Previously incubation of DENV and YFV with heme, CoPPIX and SnPPIX resulted in viral particles inactivation in a dose-dependent manner. Biliverdin, a noncyclical porphyrin, was unable to inactivate the viruses tested. Infection of HepG2 cells with porphyrin-pretreated DENV2 results in a reduced or abolished viral protein synthesis, RNA replication and cell death. Treatment of HepG2 or THP-1 cell lineage with heme or CoPPIX after DENV infection with a very low MOI resulted in a decreased DENV replication and protection from death. Heme, CoPPIX and SnPPIX possess a marked ability to inactivate DENV and YFV, impairing its ability to infect and induce cytopathic effects on target cells. These results open the possibility of therapeutic application of porphyrins or their use as models to design new antiviral drugs against DENV and YFV. © 2016 The Society for Applied Microbiology.

  20. Effect of environmental conditions on radon concentration-track density calibration factor of solid-state nuclear track detectors

    Science.gov (United States)

    El-Sersy, A.; Mansy, M.; Hussein, A.

    2004-04-01

    In this work, the effect of environmental conditions viz., temperature (T) and relative humidity (RH) on the track density--radon concentrations calibration factor (K) has been studied for CR-39 and LR-115 track detectors. The factor K was determined using a reference radon chamber in the National Institute for Standards (NIS) in Egypt. Track detectors were etched at the recommended optimum etching conditions. It is found that, the calibration factor K varies with both T and RH, so they should be considered for the sake of uncertainty reduction. Good agreement is found between the calculated and measured values of K and the compatibility between them is in the range of experimental uncertainty.

  1. The relation between methyl aminolevulinate concentration and inflammation after photodynamic therapy in healthy volunteers

    DEFF Research Database (Denmark)

    Fabricius, Susanne; Lerche, Catharina Margrethe; Philipsen, Peter Alshede;

    2013-01-01

    Inflammation and pain are well known adverse-effects in photodynamic therapy (PDT). There is currently a tendency towards introducing lower concentrations of the photosensitizer than used in the standard treatment for various indications. The aim of this study was to investigate whether reduced...... concentrations of methyl aminolevulinate (MAL) can reduce inflammation (erythema) during PDT treatment. We measured the formation of protoporphyrin IX (PpIX) using fluorescence and monitored both erythema and pain during and after PDT treatment with conventional 16% MAL and threee reduced concentrations of 2, 0.......75, and 0.25% in twenty-four healthy volunteers. We found that lowering the MAL concentration reduced PpIX fluorescence and erythema after PDT treatment. There was a strong correlation (R(2) = 0.70) between the PpIX fluorescence and erythema after treatment. A further increase in erythema after PDT...

  2. 19.-25. IX toimub Rüütelkonna hoones Kumu pärlite nädal...

    Index Scriptorium Estoniae

    2005-01-01

    23. IX kõneleb Anu Allikvee teemal "Eestlane baltisaksa kunstnike vaatepiiris"; 24. IX tutvustab Mai Levin Eugen Dückeri maale, 25. IX Ene Lamp Konrad Mäge. Vt. ka lk. 24 Tähtede nädal 26. IX-2. X - kohtumisõhtutel esinevad Marika ja Heinz Valk, Jüri Kuuskemaa, Sirje Helme, Pekka Vapaavuori, Inge Teder, Rain Lõhmus

  3. Particle number concentration near road traffic in Amsterdam (the Netherlands): Comparison of standard and real-world emission factors

    Science.gov (United States)

    Keuken, M. P.; Moerman, M.; Voogt, M.; Zandveld, P.; Verhagen, H.; Stelwagen, U.; Jonge de, D.

    2016-05-01

    In this study, NOx and particle number concentration (PNC) at an urban background and a traffic location were measured in the city of Amsterdam (the Netherlands). Modelled and measured contributions to NOx and PNC at the traffic location were used to derive real-world PN emission factors for average urban road traffic. The results for NOx were applied to validate our approach. The real-world PN emission factors (#.km-1) were 2.9E+14 (urban road) and 3E+14 (motorway). These values were at least a factor eight higher than dynamometer-based PN emission factors from COPERT 4 and HBEFA databases. The real-world PN emission factors were used to model the contribution to PNC near road traffic in 2014. This was two to three times higher than the PNC urban background along urban roads over 20,000 vehicles per day and near motorways. The discrepancy between dynamometer-based and real-world emission factors demonstrates the need for more PNC observations to assess actual PN emissions from road traffic.

  4. Risk burdens of modifiable risk factors incorporating lipoprotein (a) and low serum albumin concentrations for first incident acute myocardial infarction

    Science.gov (United States)

    Yang, Qin; He, Yong-Ming; Cai, Dong-Ping; Yang, Xiang-Jun; Xu, Hai-Feng

    2016-01-01

    Risk burdens of modifiable risk factors incorporating lipoprotein (a) (Lp(a)) and low serum albumin (LSA) concentrations for first incident acute myocardial infarction (AMI) haven’t been studied previously. Cross-sectional study of 1552 cases and 6125 controls was performed for identifying the association of risk factors with first incident AMI and their corresponding population attributable risks (PARs). Modifiable risk factors incorporating LSA and Lp(a) accounted for up to 92% of PAR for first incident AMI. Effects of these risk factors were different in different sexes across different age categories. Overall, smoking and LSA were the 2 strongest risk factors, together accounting for 64% of PAR for first incident AMI. After multivariable adjustment, Lp(a) and LSA accounted for 19% and 41%, respectively, and together for more than a half (54%) of PAR for first incident AMI. Modifiable risk factors incorporating LSA and Lp(a) have accounted for an overwhelmingly large proportion of the risk of first incident AMI, indicating most first incident AMI is preventable. The knowledge of risk burdens for first incident AMI incorporating Lp (a) and LSA may be beneficial for further reducing first incident AMI from a new angle. PMID:27748452

  5. The self-absorption correction factors for (210)Pb concentration in mining waste and influence on environmental radiation risk assessment.

    Science.gov (United States)

    Bonczyk, Michal; Michalik, Boguslaw; Chmielewska, Izabela

    2017-03-01

    The radioactive lead isotope (210)Pb occurs in waste originating from metal smelting and refining industry, gas and oil extraction and sometimes from underground coal mines, which are deposited in natural environment very often. Radiation risk assessment requires accurate knowledge about the concentration of (210)Pb in such materials. Laboratory measurements seem to be the only reliable method applicable in environmental (210)Pb monitoring. One of the methods is gamma-ray spectrometry, which is a very fast and cost-effective method to determine (210)Pb concentration. On the other hand, the self-attenuation of gamma ray from (210)Pb (46.5 keV) in a sample is significant as it does not depend only on sample density but also on sample chemical composition (sample matrix). This phenomenon is responsible for the under-estimation of the (210)Pb activity concentration level often when gamma spectrometry is applied with no regard to relevant corrections. Finally, the corresponding radiation risk can be also improperly evaluated. Sixty samples of coal mining solid tailings (sediments created from underground mining water) were analysed. Slightly modified and adapted to the existing laboratory condition, a transmission method has been applied for the accurate measurement of (210)Pb concentration . The observed concentrations of (210)Pb range between 42.2 ÷ 11,700 Bq·kg(-1) of dry mass. Experimentally obtained correction factors related to a sample density and elemental composition range between 1.11 and 6.97. Neglecting this factor can cause a significant error or underestimations in radiological risk assessment. The obtained results have been used for environmental radiation risk assessment performed by use of the ERICA tool assuming exposure conditions typical for the final destination of such kind of waste.

  6. Increase of ozone concentrations, its temperature sensitivity and the precursor factor in South China

    Directory of Open Access Journals (Sweden)

    Y. C. Lee

    2014-08-01

    Full Text Available Concerns have been raised about the possible connections between the local and regional photochemical problem and global warming. The current study assesses the trend of ozone in Hong Kong and the Pearl River Delta (PRD in South China and investigates the interannual changes of sensitivity of ozone to air temperature, as well as the trends in regional precursors. Results reveal, at the three monitoring sites from the mid-1990s to 2010, an increase in the mean ozone concentrations from 1.0 to 1.6 µg m−3 per year. The increase occurred in all seasons, with the highest rate in autumn. This is consistent with trends and temperature anomalies in the region. The increase in the sensitivity of ozone to temperature is clearly evident from the correlation between ozone (OMI [Ozone Monitoring Instrument] column amount and surface air temperature (from the Atmospheric Infrared Sounder displayed in the correlation maps for the PRD during the prominently high ozone period of July–September. It is observed to have increased from 2005 to 2010, the latter being the hottest year on record globally. To verify this temporal change in sensitivity, the ground-level trends of correlation coefficients/regression slopes are analysed. As expected, results reveal a statistically significant upward trend over a 14-year period (1997–2010. While the correlation revealed in the correlation maps is in agreement with the corresponding OMI ozone maps when juxtaposed, temperature sensitivity of surface ozone also shows an association with ozone concentration, with R=0.5. These characteristics of ozone sensitivity are believed to have adverse implications for the region. As shown by ground measurements and/or satellite analyses, the decrease in nitrogen oxides (NO2 and NOx in Hong Kong is not statistically significant while NO2 of the PRD has only very slightly changed. However, carbon dioxide has remarkably declined in the whole region. While these observations concerning

  7. Diminished concentrations of insulin-like growth factor I in cystic fibrosis

    DEFF Research Database (Denmark)

    Laursen, Erik; Juul, A; Lanng, S;

    1995-01-01

    Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data...... on IGF-I in cystic fibrosis are sparse and conflicting. From 1990-3, 235 of our 240 patients (114 males, 121 females, median age 16.2 years, ranged 0.1-44.0 years) had IGF-I measured once by radioimmunoassay. IGF-I was significantly reduced compared with a healthy Scandinavian control population: mean...... = 0.28, p cystic fibrosis and play a part in their abnormal growth pattern....

  8. Host-related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans

    DEFF Research Database (Denmark)

    Bohn, Torsten; Desmarchelier, Charles; Dragsted, Lars Ove

    2017-01-01

    Carotenoid dietary intake and their endogenous levels have been associated with a decreased risk of several chronic diseases. There are indications that carotenoid bioavailability depends, in addition to the food matrix, on host factors. These include diseases (e.g. colitis), life-style habits (e.......g. smoking), gender and age, as well as genetic variations including single nucleotide polymorphisms that govern carotenoid metabolism. These are expected to explain interindividual differences that contribute to carotenoid uptake, distribution, metabolism and excretion, and therefore possibly also...... their association with disease risk. For instance, digestion enzymes fostering micellization (PNLIP, CES), expression of uptake/efflux transporters (SRARB1, CD36, NPC1L1), cleavage enzymes (BCO1/2), intracellular transporters (FABP2), secretion into chylomicrons (APOB, MTTP), carotenoid metabolism in the blood...

  9. Host-related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans

    DEFF Research Database (Denmark)

    Bohn, Torsten; Desmarchelier, Charles; Dragsted, Lars Ove

    2017-01-01

    Carotenoid dietary intake and their endogenous levels have been associated with a decreased risk of several chronic diseases. There are indications that carotenoid bioavailability depends, in addition to the food matrix, on host factors. These include diseases (e.g. colitis), life-style habits (e.......g. smoking), gender and age, as well as genetic variations including single nucleotide polymorphisms that govern carotenoid metabolism. These are expected to explain interindividual differences that contribute to carotenoid uptake, distribution, metabolism and excretion, and therefore possibly also...... their association with disease risk. For instance, digestion enzymes fostering micellization (PNLIP, CES), expression of uptake/efflux transporters (SRARB1, CD36, NPC1L1), cleavage enzymes (BCO1/2), intracellular transporters (FABP2), secretion into chylomicrons (APOB, MTTP), carotenoid metabolism in the blood...

  10. Combinations of concentration and strain gradient hydrogen diffusion factors in palladium alloy membranes

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, F.A. [School of Chemistry, Queen' s University Belfast, Belfast (Ireland); Bucur, R.V. [Dept. Inorganic Chemistry, University Uppsala, Uppsala (Sweden); Tong, X.Q. [Dept. of Chemistry, University of Southamton, Southampton, (United Kingdom); Sakamoto, Y. [Dept. of Mater. Science, Nagasaki University, Nagasaki (Japan); Kandasamy, K. [Dept. of Physics, University of Jaffna, Jaffna (Sri Lanka)

    1998-07-01

    Utilisations of palladium and palladium alloys as membranes for hydrogen permeation have been subjects of continuing academic and technological interest. From both standpoints, certain membranes of the palladium-platinum alloy series have been particular subjects of several studies in more recent years. Such recent series of studies have illustrated some special advantages of certain Pd-Pt alloys in providing experimental evidence of general needs of appreciation that developments of elastic strain gradients arising from lattice expansions (and contractions) produced by hydrogen entry into (and removal from) interstitial lattice sites - should be considered in combination with reliable knowledge of the pressure-composition (p-c(n)) - temperature relationships of palladium and palladium alloys in considerations of hydrogen diffusion problems. Further, in particular, a body of results, obtained with Pd{sub 81},Pt{sub 19}, and Pd{sub 77}Ag{sub 23} and Pd membranes, has also drawn attention to requirements for very serious considerations also to be given to concurrent time dependent developments of lattice strain gradients in conjunction with the hydrogen concentration gradients, in regard to estimations of hydrogen diffusion coefficients, D{sub H}, including dependencies of D{sub H} on the hydrogen contents of the membranes. 34 refs.

  11. Hair cortisol concentration is unaffected by basic military training, but related to sociodemographic and environmental factors.

    Science.gov (United States)

    Boesch, Maria; Sefidan, Sandra; Annen, Hubert; Ehlert, Ulrike; Roos, Lilian; Van Uum, Stan; Russell, Evan; Koren, Gideon; La Marca, Roberto

    2015-01-01

    The analysis of hair cortisol concentrations (HCC) is a promising new biomarker for retrospective measurement of chronic stress. The effect of basic military training (BMT) on chronic stress has not yet been reported. The aim of this study was to investigate the effect of 10-week BMT on HCC, while further exploring the role of known and novel covariates. Young healthy male recruits of the Swiss Army participated twice, 10 weeks apart, in data collection (1st examination: n = 177; 2nd examination: n = 105). On two occasions, we assessed HCC, perceived stress and different candidate variables that may affect HCC (e.g. socioeconomic status, meteorological data). Military training increased perceived stress from the first to the second examination, but did not affect HCC. In line with this, there was no correlation between HCC and perceived stress ratings. This could be interpreted as a missing influence of mainly physical stress (e.g. exercise) on HCC. In contrast, significant correlations were found between HCC and ambient temperature, humidity and education. Future studies should control for meteorological data and educational status when examining HCC.

  12. 34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

    Science.gov (United States)

    2010-07-01

    ... “Remedial and Affirmative Actions” Assistance to “outside” discriminatory organizations, ; 106.31(b) (7), (c..., ; 106.41(d) Contact sport defined, 106.41(d) Equal opportunity, ; 106.41(d) Determining factors, 106.41... “Financial assistance” 106.37 and “Assistance to ‘outside’ discriminatory organizations”,...

  13. Detecting the causality influence of individual meteorological factors on local PM2.5 concentration in the Jing-Jin-Ji region

    Science.gov (United States)

    Chen, Ziyue; Cai, Jun; Gao, Bingbo; Xu, Bing; Dai, Shuang; He, Bin; Xie, Xiaoming

    2017-01-01

    Due to complicated interactions in the atmospheric environment, quantifying the influence of individual meteorological factors on local PM2.5 concentration remains challenging. The Beijing-Tianjin-Hebei (short for Jing-Jin-Ji) region is infamous for its serious air pollution. To improve regional air quality, characteristics and meteorological driving forces for PM2.5 concentration should be better understood. This research examined seasonal variations of PM2.5 concentration within the Jing-Jin-Ji region and extracted meteorological factors strongly correlated with local PM2.5 concentration. Following this, a convergent cross mapping (CCM) method was employed to quantify the causality influence of individual meteorological factors on PM2.5 concentration. The results proved that the CCM method was more likely to detect mirage correlations and reveal quantitative influences of individual meteorological factors on PM2.5 concentration. For the Jing-Jin-Ji region, the higher PM2.5 concentration, the stronger influences meteorological factors exert on PM2.5 concentration. Furthermore, this research suggests that individual meteorological factors can influence local PM2.5 concentration indirectly by interacting with other meteorological factors. Due to the significant influence of local meteorology on PM2.5 concentration, more emphasis should be given on employing meteorological means for improving local air quality.

  14. Detecting the causality influence of individual meteorological factors on local PM2.5 concentration in the Jing-Jin-Ji region

    Science.gov (United States)

    Chen, Ziyue; Cai, Jun; Gao, Bingbo; Xu, Bing; Dai, Shuang; He, Bin; Xie, Xiaoming

    2017-01-01

    Due to complicated interactions in the atmospheric environment, quantifying the influence of individual meteorological factors on local PM2.5 concentration remains challenging. The Beijing-Tianjin-Hebei (short for Jing-Jin-Ji) region is infamous for its serious air pollution. To improve regional air quality, characteristics and meteorological driving forces for PM2.5 concentration should be better understood. This research examined seasonal variations of PM2.5 concentration within the Jing-Jin-Ji region and extracted meteorological factors strongly correlated with local PM2.5 concentration. Following this, a convergent cross mapping (CCM) method was employed to quantify the causality influence of individual meteorological factors on PM2.5 concentration. The results proved that the CCM method was more likely to detect mirage correlations and reveal quantitative influences of individual meteorological factors on PM2.5 concentration. For the Jing-Jin-Ji region, the higher PM2.5 concentration, the stronger influences meteorological factors exert on PM2.5 concentration. Furthermore, this research suggests that individual meteorological factors can influence local PM2.5 concentration indirectly by interacting with other meteorological factors. Due to the significant influence of local meteorology on PM2.5 concentration, more emphasis should be given on employing meteorological means for improving local air quality. PMID:28128221

  15. Production factors influence fresh lamb longissimus colour more than muscle traits such as myoglobin concentration and pH.

    Science.gov (United States)

    Calnan, H; Jacob, R H; Pethick, D W; Gardner, G E

    2016-09-01

    M. longissimus colour was measured from 8165 lambs at 24h post-mortem using a chromameter. The impact of production factors (site and year of production, slaughter group, sex, age and breed type) and muscle traits (hot carcass weight, pH24, isocitrate dehydrogenase (ICDH) activity, myoglobin, iron and zinc concentrations) on meat lightness (L*), redness (a*), yellowness (b*), hue and chroma were analysed. Greater differences in meat colour were seen between different slaughter groups and sites of production than across the range of any muscle traits. Of the muscle traits analysed, changes in pH24 had the greatest effect on meat a* (2.5 units), while myoglobin had the greatest effect on meat L* (2.9 units). The 3.1 L* unit darkening of meat with increasing lamb age (from 140 to 400days) was accounted for by increased myoglobin concentration. These results suggest that production factors are having substantial effects on lamb colour independent of known influencing muscle traits such as myoglobin concentration and pH. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Factors, origin and sources affecting PM1 concentrations and composition at an urban background site

    Science.gov (United States)

    Squizzato, Stefania; Masiol, Mauro; Agostini, Chiara; Visin, Flavia; Formenton, Gianni; Harrison, Roy M.; Rampazzo, Giancarlo

    2016-11-01

    PM1 is widely believed to provide better information on the anthropogenic fraction of particulate matter pollution than PM2.5. However, data on PM1 are still limited in Europe as well as comprehensive information about its chemical composition and source apportionment and this gap is more evident in the pollution hot-spots still remaining in Europe, such as the Po Valley (Northern Italy). Elemental and organic carbon, 7 water soluble inorganic ions and 17 elements were quantified in 117 PM1 samples collected at an urban background site in Venice-Mestre, a large city located in the eastern Po Valley, during winter (December 2013-February 2014) and summer (May-July 2014) periods. Results show a strong seasonality for PM1 mass concentration (averages ranging from 6 ± 2 in summer to 34 ± 24 μg m- 3 in winter) and for most of the analysed species. Components mainly related to road traffic, residential heating, biomass burning and secondary inorganic aerosol (ammonium nitrate) reached their highest levels in winter, while mineral dust and marine components were elevated in summer. PMF analysis revealed 7 potential sources. Secondary inorganic aerosol (33%) and biomass burning (33%) are the major contributor in winter followed by EC-primary emissions (16%), aged sulphate (6%), road traffic (7%), fossil fuel combustion (%) and marine aerosol (3%). During summer, these sources account for 12%, 14%, 20%, 22%, 8%, 14% and 10%, respectively. Some PM1 sources are located near the sampling site (residential area, traffic road, industrial area) but a major contribution of long range transport is observed when high pollution events occur. The results give useful insights into PM1 composition in an urban area and chemical profiles of sources helpful in the interpretation of receptor model results.

  17. Phenylketonuria is not a risk factor for changes of inflammation status as assessed by interleukin 6 and interleukin 8 concentrations

    Directory of Open Access Journals (Sweden)

    Renata Mozrzymas

    2016-06-01

    Full Text Available Background. High oxidative stress and a reduced potential for free radical scavenging in phenylketonuria (PKU patients, a phenomenon confirmed in a few studies, may lead to systemic chronic inflammation. The aim of this study was to compare the inflammation status, as assessed by interleukin 6 and interleukin 8 con- centrations, in patients with PKU and in healthy controls. Material and methods. Twenty patients with classical PKU, aged 18–34 years and under dietary control, were enrolled in the study. The control group comprised of 20 healthy subjects matched for age and sex. Interleukin 6 and 8 levels were measured by enzyme-linked immunosorbent assay (ELISA kits in all study participants. Results. IL-6 concentrations in the study group ranged from 0.74 pg/ml to 1.34 pg/ml. No significant dif- ferences were found between IL-6 concentration between the study group and the control group (p = 0.989. IL-8 concentrations ranged from 17.56 pg/ml to 20.87 pg/ml. The obtained results of IL-8 levels did not differ significantly between the study group and control group (p = 0.192. No significant correlation was observed between Phe blood levels and IL-6 or IL-8 concentrations in the study group (ρ respectively: –0.225, 0.177. In a multivariate analysis, neither IL-6 nor IL-8 concentrations were correlated with sex, age, BMI and Phe levels. Conclusions. Phenylketonuria is not a risk factor for changes of inflammation status as assessed by IL-6 and IL-8 concentrations.

  18. Significant Correlation between Retinal Venous Tortuosity and Aqueous Vascular Endothelial Growth Factor Concentration in Eyes with Central Retinal Vein Occlusion.

    Science.gov (United States)

    Yasuda, Shunsuke; Kachi, Shu; Kondo, Mineo; Ueno, Shinji; Kaneko, Hiroki; Terasaki, Hiroko

    2015-01-01

    To determine whether the degree of venous tortuosity is significantly correlated with the aqueous vascular endothelial growth factor (VEGF) concentration in eyes with a central retinal vein occlusion (CRVO). We reviewed the medical records of 32 eyes of 32 patients who had macular edema due to a CRVO. All of the patients were examined at the Nagoya University Hospital and were scheduled to receive an intravitreal injection of bevacizumab (IVB) or ranibizumab (IVR) within 12 weeks of the onset of the CRVO to treat the macular edema. Aqueous humor was collected just before the IVB or IVR, and the VEGF concentration was determined by enzyme-linked immunosorbent assay (ELISA). The venous tortuosity index was calculated by dividing the length of the retinal veins by the chord length of the same segment. The correlation between the mean tortuosity index of the inferotemporal and supratemporal branches of the retinal vein and the aqueous VEGF concentration was determined. The mean aqueous VEGF concentration was 384 ± 312 pg/ml with a range of 90 to 1077 pg/ml. The degree of venous tortuosity was significantly correlated with the VEGF concentration in the aqueous. (r = 0.49, P = 0.004), with the foveal thickness (r = 0.40, P = 0.02), and with the best-corrected visual acuity (r = 0.38, P = 0.03). The significant correlation between the aqueous VEGF concentration and the venous tortuosity indicates that the degree of retinal venous tortuosity can be used to identify eyes that are at a high risk of developing neovascularization.

  19. Contrasting Food Web Factor and Body Size Relationships with Hg and Se Concentrations in Marine Biota

    Science.gov (United States)

    Karimi, Roxanne; Frisk, Michael; Fisher, Nicholas S.

    2013-01-01

    Marine fish and shellfish are primary sources of human exposure to mercury, a potentially toxic metal, and selenium, an essential element that may protect against mercury bioaccumulation and toxicity. Yet we lack a thorough understanding of Hg and Se patterns in common marine taxa, particularly those that are commercially important, and how food web and body size factors differ in their influence on Hg and Se patterns. We compared Hg and Se content among marine fish and invertebrate taxa collected from Long Island, NY, and examined associations between Hg, Se, body length, trophic level (measured by δ15N) and degree of pelagic feeding (measured by δ13C). Finfish, particularly shark, had high Hg content whereas bivalves generally had high Se content. Both taxonomic differences and variability were larger for Hg than Se, and Hg content explained most of the variation in Hg:Se molar ratios among taxa. Finally, Hg was more strongly associated with length and trophic level across taxa than Se, consistent with a greater degree of Hg bioaccumulation in the body over time, and biomagnification through the food web, respectively. Overall, our findings indicate distinct taxonomic and ecological Hg and Se patterns in commercially important marine biota, and these patterns have nutritional and toxicological implications for seafood-consuming wildlife and humans. PMID:24019976

  20. The plasma concentration of the B cell activating factor is increased in children with acute malaria.

    Science.gov (United States)

    Nduati, Eunice; Gwela, Agnes; Karanja, Henry; Mugyenyi, Cleopatra; Langhorne, Jean; Marsh, Kevin; Urban, Britta C

    2011-09-15

    Malaria-specific antibody responses in children often appear to be short-lived but the mechanisms underlying this phenomenon are not well understood. In this study, we investigated the relationship between the B-cell activating factor (BAFF) and its receptors expressed on B cells with antibody responses during and after acute malaria in children. Our results demonstrate that BAFF plasma levels increased during acute malarial disease and reflected disease severity. The expression profiles for BAFF receptors on B cells agreed with rapid activation and differentiation of a proportion of B cells to plasma cells. However, BAFF receptor (BAFF-R) expression was reduced on all peripheral blood B cells during acute infection, but those children with the highest level of BAFF-R expression on B cells maintained schizont-specific immunoglobin G (IgG) over a period of 4 months, indicating that dysregulation of BAFF-R expression on B cells may contribute to short-lived antibody responses to malarial antigens in children. In summary, this study suggests a potential role for BAFF during malaria disease, both as a marker for disease severity and in shaping the differentiation pattern of antigen-specific B cells.

  1. Serum boron concentration in rheumatoid arthritis: correlation with disease activity, functional class, and rheumatoid factor

    Directory of Open Access Journals (Sweden)

    Fadhil Muhsin

    2013-02-01

    Full Text Available Objectives: Rheumatoid arthritis (RA is a common chronic inflammatory arthropathy of unknown etiology. Trace elements have a great role in a number of biological processes. The aim of this study was to assess the serum element boron in a sample of Iraqi patients with RA and to evaluate its relationship if present with disease activity, functional class of the disease, and rheumatoid factor (RF. Methods: A cross sectional study enrolled 107 RA patients and 214 controls matched in age and sex. The American College of Rheumatology 1987 revised criteria was used for diagnosis of RA. Disease Activity Score index of 28 joints (DAS28, functional class of RA patients, RF, erythrocyte sedimentation rate (ESR were measured in patients’ group; serum boron levels were measured using a flame atomic absorption spectrophotometer in both patients and controls groups. Results: RA patients had significantly lower serum boron level than controls (P 0.05. Also, RF titer was a significant predictor of low serum boron level (P = 0.023, OR = –0.07, 95%CI –0.13-(–0.01. Conclusions: There was a significant low serum boron level in RA patients. RF titer was significant predictor of low serum boron level. This may suggest that boron element may play a role in pathophysiology of RA and its severity. Supplementation with boron element and diets rich in fruits, vegetables, nuts, and pulses may be useful. [J Exp Integr Med 2013; 3(1: 9-15

  2. Serum concentrations of brain-derived neurotrophic factor and mental disorders in imprisoned women

    Directory of Open Access Journals (Sweden)

    Renata M. Dotta-Panichi

    2015-06-01

    Full Text Available Objective:Mental disorders and early trauma are highly prevalent in female inmates. Brain-derived neurotrophic factor (BDNF plays an important role in learning, memory processes, and mood regulation. The aim of this study was to evaluate the relationship between serum BDNF levels and mental disorders among imprisoned women as compared with age- and education-matched controls.Methods:A consecutively recruited sample of 18 female prisoners with mental disorders was assessed for sociodemographic, criminal, and clinical variables using standardized instruments, the Mini International Neuropsychiatric Interview Plus (MINI Plus, and serum BDNF levels.Results:High rates of childhood sexual abuse and posttraumatic stress disorder (PTSD were found in the group of forensic patients. Serum BDNF levels in the forensic group did not differ from those of healthy controls, and were significantly higher when compared with those of women with mental disorders hospitalized in a general hospital.Conclusion:Elevated serum BDNF levels were found in imprisoned women. The results of this study may suggest neurobiological mechanisms similar to those seen in previous clinical and preclinical studies showing the involvement of BDNF in the pathophysiology of PTSD.

  3. Analysis of the influence of solar activity and atmospheric factors on 7Be air concentration by seasonal-trend decomposition

    Science.gov (United States)

    Bas, M. C.; Ortiz, J.; Ballesteros, L.; Martorell, S.

    2016-11-01

    7Be air concentrations were measured at the Universitat Politècnica de Valencia campus (in the east of Spain) during the period 2007-2014. The mean values of monthly 7Be concentrations ranged from 2.65 to 8.11 mBq/m3, showing significant intra and interannual variability. A seasonal-trend decomposition methodology was applied to identify the trend-cycle, seasonal and irregular components of the 7Be time series. The decomposition model makes it possible to estimate the influence of solar activity and atmospheric factors on the independent components, in order to find the different sources of 7Be variability. The results show that solar activity is a factor with a high inverse influence on the trend-cycle pattern of 7Be variability. Solar radiation, temperature and relative humidity are positive influential factors on the seasonal 7Be variation with a regular pattern over the years. Finally, the irregular component presents a significant negative correlation with precipitation and wind speed parameters, which have an irregular behavior over the years and seasons.

  4. Another Direct Proof of Oka's Theorem (Oka IX)

    CERN Document Server

    Noguchi, Junjiro

    2011-01-01

    In 1953 K. Oka IX solved in first and in a final form Levi's problem (Hartogs' inverse problem) for domains or Riemann domains over $\\C^n$ of arbitrary dimension. Later on a number of the proofs were given; cf.\\ e.g., Docquier-Grauert's paper in 1960, R. Narasimhan's paper in 1961/62, Gunning-Rossi's book, and H\\"ormander's book (in which the holomorphic separability is pre-assumed in the definition of Riemann domains and thus the assumption is stronger than the one in the present paper). Here we will give another direct elementary proof of Oka's Theorem, relying only on Grauert's finiteness theorem by the {\\it induction on the dimension} and the {\\it jets over Riemann domains}; hopefully, the proof is most comprehensive.

  5. THE IX EUROPEAN FORUM ON ANTIPHOSPHOLIPID ANTIBODIES. A BRIEF REVIEW

    Directory of Open Access Journals (Sweden)

    Nataliya V Seredavkina

    2014-01-01

    Full Text Available The article presents a brief review of the proceedings of the IX European Forum on antiphospholipid antibodies held in May 2013 in Krakow (Poland. The aim of the Forum is to coordinate multicenter projects focused on antiphospholipid antibodies (aPL, both clinical and fundamental research, based on cooperation between the European countries. The main purpose is to stimulate research into all aspects of aPL, to facilitate the exchange of information between institutions, and to involve many centers in different countries into scientific research on this issue. The issues of standardization of the diagnostic criteria for antiphospholipid syndrome (APS, primarily serological markers (their specificity, sensitivity and correlation with clinical manifestations, as well as non-criterial manifestations of APS, were considered at the meeting. In addition, the therapy problems were discussed.

  6. Growth factor concentrations and their placental mRNA expression are modulated in gestational diabetes mellitus: possible interactions with macrosomia

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    Khairi Hédi

    2010-02-01

    Full Text Available Abstract Background Gestational diabetes mellitus (GDM is a form of diabetes that occurs during pregnancy. GDM is a well known risk factor for foetal overgrowth, termed macrosomia which is influenced by maternal hypergycemia and endocrine status through placental circulation. The study was undertaken to investigate the implication of growth factors and their receptors in GDM and macrosomia, and to discuss the role of the materno-foeto-placental axis in the in-utero regulation of foetal growth. Methods 30 women with GDM and their 30 macrosomic babies (4.75 ± 0.15 kg, and 30 healthy age-matched pregnant women and their 30 newborns (3.50 ± 0.10 kg were recruited in the present study. Serum concentrations of GH and growth factors, i.e., IGF-I, IGF-BP3, FGF-2, EGF and PDGF-B were determined by ELISA. The expression of mRNA encoding for GH, IGF-I, IGF-BP3, FGF-2, PDGF-B and EGF, and their receptors, i.e., GHR, IGF-IR, FGF-2R, EGFR and PDGFR-β were quantified by using RT-qPCR. Results The serum concentrations of IGF-I, IGF-BP3, EGF, FGF-2 and PDGF-B were higher in GDM women and their macrosomic babies as compared to their respective controls. The placental mRNA expression of the growth factors was either upregulated (FGF-2 or PDGF-B or remained unaltered (IGF-I and EGF in the placenta of GDM women. The mRNA expression of three growth factor receptors, i.e., IGF-IR, EGFR and PDGFR-β, was upregulated in the placenta of GDM women. Interestingly, serum concentrations of GH were downregulated in the GDM women and their macrosomic offspring. Besides, the expression of mRNAs encoding for GHR was higher, but that encoding for GH was lower, in the placenta of GDM women than control women. Conclusions Our results demonstrate that growth factors might be implicated in GDM and, in part, in the pathology of macrosomia via materno-foeto-placental axis.

  7. A field study to evaluate the impact of different factors on the nutrient pollutant concentrations in green roof runoff.

    Science.gov (United States)

    Wang, Xiaochen; Zhao, Xinhua; Peng, Chenrui; Zhang, Xinbo; Wang, Jianghai

    2013-01-01

    The objectives of this study are to investigate the impact of different factors on the nutrient pollutant concentrations in green roof runoff and to provide reference data for the engineering design of dual substrate layer green roofs. The data were collected from eight different trays under three kinds of artificial rains. The results showed that except for total phosphorus, dual substrate layer green roofs behaved as a sink for most of the nutrient pollutants (significant at p < 0.05), and the first-flush effect did not occur during the 27 simulated rain events. The results also revealed that the concentration of these nutrient pollutants in the runoff strongly depended on the features of the nutrient substrates used in the green roof and the depth of the adsorption substrates. Compared with the influence of the substrates, the influence of the plant density and drainage systems was small.

  8. Application of concentrated growth factors in reconstruction of bone defects after removal of large jaw cysts: The two cases report

    Directory of Open Access Journals (Sweden)

    Mirković Siniša

    2015-01-01

    Full Text Available Introduction. Coagulation and blood clot formation in bone defects is sometimes followed by retraction of a blood clot and serum extrusion, thus producing peripheral serum-filled spaces between bony wall and coagulum. This can result in a higher incidence of postoperative complications. Stabilization of blood coagulum, which enables successful primary healing, may be accomplished by autotransplantation, allotransplantation, xenotransplantation, or application of autologous platelet concentrate and concentrated growth factors (CGF. Case report. Two patients with large cystic lesions in the upper and lower jaw were presented. In both patients postoperative bony defects were filled with autologous fibrin rich blocks containing CGF. Postoperative course passed uneventfully. Conclusion. Application of fibrin rich blocks containing CGF is one of the possible methods for reconstruction of bone defects. CGF can be applied alone or mixed with a bone graft. The method is relatively simple, without risk of transmissible and allergic diseases and economically feasible.

  9. Effect of stiffness and thickness ratio of host plate and piezoelectric patches on reduction of the stress concentration factor

    Science.gov (United States)

    Fesharaki, Javad Jafari; Madani, Seyed Ghasem; Golabi, Sa'id

    2016-09-01

    This paper focuses on the effects of stiffness ratio and thickness ratio on reducing stress concentration factor using piezoelectric patches in a rectangular plate with a hole, as a classical shape. Various locations of actuators and induction of positive/negative strains into the host plate are investigated and the best location of patches is presented. The study investigated the ratio effects and piezoelectric patches bounded on a rectangular host plate having various thicknesses and materials. Results show that the best position of actuators varies based on values of thickness and stiffness ratios of the host plate and piezoelectric patches. Also, the location of maximum stress concentration is transmitted from top and bottom of the hole to another point around the edge by changing the location of the piezoelectric actuators. To verify the results, some experimental tests are applied. The results show good agreement between the finite element analysis and experimental tests.

  10. Lead and cadmium in human teeth from Jordan by atomic absorption spectrometry: Some factors influencing their concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Alomary, A. [Department of Chemistry, Yarmouk University, Irbid (Jordan)]. E-mail: ahmedalomary1000@hotmail.com; Al-Momani, I.F. [Department of Chemistry, Yarmouk University, Irbid (Jordan); Massadeh, A.M. [Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid (Jordan)

    2006-10-01

    The aim of this study was to measure the concentrations of lead (Pb) and cadmium (Cd) in human teeth and to investigate the affecting factors. Teeth samples (n = 268) were collected from people living in different cities in Jordan including Amman, Zarqa, Al-Mafraq and Irbid and analyzed for Pb and Cd using atomic absorption spectrometry (AAS). A questionnaire was used to gather information on each person, such as age, sex, place where the patient lives, smoking, presence of amalgam fillings inside the mouth, and whether the patient uses toothpaste or not. The mean concentrations of Pb and Cd were 28.91 {mu}g/g and 0.44 {mu}g/g, respectively. The results indicate that there is a clear relation between Pb and Cd concentrations and the presence of amalgam fillings, smoking, and place of living. Pb was sex-dependent, whereas Cd was not. Our results show that Pb and Cd concentrations in samples obtained from Al-Mafraq and Irbid are higher than those obtained from Amman and Zarqa. Pb was highest in Mafraq, whereas Cd was highest in Irbid. The Pb and Cd concentrations in teeth from smokers (means: Pb = 31.89 {mu}g/g, Cd = 0.49 {mu}g/g) were significantly higher than those from nonsmokers (means: Pb = 24.07 {mu}g/g, Cd = 0.37 {mu}g/g). Pb and Cd concentrations in teeth of patients with amalgam fillings (means: Pb = 31.02 {mu}g/g and Cd = 0.52 {mu}g/g) were significantly higher than those from patients without amalgam fillings (means: Pb = 26.87 {mu}g/g and Cd = 0.41 {mu}g/g). Our results show that brushing the teeth daily with toothpaste does not significantly decrease the concentration of both Pb and Cd. The mean concentrations of Pb and Cd do not vary significantly between the ages 20-30, 31-40, and 41-50, but both increased rapidly at age 51-60.

  11. The course of preexistent immune abnormalities in HIV-negative hemophiliacs treated for 2 years with a monoclonal purified factor-VIII concentrate

    NARCIS (Netherlands)

    Smid, W. M.; van der Meer, J.; Smit, J. W.; Halie, M. R.

    1993-01-01

    The administration of factor VIII concentrates has been associated with immune abnormalities in patients with severe haemophilia A, even in the absence of HIV infection. The effects of a monoclonal purified factor VIII concentrate, Hemofil M (Baxter), on preexistent immune abnormalities were

  12. Factors influencing the formation of histaminol, hydroxytyrosol, tyrosol, and tryptophol in wine: Temperature, alcoholic degree, and amino acids concentration.

    Science.gov (United States)

    Bordiga, M; Lorenzo, C; Pardo, F; Salinas, M R; Travaglia, F; Arlorio, M; Coïsson, J D; Garde-Cerdán, T

    2016-04-15

    The validation of a HPLC-PDA-MS/MS chromatographic method for the quali/quantitative characterization of histaminol, hydroxytyrosol, tyrosol, and tryptophol in wine has been described and discussed. Four standards showed a good linearity with high correlation coefficient values (over 0.9989) and LOD and LOQ were 0.001-0.015 mg/L and 0.004-0.045 mg/L, respectively. Furthermore, this study reported how factors such as temperature, alcoholic degree, and amino acids concentration are able to influence the formation of these four alcohols in Monastrell wines. The quantification values of these alcohols has been detected both at the half and end of alcoholic fermentation, and at the end of malolactic fermentation. In relation to interactions between factors, several significant variations emerged (p ⩽ 0.001). The impact of amino acids supplementation in Monastrell must it has been demonstrated, mainly in regards to histaminol and tryptophol.

  13. The use of CA-IX as a diagnostic method for oral leukoplakia.

    Science.gov (United States)

    Pérez-Sayáns, M; Suárez-Peñaranda, J M; Torres-López, M; Supuran, C T; Gándara-Vila, P; Gayoso-Diz, P; Barros-Angueira, F; Gallas-Torreira, M; García-García, A

    2015-02-01

    The presence and degree of dysplasia are important diagnostic and prognostic criteria for oral leukoplakia, but evaluation of dysplasia is difficult and subjective. Carbonic anhydrase-IX (CA-IX) is expressed primarily in tumor cells and is considered a specific hypoxia marker. We investigated the role of CA-IX in oral leukoplakia. We investigated 30 specimens of oral leukoplakia and 35 dysplasia specimens adjacent to the tumor margin. We analyzed clinical variables including age, sex, degree of dysplasia, and smoking, clinical appearance of leukoplakia, number of lesions, location, size, clinical monitoring, malignant transformation and recurrence. For the immunohistochemical study, we used a noncommercial monoclonal antibody against human CA-IX MAb M75. We found greater CA-IX positivity in nonsmokers, erythroplakia and mottled leukoplakia, those located on the tongue, patients with multiple lesions, 2-4 cm leukoplakias and in recurrent cases, although differences were not statistically significant. All lesions in all samples without dysplasia were negative for CA-IX; however, for all other categories of dysplasia, the percentages of positivity and negativity varied. Regarding the diagnostic index values, we found a sensitivity of 32%, specificity of 100%, a positive predictive value of 100% and a negative predictive value of 13%. Leukoplakias appear mainly in females and potentially are malignant; more than 90% have some degree of dysplasia, and therefore require close clinical and histopathological monitoring. The CA-IX immunohistochemical marker may be useful for screening samples without dysplasia owing to its high specificity.

  14. High hydrostatic pressure enables almost 100% refolding of recombinant human ciliary neurotrophic factor from inclusion bodies at high concentration.

    Science.gov (United States)

    Wang, Qi; Liu, Yongdong; Zhang, Chun; Guo, Fangxia; Feng, Cui; Li, Xiunan; Shi, Hong; Su, Zhiguo

    2017-05-01

    Protein refolding from inclusion bodies (IBs) often encounters a problem of low recovery at high protein concentration. In this study, we demonstrated that high hydrostatic pressure (HHP) could simultaneously achieve high refolding concentration and high refolding yield for IBs of recombinant human ciliary neurotrophic factor (rhCNTF), a potential therapeutic for neurodegenerative diseases. The use of dilution refolding obtained 18% recovery at 3 mg/mL, even in the presence of 4 M urea. In contrast, HHP refolding could efficiently increase the recovery up to almost 100% even at 4 mg/mL. It was found that in the dilution, hydrophobic aggregates were the off-path products and their amount increased with the protein concentration. However, HHP could effectively minimize the formation of hydrophobic aggregates, leading to almost complete conversion of the rhCNTF IBs to the correct configuration. The stable operation range of concentration is 0.5-4.0 mg/mL, in which the refolding yield was almost 100%. Compared with the literatures where HHP failed to increase the refolding yield beyond 90%, the reason could be attributed to the structural difference that rhCNTF has no disulfide bond and is a monomeric protein. After purification by one-step of anionic chromatography, the purity of rhCNTF reached 95% with total process recovery of 54.1%. The purified rhCNTF showed similar structure and in vitro bioactivity to the native species. The whole process featured integration of solubilization/refolding, a high refolding yield of 100%, a high concentration of 4 mg/mL, and a simple chromatography to ensure a high productivity. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Nitrogen dioxide and respiratory illness in children. Part IV: Effects of housing and meteorologic factors on indoor nitrogen dioxide concentrations.

    Science.gov (United States)

    Spengler, J D; Schwab, M; McDermott, A; Lambert, W E; Samet, J M

    1996-12-01

    In a prospective study of infants' exposure to nitrogen dioxide (NO2)* and respiratory illness, NO2 concentrations were measured in more than 1,400 homes in Albequerque, NM, From January 1988 through June 1991 (Health Effects Institute Research Report Number 58, Parts I, II and III). This report characterizes the variability in indoor NO2 concentrations across seasons and years, and identifies factors associated with variation in concentrations between homes and across seasons. In regression analyses of winter data, NO2 levels in the infants' bedrooms were predominately determined by the presence of gas cooking ranges with continuously burning pilot lights, the presence of wall or floor furnaces, the use of the stove for space heating, and the square footage of the living space. These findings are consistent with previously published analysis of data from homes in other U.S. cities. Relatively small differences in seasonal NO2 levels were observed across years. The correlation coefficient (r) of bedroom NO2 levels obtained in the same homes was 0.66 over two winters and 0.48 over two summers. For homes that had gas cooking ranges with continuously burning pilot lights, the NO2 bedroom concentrations differed, on average, less than 5 parts per billion (ppb) across winters. These differences were hypothesized to be caused by differences in the use of indoor NO2 sources, ventilation, and ambient (outdoor) NO2 levels. We were, however, unable to demonstrate an association between year-to-year differences in seasonal indoor NO2 concentrations and reported use of cooking range, furnace, or heater, or ambient NO2 levels, or temperature.

  16. The heparan sulfate co-receptor and the concentration of fibroblast growth factor-2 independently elicit different signalling patterns from the fibroblast growth factor receptor

    Directory of Open Access Journals (Sweden)

    Duchesne Laurence

    2010-06-01

    Full Text Available Abstract Background The fibroblast growth factor receptor (FGFR interprets concentration gradients of FGF ligands and structural changes in the heparan sulfate (HS co-receptor to generate different cellular responses. However, whether the FGFR generates different signals is not known. Results We have previously shown in rat mammary fibroblasts that in cells deficient in sulfation, and so in HS co-receptor, FGF-2 can only stimulate a transient phosphorylation of p42/44 MAPK and so cannot stimulate DNA synthesis. Here we demonstrate that this is because in the absence of HS, FGF-2 fails to stimulate the phosphorylation of the adaptor FGFR substrate 2 (FRS2. In cells possessing the HS co-receptor, FGF-2 elicits a bell-shaped dose response: optimal concentrations stimulate DNA synthesis, but supramaximal concentrations (≥ 100 ng/mL have little effect. At optimal concentrations (300 pg/mL FGF-2 stimulates a sustained dual phosphorylation of p42/44 MAPK and tyrosine phosphorylation of FRS2. In contrast, 100 ng/mL FGF-2 only stimulates a transient early peak of p42/44 MAPK phosphorylation and fails to stimulate appreciably the phosphorylation of FRS2 on tyrosine. Conclusions These results suggest that the nature of the FGFR signal produced is determined by a combination of the HS co-receptor and the concentration of FGF ligand. Both the phosphorylation of the adaptor FRS2, the kinetics (sustained or transient of phosphorylation of p42/44(MAPK are varied, and so differing cellular responses are produced.

  17. Modulation of the endogenous production of protoporphyrin IX in a yeast-based model organism

    Science.gov (United States)

    Joniová, Jaroslava; Gerelli, Emmanuel; Wagnières, Georges

    2017-02-01

    The main aim of this study was to assess conditions at which simple yeast-based model organism produces maximal levels of protoporphyrin IX (PpIX) after an exogenous administration of its precursor, 5-aminolevulinic acid (ALA), and the ferrous-ion chelator 2,2'-bipyridyl. We observed that the fluorescing porphyrin, produced after these administrations, was likely to be PpIX since fluorescence spectroscopy of the porphyrins produced endogenously in yeast cells resembles that of PpIX in DMSO and in vivo in the chick's chorioallantoic membrane model. Also, fluorescence lifetimes of these porphyrins are very similar to that of PpIX in vitro and in vivo. This suggests that PpIX is the main fluorescent compound produced by yeast in our conditions. We found that the conditions at which yeast produces the maximal PpIX were a synchronous administration of 5 μM ALA and 1 mM 2,2'-bipyridyl for yeast incubated in aqueous glucose and 1 mM 2,2'-bipyridyl in the presence of YPD medium. Such a simple model is of high interest to study basic mechanisms involved in the mitochondrial respiration since PpIX, which is produced in this organelle, can be used as an oxygen sensor, or to perform photodynamic therapy and photodiagnosis. Since the absorption and scattering coefficients of this model are much smaller than those of soft tissues over the visible part of the spectrum, a version of this model loaded with appropriated amounts of light absorbing and scattering particles could be designed as a phantom to mimic tumors containing PpIX, a useful tool to optimize certain cancer photodetection set-ups.

  18. Hardware and Programmatic Progress on the Ares I-X Flight Test

    Science.gov (United States)

    Davis, Stephan R.

    2008-01-01

    In less than two years, the National Aeronautics and Space Administration (NASA) will execute the Ares I-X mission. This will be the first flight of the Ares I crew launch vehicle; which, together with the Ares V cargo launch vehicle (Figure 1), will eventually send humans to the Moon, Mars, and beyond. As the countdown to this first Ares mission continues, personnel from across the Ares I-X Mission Management Office (MMO) are finalizing designs and, in some cases, already fabricating vehicle hardware in preparation for an April 2009 launch. This paper will discuss the hardware and programmatic progress of the Ares I-X mission.

  19. Ares I-X Flight Test--The Future Begins Here

    Science.gov (United States)

    Davis, Stephan R.; Tuma, Margaret L.; Heitzman, Keith

    2007-01-01

    In less than two years, the National Aeronautics and Space Administration (NASA) will launch the Ares I-X mission. This will be the first flight of the Ares I crew launch vehicle, which, together with the Ares V cargo launch vehicle, will eventually send humans to the Moon, Mars, and beyond. As the countdown to this first Ares mission continues, personnel from across the Ares I-X Mission Management Office (MMO) are finalizing designs and fabricating vehicle hardware for a 2009 launch. This paper will discuss the hardware and programmatic progress of the Ares I-X mission.

  20. An immunohistochemical study of the expression of the hypoxia markers Glut-1 and Ca-IX in canine sarcomas.

    Science.gov (United States)

    Abbondati, E; Del-Pozo, J; Hoather, T M; Constantino-Casas, F; Dobson, J M

    2013-11-01

    Tumor hypoxia has been associated with increased malignancy, likelihood of metastasis, and increased resistance to radiotherapy and chemotherapy in human medicine. Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that is induced by tumor hypoxia and regulates the pathways involved in cellular response and adaptation to the hostile tumor microenvironment. HIF-1 induces transcription of different proteins, including Ca-IX and Glut-1, which are considered endogenous markers of chronic hypoxia in solid tumors in humans. In this study, sections from 40 canine sarcomas (20 histiocytic sarcomas and 20 low-grade soft-tissue sarcomas) were immunostained for these markers. Expression of Glut-1 was scored based on percentage of positive staining cells (0 = 50%) and intensity of cellular staining (1 = weak; 2 = strong); Ca-IX was scored based on percentage of positive cells (0 = 30%). Intratumoral microvessel density was measured using CD31 to assess intratumoral neoangiogenesis. Histiocytic sarcomas showed statistically significant higher Glut-1 immunoreactivity and angiogenesis than did low-grade soft-tissue sarcomas. Intratumoral microvessel density in histiocytic sarcomas was positively associated with Glut-1 immunoreactivity score. These findings suggest a potential role of hypoxia in the biology of these tumors and may provide a base for investigation of the potential prognostic use of these markers in naturally occurring canine tumors.

  1. Organic aerosol concentration and composition over Europe: insights from comparison of regional model predictions with aerosol mass spectrometer factor analysis

    Directory of Open Access Journals (Sweden)

    C. Fountoukis

    2014-03-01

    Full Text Available A detailed three-dimensional regional chemical transport model (PMCAMx was applied over Europe focusing on the formation and chemical transformation of organic matter. Three periods representative of different seasons were simulated, corresponding to intensive field campaigns. An extensive set of AMS measurements was used to evaluate the model and, using factor analysis results, gain more insight into the sources and transformations of organic aerosol (OA. Overall, the agreement between predictions and measurements for OA concentration is encouraging with the model reproducing two thirds of the data (daily average mass concentrations within a factor of two. Oxygenated OA (OOA is predicted to contribute 93% to total OA during May, 87% during winter and 96% during autumn with the rest consisting of fresh primary OA (POA. Predicted OOA concentrations compare well with the observed OOA values for all periods with an average fractional error of 0.53 and a bias equal to −0.07 (mean error = 0.9 μg m−3, mean bias = −0.2 μg m−3. The model systematically underpredicts fresh POA in most sites during late spring and autumn (mean bias up to −0.8 μg m−3. Based on results from a source apportionment algorithm running in parallel with PMCAMx, most of the POA originates from biomass burning (fires and residential wood combustion and therefore biomass burning OA is most likely underestimated in the emission inventory. The model performs well at all sites when the PMF-estimated low volatility OOA is compared against the OA with C* ≤ 0.1 μg m−3 and semivolatile OOA against the OA with C* > 0.1 μg m−3 respectively.

  2. Inflammation but not obesity or insulin resistance is associated with increased plasma fibroblast growth factor 23 concentration in the elderly.

    Science.gov (United States)

    Holecki, Michał; Chudek, Jerzy; Owczarek, Aleksander; Olszanecka-Glinianowicz, Magdalena; Bożentowicz-Wikarek, Maria; Duława, Jan; Mossakowska, Małgorzata; Zdrojewski, Tomasz; Skalska, Anna; Więcek, Andrzej

    2015-06-01

    Fibroblast growth factor 23 (FGF23) is a hormone involved in calcium-phosphate homoeostasis. The data of recently published studies suggest that FGF-23 may also play a role in some metabolic processes beyond mineral metabolism, such as insulin resistance or energy homoeostasis. The aim of the study was to attempt the relationships between plasma cFGF-23 (C-terminal) and iFGF-23 (intact) concentrations and the occurrence of obesity, insulin resistance and inflammation in elderly population. The analysis included 3115 elderly subjects (1485 women). During three visits, a questionnaire survey, comprehensive geriatric assessment and anthropometric measurements were performed as well as blood and urine samples were collected by trained nurses. Serum phosphorus, calcium, intact parathormone (iPTH), 25(OH)D3 , iFGF-23 and cFGF-23, insulin, glucose, albumin (also in urine), creatinine, hs-CRP, interleukin-6 and NT-proBNP concentrations were assessed. HOMA-IR was calculated according to the standard formula. Both forms of FGF23, iPTH and 25-OH-D3 levels were not related to the occurrence of obesity and insulin resistance. Increase in phosphorus, iPTH and NT-proBNP concentrations is associated with rise in plasma iFGF23 and cFGF23 levels. Additionally, increase in hs-CRP explained the elevated plasma iFGF23 levels. In multiple regression models, circulating iFGF23 and cFGF23 level's variability in elderly population were explained by changes in serum phosphorus, iPTH, eGFR, hs-CRP and NT-proBNP levels but not by BMI and HOMA-IR values. In conclusion, our study shows that increased levels of both circulating Fibroblast growth factor 23 forms in elderly subjects are associated with inflammation but not obesity or insulin resistance per se. © 2015 John Wiley & Sons Ltd.

  3. Micro-mechanics of fiber reinforced bounded and unbounded solids: effective local and non-local thermo-elastic properties, stress concentration factors, and edge effect

    Science.gov (United States)

    2005-07-01

    thermo-elastic properties, stress concentration factors, and edge effect 5. FUNDING NUMBERS FA8655-05-1-5008 6. AUTHOR(S) 7...unbounded solids, Thermo-elastic properties, Stress concentration factors, edge effect , Non-linear elastic stress, Inclusion-reinforced materials...factors, and edge effect Project manager: Maslov Borys Petrovich, Dr. Sc. in Physics and Mathematics Phone: +380-44-454-7764, Fax: –, E-mail

  4. Controlling Factors of Long-Term Trends in Mercury Wet Deposition and Precipitation Concentrations at Huntington Wildlife Forest

    Science.gov (United States)

    Ye, Z.; Mao, H.; Driscoll, C. T.

    2015-12-01

    Observations from the Mercury Deposition Network (MDN) at Huntington Wildlife Forest (HWF) suggested that a significant decline (r2 = 0.34, p = 0.03) from 2000 to 2013 in volume weighted mean (VWM) Hg concentrations in precipitation was linked to Hg emission decreases in the United States, especially in the Northeast and Midwest, and yet Hg wet deposition has remained fairly constant over the past two decades. The present study aimed to investigate the climatic, terrestrial, and anthropogenic factors that influenced the decadal pattern in Hg wet deposition in upstate NY. In spring and summer, when Hg wet deposition was the strongest, significant positive correlation (r2 = 0.89, p < 0.0001 in spring; r2 = 0.58, p = 0.002 in summer) of Hg wet deposition with precipitation was found. Increases in precipitation during these seasons could offset the decreasing of Hg concentration in precipitation. Besides, springtime positive correlation (r2 = 0.35, p = 0.02) between precipitation and the North Atlantic Oscillation (NAO) index together with geopotential height and wind speed analysis indicated that large-scale dynamical forcing was likely an important factor influencing the long term trend in springtime Hg wet deposition at HWF. To further quantify the roles of meteorological and anthropogenic factors in Hg wet deposition, the Community Multiscale Air Quality (CMAQ) model was employed using an algorithm depicting state-of-the-art Hg chemistry mechanism and up-to-date Hg emission inventories evaluated with MDN and Atmospheric Mercury Network (AMNet) measurement data. CMAQ simulations with a constant vs. realistic meteorological conditions for multiple warm seasons (including spring and summer) were used to characterize and quantify the impacts of inter-annual variability of precipitation and atmospheric circulation on Hg wet deposition. In addition, contributions to Hg wet deposition from decreases in anthropogenic emissions in NYS and nation-wide were quantified from

  5. Urinary concentrations of parabens and their association with demographic factors: A population-based cross-sectional study.

    Science.gov (United States)

    Kang, Hui-Seung; Kyung, Min-Sik; Ko, Ahra; Park, Jae-Hong; Hwang, Myung-Sil; Kwon, Ji-Eun; Suh, Jin-Hyang; Lee, Hee-Seok; Moon, Gui Im; Hong, Jin-Hwan; Hwang, In Gyun

    2016-04-01

    Parabens are broad-spectrum antimicrobial agents used in a range of consumer products, including personal care products, cosmetics, and food. Recently, the widespread use of parabens has raised concerns about the potential health risks associated with their endocrine-disrupting effect. In the present study, 2541 urine samples were collected and analyzed by liquid chromatography-mass spectrometry for the determination of the concentrations of methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP) and butyl paraben (BuP). The detection rate and geometric mean concentrations of parabens in the general population followed the order MeP (97.7%; 116ng/mL)>EtP (97.2%; 24.7ng/mL)>PrP (96.7%; 11.0ng/mL)>BuP (83.5%; 1.13ng/mL). The composition profiles showed that MeP and EtP accounted for >90% of the urinary paraben concentration. We performed statistical analysis in order to evaluate differences between demographic variables and urinary concentrations. Our results showed that adjusted proportional change of MeP, PrP, and BuP in adults were 2.67-6.13 times higher in females than in males. The urinary concentrations of PrP in adults increased significantly with age. The adjusted proportional changes of MeP and PrP in adults were associated with increased body mass index (BMI). The adjusted proportional changes of BuP and PrP in children and adolescents were 1.44 and 1.69 times higher in females than in males. However, there was no clear association between paraben concentrations and demographic variables in the children and adolescents groups. The estimated daily intake (EDIurine) of MeP and EtP in adults were 301μg/kg bw/day, which is lower than the acceptable daily intake (ADI; 10mg/kg bw/day). In summary, our results revealed that the general population in Korea was exposed to parabens during 2009-2010, and most Koreans are exposed to parabens. The urinary levels of parabens varied by age group with demographic factors in the Korean population. The results of

  6. Catchment process affecting drinking water quality, including the significance of rainfall events, using factor analysis and event mean concentrations.

    Science.gov (United States)

    Cinque, Kathy; Jayasuriya, Niranjali

    2010-12-01

    To ensure the protection of drinking water an understanding of the catchment processes which can affect water quality is important as it enables targeted catchment management actions to be implemented. In this study factor analysis (FA) and comparing event mean concentrations (EMCs) with baseline values were techniques used to asses the relationships between water quality parameters and linking those parameters to processes within an agricultural drinking water catchment. FA found that 55% of the variance in the water quality data could be explained by the first factor, which was dominated by parameters usually associated with erosion. Inclusion of pathogenic indicators in an additional FA showed that Enterococcus and Clostridium perfringens (C. perfringens) were also related to the erosion factor. Analysis of the EMCs found that most parameters were significantly higher during periods of rainfall runoff. This study shows that the most dominant processes in an agricultural catchment are surface runoff and erosion. It also shows that it is these processes which mobilise pathogenic indicators and are therefore most likely to influence the transport of pathogens. Catchment management efforts need to focus on reducing the effect of these processes on water quality.

  7. Trends in black carbon and size-resolved particle number concentrations and vehicle emission factors under real-world conditions

    Science.gov (United States)

    Krecl, Patricia; Johansson, Christer; Targino, Admir Créso; Ström, Johan; Burman, Lars

    2017-09-01

    Kerbside concentrations of NOx, black carbon (BC), total number of particles (diameter > 4 nm) and number size distribution (28-410 nm) were measured at a busy street canyon in Stockholm in 2006 and 2013. Over this period, there was an important change in the vehicle fleet due to a strong dieselisation process of light-duty vehicles and technological improvement of vehicle engines. This study assesses the impact of these changes on ambient concentrations and particle emission factors (EF). EF were calculated by using a novel approach which combines the NOx tracer method with positive matrix factorisation (PMF) applied to particle number size distributions. NOx concentrations remained rather constant between these two years, whereas a large decrease in particle concentrations was observed, being on average 60% for BC, 50% for total particle number, and 53% for particles in the range 28-100 nm. The PMF analysis yielded three factors that were identified as contributions from gasoline vehicles, diesel fleet, and urban background. This separation allowed the calculation of the average vehicle EF for each particle metric per fuel type. In general, gasoline EF were lower than diesel EF, and EF for 2013 were lower than the ones derived for 2006. The EFBC decreased 77% for both gasoline and diesel fleets, whereas the particle number EF reduction was higher for the gasoline (79%) than for the diesel (37%) fleet. Our EF are consistent with results from other on-road studies, which reinforces that the proposed methodology is suitable for EF determination and to assess the effectiveness of policies implemented to reduce vehicle exhaust emissions. However, our EF are much higher than EF simulated with traffic emission models (HBEFA and COPERT) that are based on dynamometer measurements, except for EFBC for diesel vehicles. This finding suggests that the EF from the two leading models in Europe should be revised for BC (gasoline vehicles) and particle number (all vehicles

  8. Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (A-PRF), and concentrated growth factors (CGF).

    Science.gov (United States)

    Masuki, Hideo; Okudera, Toshimitsu; Watanebe, Taisuke; Suzuki, Masashi; Nishiyama, Kazuhiko; Okudera, Hajime; Nakata, Koh; Uematsu, Kohya; Su, Chen-Yao; Kawase, Tomoyuki

    2016-12-01

    The development of platelet-rich fibrin (PRF) drastically simplified the preparation procedure of platelet-concentrated biomaterials, such as platelet-rich plasma (PRP), and facilitated their clinical application. PRF's clinical effectiveness has often been demonstrated in pre-clinical and clinical studies; however, it is still controversial whether growth factors are significantly concentrated in PRF preparations to facilitate wound healing and tissue regeneration. To address this matter, we performed a comparative study of growth factor contents in PRP and its derivatives, such as advanced PRF (A-PRF) and concentrated growth factors (CGF). PRP and its derivatives were prepared from the same peripheral blood samples collected from healthy donors. A-PRF and CGF preparations were homogenized and centrifuged to produce extracts. Platelet and white blood cell counts in A-PRF and CGF preparations were determined by subtracting those counts in red blood cell fractions, supernatant acellular serum fractions, and A-PRF/CGF exudate fractions from those counts of whole blood samples. Concentrations of growth factors (TGF-β1, PDGF-BB, VEGF) and pro-inflammatory cytokines (IL-1β, IL-6) were determined using ELISA kits. Compared to PRP preparations, both A-PRF and CGF extracts contained compatible or higher levels of platelets and platelet-derived growth factors. In a cell proliferation assay, both A-PRF and CGF extracts significantly stimulated the proliferation of human periosteal cells without significant reduction at higher doses. These data clearly demonstrate that both A-PRF and CGF preparations contain significant amounts of growth factors capable of stimulating periosteal cell proliferation, suggesting that A-PRF and CGF preparations function not only as a scaffolding material but also as a reservoir to deliver certain growth factors at the site of application.

  9. Pain during photodynamic therapy is associated with protoporphyrin IX fluorescence and fluence rate

    DEFF Research Database (Denmark)

    Wiegell, S.R.; Skiveren, J.; Philipsen, P.A.;

    2008-01-01

    and protoporphyrin IX (PpIX) fluorescence, lesion type, lesion preparation and lesion localization. Methods Twenty-six patients with actinic keratoses (AKs) in different localizations and 34 patients with facial acne vulgaris were treated with methyl aminolaevulinate-PDT. Patients with acne were illuminated using......) patients with acne had a pain score of 6 [interquartile range (IQR) 5-7] compared with 8 (IQR 6-10) when using a fluence rate of 68 mW cm(-2) (P = 0.018). After correcting the pain score for PpIX fluorescence no differences in pain scores were found between first and second acne treatment, locations of AK...... lesions or between the two types of lesions. Conclusions Pain during PDT was correlated with the PpIX fluorescence in the treatment area prior to illumination. Pain was reduced using a lower fluence rate during PDT of acne Udgivelsesdato: 2008/4...

  10. 11. IX toimus Rotermanni soolalaos happening "Olematute bändide festival"

    Index Scriptorium Estoniae

    2002-01-01

    Kiwa raamatu "Lastehaiglast põgenenud mänguasjad" (koostaja Hasso Krull, kujundaja Peeter Laurits, kaanel modell Eleonora Kampe ja Kiwa) ja sound-art-projektide esitlus. 12. IX Kiwa ja Andres Lõo loeng

  11. Evaluation of Sonochemiluminescence in a Phantom in the Presence of Protoporphyrin IX Conjugated to Nanoparticles

    Directory of Open Access Journals (Sweden)

    Ahmad Shanei

    2012-03-01

    Full Text Available Introduction When a liquid is irradiated with high-intensity and low-frequency ultrasound, acoustic cavitation occurs and there are some methods to determine and quantify this phenomenon. The existing methods for performing these experiments include sonochemiluminescence (SCL and chemical dosimetric methods. The particles in a liquid decrease the ultrasonic intensity threshold needed for cavitation onset. In this study, a new nanoconjugate made up of Protoporphyrin IX (PpIX and gold nanoparticles (GNP, i.e., Au-PpIX was used to provide nucleation sites for cavitation. The nonradiative relaxation time of PpIX in the presence of GNPs is longer than the similar time for PpIX without GNPs. This effect can be used in medical diagnostic and therapeutic applications. Materials and Methods The acoustic cavitation activity was investigated studying integrated SCL signal in the wavelength range of 400-500 nm in polyacrylamide gel phantom containing luminol using a cooled CCD spectrometer at different intensities of 1 MHz ultrasound. In order to confirm these results, a chemical dosimetric method was utilized, too. Results SCL signal level in gel phantom containing Au-PpIX was higher than the other phantoms. These results have been confirmed by the chemical dosimetric data. Conclusion This finding can be related to the existence of PpIX as a sensitizer and GNPs as cavitation nuclei. In other words, nanoparticles have acted as the sites for cavitation and have increased the cavitation rate. Another theory is that activation of PpIX has produced more free radicals and has enhanced the SCL signal level.

  12. Acute hyperinsulinemia is followed by increased serum concentrations of fibroblast growth factor 23 in type 2 diabetes patients

    DEFF Research Database (Denmark)

    Winther, Kristian; Nybo, Mads; Vind, Birgitte

    2012-01-01

    Background. Phosphate homeostasis is connected to glucose metabolism and is influenced by insulin, but the role of fibroblast growth factor 23 (FGF23) is unknown in this relation. Therefore, the levels of FGF23 and phosphate were investigated during a euglycemic-hyperinsulinemic clamp in healthy......)) to determine glucose disposal rates. Blood samples for measurement of serum FGF23 and insulin, plasma phosphate and glucose, and HbA(1c) were drawn before and after insulin infusion. Results. The three groups did not differ in baseline levels of serum FGF23. Insulin infusion increased serum FGF23...... in the diabetic group (p = 0.009), but not in the other groups. The increase in serum FGF23 correlated strongly with increase in insulin levels in the diabetic group (r = 0.83; p = 0.003). In the overall group insulin infusion suppressed plasma phosphate concentrations (p = 0.006), but with no differences between...

  13. The protein concentration of blood coagulation factor VII can be measured equally well in plasma and serum

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Overgaard, K; Gram, J

    1995-01-01

    In the Northwick Park Heart Study, the coagulant activity of factor VII (FVII:C) has been identified as a risk marker of ischaemic heart disease. In the fasting state, the protein concentration of FVII (FVII:Ag) might be an even better risk marker, because of the low coefficient of variation...... samples. Results were compared by means of linear regression, where y = 0.984 x +0.770, r = 0.96. No systematic variation existed between FVII:Ag in plasma and serum. The mean difference in FVII:Ag between plasma and serum was -1.17 (SD 11.92) arbitrary units, compared with a mean difference of 0.18 (SD 8.......31) arbitrary units between duplicate measurements of the same plasma dilution. Our findings indicate that there is a good agreement between FVII:Ag in plasma and serum. Udgivelsesdato: 1995-May...

  14. Significant Microsynteny with New Evolutionary Highlights Is Detected through Comparative Genomic Sequence Analysis of Maize CCCH IX Gene Subfamily

    Directory of Open Access Journals (Sweden)

    Wei-Jun Chen

    2015-01-01

    Full Text Available CCCH zinc finger proteins, which are characterized by the presence of three cysteine residues and one histidine residue, play important roles in RNA processing in plants. Subfamily IX CCCH proteins were recently shown to function in stress tolerances. In this study, we analyzed CCCH IX genes in Zea mays, Oryza sativa, and Sorghum bicolor. These genes, which are almost intronless, were divided into four groups based on phylogenetic analysis. Microsynteny analysis revealed microsynteny in regions of some gene pairs, indicating that segmental duplication has played an important role in the expansion of this gene family. In addition, we calculated the dates of duplication by Ks analysis, finding that all microsynteny blocks were formed after the monocot-eudicot divergence. We found that deletions, multiplications, and inversions were shown to have occurred over the course of evolution. Moreover, the Ka/Ks ratios indicated that the genes in these three grass species are under strong purifying selection. Finally, we investigated the evolutionary patterns of some gene pairs conferring tolerance to abiotic stress, laying the foundation for future functional studies of these transcription factors.

  15. Tumor necrosis factor-alpha concentration in the aqueous humor of healthy and diseased dogs: a preliminary pilot study.

    Science.gov (United States)

    Durieux, P; Etchepareborde, S; Fritz, D; Rosolen, S G

    2015-04-01

    To determine reference values of tumor necrosis factor-alpha (TNF-α) concentrations in the aqueous humor of control dogs. To show whether these values are significantly different from those obtained in dogs affected with intraocular pathology: acute anterior uveitis (AAU) or chronic primary angle closure glaucoma (PACG). Forty-four dogs were included in the study and were divided into two groups: a control group and a group with intraocular disease. Twenty-seven dogs (9 males and 18 females) were examined and found to be normal after a complete ophthalmological examination (control group), 7 (6 females and 1 male) presented with PACG, and 10 (7 females and 3 males) presented with AAU secondary to corneal perforation. One aqueous humor sample (volume ≥ 0.2 mL) was collected from one eye of all dogs. The aqueous TNF-α concentration was determined with an Elisa kit. TNF-α levels were detectable in all dogs. TNF-α levels were significantly higher in the group with intraocular disease compared to the normal control group (P=0.001). In the group with intraocular disease, TNF-α levels were significantly higher in the aqueous humor of the AAU group compared with the PACG group (P=0.001). In the dog, it is possible to measure the concentration of TNF-α in the aqueous humor. The level of TNF-α was significantly higher in the case of AAU. TNF-α is an interesting biomarker for longitudinal follow-up studies of comparative ophthalmology. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. (137)Cs inter-plant concentration ratios provide a predictive tool for coral atolls with distinct benefits over transfer factors.

    Science.gov (United States)

    Robison, William L; Hamilton, Terry F; Bogen, Kenneth T; Conrado, Cynthia L; Kehl, Steven R

    2008-01-01

    Inter-plant concentration ratios (IPCR) [Bqg(-1)(137)Cs in coral atoll tree food crops/Bqg(-1)(137)Cs in leaves of native plant species whose roots share a common soil volume] can replace transfer factors (TF) to predict (137)Cs concentration in tree food crops in a contaminated area with an aged source term. The IPCR strategy has significant benefits relative to TF strategy for such purposes in the atoll ecosystem. IPCR strategy applied to specific assessments takes advantage of the fact that tree roots naturally integrate (137)Cs over large volumes of soil. Root absorption of (137)Cs replaces large-scale, expensive soil sampling schemes to reduce variability in (137)Cs concentration due to inhomogeneous radionuclide distribution. IPCR [drinking-coconut meat (DCM)/Scaevola (SCA) and Tournefortia (TOU) leaves (native trees growing on all atoll islands)] are log-normally distributed (LND) with geometric standard deviation (GSD)=1.85. TF for DCM from Enewetak, Eneu, Rongelap and Bikini Atolls are LND with GSDs of 3.5, 3.0, 2.7, and 2.1, respectively. TF GSD for Rongelap copra coconut meat is 2.5. IPCR of Pandanus fruit to SCA and TOU leaves are LND with GSD=1.7 while TF GSD is 2.1. Because IPCR variability is much lower than TF variability, relative sampling error of an IPCR field sample mean is up 6- to 10-fold lower than that of a TF sample mean if sample sizes are small (10-20). Other IPCR advantages are that plant leaf samples are collected and processed in far less time with much less effort and cost than soil samples.

  17. 137Cs Inter-Plant Concentration Ratios Provide a Predictive Tool for Coral Atolls with Distinct Benefits Over Transfer Factors

    Energy Technology Data Exchange (ETDEWEB)

    Robison, W L; Hamilton, T F; Bogen, K; Corado, C L; Kehl, S R

    2007-07-17

    Inter-plant concentration ratios (IPCR), [Bq g{sup -1} {sup 137}Cs in coral atoll tree food-crops/Bq g{sup -1} {sup 137}Cs in leaves of native plant species whose roots share a common soil volume], can replace transfer factors (TF) to predict {sup 137}Cs concentration in tree food-crops in a contaminated area with an aged source term. The IPCR strategy has significant benefits relative to TF strategy for such purposes in the atoll ecosystem. IPCR strategy applied to specific assessments takes advantage of the fact tree roots naturally integrate 137Cs over large volumes of soil. Root absorption of {sup 137}Cs replaces large-scale, expensive soil sampling schemes to reduce variability in {sup 137}Cs concentration due to inhomogeneous radionuclide distribution. IPCR [drinking-coconut meat (DCM)/Scaevola (SCA) and Tournefortia (TOU) leaves (native trees growing on all atoll islands)] are log normally distributed (LND) with geometric standard deviation (GSD) = 1.85. TF for DCM from Enewetak, Eneu, Rongelap and Bikini Atolls are LND with GSD's of 3.5, 3.0, 2.7, and 2.1, respectively. TF GSD for Rongelap copra coconut meat is 2.5. IPCR of Pandanus fruit to SCA and TOU leaves are LND with GSD = 1.7 while TF GSD is 2.1. Because IPCR variability is much lower than TF variability, relative sampling error of an IPCR field sample mean is up 6- to 10-fold lower than that of a TF sample mean if sample sizes are small (10 to 20). Other IPCR advantages are that plant leaf samples are collected and processed in far less time with much less effort and cost than soil samples.

  18. Biodistribution of protoporphyrin IX in female genital erosive lichen planus after topical application of hexaminolevulinate.

    Science.gov (United States)

    Helgesen, Anne Lise Ording; Gjersvik, Petter; Peng, Qian; Vasovic, Vlada; Pripp, Are Hugo; Jebsen, Peter; Tanbo, Tom; Warloe, Trond

    2014-06-01

    Genital erosive lichen planus (GELP) is a chronic inflammatory disease, in women characterized by painful vulvar and vaginal erosions. To prepare for a clinical trial on photodynamic treatment (PDT), we applied hexyl 5-aminolevulinate hydrochloride (HAL) in clinically normal and affected mucosa in 12 women with GELP using two different doses (6.25 or 50mg/ml). Biopsies were taken after 30 min and 3h. The biodistribution of HAL, measured as photoactive protoporphyrin IX (PpIX), was studied using non-invasive superficial fluorescence measurements and microscopic fluorescence photometry. More PpIX was detected after application of 12.5mg HAL than after 100mg, with large inter-individual variations. PpIX levels after 3h were overall higher than after 30 min. PpIX fluorescence was not detected in skin distant to the genital area. In conclusion, 6.25mg/ml HAL applied for 3h seems adequate for HAL absorption and conversion to PpIX in submucosal inflammatory and epithelial cells and can be used in a PDT trial of GELP.

  19. Activity of Gallium Meso- and Protoporphyrin IX against Biofilms of Multidrug-Resistant Acinetobacter baumannii Isolates

    Directory of Open Access Journals (Sweden)

    David Chang

    2016-03-01

    Full Text Available Acinetobacter baumannii is a challenging pathogen due to antimicrobial resistance and biofilm development. The role of iron in bacterial physiology has prompted the evaluation of iron-modulation as an antimicrobial strategy. The non-reducible iron analog gallium(III nitrate, Ga(NO33, has been shown to inhibit A. baumannii planktonic growth; however, utilization of heme-iron by clinical isolates has been associated with development of tolerance. These observations prompted the evaluation of iron-heme sources on planktonic and biofilm growth, as well as antimicrobial activities of gallium meso- and protoporphyrin IX (Ga-MPIX and Ga-PPIX, metal heme derivatives against planktonic and biofilm bacteria of multidrug-resistant (MDR clinical isolates of A. baumannii in vitro. Ga(NO33 was moderately effective at reducing planktonic bacteria (64 to 128 µM with little activity against biofilms (≥512 µM. In contrast, Ga-MPIX and Ga-PPIX were highly active against planktonic bacteria (0.25 to 8 µM. Cytotoxic effects in human fibroblasts were observed following exposure to concentrations exceeding 128 µM of Ga-MPIX and Ga-PPIX. We observed that the gallium metal heme conjugates were more active against planktonic and biofilm bacteria, possibly due to utilization of heme-iron as demonstrated by the enhanced effects on bacterial growth and biofilm formation.

  20. Antimicrobial Activity of Gallium Protoporphyrin IX against Acinetobacter baumannii Strains Displaying Different Antibiotic Resistance Phenotypes.

    Science.gov (United States)

    Arivett, Brock A; Fiester, Steven E; Ohneck, Emily J; Penwell, William F; Kaufman, Cynthia M; Relich, Ryan F; Actis, Luis A

    2015-12-01

    A paucity of effective, currently available antibiotics and a lull in antibiotic development pose significant challenges for treatment of patients with multidrug-resistant (MDR) Acinetobacter baumannii infections. Thus, novel therapeutic strategies must be evaluated to meet the demands of treatment of these often life-threatening infections. Accordingly, we examined the antibiotic activity of gallium protoporphyrin IX (Ga-PPIX) against a collection of A. baumannii strains, including nonmilitary and military strains and strains representing different clonal lineages and isolates classified as susceptible or MDR. Susceptibility testing demonstrated that Ga-PPIX inhibits the growth of all tested strains when cultured in cation-adjusted Mueller-Hinton broth, with a MIC of 20 μg/ml. This concentration significantly reduced bacterial viability, while 40 μg/ml killed all cells of the A. baumannii ATCC 19606(T) and ACICU MDR isolate after 24-h incubation. Recovery of ATCC 19606(T) and ACICU strains from infected A549 human alveolar epithelial monolayers was also decreased when the medium was supplemented with Ga-PPIX, particularly at a 40-μg/ml concentration. Similarly, the coinjection of bacteria with Ga-PPIX increased the survival of Galleria mellonella larvae infected with ATCC 19606(T) or ACICU. Ga-PPIX was cytotoxic only when monolayers or larvae were exposed to concentrations 16-fold and 1,250-fold higher than those showing antibacterial activity, respectively. These results indicate that Ga-PPIX could be a viable therapeutic option for treatment of recalcitrant A. baumannii infections regardless of the resistance phenotype, clone lineage, time and site of isolation of strains causing these infections and their iron uptake phenotypes or the iron content of the media.

  1. The association between preoperative concentration of soluble vascular endothelial growth factor, perioperative blood transfusion, and survival in patients with primary colorectal cancer

    DEFF Research Database (Denmark)

    Werther, K; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2001-01-01

    OBJECTIVE: To investigate a possible association between the preoperative concentration of soluble vascular endothelial growth factor (sVEGF), perioperative blood transfusion, and survival in patients operated on for colorectal cancer. DESIGN: Retrospective study. SETTING: University hospital...

  2. Patients', physicians', and pharmacists' preferences towards coagulation factor concentrates to treat haemophilia with inhibitors: results from the COHIBA Study.

    Science.gov (United States)

    Scalone, L; Mantovani, L G; Borghetti, F; Von Mackensen, S; Gringeri, A

    2009-03-01

    Despite modern highly efficacious technologies, there is still a lack of consensus on how to optimally treat haemophilia patients with inhibitors. The aim of the study was to evaluate preferences towards the characteristics of different coagulation factor concentrates for haemophilia inhibitors patients, from the perspective of patients or their caregivers, haematologists and pharmacists. A discrete choice study was conducted. Potential products were described with eight selected characteristics: perceived viral safety, risk of anamnestic response, possibility of undergoing major surgery, frequency of infusions in prophylaxis, number of infusions to stop bleeding, time to stop bleeding, time to pain recovery and cost. Participants received 16 pairs of potential products and chose from each pair the option they considered better. Data were analysed with a random-effects conditional logistic model. Totally 1614 observations were obtained from 37 patients/caregivers, 39 physicians and 25 pharmacists from Italy. Cost was the most important characteristic to every group. For patients/caregivers, the next most important factors were: risk of anamnestic response, possibility of undergoing major surgery and perceived viral safety. For physicians, the next most important characteristics were: risk of anamnestic response, number of infusions to stop bleeding and possibility of undergoing major surgery. For pharmacists, the next most important factors were: time to stop bleeding, time to pain recovery and possibility of undergoing major surgery. Decisions on treatments must take into account patients clinical needs; however, preferences can also play an important role in the choice and success of treatments. The results of this study could, therefore, help decision-makers to optimize the overall benefits of treatments.

  3. PG1058 Is a Novel Multidomain Protein Component of the Bacterial Type IX Secretion System

    Science.gov (United States)

    Veith, Paul D.; Butler, Catherine A.; Nor Muhammad, Nor A.; Chen, Yu-Yen; Slakeski, Nada; Peng, Benjamin; Zhang, Lianyi; Dashper, Stuart G.; Cross, Keith J.; Cleal, Steven M.; Moore, Caroline; Reynolds, Eric C.

    2016-01-01

    Porphyromonas gingivalis utilises the Bacteroidetes-specific type IX secretion system (T9SS) to export proteins across the outer membrane (OM), including virulence factors such as the gingipains. The secreted proteins have a conserved carboxy-terminal domain essential for type IX secretion that is cleaved upon export. In P. gingivalis the T9SS substrates undergo glycosylation with anionic lipopolysaccharide (A-LPS) and are attached to the OM. In this study, comparative analyses of 24 Bacteroidetes genomes identified ten putative novel components of the T9SS in P. gingivalis, one of which was PG1058. Computer modelling of the PG1058 structure predicted a novel N- to C-terminal architecture comprising a tetratricopeptide repeat (TPR) domain, a β-propeller domain, a carboxypeptidase regulatory domain-like fold (CRD) and an OmpA_C-like putative peptidoglycan binding domain. Inactivation of pg1058 in P. gingivalis resulted in loss of both colonial pigmentation and surface-associated proteolytic activity; a phenotype common to T9SS mutants. Immunoblot and LC-MS/MS analyses of subcellular fractions revealed T9SS substrates accumulated within the pg1058 mutant periplasm whilst whole-cell ELISA showed the Kgp gingipain was absent from the cell surface, confirming perturbed T9SS function. Immunoblot, TEM and whole-cell ELISA analyses indicated A-LPS was produced and present on the pg1058 mutant cell surface although it was not linked to T9SS substrate proteins. This indicated that PG1058 is crucial for export of T9SS substrates but not for the translocation of A-LPS. PG1058 is a predicted lipoprotein and was localised to the periplasmic side of the OM using whole-cell ELISA, immunoblot and LC-MS/MS analyses of subcellular fractions. The structural prediction and localisation of PG1058 suggests that it may have a role as an essential scaffold linking the periplasmic and OM components of the T9SS. PMID:27711252

  4. Bianchi IX dynamics in bouncing cosmologies: homoclinic chaos and the BKL conjecture

    Science.gov (United States)

    Maier, Rodrigo; Damião Soares, Ivano; Valentino Tonini, Eduardo

    2015-12-01

    We examine the dynamics of a Bianchi IX model with three scale factors on a 4-dim Lorentzian brane embedded in a 5-dim conformally flat empty bulk with a timelike extra dimension. The matter content is a pressureless perfect fluid restricted to the brane, with the embedding consistently satisfying the Gauss-Codazzi equations. The 4-dim Einstein equations on the brane reduce to a 6-dim Hamiltonian dynamical system with additional terms (due to the bulk-brane interaction) that avoid the singularity and implement nonsingular bounces in the model. We examine the complex Bianchi IX dynamics in its approach to the neighborhood of the bounce which replaces the cosmological singularity of general relativity. The phase space of the model presents (i) two critical points (a saddle-center-center and a center-center-center) in a finite region of phase space, (ii) two asymptotic de Sitter critical points at infinity, one acting as an attractor to late-time acceleration and (iii) a 2-dim invariant plane, which together organize the dynamics of the phase space. The saddle-center-center engenders in the phase space the topology of stable and unstable 4-dim cylinders R × S 3, where R is a saddle direction and S 3 is the center manifold of unstable periodic orbits, the latter being the nonlinear extension of the center-center sector. By a proper canonical transformation the degrees of freedom of the dynamics are separated into one degree connected with the expansion/contraction of the scales of the model, and two rotational degrees of freedom associated with the center manifold S 3. The typical dynamical flow is thus an oscillatory mode about the orbits of the invariant plane. The stable and unstable cylinders are spanned by oscillatory orbits about the separatrix towards the bounce, leading to the homoclinic transversal intersection of the cylinders, as shown numerically in two distinct simulations. The homoclinic intersection manifold has the topology of R × S 2 consisting of

  5. Comparison of the effect of calcium gluconate and batroxobin on the release of transforming growth factor beta 1 in canine platelet concentrates

    OpenAIRE

    Silva, Raul F; Carmona, Jorge U; Rezende, Cleuza MF

    2012-01-01

    Background The clinical use of autologous platelet concentrates (also known as platelet-rich plasma) on the field of regenerative therapy, in the last decade has been the subject of several studies especially in equine medicine and surgery. The objectives of this study was: 1) to describe and compare the cellular population in whole blood, lower fraction (A) and upper fraction (B) of platelet concentrates, 2) to measure and compare the transforming growth factor beta 1 (TGF-β1) concentration ...

  6. Insulin-like Growth Factor-I Concentration and Risk of Prostate Cancer : Results from the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Price, Alison J.; Allen, Naomi E.; Appleby, Paul N.; Crowe, Francesca L.; Travis, Ruth C.; Tipper, Sarah J.; Overvad, Kim; Gronbaek, Henning; Tjonneland, Anne; Johnsen, Nina Fons; Rinaldi, Sabina; Kaaks, Rudolf; Lukanova, Annie; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Andarakis, George; Palli, Domenico; Krogh, Vittorio; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, H. Bas; Argueelles, Marcial V.; Sanchez, Maria-Jose; Chirlaque, Maria-Dolores; Barricarte, Aurelio; Larranaga, Nerea; Gonzalez, Carlos A.; Stattin, Par; Johansson, Mattias; Khaw, Kay-Tee; Wareham, Nick; Gunter, Marc; Riboli, Elio; Key, Timothy

    2012-01-01

    Background: High circulating insulin-like growth factor-I (IGF-I) concentrations have been associated with increased risk for prostate cancer in several prospective epidemiological studies. In this study, we investigate the association between circulating IGF-I concentration and risk of prostate can

  7. EFFICACY AND SAFETY OF A MONOCLONAL PURIFIED FACTOR-VIII CONCENTRATE - 5-YEAR FOLLOW-UP IN PREVIOUSLY TREATED HIV-NEGATIVE HEMOPHILIACS

    NARCIS (Netherlands)

    SMID, WM; VANDERMEER, J; HALIE, MR

    1995-01-01

    The efficacy and safety of a monoclonal purified factor VIII concentrate (Hemofil M) were assessed in a historically controlled study in 22 HIV-negative patients with haemophilia A, previously treated with various concentrates. Data from 5 years of follow-up were compared with those from the precedi

  8. Prediagnostic circulating concentrations of plasma insulin-like growth factor-I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Perez-Cornago, Aurora; Appleby, Paul N.; Tipper, Sarah; Key, Timothy J.; Allen, Naomi E.; Nieters, Alexandra; Vermeulen, Roel; Roulland, Sandrine; Casabonne, Delphine; Kaaks, Rudolf; Fortner, Renee T.; Boeing, Heiner; Trichopoulou, Antonia; La Vecchia, Carlo; Klinaki, Eleni; Hansen, Louise; Tjønneland, Anne; Bonnet, Fabrice; Fagherazzi, Guy; Boutron-Ruault, Marie Christine; Pala, Valeria; Masala, Giovanna; Sacerdote, Carlotta; Peeters, Petra H.; Bueno-de-Mesquita, H. Bas; Weiderpass, Elisabete; Dorronsoro, Miren; Quirós, J. Ramón; Barricarte, Aurelio; Gavrila, Diana; Agudo, Antonio; Borgquist, Signe; Rosendahl, Ann H.; Melin, Beatrice; Wareham, Nick; Khaw, Kay Tee; Gunter, Marc; Riboli, Elio; Vineis, Paolo; Travis, Ruth C.

    2017-01-01

    Insulin-like growth factor (IGF)-I has cancer promoting activities. However, the hypothesis that circulating IGF-I concentration is related to risk of lymphoma overall or its subtypes has not been examined prospectively. IGF-I concentration was measured in pre-diagnostic plasma samples from a nested

  9. Efficacy and safety of a monoclonal purified factor-VIII concentrate - 5-year follow-up in previously treated HIV-negative hemophiliacs

    NARCIS (Netherlands)

    Smid, W. M.; van der Meer, J.; Halie, M. R.

    1995-01-01

    The efficacy and safety of a monoclonal purified factor VIII concentrate (Hemofil M) were assessed in a historically controlled study in 22 HIV-negative patients with haemophilia A, previously treated with various concentrates. Data from 5 years of follow-up were compared with those from the

  10. Protoporphyrin IX fluorescence for enhanced photodynamic diagnosis and photodynamic therapy in murine models of skin and breast cancer

    Science.gov (United States)

    Rollakanti, Kishore Reddy

    Protoporphyrin IX (PpIX) is a photosensitizing agent derived from aminolevulinic acid. PpIX accumulates specifically within target cancer cells, where it fluoresces and produces cytotoxic reactive oxygen species. Our aims were to employ PpIX fluorescence to detect squamous cell carcinoma (SCC) of the skin (Photodynamic diagnosis, PDD), and to improve treatment efficacy (Photodynamic therapy, PDT) for basal cell carcinoma (BCC) and cutaneous breast cancer. Hyperspectral imaging and a spectrometer based dosimeter system were used to detect very early SCC in UVB-irradiated murine skin, using PpIX fluorescence. Regarding PDT, we showed that low non-toxic doses of vitamin D, given before ALA application, increase tumor specific PpIX accumulation and sensitize BCC and breast cancer cells to ALA-PDT. These optical imaging methods and the combination therapy regimen (vitamin D and ALA-PDT) are promising tools for effective management of skin and breast cancer.

  11. Quantitative Analysis of Major Factors Affecting Black Carbon Transport and Concentrations in the Unique Atmospheric Structures of Urban Environment

    Science.gov (United States)

    Liang, Marissa Shuang

    Black carbon (BC) from vehicular emission in transportation is a principal component of particulate matters ≤ 2.5 mum (PM2.5). PM2.5 and other diesel emission pollutants (e.g., NOx) are regulated by the Clean Air Act (CAA) according to the National Ambient Air Quality standards (NAAQS). This doctoral dissertation details a study on transport behaviors of black carbon and PM2.5 from transportation routes, their relations with the atmospheric structure of an urban formation, and their relations with the use of biodiesel fuels. The results have implications to near-road risk assessment and to the development of sustainable transportation solutions in urban centers. The first part of study quantified near-roadside black carbon transport as a function of particulate matter (PM) size and composition, as well as microclimatic variables (temperature and wind fields) at the interstate highway I-75 in northern Cincinnati, Ohio. Among variables examined, wind speed and direction significantly affect the roadside transport of black carbon and hence its effective emission factor. Observed non-Gaussian dispersion occurred during low wind and for wind directions at acute angles or upwind to the receptors, mostly occurring in the morning hours. Meandering of air pollutant mass under thermal inversion is likely the driving force. In contrary, Gaussian distribution predominated in daytime of strong downwinds. The roles of urban atmospheric structure, wind fields, and the urban heat island (UHI) effects were further examined on pollutant dispersion and transport. Spatiotemporal variations of traffic flow, atmospheric structure, ambient temperature and PM2.5 concentration data from 14 EPA-certified NAAQS monitoring stations, were analyzed in relation to land-use in the Cincinnati metropolitan area. The results show a decade-long UHI effects with higher interior temperature than that in exurban, and a prominent nocturnal thermal inversion frequent in urban boundary layer. The

  12. Relating Magnetic Parameters to Heavy Metal Concentrations and Environmental Factors at Formosa Mine Superfund Site, Douglas County, OR

    Science.gov (United States)

    Upton, T. L.

    2016-12-01

    Advances in the field of environmental magnetism have led to exciting new applications for this field. Magnetic minerals are ubiquitous in the environment and tend to have an affinity for heavy metals. Hence, it has been demonstrated that magnetic properties are often significantly related to concentrations of heavy metals and other pollutants. As a result, magnetic techniques have been used as proxy for determining hot spots of several types of pollution produced from a diversity of anthropogenic sources. Magnetic measurements are non-destructive and relatively inexpensive compared to geochemical analyses. The utility of environmental magnetic methods varies widely depending on biological, chemical and physical processes that create and transform soils and sediments. Applications in the direction of mapping heavy metals have been studied and shown to be quite useful in countries such as China and India but to date, little research has been done in the US. As such, there is need to expand the scope of research to a wider range of soil types and land uses, especially within the US. This study investigates the application of environmental magnetic techniques to mapping of heavy metal concentrations at the Formosa Mine Superfund Site, an abandoned mine about 25 miles southwest of Roseburg, OR. The soils and sediment at this site are derived from pyrite-rich bedrock which is weak in terms of magnetic susceptibility. Using hotspot analysis, correlation and cluster analyses, interactions between metals and magnetic parameters are investigated in relation to environmental factors such as proximity to seeps and adits. Preliminary results suggest significant correlation of magnetic susceptibility with certain heavy metals, signifying that magnetic methods may be useful in mapping heavy metal hotspots at this site. Further analysis examines the relation of various land use differences in magnetic signatures obtained throughout the Cow Creek watershed.

  13. Design of a carbonic anhydrase IX active-site mimic to screen inhibitors for possible anticancer properties.

    Science.gov (United States)

    Genis, Caroli; Sippel, Katherine H; Case, Nicolette; Cao, Wengang; Avvaru, Balendu Sankara; Tartaglia, Lawrence J; Govindasamy, Lakshmanan; Tu, Chingkuang; Agbandje-McKenna, Mavis; Silverman, David N; Rosser, Charles J; McKenna, Robert

    2009-02-17

    Recently, a convincing body of evidence has accumulated suggesting that the overexpression of carbonic anhydrase isozyme IX (CA IX) in some cancers contributes to the acidification of the extracellular matrix, which in turn promotes the growth and metastasis of the tumor. These observations have made CA IX an attractive drug target for the selective treatment of certain cancers. Currently, there is no available X-ray crystal structure of CA IX, and this lack of availability has hampered the rational design of selective CA IX inhibitors. In light of these observations and on the basis of structural alignment homology, using the crystal structure of carbonic anhydrase II (CA II) and the sequence of CA IX, a double mutant of CA II with Ala65 replaced by Ser and Asn67 replaced by Gln has been constructed to resemble the active site of CA IX. This CA IX mimic has been characterized kinetically using (18)O-exchange and structurally using X-ray crystallography, alone and in complex with five CA sulfonamide-based inhibitors (acetazolamide, benzolamide, chlorzolamide, ethoxzolamide, and methazolamide), and compared to CA II. This structural information has been evaluated by both inhibition studies and in vitro cytotoxicity assays and shows a correlated structure-activity relationship. Kinetic and structural studies of CA II and CA IX mimic reveal chlorzolamide to be a more potent inhibitor of CA IX, inducing an active-site conformational change upon binding. Additionally, chlorzolamide appears to be cytotoxic to prostate cancer cells. This preliminary study demonstrates that the CA IX mimic may provide a useful model to design more isozyme-specific CA IX inhibitors, which may lead to development of new therapeutic treatments of some cancers.

  14. In vivo imaging and quantification of carbonic anhydrase IX expression as an endogenous biomarker of tumor hypoxia.

    Directory of Open Access Journals (Sweden)

    Bagna Bao

    Full Text Available Carbonic anhydrase IX (CA IX is a transmembrane protein that has been shown to be greatly upregulated under conditions of hypoxia in many tumor cell lines. Tumor hypoxia is associated with impaired efficacy of cancer therapies making CA IX a valuable target for preclinical and diagnostic imaging. We have developed a quantitative in vivo optical imaging method for detection of CA IX as a marker of tumor hypoxia based on a near-infrared (NIR fluorescent derivative of the CA IX inhibitor acetazolamide (AZ. The agent (HS680 showed single digit nanomolar inhibition of CA IX as well as selectivity over other CA isoforms and demonstrated up to 25-fold upregulation of fluorescent CA IX signal in hypoxic versus normoxic cells, which could be blocked by 60%-70% with unlabeled AZ. CA IX negative cell lines (HCT-116 and MDA-MB-231, as well as a non-binding control agent on CA IX positive cells, showed low fluorescent signal under both conditions. In vivo FMT imaging showed tumor accumulation and excellent tumor definition from 6-24 hours. In vivo selectivity was confirmed by pretreatment of the mice with unlabeled AZ resulting in >65% signal inhibition. HS680 tumor signal was further upregulated >2X in tumors by maintaining tumor-bearing mice in a low oxygen (8% atmosphere. Importantly, intravenously injected HS680 signal was co-localized specifically with both CA IX antibody and pimonidazole (Pimo, and was located away from non-hypoxic regions indicated by a Hoechst stain. Thus, we have established a spatial correlation of fluorescence signal obtained by non-invasive, tomographic imaging of HS680 with regions of hypoxia and CA IX expression. These results illustrate the potential of HS680 and combined with FMT imaging to non-invasively quantify CA IX expression as a hypoxia biomarker, crucial to the study of the underlying biology of hypoxic tumors and the development and monitoring of novel anti-cancer therapies.

  15. Chloride concentrations, loads, and yields in four watersheds along Interstate 95, southeastern Connecticut, 2008-11: factors that affect peak chloride concentrations during winter storms

    Science.gov (United States)

    Brown, Craig J.; Mullaney, John R.; Morrison, Jonathan; Martin, Joseph W.; Trombley, Thomas J.

    2015-07-01

    Chloride (Cl-) concentrations and loads and other water chemistry characteristics were assessed to evaluate potential effects of road-deicer applications on streamwater quality in four watersheds along Interstate 95 (I–95) in southeastern Connecticut from November 1, 2008, through September 30, 2011. Streamflow and water quality were studied in the Four Mile River, Oil Mill Brook, Stony Brook, and Jordan Brook watersheds, where developed land ranged from 9 to 32 percent. Water-quality samples were collected and specific conductance was measured continuously at paired water-quality monitoring sites, upstream and downstream from I–95. Specific conductance values were related to Cl- concentrations to assist in determining the effects of road-deicing operations on the levels of Cl-in the streams. Streamflow and water-quality data were compared with weather data and with the timing, amount, and composition of deicers applied to State highways. Grab samples were collected during winter stormwater-runoff events, such as winter storms or periods of rain or warm temperatures in which melting takes place. Grab samples were also collected periodically during the spring and summer and during base-flow conditions.

  16. Enhancing diterpenoid concentration in Salvia miltiorrhiza hairy roots through pathway engineering with maize C1 transcription factor.

    Science.gov (United States)

    Zhao, Shujuan; Zhang, Jinjia; Tan, Ronghui; Yang, Li; Zheng, Xiaoyu

    2015-12-01

    Tanshinones are valuable natural diterpenoids from danshen (Salvia miltiorrhiza Bunge). Here, it was demonstrated that maize transcription factor C1 improved the accumulation of tanshinones by comprehensively upregulating the pathway genes, especially SmMDC and SmPMK in danshen hairy roots, yielding total tanshinones up to 3.59mg g(-1) of dry weight in line C1-6, a 3.4-fold increase compared with the control. Investigation of 2024bp of the SmMDC promoter fragment revealed that C1-mediated upregulation of terpenoid genes was possibly due to the direct interaction of C1 with its recognition sequences. The increase of tanshinones was accompanied by a decrease of salvianolic acid production, the other bioactive ingredient in danshen, by up to 37% compared with the control. This was the result of the downregulation of SmTAT, the entry-point gene of the tyrosine pathway, which promoted metabolic flow to anthocyanins rather than to salvianolic acids. Based on the findings of the present study, it was concluded that cis-acting elements shared by terpenoid and phenylpropanoid biosynthetic genes are partially responsible for the C1-stimulated variation of tanshinone and salvianolic acid concentrations.

  17. Inlay osteotome sinus floor elevation with concentrated growth factor application and simultaneous short implant placement in severely atrophic maxilla

    Science.gov (United States)

    Chen, Yonghui; Cai, Zhiyu; Zheng, Dingguo; Lin, Pei; Cai, Yahua; Hong, Shuxin; Lai, Yiwei; Wu, Dong

    2016-01-01

    Sinus floor elevation with simultaneous implant placement in severely atrophic maxilla is challenging. The aim of this retrospective study was to evaluate the short-term performance of modified osteotome sinus floor elevation (OSFE) with concentrated growth factor (CGF) application and concurrent placement of a short implant in cases with residual bone height (RBH) of 2–4 mm. Twenty-five short implants were installed in 16 patients with mean RBH of 3.23 mm using modified OSFE with CGFs from January 2012 to April 2014. Postoperatively, the implants were clinically evaluated, and vertical bone gain (VBG) was measured using cone beam computed tomography. The mean duration of follow-up was 19.88 months (12–32 months). All the implants were stable with an overall survival rate of 100%. The mean VBG immediately after surgery was 9.21 mm. Six months later, significant reduction of alveolar bone height (2.90 ± 0.22 mm) was found (P  0.05). Within the limits of this study, modified OSFE with CGF application and simultaneous short implant placement could yield predictable clinical results for severely atrophic maxilla with RBH of 2–4 mm. PMID:27250556

  18. First trimester maternal serum placenta growth factor (PIGF)concentrations in pregnancies with fetal trisomy 21 or trisomy 18.

    Science.gov (United States)

    Spencer, K; Liao, A W; Ong, C Y; Geerts, L; Nicolaides, K H

    2001-09-01

    Placenta growth factor (PIGF), an angiogenic factor belonging to the vascular endothelial growth factor family, pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotrophin (beta-hCG) were measured in maternal serum from 45 pregnancies with trisomy 21, 45 with trisomy 18 and 493 normal controls at 10-13 completed weeks of gestation. In the normal pregnancies maternal serum PIGF levels increased exponentially with gestation. The median multiple of the median (MoM) PIGF concentration in the trisomy 21 group (1.26 MoM) was significantly higher (ptrisomy 18 group the median PIGF was lower (0.889 MoM) but this did not quite reach significance (p=0.064). The corresponding median MoM values for PAPP-A were 1.00 MoM for the controls, 0.49 MoM for trisomy 21 and 0.16 MoM for trisomy 18. The median MoM values for free beta-hCG were 1.00 MoM for the controls, 2.05 MoM for trisomy 21 and 0.38 MoM for trisomy 18. In the control group there was a small but significant correlation of PIGF with free beta-hCG (r=+0.1024) and PAPP-A (r=+0.2288). In the trisomy 18 group there was a significant association between PIGF and free beta-hCG (r=+0.2629) but not with PAPP-A (r=+0.0038). In the trisomy 21 group there was a small but significant association with PAPP-A (r=+0.1028) but not with free beta-hCG (r=+0.0339). The separation of affected and unaffected pregnancies in maternal serum PIGF is small, and therefore it is unlikely that measurement of PIGF would improve screening for these abnormalities provided by the combination of fetal nuchal translucency and maternal serum PAPP-A and free beta-hCG. Copyright 2001 John Wiley & Sons, Ltd.

  19. Curious Variables Experiment (CURVE). IX Draconis - a Clue for Understanding Evolution of Cataclysmic Variable Stars

    CERN Document Server

    Olech, A; Mularczyk, K; Kedzierski, P; Wisniewski, M; Stachowski, G

    2004-01-01

    We report extensive photometry of frequently outbursting dwarf nova IX Draconis. During five months of observations the star went into three superoutbursts and seven ordinary outbursts. This allowed us to determine its supercycle and cycle lengths as equal to 54 +/- 1 and 3.1 +/- 0.1 days, respectively. During the Sep 2003 superoutburst, which had the best observational coverage, IX Dra displayed clear superhumps with a period of Psh=0.066968(17) days. This period was constant during the whole superoutburst. Another period, which was clearly present in the light curve of IX Dra in superoutburst, had a value of 0.06646(6) days and we interpret it as the orbital period of the binary. Thus IX Dra is the first SU UMa star showing orbital modulation during the entire superoutburst. The beat between these two periods is the main cause of an unusual phase reversal of superhumps - a phenomenon which was previously observed in ER UMa. If our interpretation of the second periodicity is correct, IX Dra has an extremely ...

  20. Screening of a novel peptide targeting the proteoglycan-like region of human carbonic anhydrase IX.

    Science.gov (United States)

    Rana, Shoaib; Nissen, Felix; Lindner, Thomas; Altmann, Annette; Mier, Walter; Debus, Juergen; Haberkorn, Uwe; Askoxylakis, Vasileios

    2013-01-01

    The extracellular domain of human carbonic anhydrase IX (CA IX) is extended by a proteoglycan-like region (PGLR). The aim of the present study was the development of novel molecules with specificity for PGLR, which may be used for tumor targeting and imaging. PGLR was chemically synthesized, and phage display biopanning was performed. The identified ligand PGLR-P1 was labeled with 125I and characterized for target binding and metabolic stability. In vitro characterization included kinetic, competition, and internalization studies on CA IX-positive renal cell carcinoma SKRC 52 cells. The CA IX-negative cell lines HEK293 wt and BxPC3 were used as negative controls. In vitro binding experiments revealed an increasing affinity of 125I-PGLR-P1 to SKRC 52 cells but not to negative control HEK293 wt and BxPC3 cells. Internalization studies indicated an exclusive cell membrane binding. Biodistribution analysis demonstrated a higher accumulation in SKRC 52 tumors than in most normal tissues after perfusion. In vivo blocking led to a significant decrease in tumor uptake. Our findings indicate that PGLR-P1 is a promising lead structure for the development of new peptide-based ligands targeting the PGLR of CA IX and reveal challenges that need to be considered for peptide-related molecular imaging.

  1. Evaluation of the potential inhibitor of Ix (Pp-Ix) protoporphyrin of the genetic damage induced by gamma rays administered to different dose reasons in Drosophila melanogaster; Evaluacion del potencial inhibidor de la protoporfirina IX (PP-IX) del dano genetico inducido por rayos gama administrados a diferentes razones de dosis en Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Flores A, J. A.

    2016-10-01

    Ionizing radiation can damage in DNA directly or indirectly by free radicals (Rl), characterized by unstable and highly reactive. To avoid damage by Rl the cell has endogenous antioxidants such as Sod, Cat, GSH or exogenous as some vitamins, but if with these mechanisms does not reach the cell homeostasis, the consequence may be the generation of chronic-disease degenerative such as cancer. This study was conducted in order to test the inhibitory role of Rl protoporphyrin Ix (Pp-Ix), induced by 20 Gy of gamma rays administered at different dose ratios using the assay of somatic mutation and recombination in the Drosophila wing. The results indicated that 20 Gy delivered at a rate of low dose (6.659 Gy/h), caused elevated frequencies of genetic damage (p <0.001), compared with those that induced a high dose reason (1111.42 Gy/h) in larvae of 48 h old. The difference is probably due to an indirect damage by Rl; when this hypothesis was approved with the possible inhibitor role of Pp-Ix (0.69 m M), damage was increased with the two reasons of tested doses. This result may be due to: 1) the Pp-Ix is not a good inhibitor of Rl, 2) the difference in the frequency of mutation found with both dose reasons, not due to Rl so that this compound did not reduce the genetic damage, and 3) that Pp-Ix acts as pro oxidant. (Author)

  2. PREFACE: The IX Mexican Workshop on Particles and Fields

    Science.gov (United States)

    Amore, Paolo; Aranda, Alfredo; Bashir, Adnan; Mondragón, Myriam; Raya, Alfredo

    2006-05-01

    The IX Mexican Workshop on Particles and Fields was held in the beautiful city of Colima, in the South-West of Mexico, from 17-22 November 2003. The proceedings of the Workshop were delayed due to problems with a previous publisher, we are very grateful that Journal of Physics: Conference Series kindly agreed to publish the proceedings rapidly at this late stage. The Workshop aimed to cover, through invited lectures delivered by internationally known experts, the most recent developments in the field. There was also a series of short seminars as well as a poster session, which allowed the whole community to participate with their most recent research results. A special session was dedicated to awarding the Division Medal to Professor Benjamin Grinstein, from The University of California, San Diego, for his outstanding contributions to the field. This volume contains the written version of the material presented at the Workshop. The Workshop was attended by more than 100 participants, including faculty members, postdocs and graduate students. It was organized by the Particles and Fields Division of the Mexican Physical Society, and generously sponsored by several institutions: Universidad de Colima, Universidad Nacional Autónoma de México, Universidad Michoacana de San Nicolás Hidalgo, Centro de Investigaciones y Estudios Avanzados del IPN (CINVESTAV), Consejo Nacional de Ciencia y Tecnología (Conacyt). The Local Organizing Committee was integrated by Paolo Amore, Alfredo Aranda, Carlos Moisés Hernóndez Suórez (Director of the Physics Faculty), Arturo Gonzólez Larios, Enrique Farías Martínez, and Myriam Cruz Calvario, all from the University of Colima. The members of the National Organizing Committee were Adnan Bashir (IFM-UMSHN), Jens Erler (IF-UNAM), Heriberto Castilla Valdés (CINVESTAV-U.Zacatenco), Gabriel López Castro (CINVESTAV-U.Zacatenco), Myriam Mondragón (IF-UNAM) and Luis Villaseñ or (IFM-UMSHN). We gratefully acknowledge the help given by

  3. Effect of microfiltration concentration factor on serum protein removal from skim milk using spiral-wound polymeric membranes.

    Science.gov (United States)

    Beckman, S L; Barbano, D M

    2013-10-01

    Our objective was to determine the effect of concentration factor (CF) on the removal of serum protein (SP) from skim milk during microfiltration (MF) at 50 °C using a 0.3-μm-pore-size spiral-wound (SW) polymeric polyvinylidene fluoride (PVDF) membrane. Pasteurized (72°C for 16 s) skim milk was MF (50 °C) at 3 CF (1.50, 2.25, and 3.00×), each on a separate day of processing starting with skim milk. Two phases of MF were used at each CF, with an initial startup-stabilization phase (40 min in full recycle mode) to achieve the desired CF, followed by a steady-state phase (90-min feed-and-bleed with recycle) where data was collected. The experiment was replicated 3 times, and SP removal from skim milk was quantified at each CF. System pressures, flow rates, CF, and fluxes were monitored during the 90-min run. Permeate flux increased (12.8, 15.3, and 19.0 kg/m(2) per hour) with decreasing CF from 3.00 to 1.50×, whereas fouled water flux did not differ among CF, indicating that the effect of membrane fouling on hydraulic resistance of the membrane was similar at all CF. However, the CF used when microfiltering skim milk (50°C) with a 0.3-μm polymeric SW PVDF membrane did affect the percentage of SP removed. As CF increased from 1.50 to 3.00×, the percentage of SP removed from skim milk increased from 10.56 to 35.57%, in a single stage bleed-and-feed MF system. Percentage SP removal from skim milk was lower than the theoretical value. Rejection of SP during MF of skim milk with SW PVDF membranes was caused by fouling of the membrane, not by the membrane itself and differences in the foulant characteristic among CF influenced SP rejection more than it influenced hydraulic resistance. We hypothesize that differences in the conditions near the surface of the membrane and within the pores during the first few minutes of processing, when casein micelles pass through the membrane, influenced the rejection of SP because more pore size narrowing and plugging occurred at

  4. Body composition analysis and adipocytokine concentrations in haemodialysis patients: abdominal fat gain as an additional cardiovascular risk factor.

    Science.gov (United States)

    González, Elena; Díez, Juan J; Pérez Torres, Almudena; Bajo, María Auxiliadora; Del Peso, Gloria; Sánchez-Villanueva, Rafael; Grande, Cristina; Rodríguez, Olaia; Coronado, Mónica; Gómez Candela, Carmen; Díaz-Almirón, Mariana; Iglesias, Pedro; Selgas, Rafael

    Abdominal fat and its increment over time in particular has become a cardiovascular risk factor in uraemic patients. To analyse changes in abdominal fat in haemodialysis patients over one year and study their possible correlation with the variation in adipocytokine serum levels. As a secondary objective, we tried to validate the data obtained by bioelectrical impedance analysis (BIA) with data obtained by dual X-ray absorptiometry (DXA). A prospective one-year study was performed in 18 patients on haemodialysis (HD). In each patient, body composition by BIA and DXA was estimated at baseline and after one year. Several adipocytokine and biochemical parameters were determined. A significant increase in phase angle [4.8° (4.1-5.6) vs. 5.2° (4.4-5.8), P<.05], BIA intracellular water [48.3% (43.1-52.3) vs. 50.3% (45.7-53.4), P<.05] and the ratio between the percentage of android/gynecoid (A/G) distribution of fat measured by DXA [1.00 (0.80-1.26) vs. 1.02 (0.91-1.30), P<.05] was observed. A statistically significant relationship between leptin and adiponectin concentrations and the percentage of fat mass measured by BIA, as well as the abdominal fat percentage estimated by DXA, was found (P<.01). HD patients exhibit a gain in fat mass over time, especially in the abdomen, evidenced by an increased A/G ratio. These findings might explain the increased cardiovascular risk in these patients. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  5. Sex, Diet, and the Social Environment: Factors Influencing Hair Cortisol Concentration in Free-Ranging Black Bears (Ursus americanus.

    Directory of Open Access Journals (Sweden)

    Diana J R Lafferty

    Full Text Available Increasingly, measures of glucocorticoid levels (e.g., cortisol, key components of the neuroendocrine stress axis, are being used to measure past hypothalamic-pituitary-adrenal (HPA activity to index psychological and physiological stress exhibited by wildlife for assessing individual and population-level well-being. However, many intrinsic and extrinsic factors affect HPA activity in animals. Using American black bears (Ursus americanus; n = 116 as an ecological model and hair cortisol concentration (HCC as an integrative measure of past HPA activity, we evaluated the influence of diet, sex and the social environment on black bear HCC in a free-ranging population that spanned adjoining ecoregions with differing densities of potential conspecific and heterospecific competitors. HCC varied by sex, with female HCC ranging from 0.6 to 10.7 pg/mg (median = 4.5 ± 1.2 mean absolute deviation [MAD] and male HCC ranging from 0.5 to 35.1 pg/mg (median = 6.2 ± 2.6 MAD. We also observed a three-way interaction among sex, δ14C and ecoregion, which may indicate that some differences in HCC between female and male black bears results from variability in the nutritional needs of larger-bodied males relative to smaller-bodied females, slight differences in food resources use between ecoregions as well as sex-based differences regarding the social environment. Once we understand what drives sex-specific differences in HCC, HCC may aid our understanding of the physiological responses by bears and other wildlife to diverse environmental challenges.

  6. Loop quantum cosmology of Bianchi IX: Inclusion of inverse triad corrections

    Science.gov (United States)

    Corichi, Alejandro; Karami, Asieh

    2016-06-01

    We consider the loop quantization of the (diagonal) Bianchi type IX cosmological model. We explore different quantization prescriptions that extend the work of Wilson-Ewing and Singh. In particular, we study two different ways of implementing the so-called inverse triad corrections. We construct the corresponding Hamiltonian constraint operators and show that the singularity is formally resolved. We find the effective equations associated with the different quantization prescriptions, and study the relation with the isotropic k = 1 model that, classically, is contained within the Bianchi IX model. Somewhat surprisingly, we find the most natural quantization does not reduce to the k = 1 model. We use geometrically defined scalar observables to explore the physical implications of each of these theories. This is the first part in a series of papers analyzing different aspects of the Bianchi IX model, with inverse corrections, within loop quantum cosmology (LQC).

  7. Inhibition of carbonic anhydrase isoforms I, II, IX and XII with secondary sulfonamides incorporating benzothiazole scaffolds.

    Science.gov (United States)

    Petrou, Anthi; Geronikaki, Athina; Terzi, Emine; Guler, Ozen Ozensoy; Tuccinardi, Tiziano; Supuran, Claudiu T

    2016-12-01

    Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. A series of benzothiazole-based sulfonamides were synthesized and tested as possible CA inhibitors. Their inhibitory activity was assessed against the cytosolic human isoforms hCA I and hCA II and the transmembrane hCA IX and hCA XII. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting hCA IX and hCA XII over the off-target ones hCA I and hCA II. Furthermore, computational procedures were used to investigate the binding mode of this class of compounds, within the active site of hCA IX.

  8. Loop quantum cosmology of Bianchi IX: Inclusion of inverse triad corrections

    CERN Document Server

    Corichi, Alejandro

    2016-01-01

    We consider the loop quantization of the (diagonal) Bianchi type IX cosmological model. We explore different quantization prescriptions that extend the work of Wilson-Ewing and Singh. In particular, we study two different ways of implementing the so-called inverse triad corrections. We construct the corresponding Hamiltonian constraint operators and show that the singularity is formally resolved. We find the effective equations associated with the different quantization prescriptions, and study the relation with the isotropic $k$=1 model that, classically, is contained within the Bianchi IX model. We use geometrically defined scalar observables to explore the physical implications of each of these theories. This is the first part in a series of papers analyzing different aspects of the Bianchi IX model, with inverse corrections, within loop quantum cosmology.

  9. Anadromous char as an alternate food choice to marine animals: A synthesis of Hg concentrations, population features and other influencing factors

    Energy Technology Data Exchange (ETDEWEB)

    Evans, Marlene S., E-mail: marlene.evans@ec.gc.ca [Environment Canada, Water Science and Technology Directorate, 11 Innovation Blvd., Saskatoon SK S7N 3H5 (Canada); Muir, Derek C.G. [Environment Canada, Water Science and Technology Directorate, 867 Lakeshore Rd., Burlington, ON L7R 4A6 (Canada); Keating, Jonathan [Environment Canada, Water Science and Technology Directorate, 11 Innovation Blvd., Saskatoon SK S7N 3H5 (Canada); Wang, Xiaowa [Environment Canada, Water Science and Technology Directorate, 867 Lakeshore Rd., Burlington, ON L7R 4A6 (Canada)

    2015-03-15

    This study was conducted to confirm sporadic measurements made over the late 1970s to the early 1990s which determined that mercury (Hg) concentrations were low in anadromous char across Arctic and subarctic Canada including northern Québec and Labrador. Over 2004–2013, anadromous char populations across northern Canada were investigated at 20 sites for Hg concentrations and life history characteristics. Hg concentrations were extremely low in anadromous char muscle, typically < 0.05 μg/g (wet weight) and, at each location, generally increased with fish length, age and nitrogen isotope (δ{sup 15}N) ratio and decreased with condition factor and %lipid; correlations with carbon isotope (δ{sup 13}C) ratio were inconsistent. Location and year were significant variables influencing Hg concentrations over the study area; longitude and latitude also were significant influencing variables. Char length, weight, age, condition factor and lipid content explained additional variance. A tendency towards higher Hg concentrations with increasing latitude may be partially related to decreasing growth of char towards the north. However, Hg concentrations in char were positively correlated with growth rates suggesting that Hg concentrations in char also were higher in the more productive study areas, including to the west where mainland riverine inputs of terrestrial carbon, nutrients, and Hg were greater. The data base for assessing time trends in char was limited by the small number of years investigated at most locations, variable fish size across years, small sample size, etc. Where temporal trends were detected, they were of increase on the long term (1970s, 1980s or early 1990s to the present) but of decrease on the short term (early 2000s to present) with Nain (Labrador) showing the converse pattern. Higher Hg concentrations were also related to lower condition factor and cooler springs. Hg concentrations in anadromous char are compared with other terrestrial, aquatic

  10. Comparison of the effect of calcium gluconate and batroxobin on the release of transforming growth factor beta 1 in canine platelet concentrates

    OpenAIRE

    Silva Raul F; Carmona Jorge U; Rezende Cleuza MF

    2012-01-01

    Abstract Background The clinical use of autologous platelet concentrates (also known as platelet-rich plasma) on the field of regenerative therapy, in the last decade has been the subject of several studies especially in equine medicine and surgery. The objectives of this study was: 1) to describe and compare the cellular population in whole blood, lower fraction (A) and upper fraction (B) of platelet concentrates, 2) to measure and compare the transforming growth factor beta 1 (TGF-β1) conce...

  11. IX Jornades d’educació emocional. Educació emocional i valors

    OpenAIRE

    Barredo Gutiérrez, Blanca; Bisquerra Alzina, Rafael; Blanco Cuch, Aida; Giner, Antoni; Pérez Escoda, Núria; Tey, Amèlia

    2013-01-01

    Barredo Gutierrez, B.; Bisquerra Alzina, R.; Blanco Cuch, A.; Giner Tarrida, A.; Perez Escoda, N.; Tey Teijón, A. (eds.) IX Jornades d’educació emocional. Educació emocional i valors / IX Jornadas de educación emocional. Educación emocional y valores. Barcelona, Universitat de Barcelona (Institut de Ciències de l’Educació), 2013. Document electrònic.valores. Barcelona, Universitat de Barcelona (Institut de Ciències de l’Educació), 2013. Document electrònic

  12. Multilevel analysis of the impact of environmental factors and agricultural practices on the concentration in hay of microorganisms responsible for farmer's lung disease.

    Science.gov (United States)

    Gbaguidi-Haore, Houssein; Roussel, Sandrine; Reboux, Gabriel; Dalphin, Jean-Charles; Piarroux, Renaud

    2009-01-01

    Farmer's lung disease (FLD) is common in eastern France. It is the main form of occupational hypersensitivity pneumonitis, caused by chronic inhalation of microorganisms (antigens) from mouldy hay, straw, or grain. The purpose of this study was to assess, with a panel of data collected between 1997-2003, environmental factors and agricultural practices that independently modify concentrations in hay of microorganisms potentially responsible for FLD. A total of 629 hay samples from 86 farms were included in statistical analyses using linear multilevel regression models allowing to consider the nested structure of the data: individual-level (batch of hay) and group-level (farm). The outcome variable of these models was the concentration in hay (logarithmic value of concentration+1) of microorganisms incriminated in FLD (Absidia corymbifera, Eurotium spp., thermophilic actinomycetes). The simultaneous analysis of batch of hay- and farm-level factors showed that bad climatic conditions of harvest, high-density hay-packing modes, (especially round bales) and altitude (2nd plateau, ]700-900] m) were the main factors associated with high concentrations of these microorganisms in hay. This study allowed clarification of the factors that influence the microbial concentration of hay with etiological agents of FLD.

  13. Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood.

    Directory of Open Access Journals (Sweden)

    Gines Escolar

    Full Text Available Apixaban is a new oral anticoagulant with a specific inhibitory action on FXa. No information is available on the reversal of the antihemostatic action of apixaban in experimental or clinical settings. We have evaluated the effectiveness of different factor concentrates at reversing modifications of hemostatic mechanisms induced by moderately elevated concentrations of apixaban (200 ng/ml added in vitro to blood from healthy donors (n = 10. Effects on thrombin generation (TG and thromboelastometry (TEM parameters were assessed. Modifications in platelet adhesive, aggregating and procoagulant activities were evaluated in studies with blood circulating through damaged vascular surfaces, at a shear rate of 600 s(-1. The potential of prothrombin complex concentrates (PCCs; 50 IU/kg, activated prothrombin complex concentrates (aPCCs; 75 IU/kg, or activated recombinant factor VII (rFVIIa; 270 μg/kg, at reversing the antihemostatic actions of apixaban, were investigated. Apixaban interfered with TG kinetics. Delayed lag phase, prolonged time to peak and reduced peak values, were improved by the different concentrates, though modifications in TG patterns were diversely affected depending on the activating reagents. Apixaban significantly prolonged clotting times (CTs in TEM studies. Prolongations in CTs were corrected by the different concentrates with variable efficacies (rFVIIa≥aPCC>PCC. Apixaban significantly reduced fibrin and platelet interactions with damaged vascular surfaces in perfusion studies (p<0.05 and p<0.01, respectively. Impairments in fibrin formation were normalized by the different concentrates. Only rFVIIa significantly restored levels of platelet deposition. Alterations in hemostasis induced by apixaban were variably compensated by the different factor concentrates investigated. However, effects of these concentrates were not homogeneous in all the tests, with PCCs showing more efficacy in TG, and rFVIIa being more effective

  14. Relationship between Serum Transforming Growth Factor β1 Concentrations and the Duration of Type 1 Diabetes Mellitus in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Katarzyna Zorena

    2013-01-01

    Full Text Available The aim of this study was to evaluate the relationship between serum transforming growth factor β1 (TGF-β1 concentrations and the duration of type 1 diabetes mellitus (T1DM in children and adolescents. One hundred and sixteen patients with T1DM and 19 healthy controls were examined. Serum TGF-β1 concentrations were measured using the cytometric bead array (CBA. A positive association between the time of diabetes duration and higher serum TGF-β1 concentrations was observed. Similarly, the prevalence of microvascular complications, such as retinopathy and nephropathy, increased with the duration of diabetes. Logistic regression analysis showed that serum TGF-β1 concentrations and the duration of the disease are independent risk factors of microangiopathy development. Higher serum TGF-β1 concentrations were associated with a significant risk of microangiopathy development after 10 years of T1DM duration. In the successive years of the disease, the effect was even stronger. The results of our study indicate that serum TGF-β1 concentrations are one of the factors that may have an impact on the progression of vascular complications in children and adolescents with T1DM.

  15. "To Study the Relationship of Academic Stress and Socio-Economic Status among IX Standard Students of Raipur City"

    Science.gov (United States)

    Khan, Suhail Ahmed; Ayyub, Khan Farhat

    2013-01-01

    This paper focuses on the relationship between academic stress and socio-economic status among IX standard students. The research was carried out in Raipur City (Chhattisgarh) on a sample of 600 IX standard students of English and Hindi medium schools. Academic Stress was measured by Stress Inventory for School Students prepared by Seema Rani…

  16. Concentrations of polycyclic aromatic hydrocarbons in New York City community garden soils: Potential sources and influential factors.

    Science.gov (United States)

    Marquez-Bravo, Lydia G; Briggs, Dean; Shayler, Hannah; McBride, Murray; Lopp, Donna; Stone, Edie; Ferenz, Gretchen; Bogdan, Kenneth G; Mitchell, Rebecca G; Spliethoff, Henry M

    2016-02-01

    A total of 69 soil samples from 20 community gardens in New York City (New York, USA) were collected and analyzed for 23 polycyclic aromatic hydrocarbons (PAHs) and black carbon. For each garden, samples were collected from nongrowing areas (non-bed) and from vegetable-growing beds, including beds with and without visible sources of PAHs. The sum of the US Environmental Protection Agency's 16 priority PAHs ranged up to 150 mg/kg, and the median (5.4 mg/kg) and mean (14.2 mg/kg) were similar to those previously reported for urban areas in the northeast United States. Isomer ratios indicated that the main sources of PAHs were petroleum, coal, and wood combustion. The PAH concentrations were significantly and positively associated with black carbon and with modeled air PAH concentrations, suggesting a consistent relationship between historical deposition of atmospheric carbon-adsorbed PAHs and current PAH soil concentrations. Median PAH soil concentration from non-bed areas was higher (7.4 mg/kg) than median concentration from beds in the same garden (4.0 mg/kg), and significantly higher than the median from beds without visible sources of PAHs (3.5 mg/kg). Median PAH concentration in beds from gardens with records of soil amendments was 58% lower compared with beds from gardens without those records. These results suggest that gardening practices in garden beds without visible sources of PAHs contribute to reduce PAH soil concentrations.

  17. The X-ray spectral evolution of the ultraluminous X-ray source Holmberg IX X-1

    Science.gov (United States)

    Luangtip, Wasutep; Roberts, Timothy P.; Done, Chris

    2016-08-01

    We present a new analysis of X-ray spectra of the archetypal ultraluminous X-ray source (ULX) Holmberg IX X-1 obtained by the Swift, XMM-Newton and NuSTAR observatories. This ULX is a persistent source, with a typical luminosity of ˜1040 erg s-1, that varied by a factor of 4-5 over eight years. We find that its spectra tend to evolve from relatively flat or two-component spectra in the medium energy band (1-6 keV), at lower luminosities, to a spectrum that is distinctly curved and disc-like at the highest luminosities, with the peak energy in the curved spectrum tending to decrease with increased luminosity. We argue that the spectral evolution of the ULX can be explained by super-Eddington accretion models, where in this case we view the ULX down the evacuated funnel along its rotation axis, bounded by its massive radiatively driven wind. The spectral changes then originate in enhanced geometric beaming as the accretion rate increases and wind funnel narrows, causing the scattered flux from the central regions of the supercritical flow to brighten faster than the isotropic thermal emission from the wind, and so the curved hard spectral component to dominate at the highest luminosities. The wind also Compton down-scatters photons at the edge of the funnel, resulting in the peak energy of the spectrum decreasing. We also confirm that Holmberg IX X-1 displays spectral degeneracy with luminosity, and suggest that the observed differences are naturally explained by precession of the black hole rotation axis for the suggested wind geometry.

  18. [Rheumatoid arthritis among mapuche aborigines. A 16 years experience in the IX Region of the Chile].

    Science.gov (United States)

    Kaliski, S; Bustos, L; Artigas, C; Alarcón, C; Vega, M A; Cárdenas, C

    2001-03-01

    Mapuche, Chilean natives, represent approximately 9.8% of Chilean population and in the IX region of the country, they account for 18.4% of population over 15 years old. They preserve some socio-cultural characteristics that make them different to the rest of the population. To describe the epidemiological characteristics rheumatoid arthritis among Mapuche natives. Retrospective review of patients of Mapuche origin with rheumatoid arthritis, seen at Temuco Hospital between 1980 and 1996. Among 308 cases gathered, only 106 (93 women, aged 55 +/- 10 years old) complied with 1987 American College of Rheumatology (ACR) criteria for rheumatoid arthritis. The disease began between 29 and 52 years old in 73% of patients and the mean delay in diagnosis was 4.4 years. At diagnosis, 99% had symmetric poliarthritis, 28.3% had either fatigue, fever or weight loss, and 46.9% were in class III or in class IV of ACR-1991. Fifty three percent of patients developed Sicca syndrome, 36% developed nodules, 23% developed Raynaud phenomenon, 11% developed pulmonary involvement, 7% developed vasculitis, 5% developed neurological manifestations and 19% developed ophthalmologic involvement. Rheumatoid factor was positive in 78% and 73% had erosions. HLA DR4 was (+) in 60% of 30 patients. Thirty percent required 3 or more disease modifying drugs and prednisone over 10 mg/day. There was no correlation between functional capacity and several other features of the disease. Mapuche rheumatoid arthritis patients are detected late and have a poor functional capacity at the time of diagnosis. They also have a higher proportion of extraarticular manifestations, more erosions and require more aggressive treatments.

  19. Expression of carbonic anhydrase IX (CAIX) in malignant mesothelioma. An immunohistochemical and immunocytochemical study.

    Science.gov (United States)

    Capkova, L; Koubkova, L; Kodet, R

    2014-01-01

    Malignant mesothelioma is an aggressive tumor with a poor prognosis. Carbonic anhydrase IX (CAIX) is a membranously located metalloenzyme involved in pH homeostasis with influence on regulation of cell proliferation, oncogenesis and tumor progression. Much attention has been paid recently to carboanhydrases and their inhibitors as they offer an opportunity for both developing novel anticancer drugs, as well as diagnostic and prognostic tools. This study was designed to assess the expression of CAIX in malignant pleural and peritoneal mesotheliomas, their benign counterparts, and in pleural effusions from patients with malignant mesothelioma, metastatic carcinoma or a benign disease. Tissue blocks from 51 malignant mesotheliomas of pleura (47 cases; 41 epithelioid, 2 biphasic, 4 sarcomatoid) and peritoneum (4 cases; all epithelioid), 14 cases with normal or reactive pleural tissue, and 19 cell blocks were analyzed. CAIX expression was determined using immunohistochemistry and its membranous immunoreactivity was semiquantitatively evaluated. Specimens were divided into five subgroups according to the staining pattern and intensity.Overall, 92.2% (47/51) of mesotheliomas expressed CAIX. All epithelioid mesotheliomas showed CAIX positivity, which was predominantly strong and diffuse (73.3%, 33/45). Sarcomatoid mesotheliomas and sarcomatoid areas in biphasic mesotheliomas were negative. A strong diffuse staining was observed in all cases of normal mesothelia. In pleural effusions, CAIX expression was observed in malignant cells as well as in benign mesothelial cells. In conclusion, CAIX is expressed virtually in all mesotheliomas except for sarcomatoid subtype, and in benign mesothelia. There are probably more mechanisms of CAIX overexpression than hypoxia-induced in malignant mesothelioma, with the influence of other tissue specific transcription or growth factors depending on the type of the cell lineage. CAIX immunoreactivity is not a reliable diagnostic marker for

  20. Comparison of the effect of calcium gluconate and batroxobin on the release of transforming growth factor beta 1 in canine platelet concentrates

    Directory of Open Access Journals (Sweden)

    Silva Raul F

    2012-07-01

    Full Text Available Abstract Background The clinical use of autologous platelet concentrates (also known as platelet-rich plasma on the field of regenerative therapy, in the last decade has been the subject of several studies especially in equine medicine and surgery. The objectives of this study was: 1 to describe and compare the cellular population in whole blood, lower fraction (A and upper fraction (B of platelet concentrates, 2 to measure and compare the transforming growth factor beta 1 (TGF-β1 concentration in plasma and both platelet concentrates after be activated with calcium gluconate or batroxobin plus calcium gluconate and, 3 to determine correlations between cell counts in platelet concentrates and concentrations of TGF-β1. Blood samples were taken from 16 dogs for complete blood count, plasma collection and platelet concentrates preparation. The platelet concentrates (PC were arbitrarily divided into two fractions, specifically, PC-A (lower fraction and PC-B (upper fraction. The Platelet concentrates were analyzed by hemogram. After activated with calcium gluconate or batroxobin plus calcium gluconate, TGF-β1 concentration was determined in supernatants of platelet concentrates and plasma. Results There were differences statistically significant (P 1 concentration between whole blood, plasma and both platelet concentrates. A significant correlation was found between the number of platelets in both platelet concentrates and TGF-β1 concentration. Platelet collection efficiency was 46.34% and 28.16% for PC-A and PC-B, respectively. TGF-β1 concentration efficiency for PC activated with calcium gluconate was 47.75% and 31.77%, for PC-A and PC-B, respectively. PC activated with batroxobin plus CG showed 46.87% and 32.24% for PC-A and PC-B, respectively. Conclusions The methodology used in this study allows the concentration of a number of platelets and TGF-β1 that might be acceptable for a biological effect for clinical or experimental use as a

  1. Short communication: Factors affecting vitamin B12 concentration in milk of commercial dairy herds: An exploratory study.

    Science.gov (United States)

    Duplessis, M; Pellerin, D; Cue, R I; Girard, C L

    2016-06-01

    Only bacteria can synthesize vitamin B12, and this requires adequate Co supply. The natural source of vitamin B12 in human diets comes from animal products, especially those from ruminants. This study aimed to describe variability regarding vitamin B12 concentration in milk among and within commercial dairy herds in early lactation. A secondary objective was to explore potential causes for this variability such as genetic variation and diet characteristics. In total, 399 dairy cows (135 primiparous and 264 multiparous; 386 Holstein and 13 Jersey cows) in 15 commercial herds were involved. Milk samples were taken at 27.4±4.1 and 55.4±4.1d in milk. Neither parity (primiparous vs. multiparous) nor sampling time affected milk concentrations of vitamin B12. Nevertheless, vitamin B12 concentration in milk was highly variable among and within dairy herds. The lowest vitamin B12 concentration in milk of cows was observed in the Jersey herd. Among herds, vitamin B12 concentration in milk ranged from 2,309 to 3,878 pg/mL; one glass (250mL) of milk from those herds would provide between 23 and 40% of the vitamin B12 recommended daily allowance. Among individual cows, however, this provision varied between 16 and 57% of the recommendation. In spite of the limited size of the studied population, the heritability value was 0.23, suggesting that genetic selection could modify milk vitamin B12 concentration. We observed a positive relationship between milk vitamin B12 concentration and dietary acid detergent fiber content and a negative relationship between milk concentration of vitamin B12 and dietary crude protein content.

  2. Factors affecting total dissolved solids concentration of γ-ray-irradiated aqueous hexamethylenetetramine solution: a dosimetric study.

    Science.gov (United States)

    Sife-Eldeen, Kh A

    2014-12-01

    A new γ-ray-radiation dosimetric system (TDS-HMTA), comprising a 'total dissolved solids (TDS)' meter and 0.02 M aqueous hexamethylenetetramine (HMTA) solution, is introduced for medical and biological applications. Gamma-ray radiolysis of aqueous HTMA solutions increases the concentrations (ppm) of TDS, which is measured by the TDS meter. The effects of HMTA concentration, absorbed radiation dose, absorbed dose rate, and storage time on the TDS concentration of irradiated HMTA solutions were studied. It was found that 0.02 M aqueous HMTA solution yields the highest sensitivity to γ-ray-radiation according to TDS concentration measurements. The effect of absorbed radiation dose was studied in the range 1.64-435.5 kGy. The TDS concentration increases linearly up to the maximum of the studied absorbed radiation dose range (R(2) = 0.9965). The overall coefficient of variation (CV %) associated with TDS concentration measurements of 0.02 M HMTA solution as a function of absorbed dose was found to be 0.732%. The effect of dose rate on the TDS concentration was studied in the range 0.33-3.31 kGy/h. It was found, also, that the TDS concentration is relatively stable over a storage period of 144 h after irradiation with different doses. The tissue equivalency of 0.02 M aqueous HMTA solutions allow it to be used for radiation dose measurement during sterilization in human tissue banks. Therefore, this system (TDS-HMTA) could be considered as a promising candidate for γ-ray radiation dosimetry in technical, medical and research fields.

  3. Factors influencing the atmospheric concentrations of PCBs at an abandoned e-waste recycling site in South China.

    Science.gov (United States)

    Wang, Yan; Wu, Xiaowei; Hou, Minmin; Zhao, Hongxia; Chen, Ruize; Luo, Chunling; Zhang, Gan

    2017-02-01

    The diurnal atmospheric concentrations of polychlorinated biphenyls (PCBs) were investigated at an abandoned e-waste recycling site in South China during winter and summer. Total PCB concentrations during winter and summer were 27.6-212 and 368-1704pg/m(3) in the particulate phase and 270-697 and 3000-15,500pg/m(3) in the gaseous phase, respectively. Both gaseous and particulate PCB concentrations and compositions exhibited significant difference between winter and summer samples, but no diurnal variations during the measurement period. The correlation analysis between PCB concentrations and meteorological conditions, including atmospheric temperature, humidity, and mixing layer height, suggested that the seasonal variability of atmospheric PCB concentrations was strongly temperature-dependent, while the diurnal variability was probably source-dependent. The temperature-driven variations can also be proved by the significant linear correlation between ln P and 1/T in the Clausius-Clapeyron plot. Although government has implemented controls to reduce e-waste pollution, both the relatively high concentrations of PCBs and the diurnal variation in the air suggested that emissions from occasional e-waste recycling activities may still exist in this recycling area. These results underline the importance of continuing e-waste recycling site management long after abandonment.

  4. The role of sensitivity of ALA (PpIX)-based PDT on Human embryonic kidney cell line (HEK293T)

    Science.gov (United States)

    Fakhar-e-Alam, M.; Atif, M.; Rehman, T.; Sadia, H.; Firdous, S.

    2011-08-01

    Present study evaluates the effects of photodynamic therapy (PDT) with aminolevulinic acid (5-ALA) as photo sensitizer using Human embryonic kidney (HEK293T) cell line as an experimental model. Porphyrins derivatives are used as active cytotoxic antitumor agents in PDT. Above mentioned cell line were irradiated with red light (a diode laser, λ = 635 nm) at different doses (0-160 J/cm2) of light. The influence/effectiveness of incubation time, various concentrations of aminolevulinic acid (5-ALA) and light doses on the cellular viability was studied. HEK293T cells were deliberated by exposing the ALA-PpIX (0-1000 μg/ml) of concentrations. The optimal uptakes of photosensitizer (PS) in cell lines were investigated by means of spectro photo metric measurements. Cells viability was determined by means of neutral red assay (NRA). It was observed that alone, neither photosensitizer nor light dose have significant effect on cells viability, but optimal concentration of PS along with suitable dose of light exhibit effective impact on the viability of cell. Our results showed that light doses of 40 J/cm2 demonstrates effective PDT outcome for HEK293T cell line when incubated with 400 μg/ml, with wrapping up view that HEK293T cell line is very sensitive to ALA-mediated PDT as compared to cell line published in our data. At the end results has been verified by using reactive oxygen species (ROS) measure test.

  5. Big Men on Campus: Administrative Response to Title IX and the Development of Women's Sports in the Big Ten Conference, 1972-1982

    Science.gov (United States)

    Ramsey, Jeffrey T.

    2014-01-01

    Signed into law in 1972, Title IX of the Education Amendments was designed to eliminate gender discrimination throughout the American educational system. Title IX applied to all educational programs at any level of schooling including admissions, financial aid, academic programs, and social organizations. However, Title IX has primarily been…

  6. Lycopene supplementation elevates circulating insulin-like growth factor binding protein-1 and -2 concentrations in persons at greater risk of colorectal cancer.

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bonfrer, J.M.G.; Korse, C.M.; Doorn, J. van; Cats, A.; Depla, A.C.; Timmer, R.; Witteman, B.J.M.; Leeuwen, F.E. van; Veer, L.J. van 't; Rookus, M.A.; Kampman, E.

    2007-01-01

    BACKGROUND: Higher circulating insulin-like growth factor I (IGF-I) concentrations have been related to a greater risk of cancer. Lycopene intake is inversely associated with cancer risk, and experimental studies have shown that it may affect the IGF system, possibly through an effect on IGF-binding

  7. Lycopene supplementation elevates circulating insulin-like growth factor-binding protein-1 and-2 concentrations in persons at greater risk of colorectal cancer

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bonfrer, J.M.; Korse, C.M.; Doorn, J.; Cats, A.; Depla, A.C.; Timmer, R.; Witteman, B.J.M.; Leeuwen, van F.E.; van't Veer, L.J.; Rookus, M.A.; Kampman, E.

    2007-01-01

    Background: Higher circulating insulin-like growth factor I (IGF-I) concentrations have been related to a greater risk of cancer. Lycopene intake is inversely associated with cancer risk, and experimental studies have shown that it may affect the IGF system, possibly through an effect on IGF-binding