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Sample records for limpet hemocyanin conjugate

  1. SYNTHESIS OF 25-HYDROXYVITAMIN D3 CONJUGATE WITH KEYHOLE LIMPET HEMOCYANIN AND OBTAINING OF IMMUNE SERA

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    А. O. Mazanova

    2015-08-01

    Full Text Available The study was aimed at obtaining polyclonal antibodies that recognize 25-Hydroxyvitamin D3, for their further specifications and applications in immunochemical test systems of 25-Hydroxyvitamin D3, determination in blood serum. We used the methods of chemical synthesis of immunoconjugates (modified carbodiimide method using N´-ethyl carbodiimide, thin layer chromatography, gel filtration and indirect immunoenzyme analysis ELISA. The work describes the stages of the synthesis of 25-Hydroxyvitamin D3, immunoconjugate with keyhole limpet hemocyanin (KLH, which was used for receiving immune sera. As a result of mouse and rabbit immunization antisera were obtained and antibody titers against 25-Hydroxyvitamin D3, were tested by immunoenzyme assay. It was demonstrated that the titer of specific antibodies was higher in rabbits compared with mice. The resulting polyclonal antibodies can be used for the development of immunochemical test systems for screening studies of 25-Hydroxyvitamin D3, content in human blood serum as a marker of vitamin D3 availability.

  2. Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer

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    Sabbatini, Paul J; Ragupathi, Govind; Hood, Chandra

    2007-01-01

    PURPOSE: To characterize the safety and immunogenicity of a heptavalent antigen-keyhole limpet hemocyanin (KLH) plus QS21 vaccine construct in patients with epithelial ovarian, fallopian tube, or peritoneal cancer in second or greater complete clinical remission. EXPERIMENTAL DESIGN: Eleven......). RESULTS: Eleven patients were included in the safety analysis; 9 of 11 patients remained on study for at least 2 weeks past fourth vaccination and were included in the immunologic analysis (two withdrew, disease progression). The vaccine was well tolerated. Self-limited and mild fatigue (maximum grade 2...... patients in this pilot trial received a heptavalent vaccine s.c. containing GM2 (10 microg), Globo-H (10 microg), Lewis Y (10 microg), Tn(c) (3 microg), STn(c) (3 microg), TF(c) (3 microg), and Tn-MUC1 (3 microg) individually conjugated to KLH and mixed with adjuvant QS21(100 microg). Vaccinations were...

  3. A Novel Immunomodulatory Hemocyanin from the Limpet Fissurella latimarginata Promotes Potent Anti-Tumor Activity in Melanoma

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    Arancibia, Sergio; Espinoza, Cecilia; Salazar, Fabián; Del Campo, Miguel; Tampe, Ricardo; Zhong, Ta-Ying; De Ioannes, Pablo; Moltedo, Bruno; Ferreira, Jorge; Lavelle, Ed C.; Manubens, Augusto; De Ioannes, Alfredo E.; Becker, María Inés

    2014-01-01

    PUBLISHED Hemocyanins, the huge oxygen-transporting glycoproteins of some mollusks, are used as immunomodulatory proteins with proven anti-cancer properties. The biodiversity of hemocyanins has promoted interest in identifying new anti-cancer candidates with improved immunological properties. Hemocyanins promote Th1 responses without known side effects, which make them ideal for long-term sustained treatment of cancer. In this study, we evaluated a novel hemocyanin from the limpet/gastropo...

  4. Interaction of Chelerythrine with Keyhole Limpet Hemocyanin: a Fluorescence Spectroscopy and Molecular Docking Study

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    Zhong, M.; Long, R. Q.; Wang, Y. H.; Chen, C. L.

    2018-05-01

    The quenching mechanism between chelerythrine (CHE) and keyhole limpet hemocyanin (KLH) was investigated using fluorescence spectroscopy and molecular docking. The experiments were conducted at three different temperatures (293, 298, and 303 K). The results revealed that the intrinsic fluorescence of KLH was strongly quenched by CHE through a static quenching mechanism. The thermodynamic parameters (ΔG, ΔH, and ΔS) of the interaction were calculated, indicating that the interaction between CHE and KLH was spontaneous and that van der Waals forces and hydrogen bond formation played major roles in the binding process. The intrinsic fluorescence of the tyrosine and tryptophan residues in KLH was studied by synchronous fluorescence, which suggested that CHE changed the conformation of KLH. Finally, molecular docking was used to obtain detailed information on the binding sites and binding affinities between CHE and KLH.

  5. A novel immunomodulatory hemocyanin from the limpet Fissurella latimarginata promotes potent anti-tumor activity in melanoma.

    Directory of Open Access Journals (Sweden)

    Sergio Arancibia

    Full Text Available Hemocyanins, the huge oxygen-transporting glycoproteins of some mollusks, are used as immunomodulatory proteins with proven anti-cancer properties. The biodiversity of hemocyanins has promoted interest in identifying new anti-cancer candidates with improved immunological properties. Hemocyanins promote Th1 responses without known side effects, which make them ideal for long-term sustained treatment of cancer. In this study, we evaluated a novel hemocyanin from the limpet/gastropod Fissurella latimarginata (FLH. This protein has the typical hollow, cylindrical structure of other known hemocyanins, such as the keyhole limpet hemocyanin (KLH and the Concholepas hemocyanin (CCH. FLH, like the KLH isoforms, is composed of a single type of polypeptide with exposed N- and O-linked oligosaccharides. However, its immunogenicity was significantly greater than that of KLH and CCH, as FLH induced a stronger humoral immune response and had more potent anti-tumor activity, delaying tumor growth and increasing the survival of mice challenged with B16F10 melanoma cells, in prophylactic and therapeutic settings. Additionally, FLH-treated mice demonstrated increased IFN-γ production and higher numbers of tumor-infiltrating CD4(+ lymphocytes. Furthermore, in vitro assays demonstrated that FLH, but not CCH or KLH, stimulated the rapid production of pro-inflammatory cytokines (IL-6, IL-12, IL-23 and TNF-α by dendritic cells, triggering a pro-inflammatory milieu that may explain its enhanced immunological activity. Moreover, this effect was abolished when deglycosylated FLH was used, suggesting that carbohydrates play a crucial role in the innate immune recognition of this protein. Altogether, our data demonstrate that FLH possesses increased anti-tumor activity in part because it activates a more potent innate immune response in comparison to other known hemocyanins. In conclusion, FLH is a potential new marine adjuvant for immunization and possible cancer

  6. A novel immunomodulatory hemocyanin from the limpet Fissurella latimarginata promotes potent anti-tumor activity in melanoma.

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    Arancibia, Sergio; Espinoza, Cecilia; Salazar, Fabián; Del Campo, Miguel; Tampe, Ricardo; Zhong, Ta-Ying; De Ioannes, Pablo; Moltedo, Bruno; Ferreira, Jorge; Lavelle, Ed C; Manubens, Augusto; De Ioannes, Alfredo E; Becker, María Inés

    2014-01-01

    Hemocyanins, the huge oxygen-transporting glycoproteins of some mollusks, are used as immunomodulatory proteins with proven anti-cancer properties. The biodiversity of hemocyanins has promoted interest in identifying new anti-cancer candidates with improved immunological properties. Hemocyanins promote Th1 responses without known side effects, which make them ideal for long-term sustained treatment of cancer. In this study, we evaluated a novel hemocyanin from the limpet/gastropod Fissurella latimarginata (FLH). This protein has the typical hollow, cylindrical structure of other known hemocyanins, such as the keyhole limpet hemocyanin (KLH) and the Concholepas hemocyanin (CCH). FLH, like the KLH isoforms, is composed of a single type of polypeptide with exposed N- and O-linked oligosaccharides. However, its immunogenicity was significantly greater than that of KLH and CCH, as FLH induced a stronger humoral immune response and had more potent anti-tumor activity, delaying tumor growth and increasing the survival of mice challenged with B16F10 melanoma cells, in prophylactic and therapeutic settings. Additionally, FLH-treated mice demonstrated increased IFN-γ production and higher numbers of tumor-infiltrating CD4(+) lymphocytes. Furthermore, in vitro assays demonstrated that FLH, but not CCH or KLH, stimulated the rapid production of pro-inflammatory cytokines (IL-6, IL-12, IL-23 and TNF-α) by dendritic cells, triggering a pro-inflammatory milieu that may explain its enhanced immunological activity. Moreover, this effect was abolished when deglycosylated FLH was used, suggesting that carbohydrates play a crucial role in the innate immune recognition of this protein. Altogether, our data demonstrate that FLH possesses increased anti-tumor activity in part because it activates a more potent innate immune response in comparison to other known hemocyanins. In conclusion, FLH is a potential new marine adjuvant for immunization and possible cancer immunotherapy.

  7. Oral antibiotics enhance antibody responses to keyhole limpet hemocyanin in orally but not muscularly immunized chickens.

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    Murai, Atsushi; Kitahara, Kazuki; Okumura, Shouta; Kobayashi, Misato; Horio, Fumihiko

    2016-02-01

    Recent studies have emphasized the crucial role of gut microbiota in triggering and modulating immune response. We aimed to determine whether the modification of gut microbiota by oral co-administration of two antibiotics, ampicillin and neomycin, would lead to changes in the antibody response to antigens in chickens. Neonatal chickens were given or not given ampicillin and neomycin (0.25 and 0.5 g/L, respectively) in drinking water. At 2 weeks of age, the chicks were muscularly or orally immunized with antigenic keyhole limpet hemocyanin (KLH), and then serum anti-KLH antibody levels were examined by ELISA. In orally immunized chicks, oral antibiotics treatment enhanced antibody responses (IgM, IgA, IgY) by 2-3-fold compared with the antibiotics-free control, while the antibiotics did not enhance antibody responses in the muscularly immunized chicks. Concomitant with their enhancement of antibody responses, the oral antibiotics also lowered the Lactobacillus species in feces. Low doses of antibiotics (10-fold and 100-fold lower than the initial trial), which failed to change the fecal Lactobacillus population, did not modify any antibody responses when chicks were orally immunized with KLH. In conclusion, oral antibiotics treatment enhanced the antibody response to orally exposed antigens in chickens. This enhancement of antibody response was associated with a modification of the fecal Lactobacillus content, suggesting a possible link between gut microbiota and antibody response in chickens. © 2015 Japanese Society of Animal Science.

  8. A quantitative trait locus for a primary antibody response to keyhole limpet hemocyanin on chicken chromosome 14-Confirmation and candidate gene approach

    NARCIS (Netherlands)

    Siwek, M.; Slawinska, A.; Nieuwland, M.G.B.; Witkowski, A.; Zieba, G.; Minozzi, G.; Knol, E.F.; Bednarczyk, M.

    2010-01-01

    A QTL involved in the primary antibody response toward keyhole limpet hemocyanin (KLH) was detected on chicken chromosome 14 in the experimental population, which was created by crossing commercial White Leghorn and a Polish native chicken breed (green-legged partridgelike). The current QTL location

  9. HUMORAL IMMUNE-RESPONSE TO 2,4-DINITROPHENYL KEYHOLE LIMPET HEMOCYANIN IN ANTIGEN-FREE, GERM-FREE AND CONVENTIONAL BALB/C MICE

    NARCIS (Netherlands)

    BOS, NA; PLOPLIS, VA

    The B cell immune response to 2,4-dinitrophenyl (DNP) keyhole limpet hemocyanin was compared in antigen-free, germ-free and conventional BALB/c mice. The numbers of total and of DNP-specific IgM-, IgG- and IgA-secreting cells in the spleen were determined by enzyme-linked immunosorbent plaque assays

  10. Effect of HI-6 on cytokines production after immunity stimulation by keyhole limpet hemocyanin in a mouse model.

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    Pohanka, Miroslav

    2014-01-01

    HI-6 or asoxime in some sources is an antidotum for nerve agents. In recent experiments, implication of HI-6 in immunity response was proved; however, the issue was not studied in details. In this experiment, role of cytokines in HI-6 impact on immunity was searched. DESIG N: BALB/c mice were exposed to saline, HI-6 in a dose 1-100 mg/kg and/or 1 keyhole limpet hemocyanin (KLH) 1 mg/kg. Mice were sacrificed 21 days after experiment beginning and interleukins (IL) 1, 2, 4, 6 were determined by Enzyme Linked Immunosorbent Assay (ELISA). The animals had no pathological manifestation. From the tested cytokines, no significant alteration was found for the IL-1, IL-4 and IL-6. IL-2 was significantly increased in a dose response manner. The experimental data well correlates with the previous work where HI-6 caused increase of antibodies production. HI-6 is suitable to be used as an adjuvant whenever immunity should be pharmacologically altered.

  11. Haliotis tuberculata hemocyanin (HtH): analysis of oligomeric stability of HtH1 and HtH2, and comparison with keyhole limpet hemocyanin KLH1 and KLH2.

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    Harris, J R; Scheffler, D; Gebauer, W; Lehnert, R; Markl, J

    2000-12-01

    The multimeric/higher oligomeric states of the two isoforms of Haliotis tuberculata hemocyanin (HtH1 and HtH2) have been assessed by transmission electron microscopy (TEM) of negatively stained specimens, for comparison with previously published structural data from keyhole limpet hemocyanin (KLH1 and KLH2) [see Harris, J.R., Gebauer, W., Guderian, F.U., Markl, J., 1997a. Keyhole limpet hemocyanin (KLH), I: Reassociation from Immucothel followed by separation of KLH1 and KLH2. Micron, 28, 31-41; Harris, J.R., Gebauer, W., Söhngen, S.M., Nermut, M.V., Markl, J., 1997b. Keyhole limpet hemocyanin (KLH). II: Characteristic reassociation properties of purified KLH1 and KLH2. Micron, 28, 43-56; Harris, J.R., Gebauer, W., Adrian, M., Markl, J., 1998. Keyhole limpet hemocyanin (KLH): Slow in vitro reassociation of KLH1 and KLH2 from Immucothel. Micron, 29, 329-339]. In purified samples of both HtH isoforms, the hollow cylindrical ca 8MDa didecamer predominates together with a small number of decamers, but tri- and longer multidecamers are detectable only in the HtH2. The stability of the two HtH isoforms under varying ionic conditions have been monitored, thereby enabling conditions for the production of stable decamers to be established. The ability of these decamers to reform multimers in the presence of 10 and 100mM concentrations of calcium and magnesium ions in Tris-HCl buffer (pH 7.4), and also of individual HtH1 and HtH2 subunits (produced by pH 9.6 dissociation in glycine-NaOH buffer), to reassociate in the presence of calcium and magnesium ions, has been assessed. For the HtH1 decamers, the predominant multimeric product is the didecamer at 10 and 100mM calcium and magnesium concentrations, whereas for the HtH2 decamers, large numbers of multidecamers are produced, with the reaction proceeding more completely at the higher calcium and magnesium concentration. With the HtH1 subunit, reassociation in the presence of 10 and 100mM calcium and magnesium ions yielded

  12. MEASUREMENT OF AFFINITY IN SERUM SAMPLES OF ANTIGEN-FREE, GERM-FREE AND CONVENTIONAL MICE AFTER HYPERIMMUNIZATION WITH 2,4-DINITROPHENYL KEYHOLE LIMPET HEMOCYANIN, USING SURFACE-PLASMON RESONANCE

    NARCIS (Netherlands)

    BAKKER, R; LASONDER, E; BOS, NA

    We previously investigated the primary and secondary responses and hyperimmunization to the T cell-dependent antigen 2,4-dinitrophenyl keyhole limpet hemocyanin (DNP-KLH) in antigen-free (AF), germ-free (GF) and conventional (CV) mice. Both the absolute and relative numbers of DNP-specific

  13. Dairy Cows Naturally Infected with Bovine Leukemia Virus Exhibit Abnormal B- and T-Cell Phenotypes after Primary and Secondary Exposures to Keyhole Limpet Hemocyanin

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    Frie, Meredith C.; Sporer, Kelly R. B.; Benitez, Oscar J.; Wallace, Joseph C.; Droscha, Casey J.; Bartlett, Paul C.; Coussens, Paul M.

    2017-01-01

    Bovine leukemia virus (BLV) is a retrovirus that is highly prevalent in US dairy herds: over 83% are BLV infected and the within-herd infection rate can be almost 50% on average. While BLV is known to cause lymphosarcomas, only 5% or fewer infected cattle will develop lymphoma; this low prevalence of cancer has historically not been a concern to dairy producers. However, more recent research has found that BLV+ cows without lymphoma produce less milk and have shorter lifespans than uninfected herdmates. It has been hypothesized that BLV infection interferes with normal immune function in infected cattle, and this could lead to reduced dairy production. To assess how naturally infected BLV+ cows responded to a primary and secondary immune challenge, 10 BLV+ and 10 BLV− cows were injected subcutaneously with keyhole limpet hemocyanin (KLH) and dimethyldioctadecylammonium bromide. B- and T-cell responses were characterized over the following 28 days. A total of 56 days after primary KLH exposure, cows were re-injected with KLH and B- and T-cell responses were characterized again over the following 28 days. BLV+ cows produced less KLH-specific IgM after primary immune stimulation; demonstrated fewer CD45R0+ B cells, altered proportions of CD5+ B cells, altered expression of CD5 on CD5+ B cells, and reduced MHCII surface expression on B cells ex vivo; exhibited reduced B-cell activation in vitro; and displayed an increase in BLV proviral load after KLH exposure. In addition, BLV+ cows had a reduced CD45R0+γδ+ T-cell population in the periphery and demonstrated a greater prevalence of IL4-producing T cells in vitro. All together, our results demonstrate that both B- and T-cell immunities are disrupted in BLV+ cows and that antigen-specific deficiencies can be detected in BLV+ cows even after a primary immune exposure. PMID:28770217

  14. Immunotherapeutic effect of Concholepas hemocyanin in the murine bladder cancer model: evidence for conserved antitumor properties among hemocyanins.

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    Moltedo, Bruno; Faunes, Fernando; Haussmann, Denise; De Ioannes, Pablo; De Ioannes, Alfredo E; Puente, Javier; Becker, María Inés

    2006-12-01

    We determined the antitumor properties of a newly available hemocyanin obtained from the Chilean gastropod Concholepas concholepas (Biosonda Corp., Santiago, Chile) in a syngeneic heterotopic mouse bladder carcinoma model. Since keyhole limpet hemocyanin (Pierce, Rockford, Illinois) is used increasingly in biomedicine as a carrier for vaccines and an immunotherapeutic agent for bladder transitional cell carcinoma, there is a growing interest in finding new substances that share its potent immunomodulatory properties. Considering that keyhole limpet hemocyanin and Concholepas concholepas hemocyanin differ significantly, it was not possible to predict a priori the antitumor properties of Concholepas concholepas hemocyanin. C3H/He mice were primed with Concholepas concholepas hemocyanin before subcutaneous implantation of mouse bladder tumor-2 cells. Treatment consisted of a subcutaneous dose of Concholepas concholepas hemocyanin (1 mg or 100 mug) at different intervals after implantation. Keyhole limpet hemocyanin and phosphate buffered saline served as positive and negative controls, respectively. In addition, experiments were designed to determine which elements of the immune response were involved in its adjuvant immunostimulatory effect. Mice treated with Concholepas concholepas hemocyanin showed a significant antitumor effect, as demonstrated by decreased tumor growth and incidence, prolonged survival and lack of toxic effects. These effects were similar to those achieved with keyhole limpet hemocyanin. We found that each hemocyanin increased natural killer cell activity but the effect of Concholepas concholepas hemocyanin was stronger. Analysis of serum from treated mice showed an increased interferon-gamma and low interleukin-4, which correlated with antibody isotypes, confirming that hemocyanins induce a T helper type 1 cytokine profile. To our knowledge our results are the first demonstration of the antitumor effect of a hemocyanin other than keyhole limpet

  15. [Hemocyanins as immunostimulants].

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    Del Campo, Miguel; Arancibia, Sergio; Nova, Esteban; Salazar, Fabián; González, Andrea; Moltedo, Bruno; De Ioannes, Pablo; Ferreira, Jorge; Manubens, Augusto; Becker, María Inés

    2011-02-01

    Hemocyanins, the giant oxygen transporter glycoproteins of diverse mollusks, are xenogenic to the mammalian immune system and they display a remarkable immuno-genicity. Therefore they are ideal non-specific immunostimulants to treat some types of cancer. They are used as an alternative therapy for superficial urinary bladder cancer (SBC), that has been traditionally treated with Bacillus Calmette-Guerin (BCG). In contrast to BCG, hemocyanins do not cause side-effects, making them ideal for long-term repetitive treatments. Hemocyanins have also been exploited as carriers to develop antibodies against hapten molecules and peptides, as carrier-adjuvants for cutting-edge vaccines against cancer, drug addiction, and infectious diseases and in the diagnosis of parasitic diseases, such as Schistosomiasis. The hemocyanin from Megathura crenulata, also known as keyhole limpet hemocyanin (KLH), has been used for over thirty years for the purposes described above. More recently, hemoc yanin from the Chilean mollusk Concholepas concholepas (CCH) has proved to be a reliable alternative to KLH, either as carrier protein, and as a likely alternative for the immunotherapy of SBC. Despite KLH and CCH differ significantly in their origin and structure, we have demonstrated that both hemocyanins stimulate the immune system of mammals in a similar way by inducing a potent Thl-polarized cellular and humoral response.

  16. Antitumor activity and carrier properties of novel hemocyanins coupled to a mimotope of GD2 ganglioside.

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    Palacios, Miriam; Tampe, Ricardo; Del Campo, Miguel; Zhong, Ta-Ying; López, Mercedes N; Salazar-Onfray, Flavio; Becker, María Inés

    2018-04-25

    Conjugation to carrier proteins is a way to improve the immunogenicity of peptides. Such is the case for peptides mimicking carbohydrate tumor-associated antigens in cancer vaccine development. The most used protein for this purpose is the keyhole limpet hemocyanin (KLH) from Megathura crenulata. Its limited bioavailability has prompted interest in finding new candidates; nevertheless, it is not known whether other hemocyanins might be equally efficient as carrier of carbohydrate peptide mimotopes to promotes anti-tumor responses. Here, we evaluated the carrier and antitumor activity of novel hemocyanins with documented immunogenicity obtained from Concholepas concholepas (CCH) and Fissurella latimarginata (FLH), coupled through sulfo-SMCC to P10, a mimetic peptide of GD2, the major ganglioside constituent of neuroectodermal tumors, and incorporating AddaVax as an adjuvant. The humoral immune responses of mice showed that CCH-P10 and FLH-P10 conjugates elicited specific IgM and IgG antibodies against P10 mimotope, similar to those obtained with KLH-P10, which was used as a positive control. The CCH-P10 and FLH-P10 antisera, exhibited cross-reactivity with murine and human melanoma cells, like anti-CCH and anti-FLH sera suggesting a cross-reaction of CCH and FLH glycosylations with carbohydrate epitopes on the tumor cell surfaces, similar to the KLH antisera. When mice were primed with each hemocyanin-P10 and challenged with melanoma cells, better antitumor effects were observed for FLH-P10 than for CCH-P10 and, as for KLH-P10, irrespective of conjugation. These data demonstrate that CCH and FLH are useful carriers of carbohydrate mimotopes; however, the best antitumor activity of FLH preparations, indicate that is a suitable candidate for further cancer vaccines research. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  17. Hemocyanins Stimulate Innate Immunity by Inducing Different Temporal Patterns of Proinflammatory Cytokine Expression in Macrophages.

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    Zhong, Ta-Ying; Arancibia, Sergio; Born, Raimundo; Tampe, Ricardo; Villar, Javiera; Del Campo, Miguel; Manubens, Augusto; Becker, María Inés

    2016-06-01

    Hemocyanins induce a potent Th1-dominant immune response with beneficial clinical outcomes when used as a carrier/adjuvant in vaccines and nonspecific immunostimulant in cancer. However, the mechanisms by which hemocyanins trigger innate immune responses, leading to beneficial adaptive immune responses, are unknown. This response is triggered by a proinflammatory signal from various components, of which macrophages are an essential part. To understand how these proteins influence macrophage response, we investigated the effects of mollusks hemocyanins with varying structural and immunological properties, including hemocyanins from Concholepas concholepas, Fissurella latimarginata, and Megathura crenulata (keyhole limpet hemocyanin), on cultures of peritoneal macrophages. Hemocyanins were phagocytosed and slowly processed. Analysis of this process showed differential gene expression along with protein levels of proinflammatory markers, including IL-1β, IL-6, IL-12p40, and TNF-α. An extended expression analysis of 84 cytokines during a 24-h period showed a robust proinflammatory response for F. latimarginata hemocyanin in comparison with keyhole limpet hemocyanin and C. concholepas hemocyanin, which was characterized by an increase in the transcript levels of M1 cytokines involved in leukocyte recruitment. These cytokine genes included chemokines (Cxcl1, Cxcl3, Cxcl5, Ccl2, and Ccl3), ILs (Il1b and Ifng), growth factors (Csf2 and Csf3), and TNF family members (Cd40lg). The protein levels of certain cytokines were increased. However, every hemocyanin maintains downregulated key M2 cytokine genes, including Il4 and Il5 Collectively, our data demonstrate that hemocyanins are able to trigger the release of proinflammatory factors with different patterns of cytokine expression, suggesting differential signaling pathways and transcriptional network mechanisms that lead to the activation of M1-polarized macrophages. Copyright © 2016 by The American Association of

  18. Molluskan Hemocyanins Activate the Classical Pathway of the Human Complement System through Natural Antibodies.

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    Pizarro-Bauerle, Javier; Maldonado, Ismael; Sosoniuk-Roche, Eduardo; Vallejos, Gerardo; López, Mercedes N; Salazar-Onfray, Flavio; Aguilar-Guzmán, Lorena; Valck, Carolina; Ferreira, Arturo; Becker, María Inés

    2017-01-01

    Molluskan hemocyanins are enormous oxygen-carrier glycoproteins that show remarkable immunostimulatory properties when inoculated in mammals, such as the generation of high levels of antibodies, a strong cellular reaction, and generation of non-specific antitumor immune responses in some types of cancer, particularly for superficial bladder cancer. These proteins have the ability to bias the immune response toward a T h 1 phenotype. However, despite all their current uses with beneficial clinical outcomes, a clear mechanism explaining these properties is not available. Taking into account reports of natural antibodies against the hemocyanin of the gastropod Megathura crenulata [keyhole limpet hemocyanin (KLH)] in humans as well as other vertebrate species, we report here for the first time, the presence, in sera from unimmunized healthy donors, of antibodies recognizing, in addition to KLH, two other hemocyanins from gastropods with documented immunomodulatory capacities: Fisurella latimarginata hemocyanin (FLH) and Concholepas concholepas hemocyanin (CCH). Through an ELISA screening, we found IgM and IgG antibodies reactive with these hemocyanins. When the capacity of these antibodies to bind deglycosylated hemocyanins was studied, no decreased interaction was detected. Moreover, in the case of FLH, deglycosylation increased antibody binding. We evaluated through an in vitro complement deposition assay whether these antibodies activated the classical pathway of the human complement system. The results showed that all three hemocyanins and their deglycosylated counterparts elicited this activation, mediated by C1 binding to immunoglobulins. Thus, this work contributes to the understanding on how the complement system could participate in the immunostimulatory properties of hemocyanins, through natural, complement-activating antibodies reacting with these proteins. Although a role for carbohydrates cannot be completely ruled out, in our experimental setting

  19. Limpet market attack

    International Nuclear Information System (INIS)

    Piro, P.

    2004-01-01

    Wave turbine technology is reaching maturity. The scottish firm, Wavegen, one of the world leaders in the sector, has installed its first commercial model, ''limpet'' in the faroe islands. This document presents an economic evaluation of the project and discusses also on the crucial problem of this produced electricity transport and deliver. (A.L.B.)

  20. Islay LIMPET project monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Heath, T.

    2002-07-01

    Wavegen was contracted by the DTI as part of its Sustainable Energy Programmes to monitor and report on the final stages of the construction, installation of turbo-generation equipment, commissioning and operation of the LIMPET wave energy system. The report discusses the choice of technology, where the system was installed, power take off, construction of the collector, installation of the turbo-generator, maintenance, operation, management and planning issues. The performance of the system was found to be poorer than expected and the reasons for this were identified. The main conclusions were that the system is sufficiently robust to operate in the marine environment and downtimes are expected to be short.

  1. The diversity and evolution of chelicerate hemocyanins

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    Rehm Peter

    2012-02-01

    Full Text Available Abstract Background Oxygen transport in the hemolymph of many arthropod species is facilitated by large copper-proteins referred to as hemocyanins. Arthropod hemocyanins are hexamers or oligomers of hexamers, which are characterized by a high O2 transport capacity and a high cooperativity, thereby enhancing O2 supply. Hemocyanin subunit sequences had been available from horseshoe crabs (Xiphosura and various spiders (Araneae, but not from any other chelicerate taxon. To trace the evolution of hemocyanins and the emergence of the large hemocyanin oligomers, hemocyanin cDNA sequences were obtained from representatives of selected chelicerate classes. Results Hemocyanin subunits from a sea spider, a scorpion, a whip scorpion and a whip spider were sequenced. Hemocyanin has been lost in Opiliones, Pseudoscorpiones, Solifugae and Acari, which may be explained by the evolution of trachea (i.e., taxon Apulmonata. Bayesian phylogenetic analysis was used to reconstruct the evolution of hemocyanin subunits and a relaxed molecular clock approach was applied to date the major events. While the sea spider has a simple hexameric hemocyanin, four distinct subunit types evolved before Xiphosura and Arachnida diverged around 470 Ma ago, suggesting the existence of a 4 × 6mer at that time. Subsequently, independent gene duplication events gave rise to the other distinct subunits in each of the 8 × 6mer hemocyanin of Xiphosura and the 4 × 6mer of Arachnida. The hemocyanin sequences were used to infer the evolutionary history of chelicerates. The phylogenetic trees support a basal position of Pycnogonida, a sister group relationship of Xiphosura and Arachnida, and a sister group relationship of the whip scorpions and the whip spiders. Conclusion Formation of a complex hemocyanin oligomer commenced early in the evolution of euchelicerates. A 4 × 6mer hemocyanin consisting of seven subunit types is conserved in most arachnids since more than 400 Ma, although some

  2. The oxygen-binding properties of hemocyanin from the mollusk Concholepas concholepas.

    Science.gov (United States)

    González, Andrea; Nova, Esteban; Del Campo, Miguel; Manubens, Augusto; De Ioannes, Alfredo; Ferreira, Jorge; Becker, María Inés

    2017-12-01

    Hemocyanins have highly conserved copper-containing active sites that bind oxygen. However, structural differences among the hemocyanins of various mollusks may affect their physicochemical properties. Here, we studied the oxygen-binding cooperativity and affinity of Concholepas concholepas hemocyanin (CCH) and its two isolated subunits over a wide range of temperatures and pH values. Considering the differences in the quaternary structures of CCH and keyhole limpet hemocyanin (KLH), we hypothesized that the heterodidecameric CCH has different oxygen-binding parameters than the homodidecameric KLH. A novel modification of the polarographic method was applied in which rat liver submitochondrial particles containing cytochrome c oxidase were introduced to totally deplete oxygen of the test solution using ascorbate as the electron donor. This method was both sensitive and reproducible. The results showed that CCH, like other hemocyanins, exhibits cooperativity, showing an inverse relationship between the oxygen-binding parameters and temperature. According to their Hill coefficients, KLH has greater cooperativity than CCH at physiological pH; however, CCH is less sensitive to pH changes than KLH. Appreciable differences in binding behavior were found between the CCH subunits: the cooperativity of CCH-A was not only almost double that of CCH-B, but it was also slightly superior to that of CCH, thus suggesting that the oxygen-binding domains of the CCH subunits are different in their primary structure. Collectively, these data suggest that CCH-A is the main oxygen-binding domain in CCH; CCH-B may play a more structural role, perhaps utilizing its surprising predisposition to form tubular polymers, unlike CCH-A, as demonstrated here using electron microscopy. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Kinetic catalytic studies of scorpion's hemocyanin

    International Nuclear Information System (INIS)

    Queinnec, E.; Vuillaume, M.; Gardes-Albert, M.; Ferradini, C.; Ducancel, F.

    1991-01-01

    Hemocyanins are copper proteins which function as oxygen carriers in the haemolymph of Molluscs and Arthropods. They possess enzymatic properties: peroxidatic and catalatic activities, although they have neither iron nor porphyrin ring at the active site. The kinetics of the catalytic reaction is described. The reaction of superoxide anion with hemocyanin has been studied using pulse radiolysis at pH 9. The catalytic rate constant is 3.5 X 10 7 mol -1 .l.s -1 [fr

  4. Ontogeny of decapod crustacean hemocyanin: effects of temperature and nutrition.

    Science.gov (United States)

    Terwilliger, N; Dumler, K

    2001-03-01

    Hemocyanin is present throughout the decapod crustacean's life, usually as one-hexamer and two-hexamer oligomers. Hemocyanins of some decapod crustaceans undergo changes in subunit composition and oxygen affinity during development. Maternal hemocyanin is taken up from the hemolymph via endocytosis by the oocyte. Embryo hemocyanin differs in subunit composition from hemocyanin of oocyte and adult crab and may represent the onset of hemocyanin synthesis. Complex changes in expression of hemocyanin subunits occur through megalopa and early juvenile stages of the crab Cancer magister, culminating in the pattern of adult hemocyanin. The influences of food availability and temperature on development, growth and hemocyanin ontogeny in early juvenile C. magister have been studied. Crabs were raised in warm or cold sea water and fed high or low levels of food for 6 months. While intermolt period was shorter in crabs fed high food levels, especially those raised in warm water, crabs reared in cold water with high food levels attained the largest sizes. Thus increased food availability affects growth more than increased temperature. Adult hemocyanin appeared at about the same number of weeks after the start of the experiment for crabs in the warm water/high food, warm water/low food and cold water/high food groups, even though warm water/low food crabs had molted fewer times. Crabs in the cold water/low food group expressed adult hemocyanin much later than the other groups. Molt stage and maturation from juvenile to adult are not absolutely coupled, and food availability has a greater influence than temperature on hemocyanin ontogeny.

  5. COMPARATIVE ELECTRON-MICROSCOPY AND IMAGE-ANALYSIS OF OXY-HEMOCYANIN AND DEOXY-HEMOCYANIN FROM THE SPINY LOBSTER PANULIRUS-INTERRUPTUS

    NARCIS (Netherlands)

    DEHAAS, F; VANBREEMEN, JFL; BOEKEMA, EJ; KEEGSTRA, W; VANBRUGGEN, EFJ

    Structural differences between oxy-hemocyanin and deoxy-hemocyanin from the spiny lobster P. interruptus were studied by electron microscopy and image analysis of negatively stained preparations. Projections of the hexameric P. interruptus hemocyanin from electron microscopy were compared with

  6. A novel immunomodulatory hemocyanin from the limpet Fissurella latimarginata promotes potent anti-tumor activity in melanoma

    OpenAIRE

    LAVELLE, EDWARD

    2014-01-01

    PUBLISHED Porous silicon (pSi) microparticles, in diverse sizes and shapes, can be functionalized to present pathogen-associated molecular patterns that activate dendritic cells. Intraperitoneal injection of MPL-adsorbed pSi microparticles, in contrast to free MPL, resulted in the induction of local inflammation, reflected in the recruitment of neutrophils, eosinophils and proinflammatory monocytes, and the depletion of resident macrophages and mast cells at the injection site. Injection o...

  7. Antibacterial activity of hemocyanin from red swamp crayfish (Procambarus clarkii).

    Science.gov (United States)

    Qin, Zhendong; Babu, V Sarath; Wan, Quanyuan; Muhammad, Asim; Li, Jun; Lan, Jiangfeng; Lin, Li

    2018-04-01

    Hemocyanins (HMC): the copper-containing respiratory proteins present in invertebrate hemolymph, which plays many essential roles in the immune system. Currently, little is known about the HMC domains of Procambarus clarkii (P. clarkii) and their function in antimicrobial immune response. In this present study, we comparatively studied the expression pattern of native PcHMC with the three recombinant proteins of variable domains of crayfish hemocyanin (PcHMC-N, N-terminal domain of hemocyanin; PcHMC-T, tyrosinase domain of hemocyanin; PcHMC-C, C-terminal domain of hemocyanin). The results showed that three purified recombinant proteins had a strong binding to various bacteria and lipopolysaccharides that further highly agglutinated. The HMCs recombinant proteins showed strong antibacterial activity against V. parahaemolyticus and S. aureus by bacterial growth inhibition, phenoloxidase (PO) and phagocytosis assays. Specifically, rPcHMC1-T and rPcHMC1-C inhibited both the bacteria efficiently, rPcHMC1-T was highly upregulated the PO activity than the other recombinant proteins. Whereas, recombinant proteins pretreated crayfish hemocytes participated in phagocytosis activity, rPcHMC1-N and rPcHMC1-C proteins had a profound effect than the rPcHMC1-T on S. aureus and V. parahaemolyticus phagocytosis. The crayfish hemocyanin domains clearly exhibited antibacterial and phagocytic activities against both the bacteria, suggesting that its variable domains of hemocyanin have the different function on specific pathogen during the assault of pathogens. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Oligomeric stability of Rapana venosa hemocyanin (RvH) and its structural subunits.

    Science.gov (United States)

    Dolashka-Angelova, Pavlina; Schwarz, Heinz; Dolashki, Aleksandar; Stevanovic, Stefan; Fecker, Miriam; Saeed, Muhammad; Voelter, Wolfgang

    2003-03-21

    The two structural subunits RvH1 and RvH2 were separated after overnight dialysis of Rapana venosa Hc against 130 mM Gly/NaOH buffer, pH 9.6, on an ion exchange column Hiload 26/10 Sepharose Q using a fast performance liquid chromatography (FPLC) system. The reassociation characteristics of these two RvH isoforms and the native molecule were studied in buffers with different pH values and concentrations of Ca(2+) and Mg(2+). Reassociation of mixed RvH subunits was performed over a period of several days using a stabilizing buffer (SB) of pH 7.0 containing different concentrations of Ca(2+) and Mg(2+) ions. After 2 days of dialysis, an RvH subunit mixture of didecamers and multidecamers was observed in the presence of 100 mM CaCl(2) and MgCl(2), though RvH1 and RvH2 are biochemically and immunologically different and have also different dissociation properties. The reassociation, performed at pH 9.6 with 2 mM CaCl(2) and MgCl(2) at 4 degrees C over a period of one to several weeks, led to the formation of decameric oligomers, while didecamers formed predominantly in the SB at pH 7.0. Higher concentrations of calcium and magnesium ions led to a more rapid reassociation of RvH1 resulting in long stable multidecamers and helical tubules, which were stable and slowly dissociated into shorter multidecamers and decamers at higher pH values. The reassociation of the RvH2 structural subunit in the same buffers processed slowly and yielded didecamers, shorter tubule polymers and long multidecamers which are less stable at higher pH values. The stability of RvH isoforms under varying ionic conditions is compared with the stability of keyhole limpet (KLH, Megathura crenulata) hemocyanin (KLH) and Haliotis tuberculata hemocyanin (HtH) isoforms. The process of dissociation and reassociation is connected with changes of the fluorescence intensity at 600 nm, which can be explained by differences in opalescence of the solutions of these two isoforms. The solutions of longer tubule

  9. Nitrate binding to Limulus polyphemus subunit type II hemocyanin and its functional implications

    NARCIS (Netherlands)

    Hazes, B; Magnus, KA; Kalk, KH; Bonaventura, C; Hol, WGJ

    1996-01-01

    The horseshoe crab, Limulus polyphemus, employs hemocyanin as an oxygen carrier in its hemolymph. This hemocyanin displays cooperative oxygen binding and heterotropic allosteric regulation by protons, chloride ions and divalent cations. Here, we report the crystal structure of Limulus polyphemus

  10. New Data on the Presence of Hemocyanin in Plecoptera: Recomposing a Puzzle

    OpenAIRE

    Amore, Valentina; Gaetani, Brunella; Angeles Puig, Maria; Fochetti, Romolo

    2011-01-01

    The specific role of hemocyanin in Plecoptera (stoneflies) is still not completely understood, since none of the hypotheses advanced have proven fully convincing. Previous data show that mRNA hemocyanin sequences are not present in all Plecoptera, and that hemocyanin does not seem to be uniformly distributed within the order. All species possess hexamerins, which are multifunction proteins that probably originated from hemocyanin. In order to obtain an increasingly detailed pic...

  11. Spectroscopic properties and conformational stability of Concholepas concholepas hemocyanin.

    Science.gov (United States)

    Idakieva, Krassimira; Nikolov, Peter; Chakarska, Irena; Genov, Nicolay; Shnyrov, Valery L

    2008-01-01

    The structure in solution and conformational stability of the hemocyanin from the Chilean gastropod mollusk Concholepas concholepas (CCH) and its structural subunits, CCH-A and CCH-B, were studied using fluorescence spectroscopy and differential scanning calorimetry (DSC). The fluorescence properties of the oxygenated and apo-form (copper-deprived) of the didecamer and its subunits were characterized. Besides tryptophan residues buried in the hydrophobic interior of the protein molecule also exposed fluorophores determine the fluorescence emission of the oxy- and apo-forms of the investigated hemocyanins. The copper-dioxygen system at the binuclear active site quenches the tryptophan emission of the oxy-forms of CCH and its subunits. The removal of this system increases the fluorescence quantum yield and causes structural rearrangement of the microenvironment of the emitting tryptophan residues in the respective apo-forms. Time-resolved fluorescence measurements show that the oxygenated and copper-deprived forms of the CCH and its subunits exist in different conformations. The thermal denaturation of the hemocyanin is an irreversible process, under kinetic control. A successive annealing procedure was applied to obtain the experimental deconvolution of the irreversible thermal transitions. Arrhenius equation parameter for the two-state irreversible model of the thermal denaturation of oxy-CCH at pH 7.2 was estimated. Both factors, oligomerization and the copper-dioxygen system at the active site, are important for stabilizing the structure of the hemocyanin molecule.

  12. Temperature effects on hemocyanin oxygen binding in an antarctic cephalopod.

    Science.gov (United States)

    Zielinski, S; Sartoris, F J; Pörtner, H O

    2001-02-01

    The functional relevance of oxygen transport by hemocyanin of the Antarctic octopod Megaleledone senoi and of the eurythermal cuttlefish Sepia officinalis was analyzed by continuous and simultaneous recordings of changes in pH and hemocyanin oxygen saturation in whole blood at various temperatures. These data were compared to literature data on other temperate and cold-water cephalopods (octopods and giant squid). In S. officinalis, the oxygen affinity of hemocyanin changed at deltaP50/degrees C = 0.12 kPa (pH 7.4) with increasing temperatures; this is similar to observations in temperate octopods. In M. senoi, thermal sensitivity was much smaller (delta log P50/delta pH) increased with increasing temperature in both the cuttlefish and the Antarctic octopod. At low PO2 (1.0 kPa) and pH (7.2), the presence of a large venous oxygen reserve (43% saturation) insensitive to pH reflects reduced pH sensitivity and high oxygen affinity in M. senoi hemocyanin at 0 degrees C. In S. officinalis, this reserve was 19% at pH 7.4, 20 degrees C, and 1.7 kPa O2, a level still higher than in squid. These findings suggest that the lower metabolic rate of octopods and cuttlefish compared to squid is reflected in less pH-dependent oxygen transport. Results of the hemocyanin analysis for the Antarctic octopod were similar to those reported for Vampyroteuthis--an extremely high oxygen affinity supporting a very low metabolic rate. In contrast to findings in cold-adapted giant squid, the minimized thermal sensitivity of oxygen transport in Antarctic octopods will reduce metabolic scope and thereby contribute to their stenothermality.

  13. New data on the presence of hemocyanin in Plecoptera: recomposing a puzzle.

    Science.gov (United States)

    Amore, Valentina; Gaetani, Brunella; Puig, Maria Angeles; Fochetti, Romolo

    2011-01-01

    The specific role of hemocyanin in Plecoptera (stoneflies) is still not completely understood, since none of the hypotheses advanced have proven fully convincing. Previous data show that mRNA hemocyanin sequences are not present in all Plecoptera, and that hemocyanin does not seem to be uniformly distributed within the order. All species possess hexamerins, which are multifunction proteins that probably originated from hemocyanin. In order to obtain an increasingly detailed picture on the presence and distribution of hemocyanin across the order, this study presents new data regarding nymphs and adults of selected Plecoptera species. Results confirm that the hemocyanin expression differs among nymphs in the studied stonefly species. Even though previous studies have found hemocyanin in adults of two stonefly species it was not detected in the present study, even in species where nymphs show hemocyanin, suggesting that the physiological need of this protein can change during life cycle. The phylogenetic pattern obtained using hemocyanin sequences matches the accepted scheme of traditional phylogeny based on morphology, anatomy, and biology. It is remarkable to note that the hemocyanin conserved region acts like a phylogenetic molecular marker within Plecoptera.

  14. The responses of South African patellid limpets to invertebrate ...

    African Journals Online (AJOL)

    The starfish Marthasterias glacialis is a generalized predator, feeding particularly on Choromytilus meridionalis, but also on several limpets, notably Patella longicosta. Thais dubia (Gastropoda) feeds mainly on barnacles, mussels, and Patella granulans. The gastropods Burnupena delalandii and B. cincta are principally ...

  15. Comparative electron microscopy and image analysis of oxy- and deoxy-hemocyanin from the spiny lobster Panulirus interruptus

    NARCIS (Netherlands)

    Haas, Felix de; Breemen, Jan F.L. van; Boekema, Egbert J.; Keegstra, Wilko; Bruggen, Ernst F.J. van

    1993-01-01

    Structural differences between oxy-hemocyanin and deoxy-hemocyanin from the spiny lobster P. interruptus were studied by electron microscopy and image analysis of negatively stained preparations. Projections of the hexameric P. interruptus hemocyanin from electron microscopy were compared with

  16. The hemocyanin of the ramshorn snail, Marisa cornuarietis (Linné).

    Science.gov (United States)

    Herskovits, T T; Otero, R M; Hamilton, M G

    1990-01-01

    1. The hemocyanin of the freshwater snail, Marisa cornuarietis exists predominantly as a di-decamer with the approximate mol. wt of 8.5 x 10(6) and a sedimentation coefficient of 100 S. Sedimentation and scanning transmission electron microscopy experiments indicate that about 15-20% of the hemocyanin forms tri-decameric and possibly higher aggregates with mol. wts of 12.5 x 10(6) and 130 S. 2. The fully dissociated subunits in 8.0 M urea and 6.0 M GdmCl have mol. wts of 4.1 to 4.7 x 10(5) which is close to one-twentieth of the major di-decameric component of the native hemocyanin. 3. Subunit dissociation by the urea series and the Hofmeister salt series of reagents suggests hydrophobic stabilization of the decamers or half-molecules of the parent hemocyanin. As with the other molluscan hemocyanins the order of effectiveness of the ureas as dissociating agents shows increased efficacy with increasing hydrophobicity or chain-length of the urea substituents. 4. Denaturation of the hemocyanin subunits by the ureas and Hofmeister salt series, investigated by circular dichroism measurements, essentially follow the same trend in effectiveness as observed by changes in subunit dissociation followed by light-scattering mol. wt measurements. 5. The observed denaturation transitions are shifted to much higher ranges of reagent concentration than the concentrations required for the dissociation of the hemocyanin subunits.

  17. Identification of a novel alternative splicing variant of hemocyanin from shrimp Litopenaeus vannamei.

    Science.gov (United States)

    Zhao, Shan; Lu, Xin; Zhang, Yueling; Zhao, Xianliang; Zhong, Mingqi; Li, Shengkang; Lun, Jingsheng

    2013-01-01

    Recent evidences suggest that invertebrates express families of immune molecules with high levels of sequence diversity. Hemocyanin is an important non-specific immune molecule present in the hemolymph of both mollusks and arthropods. In the present study, we characterized a novel alternative splicing variant of hemocyanin (cHE1) from Litopenaeus vannamei that produced mRNA transcript of 2579 bp in length. The isoform contained two additional sequences of 296 and 267 bp in the 5'- and 3'-terminus respectively, in comparison to that of wild type hemocyanin (cHE). Sequence of cHE1 shows 100% identity to that of hemocyanin genomic DNA (HE, which does not form an open reading frame), suggesting that cHE1 might be an alternative splicing variant due to intron retention. Moreover, cHE1 could be detected by RT-PCR from five tissues (heart, gill, stomach, intestine and brain), and from shrimps at stages from nauplius to mysis larva. Further, cHE1 mRNA transcripts were significantly increased in hearts after 12h of infection with Vibrio parahemolyticus or poly I: C, while no significant difference in the transcript levels of hepatopancreas cHE was detected in the pathogen-treated shrimps during the period. In summary, these studies suggested a novel splicing variant of hemocyanin in shrimp, which might be involved in shrimp resistance to pathogenic infection. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. CRYSTAL-STRUCTURE OF DEOXYGENATED LIMULUS-POLYPHEMUS SUBUNIT-II HEMOCYANIN AT 2.18-ANGSTROM RESOLUTION - CLUES FOR A MECHANISM FOR ALLOSTERIC REGULATION

    NARCIS (Netherlands)

    HAZES, B; MAGNUS, KA; BONAVENTURA, C; BONAVENTURA, J; DAUTER, Z; KALK, KH; HOL, WGJ

    The crystal structure of Limulus polyphemus subunit type II hemocyanin in the deoxygenated state has been determined to a resolution of 2.18 angstrom. Phase information for this first structure of a cheliceratan hemocyanin was obtained by molecular replacement using the crustacean hemocyanin

  19. Abalone Hemocyanin Blocks the Entry of Herpes Simplex Virus 1 into Cells: a Potential New Antiviral Strategy

    Science.gov (United States)

    Talaei Zanjani, Negar; Miranda-Saksena, Monica; Valtchev, Peter; Hueston, Linda; Diefenbach, Eve; Sairi, Fareed; Gomes, Vincent G.

    2015-01-01

    A marine-derived compound, abalone hemocyanin, from Haliotis rubra was shown to have a unique mechanism of antiviral activity against herpes simplex virus 1 (HSV-1) infections. In vitro assays demonstrated the dose-dependent and inhibitory effect of purified hemocyanin against HSV-1 infection in Vero cells with a 50% effective dose (ED50) of 40 to 50 nM and no significant toxicity. In addition, hemocyanin specifically inhibited viral attachment and entry by binding selectively to the viral surface glycoproteins gD, gB, and gC, probably by mimicking their receptors. However, hemocyanin had no effect on postentry events and did not block infection by binding to cellular receptors for HSV. By the use of different mutants of gD and gB and a competitive heparin binding assay, both protein charge and conformation were shown to be the driving forces of the interaction between hemocyanin and viral glycoproteins. These findings also suggested that hemocyanin may have different motifs for binding to each of the viral glycoproteins B and D. The dimer subunit of hemocyanin with a 10-fold-smaller molecular mass exhibited similar binding to viral surface glycoproteins, showing that the observed inhibition did not require the entire multimer. Therefore, a small hemocyanin analogue could serve as a new antiviral candidate for HSV infections. PMID:26643336

  20. Positive and negative effects of habitat-forming algae on survival, growth and intra-specific competition of limpets.

    Directory of Open Access Journals (Sweden)

    Ezequiel M Marzinelli

    Full Text Available Understanding the effects of environmental change on the distribution and abundance of strongly interacting organisms, such as intertidal macroalgae and their grazers, needs a thorough knowledge of their underpinning ecological relationships. Control of grazer-plant interactions is bi-directional on northwestern European coasts: grazing by limpets structures populations of macroalgae, while macroalgae provide habitat and food for limpets. Scottish shores dominated by the macroalga Fucus vesiculosus support lower densities and larger sizes of limpets Patella vulgata than shores with less Fucus. These patterns may be due to differences in inter-size-class competitive interactions of limpets among shores with different covers of Fucus. To examine this model, densities of small and large limpets were manipulated in plots with and without Fucus. Amounts of biofilm were measured in each plot. The presence of Fucus increased survival but hindered growth of small (15 mm TL limpets, which were negatively affected by the presence of large limpets (31 mm TL. In contrast, large limpets were not affected by the presence of Fucus or of small limpets. This suggests the occurrence of asymmetric inter-size-class competition, which was influenced by the presence of macroalgae. Macroalgae and increased densities of limpets did not influence amounts of biofilm. Our findings highlight the role of interactions among organisms in generating ecological responses to environmental change.

  1. SUBANTARCTIC LIMPET POPULATIONS TODAY AND HUMAN IMPACT ABOUT 1,400 YEARS AGO

    OpenAIRE

    Thatje,Sven; Ríos,Carlos

    2010-01-01

    Age, growth and length frequency data of the subantarctic intertidal limpets Nacella (Patinigera) magellanica and Nacella (Patinigera) deaurata (gmelin, 1791) were investigated at Bahía Laredo in the eastern part of the Straits of Magellan (South america). data were obtained from (i) recent populations and (ii) from shells of the same species, excavated from an indian tribe kitchen midden nearby. Conventional 14C age determination showed the shells of both limpet-species from this midden to b...

  2. Research into the further development of the LIMPET shoreline wave energy plant

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-07-01

    This report summarises the findings of a project focussing on technical issues associated with the design of the LIMPET shoreline oscillating water column (OWC) wave energy plant. Fifteen tasks are listed as the objectives of the project which was carried out to broaden the knowledge of the wave environment and the construction and operation of a wave energy plant. The experience gained in LIMPET instrumentation, control systems, and grid integration issues are discussed.

  3. Primary structure of the oligosaccharide moiety of hemocyanin from the scorpion Androctonus australis

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Debeire, P.; Montreuil, J.; Goyffon, M.; Kuik, J.A. van; Halbeek, H. van

    1986-01-01

    Hemocyanin, the copper-containing glycoprotein that serves as an oxygen carrier in the hemolymph of some arthropods and molluscs, was obtained from the blood of the scorpion Androctonus australis. Sugar analysis of the glycoprotein revealed that its carbohydrate moiety is of the N-glycosylic type.

  4. Concholepas hemocyanin biosynthesis takes place in the hepatopancreas, with hemocytes being involved in its metabolism.

    Science.gov (United States)

    Manubens, Augusto; Salazar, Fabián; Haussmann, Denise; Figueroa, Jaime; Del Campo, Miguel; Pinto, Jonathan Martínez; Huaquín, Laura; Venegas, Alejandro; Becker, María Inés

    2010-12-01

    Hemocyanins are copper-containing glycoproteins in some molluscs and arthropods, and their best-known function is O(2) transport. We studied the site of their biosynthesis in the gastropod Concholepas concholepas by using immunological and molecular genetic approaches. We performed immunohistochemical staining of various organs, including the mantle, branchia, and hepatopancreas, and detected C. concholepas hemocyanin (CCH) molecules in circulating and tissue-associated hemocytes by electron microscopy. To characterize the hemocytes, we purified them from hemolymph. We identified three types of granular cells. The most abundant type was a phagocyte-like cell with small cytoplasmic granules. The second type contained large electron-dense granules. The third type had vacuoles containing hemocyanin molecules suggesting that synthesis or catabolism occurred inside these cells. Our failure to detect cch-mRNA in hemocytes by reverse transcription with the polymerase chain reaction (RT-PCR) led us to propose that hemocytes instead played a role in CCH metabolism. This hypothesis was supported by colloidal gold staining showing hemocyanin molecules in electron-dense granules inside hemocytes. RT-PCR analysis, complemented by in situ hybridization analyses with single-stranded antisense RNAs as specific probes, demonstrated the presence of cch-mRNA in the hepatopancreas; this was consistent with the specific hybridization signal and confirmed the hepatopancreas as the site of CCH synthesis. Finally, we investigated the possibility that CCH catabolism in hemocytes was involved in the host immune response and in the generation of secondary metabolites such as antimicrobial peptides and phenoloxidase.

  5. Structural determination of the carbohydrate chains from arthropod and mollusc hemocyanin by means of 500-MHz 1H-NMR spectroscopy

    International Nuclear Information System (INIS)

    Kuik, J.A. van.

    1987-01-01

    In this thesis carbohydrate structures of hemocyanins of arthropods and molluscs are studied. Hemocyanins are high-molecular-mass, copper-containing oxygen-transport proteins. The function of these carbohydrate chains are yet still unknown. It is not probable that they play a role in the oxygen-binding processes. They are rather thought to have a function in the build-up of the hemocyanin molecules. 286 refs.; 30 figs.; 25 tabs

  6. Immunomodulatory properties of Concholepas concholepas hemocyanin against francisellosis in a zebrafish model

    OpenAIRE

    Lagos, Leidy; Tandberg, Julia Isabel; Becker, María Inés; Winther-Larsen, Hanne Cecilie

    2017-01-01

    The development of vaccines for aquaculture has been an important milestone in providing a continuous and sustainable production. Most of the vaccines currently on the market for aquaculture include oil as adjuvant. Nevertheless, several studies reported an occurrence of side effects after their use in farmed fish. As a result, there is a need for new and improved adjuvants that can stimulate the immune system while causing as few side-effects as possible. Hemocyanins are versatile macromolec...

  7. Hemocyanin of the molluscan Concholepas concholepas exhibits an unusual heterodecameric array of subunits.

    Science.gov (United States)

    De Ioannes, Pablo; Moltedo, Bruno; Oliva, Harold; Pacheco, Rodrigo; Faunes, Fernando; De Ioannes, Alfredo E; Becker, María Inés

    2004-06-18

    We describe here the structure of the hemocyanin from the Chilean gastropod Concholepas concholepas (CCH), emphasizing some attributes that make it interesting among molluscan hemocyanins. CCH exhibits a predominant didecameric structure as revealed by electron microscopy and a size of 8 MDa by gel filtration, and, in contrast with other mollusc hemocyanins, its stabilization does not require additional Ca(2+) and/or Mg(2+) in the medium. Polyacrylamide gel electrophoresis studies, analyses by a MonoQ FPLC column, and Western blots with specific monoclonal antibodies showed that CCH is made by two subunits noncovalently linked, named CCH-A and CCH-B, with molecular masses of 405 and 350 kDa, respectively. Interestingly, one of the subunits undergoes changes within the macromolecule; we demonstrated that CCH-A has an autocleavage site that under reducing conditions is cleaved to yield two polypeptides, CCH-A1 (300 kDa) and CCH-A2 (108 kDa), whereas CCH-B remains unchanged. The CCH-A nick occurs at 4 degrees C, increases at 37 degrees C, and is not inhibited by the addition of protease inhibitors and/or divalent cations. Since the CCH structure is a heterodimer, we investigated whether subunits would be either intermingled, forming heterodecamers, or assembled as two homogeneous decamers. Light scattering and electron microscope studies of the in vitro reassociation of purified CCH subunits demonstrated that the sole addition of Mg(2+) is needed for its reassembly into the native decameric molecule; no homodecamer reorganization was found with either CCH-A or CCH-B subunits alone. Our evidence showed that C. concholepas hemocyanin is an unusual example of heterodecameric organization.

  8. Cryo-EM structure of isomeric molluscan hemocyanin triggered by viral infection.

    Directory of Open Access Journals (Sweden)

    Hongtao Zhu

    Full Text Available Hemocyanins (Hcs of arthropods and mollusks function not only as oxygen transporters, but also as phenoloxidases (POs. In invertebrates, PO is an important component in the innate immune cascade, where it functions as the initiator of melanin synthesis, a pigment involved in encapsulating and killing of pathogenic microbes. Although structures of Hc from several species of invertebrates have been reported, the structural basis for how PO activity is triggered by structural changes of Hc in vivo remains poorly understood. Here, we report a 6.8 Å cryo-electron microscopy (cryo-EM structure of the isomeric form of hemocyanin, which was isolated from Abalone Shriveling syndrome-associated Virus (AbSV infected abalone (Halitotis diversicolor, and build a pseudoatomic model of isomeric H. diversicolor hemocyanin 1 (HdH1. Our results show that, compared with native form of HdH1, the architecture of isomeric HdH1 turns into a more relaxed form. The interactions between certain functional units (FUs present in the native form of Hc either decreased or were totally abolished in the isomeric form of Hc. As a result of that, native state Hc switches to its isomeric form, enabling it to play its role in innate immune responses against invading pathogens.

  9. Effects of molting and environmental factors on trace metal body-burdens and hemocyanin concentrations in the American lobster, Homarus americanus.

    NARCIS (Netherlands)

    Engel, D.W.; Brouwer, M.H.J.; Mercaldo-Allen, R.

    2001-01-01

    Hemocyanin concentrations in the hemolymph of marine crustacea are dependent on the molt cycle and on environmental conditions. Studies in our laboratories have found that hemocyanin levels in blue crabs are reduced after ecdysis and under conditions of environmental stress (Engel, Brouwer, &

  10. Contamination of limpets (Patella vulgata) following the Sea Empress oil spill

    International Nuclear Information System (INIS)

    Glegg, G.A.; Hickman, L.; Rowland, S.J.

    1999-01-01

    Following the grounding of the Sea Empress oil tanker at the entrance to Milford Haven, UK, in February 1997, samples of limpets (Patella vulgata) were collected from local coastal sites (after 2 weeks and 4 and 7 months) and analysed for oil contamination. Initially, relatively high concentrations of volatile two and three ring aromatic hydrocarbons (up to 86 μg g -1 dry weight) were found which decreased by order of magnitude between surveys. These results are compared with a similar rapid decrease in concentrations of volatile hydrocarbons while loss of heavier components is slower. An assessment of the non-volatile fingerprint sterane hydrocarbons showed limpet samples to be contaminated with hydrocarbons but was inconclusive about the source of those hydrocarbons. Another common fingerprint, the pristane:phytane ratio was investigated but this was found to be masked by the presence of natural biogenic compounds. (Author)

  11. Shell alterations in limpets as putative biomarkers for multi-impacted coastal areas.

    Science.gov (United States)

    Begliomini, Felipe Nincao; Maciel, Daniele Claudino; de Almeida, Sérgio Mendonça; Abessa, Denis Moledo; Maranho, Luciane Alves; Pereira, Camilo Seabra; Yogui, Gilvan Takeshi; Zanardi-Lamardo, Eliete; Castro, Ítalo Braga

    2017-07-01

    During the last years, shell alterations in gastropods have been proposed as tools to be used in monitoring programs. However, no studies were so far performed investigating the relationships among shell parameters and classical biomarkers of damage. The relationship between shell alterations (biometrics, shape and elemental composition) and biomarkers (LPO and DNA strand break) was evaluated in the limpet L. subrugosa sampled along a contamination gradient in a multi-impacted coastal zone from southeastern Brazil. Statistically significant differences were detected among sites under different pollution levels. The occurrence of shell malformations was consistent with environmental levels of several hazardous substances reported for the studied area and related to lipid peroxidation and DNA damage. In addition, considering the low mobility, wide geographic distribution, ease of collection and abundance of limpets in coastal zones, this putative tool may be a cost-effective alternative to traditional biomarkers. Thus, shell alterations in limpets seem to be good proxies for assessing biological adverse effects in multi-impacted coastal zones. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Immunomodulatory properties of Concholepas concholepas hemocyanin against francisellosis in a zebrafish model.

    Science.gov (United States)

    Lagos, Leidy; Tandberg, Julia I; Becker, María Inés; Winther-Larsen, Hanne C

    2017-08-01

    The development of vaccines for aquaculture has been an important milestone in providing a continuous and sustainable production. Most of the vaccines currently on the market for aquaculture include oil as adjuvant. Nevertheless, several studies reported an occurrence of side effects after their use in farmed fish. As a result, there is a need for new and improved adjuvants that can stimulate the immune system while causing as few side-effects as possible. Hemocyanins are versatile macromolecules with strong immunogenic and immunomodulatory properties. Due to these characteristics, hemocyanin from Concholepas concholepas (CCH) has been biochemically characterized and evaluated as vaccine adjuvant in mice and humans. Francisellosis is a chronic granulomatous disease, which can result in high mortality depending on the host. The disease is caused by the facultative intracellular Gram-negative bacteria Francisella noatunensis, which remains an unsolved problem for the aquaculture, as no efficient vaccines are available. The aim of the present work was to investigate the immunoregulatory properties of CCH against francisellosis in an experimental zebrafish model. When immunized with CCH, zebrafish were protected from subsequent challenge with a lethal dose of Francisella noatunensis subsp. orientalis. Subsequently the mRNA expression levels of several immune-related genes were studied, including mhcii, il12a, tnfα and ifng1-1. Taken together, the data report the immunoregulatory properties of CCH and its potential use as a vaccine adjuvant for aquaculture. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Radioprotective effect of Rapana thomasiana hemocyanin in gamma induced acute radiation syndrome

    International Nuclear Information System (INIS)

    Kindekov, Ivan; Vassilieva, Vladimir; Aljakova, Mitko; Mileva, Milka; Krastev, Dimo; Raynova, Yuliana; Idakieva, Krassimira; Doumanov, Lyuba

    2014-01-01

    The radioprotective effect of Rapana thomasiana hemocyanin (RtH) against radiation-induced injuries (stomach ulcers, survival time and endogenous haemopoiesis) and post-radiation recovery was investigated in male albino mice (C3H strain). Radiation course was in a dose of 7.5 Gy (LD 100/30 - dose that kills 100% of the mice at 30 days) from "1"3"7Cs with a dose of 2.05 Gy/ min. Radiation injuries were manifested by inducing 2 hematopoietic form of acute radiation syndrome. RtH was administered intraperitoneally in a single dose of 50, 100, 150 and 200 mg/kg body weight (b. w.) once a day for five consecutive days before irradiation. The results obtained showed that radiation exposure led to (1) 100% mortality rate, (2) ulceration in the stomach mucosa and (3) decrease formation of spleen colonies as a marker of endogenous haemopoiesis. Administration of RtH at a dose of 200 mg/kg provided better protection against radiation-induced stomach ulceration, mitigated the lethal effects of radiation exposure and recovered endogenous haemopoiesis versus irradiated but not supplemented mice. It could be expected that RtH will find a use in mitigating radiation induced injury and enhanced radiorecovery. Keywords: Rapana thomasiana hemocyanin; acute radiation syndrome; radioprotective effect; spleen colony assay; stomach ulcerations

  14. EPR study of manganese(II) binding to 55'-ATP, hemoglobin, and hemocyanin

    Energy Technology Data Exchange (ETDEWEB)

    Chang, S.S. (Duquesne Univ., Pittsburgh); Li, N.C.; Pratt, D.W.

    1975-01-01

    Several divalent metal ions affect the oxygen affinity of hemoglobin and hemocyanin. It is important, therefore, to understand the nature of metal-ion binding to these proteins. By comparing the EPR spectra of Mn(II), 0.001 M, in the absence and presence of carboxyhemoglobin or Limulus oxyhemocyanin (pH 7.3, Trizma buffer), the number of Mn binding sites, n, and the binding constant, K, can be determined. For carboxyhemoglobin, HbCO, we find 0.5 Mn binding sites per heme, K = 450 M/sup -1/. Each hemoglobin tetramer therefore binds two manganous ions suggesting that Mn(II), like Cu(II), may bind preferentially to one of the two types of subunits in hemoglobin. For hemocyanin, HcO/sub 2/, we find n = 5.8, K = 1.55 x 10/sup 3/ M/sup -1/. Each oxyhemocyanine therefore binds approximately six manganous ions, and the binding constant is three times larger than that for HbCO. We have also carried out similar experiments on 5'-ATP, and on solutions of HbCO and ATP containing McCl/sub 2/ or ZnCl/sub 2/. Zn(II) effectively competes with Mn(II) in binding hemoglobin and ATP, whereas Mg(II) does not, in accord with expectations from data on oxygen affinity of hemoglobin. (auth)

  15. Investigation on the interaction between an antimicrobial in aquaculture, malachite green and hemocyanin from mud crab Scylla paramamosain.

    Science.gov (United States)

    Li, Zhenxing; Tang, Boping; Zhang, Hongmei

    2015-01-25

    Interaction between malachite green and hemocyanin of crab plays a crucial role in the metabolism, distribution, and efficacy of toxic dyes in aquaculture. The mechanism of interaction between malachite green and Hc from mud crab was studied by using multi-spectral methods and molecular modeling in this work. The spectroscopic and thermodynamic data show that the interaction is a spontaneous process with the estimated enthalpy and entropy changes of -14.85(±1.86) kJ mol(-1) and 30.38(±5.21) J mol(-1) K(-1), respectively. The binding sites of malachite green in hemocyanin mainly locate in the interface of protein. The hydrophobic and electrostatic forces are the primary contributors to the interaction between hemocyanin and malachite green. The results of ultraviolet-vis absorbance, circular dichroism, and synchronous fluorescence spectroscopy suggest that the binding of malachite green to hemocyanin induces some conformational changes of protein. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Long-term fluctuations in intertidal communities in an Irish sea-lough: Limpet-fucoid cycles

    Science.gov (United States)

    Little, Colin; Trowbridge, Cynthia D.; Pilling, Graham M.; Stirling, Penny; Morritt, David; Williams, Gray A.

    2017-09-01

    Long-term cyclical changes in rocky shore community structure were documented over two decades at sheltered shores in Lough Hyne Marine Reserve, County Cork, Ireland. Three peaks of abundance were recorded for the limpet, Patella vulgata (1990-5, 2002-6 and 2010-14) with oscillations that varied in amplitude and frequency among sites. The cover of the fucoid Fucus vesiculosus varied inversely with limpet abundance and showed the strongest negative correlation with a lag time of 0-2 years. The species complex Fucus spiralis/guiryi showed a weaker correlation with a lag time of 1-2 years. Two other fucoid species showed no such negative correlations despite their close proximity to limpets within the lough's compressed tidal range. There was no relationship between overall barnacle cover (dominated by Austrominius modestus) and the limpet-fucoid cycles, suggesting that the shelter provided by A. modestus for algae to escape from limpet grazing pressure may not be necessary for these cycles to occur on wave-sheltered shores.

  17. Hemocyanin-derived phenoloxidase activity is dependent on dodecameric structure in shrimp Litopenaeus vannamei

    Directory of Open Access Journals (Sweden)

    Wang Ke-Zhou

    2015-01-01

    Full Text Available Hemocyanin (Hc is a multifunctional protein in both mollusks and arthropods. Phenoloxidase (PO activities are the most important physiological functions for Hcs after conversion. In shrimp, Hc occurs as two oligomer forms, dodecamers and hexamers. Differences in the transport oxygen capacity and agglutination activity between the two oligomers of shrimp Hc have been found. In the present study, we investigated the differences in the Hc-derived PO activity between the dodecameric and hexameric Hc forms of the shrimp Litopenaeus vannamei. The two oligomers were separated by non-denaturing polyacrylamide gel electrophoresis, converted by trypsin cleavage and their PO activities were determined by oxidation of L-DOPA. The dodecamers exhibited PO activity after enzymatic conversion while the hexamers did not exhibit PO activity. This result provides new insight into the structural/functional relationships of Hcs.

  18. Immunodominant role of CCHA subunit of Concholepas hemocyanin is associated with unique biochemical properties.

    Science.gov (United States)

    Becker, María Inés; Fuentes, Alejandra; Del Campo, Miguel; Manubens, Augusto; Nova, Esteban; Oliva, Harold; Faunes, Fernando; Valenzuela, María Antonieta; Campos-Vallette, Marcelo; Aliaga, Alvaro; Ferreira, Jorge; De Ioannes, Alfredo E; De Ioannes, Pablo; Moltedo, Bruno

    2009-03-01

    Hemocyanin, the oxygen transporter metallo-glycoprotein from mollusks, shows strong relationship between its notable structural features and intrinsic immunomodulatory effects. Here we investigated the individual contribution of CCHA and CCHB subunits from Concholepas hemocyanin (CCH) to in vivo humoral immune response and their pre-clinical evaluation as immunotherapeutic agent in a mice bladder cancer model, in relation to their biochemical properties. To this end, subunits were purified and well characterized. Homogeneous subunits were obtained by anionic exchange chromatography, and its purity assessed by electrophoretic and immunochemical methods. While each CCH subunit contains eight functional units showing partial cross reaction, the vibrational spectral analysis showed several spectral differences, suggesting structural differences between them. In addition, we demonstrated differences in the carbohydrate content: CCHA had a 3.6% w/w sugar with both N- and O-linked moieties. In turn, CCHB had a 2.5% w/w sugar with N-linked, while O-linked moieties were nearly absent. Considering these differences, it was not possible to predict a priori whether the immunogenic and immunotherapeutic properties of subunits might be similar. Surprisingly, both subunits by itself induced a humoral response, and showed an antitumor effect in the bladder carcinoma cell line MBT-2. However, when immunologic parameters were analyzed, CCHA showed better efficiency than CCHB. No allergic reactions or any toxic effects were observed in mice treated with CCHA, sustaining its potential therapeutic use. Our study supports that CCHA subunit accounts for the most important features involved in the immunogenicity of CCH, such as better hydrophilicity and higher content of carbohydrates.

  19. Oxygen and carbon dioxide transporting qualities of hemocyanin in the hemolymph of a natant decapod Palaemon adspersus

    DEFF Research Database (Denmark)

    Weber, Roy E.; Hagerman, L.

    1981-01-01

    , pH dependent Bohr factor (=logP 50/pH=-2.0 and -0.9 at pH 7.85 and 7.4, respectively) (Figs. 1 and 2). These qualities are distinct from those typifying reptant hemocyanins and appear illsuited for O2 transport at low ambient tensions, but well-adapted for O2 delivery in tissues at high PO2...

  20. Enhanced structural stability of Concholepas hemocyanin increases its immunogenicity and maintains its non-specific immunostimulatory effects.

    Science.gov (United States)

    Arancibia, Sergio; Del Campo, Miguel; Nova, Esteban; Salazar, Fabián; Becker, María Inés

    2012-03-01

    Hemocyanins, which boost the immune system of mammals, have been used as carrier-adjuvants to promote Ab production against haptens and peptides, as immunostimulants during therapy for bladder carcinoma and as a component in therapeutic vaccines for cancer. These biomedical applications have led to growing interest in obtaining hemocyanins with high immunogenicity. Here, we study the immunological properties of a modified oxidized Concholepas concholepas hemocyanin (Ox-CCH) obtained by the oxidation of its carbohydrates using sodium periodate. We assessed the internalization of Ox-CCH into DCs and its immunogenicity and antitumor effects. Transmission electron microscopy showed no changes in Ox-CCH quaternary structure with respect to native CCH, although proteolytic treatment followed by SDS-PAGE analysis demonstrated that Schiff bases were formed. Interestingly, DCs internalized Ox-CCH faster than CCH, mainly through macropinocytosis. During this process, Ox-CCH remained inside endosome-like structures for a longer period. Mouse immunization experiments demonstrated that Ox-CCH is more immunogenic and a better carrier than CCH. Moreover, Ox-CCH showed a significant antitumor effect in the B16F10 melanoma model similar to that produced by CCH, inducing IFN-γ secretion. Together, these data demonstrate that the aldehydes formed by the periodate oxidation of sugar moieties stabilizes the CCH structure, increasing its adjuvant/immunostimulatory carrier effects. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Dose-response effects in immunizations with keyhole limpet haemocyanin and rabies vaccine: shift in some immunodeficiency states

    NARCIS (Netherlands)

    Korver, K.; Boeschoten, E. W.; Krediet, R. T.; van Steenis, G.; Schellekens, P. T.

    1987-01-01

    We investigated the primary antibody response to the antigens keyhole limpet haemocyanin (KLH) and rabies vaccine (RV). Eighty-one healthy volunteers were injected with nine doses of KLH (ranging from 10 to 2500 micrograms) and 66 volunteers with six doses of RV (ranging from 17 to 680 micrograms

  2. The Regulation of Polysaccharide Specific Humoral Immune Response Against Intact Streptococcus Pneumoniae

    Science.gov (United States)

    2008-06-19

    periods of time, and 25% to 75% of infants carry pneumococci at any given time. High colonization rates are promoted by children who are in close ...PC- keyhole limpet hemocyanin (KLH) was synthesized as described previously (Wu, Vos et al. 1999). The resulting conjugate had a substitution degree...635 lasers and results generated using Winlist software. For isolation of MZB and FB cells, RBC-lysed spleen cells were 44 stained for these B cell

  3. Conservation genetics of a critically endangered limpet genus and rediscovery of an extinct species.

    Directory of Open Access Journals (Sweden)

    Diarmaid Ó Foighil

    Full Text Available A third of all known freshwater mollusk extinctions worldwide have occurred within a single medium-sized American drainage. The Mobile River Basin (MRB of Alabama, a global hotspot of temperate freshwater biodiversity, was intensively industrialized during the 20(th century, driving 47 of its 139 endemic mollusk species to extinction. These include the ancylinid limpet Rhodacmea filosa, currently classified as extinct (IUCN Red List, a member of a critically endangered southeastern North American genus reduced to a single known extant population (of R. elatior in the MRB.We document here the tripling of known extant populations of this North American limpet genus with the rediscovery of enduring Rhodacmea filosa in a MRB tributary and of R. elatior in its type locality: the Green River, Kentucky, an Ohio River Basin (ORB tributary. Rhodacmea species are diagnosed using untested conchological traits and we reassessed their systematic and conservation status across both basins using morphometric and genetic characters. Our data corroborated the taxonomic validity of Rhodacmea filosa and we inferred a within-MRB cladogenic origin from a common ancestor bearing the R. elatior shell phenotype. The geographically-isolated MRB and ORB R. elatior populations formed a cryptic species complex: although overlapping morphometrically, they exhibited a pronounced phylogenetic disjunction that greatly exceeded that of within-MRB R. elatior and R. filosa sister species.Rhodacmea filosa, the type species of the genus, is not extinct. It persists in a Coosa River tributary and morphometric and phylogenetic analyses confirm its taxonomic validity. All three surviving populations of the genus Rhodacmea merit specific status. They collectively contain all known survivors of a phylogenetically highly distinctive North American endemic genus and therefore represent a concentrated fraction of continental freshwater gastropod biodiversity. We recommend the establishment

  4. Ocean acidification increases the sensitivity of and variability in physiological responses of an intertidal limpet to thermal stress

    Science.gov (United States)

    Wang, Jie; Russell, Bayden D.; Ding, Meng-Wen; Dong, Yun-Wei

    2018-05-01

    Understanding physiological responses of organisms to warming and ocean acidification is the first step towards predicting the potential population- and community-level ecological impacts of these stressors. Increasingly, physiological plasticity is being recognized as important for organisms to adapt to the changing microclimates. Here, we evaluate the importance of physiological plasticity for coping with ocean acidification and elevated temperature, and its variability among individuals, of the intertidal limpet Cellana toreuma from the same population in Xiamen. Limpets were collected from shaded mid-intertidal rock surfaces. They were acclimated under combinations of different pCO2 concentrations (400 and 1000 ppm, corresponding to a pH of 8.1 and 7.8) and temperatures (20 and 24 °C) in a short-term period (7 days), with the control conditions (20 °C and 400 ppm) representing the average annual temperature and present-day pCO2 level at the collection site. Heart rates (as a proxy for metabolic performance) and expression of genes encoding inducible and constitutive heat-shock proteins (hsp70 and hsc70) at different heat-shock temperatures (26, 30, 34, and 38 °C) were measured. Hsp70 and Hsc70 play important roles in protecting cells from heat stresses, but have different expression patterns, with Hsp70 significantly increased in expression during stress and Hsc70 constitutively expressed and only mildly induced during stress. Analysis of heart rate showed significantly higher temperature coefficients (Q10 rates) for limpets at 20 °C than at 24 °C and post-acclimation thermal sensitivity of limpets at 400 ppm was lower than at 1000 ppm. Expression of hsp70 linearly increased with the increasing heat-shock temperatures, with the largest slope occurring in limpets acclimated under a future scenario (24 °C and 1000 ppm pCO2). These results suggested that limpets showed increased sensitivity and stress response under future conditions. Furthermore, the

  5. Behavioural and physiological responses of limpet prey to a seastar predator and their transmission to basal trophic levels.

    Science.gov (United States)

    Manzur, Tatiana; Vidal, Francisco; Pantoja, José F; Fernández, Miriam; Navarrete, Sergio A

    2014-07-01

    Besides the well-documented behavioural changes induced by predators on prey, predator-induced stress can also include a suite of biochemical, neurological and metabolic changes that may represent important energetic costs and have long-lasting effects on individuals and on the demography of prey populations. The rapid transmission of prey behavioural changes to lower trophic levels, usually associated with alteration of feeding rates, can substantially change and even reverse direction over the long term as prey cope with the energetic costs associated with predation-induced stress. It is therefore critical to evaluate different aspects and assess the costs of non-consumptive predator effects on prey. We investigated the behavioural and physiological responses of an herbivorous limpet, Fissurella limbata, to the presence of chemical cues and direct non-lethal contact by the common seastar predator, Heliaster helianthus. We also evaluated whether the limpets feeding behaviour was modified by the predator and whether this translated into positive or negative effects on biomass of the green alga, Ulva sp. Our experimental results show the presence of Heliaster led to increased movement activity, increased distances travelled, changes in time budget over different environmental conditions and increased feeding rate in the keyhole limpets. Moreover, additional experiments showed that, beyond the increased metabolic rate associated with limpet increased activity, predator chemical cues heighten metabolic rate as part of the induced stress response. Changes in individual movement and displacement distances observed through the 9-day experiment can be interpreted as part of the escape response exhibited by limpets to reduce the risk of being captured by the predator. Increased limpet feeding rate on algae can be visualized as a way individuals compensate for the elevated energetic costs of movement and heightened metabolic rates produced by the predator-induced stress

  6. Monoclonal antibodies to molluskan hemocyanin from Concholepas concholepas demonstrate common and specific epitopes among subunits.

    Science.gov (United States)

    Oliva, Harold; Moltedo, Bruno; De Ioannes, Pablo; Faunes, Fernando; De Ioannes, Alfredo E; Becker, María Inés

    2002-10-01

    We studied the reactivity of mouse monoclonal antibodies (MAbs) against the hemocyanin from the Chilean marine gastropod Concholepas concholepas (CCH). This protein has been successfully used as a carrier to produce antibodies to haptens and peptides. All MAbs (13) belonging to IgG subclass exhibit dissociation constants (K(d)) from 1 x 10(-7) M to 1 x 10(-9) M. MAbs were characterized by enzyme-linked immunosorbant assay (ELISA) using CCH treated with different procedures, including dissociation into CCH-A and CCH-B subunits, Western blot, enzymatic digestion, chemical deglycosylation, and thermal denaturation. MAbs were classified into three categories, according to subunit specificity by ELISA. The epitope distribution shows that CCH subunits display common epitopes (group I, 5 MAbs, 1H5, 2A8, 3A5, 3B3, and 3E3), as well as specific epitopes for CCH-A subunits (group II, 3 MAbs, 1B8, 4D8, and 8E5) and for CCH-B subunits (group III, 5 MAbs, 1A4, 1E4, 2H10, 3B7, and 7B4). The results can be summarized as follows: (1). six antibodies react with thermal denatured CCH, suggesting that they recognize linear epitopes, whereas seven recognize conformational epitopes; (2). oxidation of carbohydrate moieties does not affect the binding of the MAbs; (3). enzymatic digestion of CCH decreases the reactivity of all antibodies irrespective of the protease used (elastase or trypsin); (4). bringing together the above data, in addition to epitopic complementarity analysis, we identified 12 different epitopes on the CCH molecule recognized by these MAbs. The anti-CCH MAbs presented here can be useful tools to understand the subunit organization of the CCH and its complex structure, which can explain its immunogenic and immunostimulating properties in mammals.

  7. Molecular and functional characterization of hemocyanin of the giant African millipede, Archispirostreptus gigas.

    Science.gov (United States)

    Damsgaard, Christian; Fago, Angela; Hagner-Holler, Silke; Malte, Hans; Burmester, Thorsten; Weber, Roy E

    2013-05-01

    In contrast to other terrestrial arthropods, where gaseous O2 that fuels aerobic metabolism diffuses to the tissues in tracheal tubes, and most other metazoans, where O2 is transported to tissues by circulating respiratory proteins, the myriapods (millipedes and centipedes) strikingly have tracheal systems as well as circulating hemocyanin (Hc). In order to elucidate the evolutionary origin and biological significance of millipede Hc, we report the molecular structure (subunit composition and amino acid sequence) of multimeric (36-mer) Hc from the forest floor-dwelling giant African millipede Archispirostreptus gigas and its allosteric oxygen-binding properties under various physico-chemical conditions. Archispirostreptus gigas Hc consists of only a single subunit type with differential glycosylation. Phylogenic analysis revealed that millipede Hc is a sister group to centipede HcA, which supports an early divergence of distinct Hc subunits in myriapods and an ancient origin of multimeric Hcs. Archispirostreptus gigas Hc binds O2 with a high affinity and shows a strong Bohr effect. O2 binding is, moreover, modulated by Ca(2+) ions, which increase the O2 affinity of the Hc in the tense (T; deoxygenated) as well as the relaxed (R; oxygenated) states, and by (l)-lactate, which modulates Hc-O2 affinity by changing the allosteric equilibrium constant, L. Cooperativity in O2 binding at half O2 saturation (n50) is pH dependent and maximal at ~pH 7.4, and the number of interacting O2-binding sites (q) is markedly increased by binding Ca(2+). The data are discussed in the light of the mutually supplementary roles of Hc and the tracheal system for tissue O2 supply.

  8. A highly conspicuous mineralized composite photonic architecture in the translucent shell of the blue-rayed limpet

    OpenAIRE

    Li, Ling; Kolle, Stefan; Weaver, James C.; Ortiz, Christine; Aizenberg, Joanna; Kolle, Mathias

    2015-01-01

    Many species rely on diverse selections of entirely organic photonic structures for the manipulation of light and the display of striking colours. Here we report the discovery of a mineralized hierarchical photonic architecture embedded within the translucent shell of the blue-rayed limpet Patella pellucida. The bright colour of the limpet’s stripes originates from light interference in a periodically layered zig-zag architecture of crystallographically co-oriented calcite lamellae. Beneath t...

  9. Dietary protein and carbohydrate requirement of juvenile Hawaiian limpet (Cellana sandwicensis Pease, 1861 fed practical diet

    Directory of Open Access Journals (Sweden)

    Nhan Thai Hua

    2016-10-01

    Full Text Available Abstract This study was conducted to evaluate dietary protein and carbohydrate requirement of juvenile Hawaiian limpets Cellana sandwincensis. A total of 64 juvenile limpets (3.12 ± 0.86 g were fed five different dietary protein levels ranging from 270 to 470 g kg−1 for 90 days. Carbohydrate and lipid levels were held constant at 180 and 49.7 g kg−1, respectively. Weight gain and growth rates of the animals did not differ significantly (P > 0.05 among the protein levels ranging from 270 g kg−1 (0.30 % day−1 to 470 g kg−1 (0.23 % day−1. Next, opihi were fed four diets with protein levels from 210 to 500 g kg−1 with a constant carbohydrate level at 120 g kg−1. Weight gain and specific growth rates of opihi increased with increasing dietary protein from 210 to 350 g kg−1, and significantly (P < 0.05 decreased at the 500 g kg−1 diet. Highest weight gain, growth rates, and protein efficiency ratio were achieved at 350 g kg−1. Elevated carbohydrate levels (180–370 g kg−1 produced a significant difference (P < 0.05 in growth. The fastest growth rates of animals were obtained with 270 g kg−1 (0.27 % day−1 and 320 g kg−1 (0.26 % day−1. The weight gain of animals fed 180 and 370 g kg−1 carbohydrate diets were significantly (P < 0.05 lower than those of animals fed 270 and 320 g kg−1. We conclude that about 350 g kg−1 protein and 320 g kg−1 carbohydrate levels could be used for opihi.

  10. Cellular biomarker responses of limpets (Mollusca as measure of sensitivity to cadmiumcontamination

    Directory of Open Access Journals (Sweden)

    Koot Reinecke

    2008-09-01

    Full Text Available Due to the availability and chemical nature of some heavy metals, sub-lethal toxicant levels may persist in the ocean waters and may cause physiological problems and toxicity in invertebrates and other marine organisms. Although studies of metal concentrations in False Bay showed relatively low mean concentrations of Cd, invertebrates such as molluscs, crustaceans and many other groups are able to accumulate high levels of heavy metals in their tissues and still survive in the heaviest polluted areas. They can accumulate numerous pollutants from natural waters in quantities that are many orders of magnitude higher than background levels. Bioaccumulation ofcadmium in intertidal species could cause stress which may be measurable at the cellular level. A variety of limpet species that may serve as suitable ecotoxicological monitoring species occur in abundance on rocky shores along the South African coastline. The aim of this study was to obtain sensitivity data which could contribute to the selection of a suitable monitoring species and the eventual establishment of a species sensitivity distribution model (SSD with a biomarker responseas endpoint. The limpets Cymbula oculus, Scutellastra longicosta, Cymbula granatina and Scutellastragranularis as well as water samples were collected at two localities in False Bay, South Africa. Analysis of water and biological samples were done by atomic absorption spectrometry. Exposures were done to three different sublethal concentrations of cadmium in the laboratory in static flow tanks over three days. There was a moderate increase in cadmium body concentrations over time. Results obtained at three exposure concentrations showed no significant differences in metal concentrations between the different C. oculus samples. Significant differences were obtained between the control and the exposure groups for each exposure time except between the control and the 1mg/L CdCl2 exposure group after 24 and 72 hours of

  11. Differential precocious sexual development of Proctoeces lintoni (Digenea: Fellodistomidae) in three sympatric species of keyhole limpets Fissurella spp. may affect transmission to the final host.

    Science.gov (United States)

    Balboa, L; George-Nascimento, M; Ojeda, F P

    2001-10-01

    The prevalence, abundance, and developmental status of the digenetic trematode Proctoeces lintoni Siddiqui et Cable 1960 were compared in 3 species of keyhole limpets Fissurella. A total of 197 limpets was collected at Caleta Chome, south-central Chile. Fissurella picta and F. costata had the highest prevalence of infection, whereas F. picta showed the greatest abundance of parasites, which increased with host shell length. However, the frequency of P. lintoni specimens with eggs in the uterus was greatest in F. costata. These results suggest that an increased rate of development of a parasite in the intermediate host may shorten the residence time necessary for maturation in the final host. Thus, faster development of the parasite in F. costata suggests the possibility that the parasites transmitted through this host species have shorter maturation times in clingfishes than individuals transmitted via other limpet species.

  12. Barriers to gene flow in the marine environment: insights from two common intertidal limpet species of the Atlantic and Mediterranean.

    Directory of Open Access Journals (Sweden)

    Alexandra Sá-Pinto

    Full Text Available Knowledge of the scale of dispersal and the mechanisms governing gene flow in marine environments remains fragmentary despite being essential for understanding evolution of marine biota and to design management plans. We use the limpets Patella ulyssiponensis and Patella rustica as models for identifying factors affecting gene flow in marine organisms across the North-East Atlantic and the Mediterranean Sea. A set of allozyme loci and a fragment of the mitochondrial gene cytochrome C oxidase subunit I were screened for genetic variation through starch gel electrophoresis and DNA sequencing, respectively. An approach combining clustering algorithms with clinal analyses was used to test for the existence of barriers to gene flow and estimate their geographic location and abruptness. Sharp breaks in the genetic composition of individuals were observed in the transitions between the Atlantic and the Mediterranean and across southern Italian shores. An additional break within the Atlantic cluster separates samples from the Alboran Sea and Atlantic African shores from those of the Iberian Atlantic shores. The geographic congruence of the genetic breaks detected in these two limpet species strongly supports the existence of transpecific barriers to gene flow in the Mediterranean Sea and Northeastern Atlantic. This leads to testable hypotheses regarding factors restricting gene flow across the study area.

  13. Top-down impact through a bottom-up mechanism: the effect of limpet grazing on growth, productivity and carbon allocation of Zostera marina L. (eelgrass).

    Science.gov (United States)

    Zimmerman, Richard C; Kohrs, Donald G; Alberte, Randall S

    1996-09-01

    The unusual appearance of a commensal eelgrass limpet [Tectura depicta (Berry)] from southern California at high density (up to 10 shoot -1 ) has coincided with the catastrophic decline of a subtidal Zostera marina L. meadow in Monterey Bay, California. Some commensal limpets graze the chloroplast-rich epidermis of eelgrass leaves, but were not known to affect seagrass growth or productivity. We evaluated the effect on eelgrass productivity of grazing by limpets maintained at natural densities (8±2 shoot -1 ) in a natural light mesocosm for 45 days. Growth rates, carbon reserves, root proliferation and net photosynthesis of grazed plants were 50-80% below those of ungrazed plants, but biomass-specific respiration was unaffected. The daily period of irradiance-saturated photosynthesis (H sat ) needed to maintain positive carbon balance in grazed plants approached 13.5 h, compared with 5-6 h for ungrazed plants. The amount of carbon allocated to roots of ungrazed plants was 800% higher than for grazed plants. By grazing the chlorophyll-rich epidermis, T. depicta induced carbon limitation in eelgrass growing in an other-wise light-replete environment. Continued northward movement of T. depicta, may have significant impacts on eelgrass production and population dynamics in the northeast Pacific, even thought this limpet consumes very little plant biomass. This interaction is a dramatic example of top-down control (grazing/predation) of eelgrass productivity and survival operating via a bottom-up mechanism (photosynthesis limitation).

  14. Genetics, Gene Flow, and Glaciation: The Case of the South American Limpet Nacella mytilina.

    Directory of Open Access Journals (Sweden)

    Claudio A González-Wevar

    Full Text Available Glacial episodes of the Quaternary, and particularly the Last Glacial Maximum (LGM drastically altered the distribution of the Southern-Hemisphere biota, principally at higher latitudes. The irregular coastline of Patagonia expanding for more than 84.000 km constitutes a remarkable area to evaluate the effect of Quaternary landscape and seascape shifts over the demography of near-shore marine benthic organisms. Few studies describing the biogeographic responses of marine species to the LGM have been conducted in Patagonia, but existing data from coastal marine species have demonstrated marked genetic signatures of post-LGM recolonization and expansion. The kelp-dweller limpet Nacella mytilina is broadly distributed along the southern tip of South America and at the Falkland/Malvinas Islands. Considering its distribution, abundance, and narrow bathymetry, N. mytilina represents an appropriate model to infer how historical and contemporary processes affected the distribution of intraspecific genetic diversity and structure along the southern tip of South America. At the same time, it will be possible to determine how life history traits and the ecology of the species are responsible for the current pattern of gene flow and connectivity across the study area. We conducted phylogeographic and demographic inference analyses in N. mytilina from 12 localities along Pacific Patagonia (PP and one population from the Falkland/Malvinas Islands (FI. Analyses of the mitochondrial gene COI in 300 individuals of N. mytilina revealed low levels of genetic polymorphism and the absence of genetic differentiation along PP. In contrast, FI showed a strong and significant differentiation from Pacific Patagonian populations. Higher levels of genetic diversity were also recorded in the FI population, together with a more expanded genealogy supporting the hypothesis of glacial persistence of the species in these islands. Haplotype genealogy, and mismatch analyses in

  15. Genetics, Gene Flow, and Glaciation: The Case of the South American Limpet Nacella mytilina

    Science.gov (United States)

    González-Wevar, Claudio A.; Rosenfeld, Sebastián; Segovia, Nicolás I.; Hüne, Mathias; Gérard, Karin; Ojeda, Jaime; Mansilla, Andrés; Brickle, Paul; Díaz, Angie; Poulin, Elie

    2016-01-01

    Glacial episodes of the Quaternary, and particularly the Last Glacial Maximum (LGM) drastically altered the distribution of the Southern-Hemisphere biota, principally at higher latitudes. The irregular coastline of Patagonia expanding for more than 84.000 km constitutes a remarkable area to evaluate the effect of Quaternary landscape and seascape shifts over the demography of near-shore marine benthic organisms. Few studies describing the biogeographic responses of marine species to the LGM have been conducted in Patagonia, but existing data from coastal marine species have demonstrated marked genetic signatures of post-LGM recolonization and expansion. The kelp-dweller limpet Nacella mytilina is broadly distributed along the southern tip of South America and at the Falkland/Malvinas Islands. Considering its distribution, abundance, and narrow bathymetry, N. mytilina represents an appropriate model to infer how historical and contemporary processes affected the distribution of intraspecific genetic diversity and structure along the southern tip of South America. At the same time, it will be possible to determine how life history traits and the ecology of the species are responsible for the current pattern of gene flow and connectivity across the study area. We conducted phylogeographic and demographic inference analyses in N. mytilina from 12 localities along Pacific Patagonia (PP) and one population from the Falkland/Malvinas Islands (FI). Analyses of the mitochondrial gene COI in 300 individuals of N. mytilina revealed low levels of genetic polymorphism and the absence of genetic differentiation along PP. In contrast, FI showed a strong and significant differentiation from Pacific Patagonian populations. Higher levels of genetic diversity were also recorded in the FI population, together with a more expanded genealogy supporting the hypothesis of glacial persistence of the species in these islands. Haplotype genealogy, and mismatch analyses in the FI population

  16. Oxidative stress generated by diesel seawater contamination in the digestive gland of the Antarctic limpet, Nacella concinna

    Energy Technology Data Exchange (ETDEWEB)

    Ansaldo, M. [Instituto Antartico Argentino, Buenos Aires (Argentina); Najle, R. [Universidad del Centro de la Provincia de Buenos Aires, Tandil (Argentina). Facultad Cs. Veterinarias; Luquet, C.M. [Universidad de Buenos Aires, Ciudad Univ. (Argentina). Dept. de Biodiversidad y Biologia Experimental

    2005-05-01

    The aim of this work was to investigate the activity of antioxidant enzymes and oxidative damage in the digestive gland of the limpet Nacella concinna, and their suitability as biomarkers for hydrocarbon pollution in Antarctic coasts. Three groups of 30 individuals each were kept in seawater containing 0%, 0.05% or 0.1% diesel. Superoxide dismutase, catalase, glutathione S transferase and glutathione peroxidase activities, as well as lipid peroxidation and protein oxidation were studied in 18 animals of each group after 24, 48 and 168 h of exposure. The activity levels of most enzymes were increased by diesel in a dose-dependent manner. Glutathione peroxidase showed the most clear effect; its activity significantly increased in the 0.1% diesel group respect to the control. Lipid peroxidation and protein oxidation were significantly increased by diesel after 168 h. Both variables were higher in the group exposed to the lowest dose. (author)

  17. Thermal reaction norms and the scale of temperature variation: latitudinal vulnerability of intertidal nacellid limpets to climate change.

    Directory of Open Access Journals (Sweden)

    Simon A Morley

    Full Text Available The thermal reaction norms of 4 closely related intertidal Nacellid limpets, Antarctic (Nacella concinna, New Zealand (Cellana ornata, Australia (C. tramoserica and Singapore (C. radiata, were compared across environments with different temperature magnitude, variability and predictability, to test their relative vulnerability to different scales of climate warming. Lethal limits were measured alongside a newly developed metric of "duration tenacity", which was tested at different temperatures to calculate the thermal reaction norm of limpet adductor muscle fatigue. Except in C. tramoserica which had a wide optimum range with two break points, duration tenacity did not follow a typical aerobic capacity curve but was best described by a single break point at an optimum temperature. Thermal reaction norms were shifted to warmer temperatures in warmer environments; the optimum temperature for tenacity (T(opt increased from 1.0°C (N. concinna to 14.3°C (C. ornata to 18.0°C (an average for the optimum range of C. tramoserica to 27.6°C (C. radiata. The temperature limits for duration tenacity of the 4 species were most consistently correlated with both maximum sea surface temperature and summer maximum in situ habitat logger temperature. Tropical C. radiata, which lives in the least variable and most predictable environment, generally had the lowest warming tolerance and thermal safety margin (WT and TSM; respectively the thermal buffer of CT(max and T(opt over habitat temperature. However, the two temperate species, C. ornata and C. tramoserica, which live in a variable and seasonally unpredictable microhabitat, had the lowest TSM relative to in situ logger temperature. N. concinna which lives in the most variable, but seasonally predictable microhabitat, generally had the highest TSMs. Intertidal animals live at the highly variable interface between terrestrial and marine biomes and even small changes in the magnitude and predictability of their

  18. Thermal reaction norms and the scale of temperature variation: latitudinal vulnerability of intertidal nacellid limpets to climate change.

    Science.gov (United States)

    Morley, Simon A; Martin, Stephanie M; Day, Robert W; Ericson, Jess; Lai, Chien-Houng; Lamare, Miles; Tan, Koh-Siang; Thorne, Michael A S; Peck, Lloyd S

    2012-01-01

    The thermal reaction norms of 4 closely related intertidal Nacellid limpets, Antarctic (Nacella concinna), New Zealand (Cellana ornata), Australia (C. tramoserica) and Singapore (C. radiata), were compared across environments with different temperature magnitude, variability and predictability, to test their relative vulnerability to different scales of climate warming. Lethal limits were measured alongside a newly developed metric of "duration tenacity", which was tested at different temperatures to calculate the thermal reaction norm of limpet adductor muscle fatigue. Except in C. tramoserica which had a wide optimum range with two break points, duration tenacity did not follow a typical aerobic capacity curve but was best described by a single break point at an optimum temperature. Thermal reaction norms were shifted to warmer temperatures in warmer environments; the optimum temperature for tenacity (T(opt)) increased from 1.0°C (N. concinna) to 14.3°C (C. ornata) to 18.0°C (an average for the optimum range of C. tramoserica) to 27.6°C (C. radiata). The temperature limits for duration tenacity of the 4 species were most consistently correlated with both maximum sea surface temperature and summer maximum in situ habitat logger temperature. Tropical C. radiata, which lives in the least variable and most predictable environment, generally had the lowest warming tolerance and thermal safety margin (WT and TSM; respectively the thermal buffer of CT(max) and T(opt) over habitat temperature). However, the two temperate species, C. ornata and C. tramoserica, which live in a variable and seasonally unpredictable microhabitat, had the lowest TSM relative to in situ logger temperature. N. concinna which lives in the most variable, but seasonally predictable microhabitat, generally had the highest TSMs. Intertidal animals live at the highly variable interface between terrestrial and marine biomes and even small changes in the magnitude and predictability of their

  19. Optical phase conjugation

    CERN Document Server

    Fisher, Robert A

    1983-01-01

    This book appears at a time of intense activity in optical phase conjugation. We chose not to await the maturation of the field, but instead to provide this material in time to be useful in its development. We have tried very hard to elucidate and interrelate the various nonlinear phenomena which can be used for optical phase conjugation.

  20. Los patelogastrópodos intermareales de Chile y Perú Intertidal limpets of Chile and Peru

    Directory of Open Access Journals (Sweden)

    CARMEN ESPOZ

    2004-06-01

    diversos del mundo. Más aún, esta variabilidad y flexibilidad pueden ser responsables de las confusiones taxonómicas que han rodeado a este conjunto faunísticoIn this study we present a classification system reflecting the phylogenetic relationships for the intertidal patellogastropods of Chile and Peru. We infer phylogenetic relationships between limpets species using DNA sequences from the 16S region of the mitochondrial genome. We include a comparative limpet study of: shell structure, color and morphological patterns of the shell, radular teeth and anatomy. Additionally, we provide information about the distribution and ecology for members of this group within the studied area. The results show a Chilean-Peruvian Lottiidae fauna consisting of at least nine species, which are grouped into a single monophyletic clade Scurria (S. variabilis, S. zebrina, S. viridula, S. plana, S. scurra, S. araucana, S. ceciliana and a non identificated species, and a "problematic taxon" preliminarily assigned to the genus Lottia (Lottia orbignyi. The group of species is present in the intertidal rocky shores between 5º S and 54º S, from the upper to the lower intertidal fringes, ranging from exposed to protected areas. The systematic outcome of this study suggests the synonymization of S. parasitica to S. variabilis, and of S. ceciliana to S. boehmita. According to our field results, the species S. variabilis shows at least three ecophenotypes: (1 on rocky substrates along the full geographic range, (2 on the shells of the key-hole limpets: Fissurella crassa and F. limbata mainly in central and south of Chile, and (3 on the chiton plates of Enoplochiton niger in the north of Chile and south of Perú. S. ceciliana is a species in which morphology and color patterns are highly variable. In general, this variability indicates that the Chilean-Peruvian limpet species are among the most complex and diverse limpet fauna in the world. This, may reflects the taxonomic confusion which has

  1. Polybrominated diphenyl ethers do not affect metamorphosis but alter the proteome of the invasive slipper limpet Crepidula onyx.

    Science.gov (United States)

    Mukherjee, Joy; Po, Beverly H K; Chiu, Jill M Y; Wu, Rudolf S S; Qian, Pei-Yuan; Thiyagarajan, Vengatesen

    2013-08-15

    Man-made polybrominated diphenyl ethers (PBDEs) used as flame retardants in various consumer products may be harmful to marine organisms. Larvae of some marine invertebrates, especially invasive species, can develop resistance to PBDEs through altered protein expression patterns or proteome plasticity. This is the first report of a proteomics approach to study BDE-47 induced molecular changes in the invasive limpet Crepidula onyx. Larvae of C. onyx were cultured for 5 days (hatching to metamorphosis) in the presence of BDE-47 (1 μg L(-1)). Using a 2-DE proteomics approach with triple quadrupole and high-resolution TOF-MS, we showed that BDE-47 altered the proteome structure but not the growth or metamorphosis of C. onyx larvae. We found eight significant differentially expressed proteins in response to BDE-47, deemed the protein expression signature, consisting of cytoskeletal, stress tolerance, metabolism and energy production related proteins. Our data suggest C. onyx larvae have adequate proteome plasticity to tolerate BDE-47 toxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Qualidade conjugal: mapeando conceitos

    Directory of Open Access Journals (Sweden)

    Clarisse Mosmann

    2006-12-01

    Full Text Available Apesar da ampla utilização do conceito de qualidade conjugal, identifica-se falta de clareza conceitual acerca das variáveis que o compõem. Esse artigo apresenta revisão da literatura na área com o objetivo de mapear o conceito de qualidade conjugal. Foram analisadas sete principais teorias sobre o tema: Troca Social, Comportamental, Apego, Teoria da Crise, Interacionismo Simbólico. Pelos postulados propostos nas diferentes teorias, podem-se identificar três grupos de variáveis fundamentais na definição da qualidade conjugal: recursos pessoais dos cônjuges, contexto de inserção do casal e processos adaptativos. Neste sentido, a qualidade conjugal é resultado do processo dinâmico e interativo do casal, razão deste caráter multidimensional.

  3. Conjugate Gaze Palsies

    Science.gov (United States)

    ... version Home Brain, Spinal Cord, and Nerve Disorders Cranial Nerve Disorders Conjugate Gaze Palsies Horizontal gaze palsy Vertical ... Version. DOCTORS: Click here for the Professional Version Cranial Nerve Disorders Overview of the Cranial Nerves Internuclear Ophthalmoplegia ...

  4. Conjugated Polymer Solar Cells

    National Research Council Canada - National Science Library

    Paraschuk, Dmitry Y

    2006-01-01

    This report results from a contract tasking Moscow State University as follows: Conjugated polymers are promising materials for many photonics applications, in particular, for photovoltaic and solar cell devices...

  5. Polymers for Protein Conjugation

    Directory of Open Access Journals (Sweden)

    Gianfranco Pasut

    2014-01-01

    Full Text Available Polyethylene glycol (PEG at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones.

  6. Development of Immunoassay Based on Monoclonal Antibody Reacted with the Neonicotinoid Insecticides Clothianidin and Dinotefuran

    OpenAIRE

    Uchigashima, Mikiko; Watanabe, Eiki; Ito, Shigekazu; Iwasa, Seiji; Miyake, Shiro

    2012-01-01

    Enzyme-linked immunosorbent assay (ELISA) based on a monoclonal antibody (MoAb) was developed for the neonicotinoid insecticide clothianidin. A new clothianidin hapten (3-[5-(3-methyl-2-nitroguanidinomethyl)-1,3-thiazol-2-ylthio] propionic acid) was synthesized and conjugated to keyhole limpet hemocyanin, and was used for monoclonal antibody preparation. The resulting MoAb CTN-16A3-13 was characterized by a direct competitive ELISA (dc-ELISA). The 50% of inhibition concentration value with cl...

  7. Vectors for Treatment of Metastatic Breast Cancer

    Science.gov (United States)

    2006-08-01

    hMUC-1/ecdCD40L protein (F): bacterial cell lysate (), keyhole limpet hemocyanin (KLH)- conjugated hMUC-1 Ag with (E) and without (‚) IFA, and PBS...antimouse CD11C antibody were added to the purified DCs. (iii) Cells exposed to a laser excitatory for phycoerythrin. (iv) Cells exposed to a laser ...under nondenaturing conditions was close to 3 Figure 4. The ecdhMUC1 protein released from Ad-sig-ecdhMUC1/ecdCD40L vector–infected cells forms

  8. Annual gametogenesis and reproductive effort of the limpet Cellana grata (Gould, 1859) (Gastropoda: Nacellidae) in a rocky intertidal beach at Ulleungdo Island off the east coast of Korea

    Science.gov (United States)

    Yang, Hyun-Sung; Kang, Do-Hyung; Park, Heung-Sik; Choi, Kwang-Sik

    2017-12-01

    Widely distributed from the northern coast of Vietnam to the northern Japan, the limpet Cellana grata (Gould, 1859) occurs commonly on the south and east coasts of Korea. Despite their wide distribution range, few studies have investigated the annual gametogenesis and reproductive effort of C. grata. In an attempt to understand the reproductive physiology of the limpet, we investigated the annual gametogenesis and reproductive effort of C. grata from Ulleungdo Island off the east coast of Korea. Histology revealed that the gonial mitosis commenced in January, as the female exhibited small oogonia (10-40 μm) in the follicle. From March to June, the oocyte size increased dramatically, and fully mature eggs (110-170 μm in diameter) appeared in early summer. First spawning males and females were observed in July, as the surface seawater temperature (SST) reached 22.1°C. The spawning male and females could be observed until the end of December. Gonad somatic index (GSI), a ratio of gonad mass to the total tissue weight, of the male ranged from 0.6 (April) to 17.9 (July), while the female GSI varied from 1.0 (February) to 18.3 (July). GSI of male and female declined rapidly from July to August, suggesting that the major purse of the spawning at the study site was between July and August. Our study suggested that the commercial catch of C. grata during July and August must be suspended at Ulleungdo Island, in order to protect the spawning limpets, which enhances C. grata recruitment and the population.

  9. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  10. Photoluminescence in conjugated polymers

    International Nuclear Information System (INIS)

    Furst, J.E.; Laugesen, R.; Dastoor, P.; McNeill, C.

    2002-01-01

    Full text: Conjugated polymers combine the electronic and optical properties of semiconductors with the processability of polymers. They contain a sequence of alternate single and double carbon bonds so that the overlap of unhybridised p z orbitals creates a delocalised ρ system which gives semiconducting properties with p-bonding (valence) and p* -antibonding (conduction) bands. Photoluminesence (PL) in conjugated polymers results from the radiative decay of singlet excitons confined to a single chain. The present work is the first in a series of studies in our laboratory that will characterize the optical properties of conjugated polymers. The experiment involves the illumination of thin films of conjugated polymer with UV light (I=360 nm) and observing the subsequent fluorescence using a custom-built, fluorescence spectrometer. Photoluminesence spectra provide basic information about the structure of the polymer film. A typical spectrum is shown in the accompanying figure. The position of the first peak is related to the polymer chain length and resolved multiple vibronic peaks are an indication of film structure and morphology. We will also present results related to the optical degradation of these materials when exposed to air and UV light

  11. DNA-cell conjugates

    Science.gov (United States)

    Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki

    2018-05-15

    The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.

  12. DNA-cell conjugates

    Science.gov (United States)

    Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki

    2016-05-03

    The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.

  13. Benthic diatoms from Potter Cove, 25 de Mayo (King George) Island, Antarctica: Mucilage and glucan storage as a C-source for limpets

    Science.gov (United States)

    Daglio, Yasmin; Sacristán, Hernán; Ansaldo, Martín; Rodríguez, María C.

    2018-03-01

    Biofilms were allowed to develop on ceramic tiles placed in closed containers on the shore of Potter Cove, 25 de Mayo (King George) Island. Water pumping from the cove inside the containers extended for 25 days. Diatoms were the dominant microalgae in these biofilms, which were removed from a set of tiles to a) characterize the extracellular mucilage, b) carry out floristic determination and c) perform grazing experiments with the limpet Nacella concinna. Biofilms mucilaginous matrix consisted of proteins and carbohydrates. Room temperature aqueous extraction of the freeze-dried material rendered a fraction enriched in the storage glucan chrysolaminarin, its identity confirmed by methylation structural analyses. Hot water extracted products showed greater heterogeneity in monosaccharide composition, including glucose, mannose, galactose, fucose, xylose and rhamnose. Diatom identification revealed that Pseudogomphonema kamtschaticum was the dominant species followed by several Navicula species, Nitzschia pellucida and Synedra kerguelensis. Photographical survey of colonized tiles placed in glass flasks together with a specimen of Nacella concinna exhibited between 5 and 30% removal of the biofilms coverage after 24 h of exposure to the limpet, suggesting that EPS and chrysolaminarin constitute a C-source for the gastropod.

  14. Limpet Shells from the Aterian Level 8 of El Harhoura 2 Cave (Témara, Morocco): Preservation State of Crossed-Foliated Layers

    Science.gov (United States)

    Nouet, Julius; Chevallard, Corinne; Farre, Bastien; Nehrke, Gernot; Campmas, Emilie; Stoetzel, Emmanuelle; El Hajraoui, Mohamed Abdeljalil; Nespoulet, Roland

    2015-01-01

    The exploitation of mollusks by the first anatomically modern humans is a central question for archaeologists. This paper focuses on level 8 (dated around ∼ 100 ka BP) of El Harhoura 2 Cave, located along the coastline in the Rabat-Témara region (Morocco). The large quantity of Patella sp. shells found in this level highlights questions regarding their origin and preservation. This study presents an estimation of the preservation status of these shells. We focus here on the diagenetic evolution of both the microstructural patterns and organic components of crossed-foliated shell layers, in order to assess the viability of further investigations based on shell layer minor elements, isotopic or biochemical compositions. The results show that the shells seem to be well conserved, with microstructural patterns preserved down to sub-micrometric scales, and that some organic components are still present in situ. But faint taphonomic degradations affecting both mineral and organic components are nonetheless evidenced, such as the disappearance of organic envelopes surrounding crossed-foliated lamellae, combined with a partial recrystallization of the lamellae. Our results provide a solid case-study of the early stages of the diagenetic evolution of crossed-foliated shell layers. Moreover, they highlight the fact that extreme caution must be taken before using fossil shells for palaeoenvironmental or geochronological reconstructions. Without thorough investigation, the alteration patterns illustrated here would easily have gone unnoticed. However, these degradations are liable to bias any proxy based on the elemental, isotopic or biochemical composition of the shells. This study also provides significant data concerning human subsistence behavior: the presence of notches and the good preservation state of limpet shells (no dissolution/recrystallization, no bioerosion and no abrasion/fragmentation aspects) would attest that limpets were gathered alive with tools by

  15. Limpet Shells from the Aterian Level 8 of El Harhoura 2 Cave (Témara, Morocco: Preservation State of Crossed-Foliated Layers.

    Directory of Open Access Journals (Sweden)

    Julius Nouet

    Full Text Available The exploitation of mollusks by the first anatomically modern humans is a central question for archaeologists. This paper focuses on level 8 (dated around ∼ 100 ka BP of El Harhoura 2 Cave, located along the coastline in the Rabat-Témara region (Morocco. The large quantity of Patella sp. shells found in this level highlights questions regarding their origin and preservation. This study presents an estimation of the preservation status of these shells. We focus here on the diagenetic evolution of both the microstructural patterns and organic components of crossed-foliated shell layers, in order to assess the viability of further investigations based on shell layer minor elements, isotopic or biochemical compositions. The results show that the shells seem to be well conserved, with microstructural patterns preserved down to sub-micrometric scales, and that some organic components are still present in situ. But faint taphonomic degradations affecting both mineral and organic components are nonetheless evidenced, such as the disappearance of organic envelopes surrounding crossed-foliated lamellae, combined with a partial recrystallization of the lamellae. Our results provide a solid case-study of the early stages of the diagenetic evolution of crossed-foliated shell layers. Moreover, they highlight the fact that extreme caution must be taken before using fossil shells for palaeoenvironmental or geochronological reconstructions. Without thorough investigation, the alteration patterns illustrated here would easily have gone unnoticed. However, these degradations are liable to bias any proxy based on the elemental, isotopic or biochemical composition of the shells. This study also provides significant data concerning human subsistence behavior: the presence of notches and the good preservation state of limpet shells (no dissolution/recrystallization, no bioerosion and no abrasion/fragmentation aspects would attest that limpets were gathered alive

  16. Ancient limpet shells as paleo-environmental and ethno-archaeological archives: the case of Beniguet Island's shell middens (Iroise Sea)

    Science.gov (United States)

    Cudennec, Jean-François; Stephan, Pierre; Dupont, Catherine; Pailler, Yvan; Thébault, Julien; Schöne, Bernd; Paulet, Yves-Marie

    2017-04-01

    During the winter 2013-2014, severe storm events caused a coastal erosion in the southern part of the Beniguet Island (Brittany, France). The associated shoreline retreat had uncovered three layers of shell middens interbedded into an aeolian sand dune deposit. From several radiocarbon dating crossed with the study of ceramic and lithic contents, the shell middens were dated to the Final Neolithic (2400 BC), the Early Bronze Age (2000 BC) and the Early Middle Age (800 AD) respectively. This site offers a unique opportunity to collect two types of information: palaeo-environmental (palaeo-temperature of sea water) and archaeological (determination of harvest season). In this study, we focus on gastropod of the genus Patella which represent 90% of the remains found in this midden. This organism is potentially a highly valuable archive for these environments because they are intertidal and relatively sedentary. We studied the growth rings in the outer calcitic layer of individual limpet shells from the Neolithic, Early Bronze Age and Present Day populations. We report here the results of δ18O analyses. We found a similarity between the reconstructed palaeo-temperature in the Neolithic and the Present periods (between 13 and 14°C in summer and about 8 - 9°C in winter). However, palaeo-temperatures of the Early Bronze Age shells are significantly lower in winter (5 - 6 °C). Moreover, the initial results of the δ18O analyses at the margin of these shells showed that they were harvested during a specific season (end of spring or early summer). Additional work will be done to address questions about shell growth dynamics of these species. These results confirm the interest of using ancient limpet shells as palaeo-environmental and archaeological archives.

  17. Organometallic B12-DNA conjugate

    DEFF Research Database (Denmark)

    Hunger, Miriam; Mutti, Elena; Rieder, Alexander

    2014-01-01

    Design, synthesis, and structural characterization of a B12-octadecanucleotide are presented herein, a new organometallic B12-DNA conjugate. In such covalent conjugates, the natural B12 moiety may be a versatile vector for controlled in vivo delivery of oligonucleotides to cellular targets in hum...

  18. Conjugation in Escherichia coli

    Science.gov (United States)

    Boyer, Herbert

    1966-01-01

    Boyer, Herbert (Yale University, New Haven, Conn.). Conjugation in Escherichia coli. J. Bacteriol. 91:1767–1772. 1966.—The sex factor of Escherichia coli K-12 was introduced into an E. coli B/r strain by circumventing the host-controlled modification and restriction incompatibilities known to exist between these closely related strains. The sexual properties of the constructed F+ B strain and its Hfr derivatives were examined. These studies showed that the E. coli strain B/r F+ and Hfr derivatives are similar to the E. coli strain K-12 F+ and Hfr derivatives. However, the site of sex factor integration was found to be dependent on the host genome. PMID:5327905

  19. Electrochromic in conjugated polymers

    International Nuclear Information System (INIS)

    Picado Valenzuela, Alfredo

    2007-01-01

    This revision considered object the description of one of the materials with the greatest potential in the field of electrochromic (mainly in the visible region): the conjugated polymers (CP), area of enormous potential both now and in a short time ahead. The CP are insulating materials and organic semiconductors in a state not doped. They can be doped positively or negatively being observed a significant increase in the conductivity and being generated a color change in these materials. The understanding of how optical properties vary based on the chemical structure of the polymer or its mixtures and more precisely of the alternatives that can be entered into the conjugated system or π system to obtain a material that besides to be flexible, environmentally stable, presents the colored states. The revision was centred chiefly in the polypyrrole (Ppy), the polythiophene (PTh) and their derivatives such as poly (3.4-ethylenedioxythiophene) (PEDOT). The advantage of using monomers with variable structure, to adjust the composition of the copolymer, or to blend with the PC, allows to obtain a variety of colored states that can be modulated through the visible spectrum and even with applications to wavelengths outside of this region. Because the PC presented at least two different colored states can be varied continuously as a function of the voltage applied. In some cases, they may submit multicoloured statements, which offers a range of possibilities for their application in flexible electronic devices type screens and windows. Applications include smart windows, camouflage clothing and data screens. This type of material is emerging as one of the substitutes of the traditional inorganic semiconductor, with the advantage of its low cost, high flexibility and the possibility to generate multiple colors through the handling of the monomers in the structure and control of energy of his band gap. (author) [es

  20. Block-conjugate-gradient method

    International Nuclear Information System (INIS)

    McCarthy, J.F.

    1989-01-01

    It is shown that by using the block-conjugate-gradient method several, say s, columns of the inverse Kogut-Susskind fermion matrix can be found simultaneously, in less time than it would take to run the standard conjugate-gradient algorithm s times. The method improves in efficiency relative to the standard conjugate-gradient algorithm as the fermion mass is decreased and as the value of the coupling is pushed to its limit before the finite-size effects become important. Thus it is potentially useful for measuring propagators in large lattice-gauge-theory calculations of the particle spectrum

  1. Entanglements in Conjugated Polymers

    Science.gov (United States)

    Xie, Renxuan; Lee, Youngmin; Aplan, Melissa; Caggiano, Nick; Gomez, Enrique; Colby, Ralph

    Conjugated polymers, such as poly(3-hexylthiophene-2,5-diyl) (P3HT) and poly-((9,9-dioctylfluorene)-2,7-diyl-alt-[4,7-bis(thiophen-5-yl)-2,1,3-benzothiadiazole]-2',2''-diyl) (PFTBT), are widely used as hole and electron transport materials in a variety of electronic devices. However, fundamental knowledge regarding chain entanglements and nematic-to-isotropic transition is still lacking and are crucial to maximize charge transport properties. A systematic melt rheology study on P3HT with various molecular weights and regio regularities was performed. We find that the entanglement molecular weight Me is 5.0 kg/mol for regiorandom P3HT, but the apparent Me for regioregular P3HT is significantly higher. The difference is postulated to arise from the presence of a nematic phase only in regioregular P3HT. Analogously, PFTBT shows a clear rheological signature of the nematic-to-isotropic transition as a reversible sharp transition at 278 C. Shearing of this nematic phase leads to anisotropic crystalline order in PFTBT. We postulate that aligning the microstructure will impact charge transport and thereby advance the field of conducting polymers. National Science Foundation.

  2. Protein carriers of conjugate vaccines

    Science.gov (United States)

    Pichichero, Michael E

    2013-01-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

  3. Conjugated Fatty Acid Synthesis

    Science.gov (United States)

    Rawat, Richa; Yu, Xiao-Hong; Sweet, Marie; Shanklin, John

    2012-01-01

    Conjugated linolenic acids (CLNs), 18:3 Δ9,11,13, lack the methylene groups found between the double bonds of linolenic acid (18:3 Δ9,12,15). CLNs are produced by conjugase enzymes that are homologs of the oleate desaturases FAD2. The goal of this study was to map the domain(s) within the Momordica charantia conjugase (FADX) responsible for CLN formation. To achieve this, a series of Momordica FADX-Arabidopsis FAD2 chimeras were expressed in the Arabidopsis fad3fae1 mutant, and the transformed seeds were analyzed for the accumulation of CLN. These experiments identified helix 2 and the first histidine box as a determinant of conjugase product partitioning into punicic acid (18:3 Δ9cis,11trans,13cis) or α-eleostearic acid (18:3 Δ9cis,11trans,13trans). This was confirmed by analysis of a FADX mutant containing six substitutions in which the sequence of helix 2 and first histidine box was converted to that of FAD2. Each of the six FAD2 substitutions was individually converted back to the FADX equivalent identifying residues 111 and 115, adjacent to the first histidine box, as key determinants of conjugase product partitioning. Additionally, expression of FADX G111V and FADX G111V/D115E resulted in an approximate doubling of eleostearic acid accumulation to 20.4% and 21.2%, respectively, compared with 9.9% upon expression of the native Momordica FADX. Like the Momordica conjugase, FADX G111V and FADX D115E produced predominantly α-eleostearic acid and little punicic acid, but the FADX G111V/D115E double mutant produced approximately equal amounts of α-eleostearic acid and its isomer, punicic acid, implicating an interactive effect of residues 111 and 115 in punicic acid formation. PMID:22451660

  4. Temporal patterns of cardiac performance and genes encoding heat shock proteins and metabolic sensors of an intertidal limpet Cellana toreuma during sublethal heat stress.

    Science.gov (United States)

    Zhang, Shu; Han, Guo-dong; Dong, Yun-wei

    2014-04-01

    Intertidal invertebrates develop effective physiological adaptations to cope with the rapidly changing thermal environment in the intertidal zone. In the present study, the temporal patterns of heart rate, protein carbonyl groups, and genes encoding heat shock proteins (hsp70 and hsp90) and metabolic sensors (ampkα, ampkβ and sirt1) were measured to study the effect of sublethal heat stress on the cardiac function, oxidative stress, heat shock response and cellular metabolism of an intertidal limpet Cellana toreuma. All the physiological parameters are sensitive to temperature and duration of heat stress. Spearman correlation analysis revealed that the correlations between heart rate and levels of heat shock proteins mRNA and metabolic sensors mRNA were statistically significant. These results further suggest that cardiac function plays crucial roles in cellular energy metabolism and heat shock responses. The significant increase of protein carbonyl groups at 34°C after 4h exposure indicated that the failure of cardiac function and the increase of anaerobic metabolism partly leads to the increase of protein carbonyl groups. Generally, the physiological responses to heat stress are sensitive to temperature and are energy-consumptive, as indicated by the upregulation of metabolic sensors mRNA. However, the upregulation of heat shock proteins and metabolic sensors at the post-transcriptional level and related functions need to be confirmed in further experiments. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Research study of conjugate materials; Conjugate material no chosa kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-03-01

    The paper reported an introductory research on possibilities of new glass `conjugate materials.` The report took up the structure and synthetic process of conjugate materials to be researched/developed, classified them according to structural elements on molecular, nanometer and cluster levels, and introduced the structures and functions. Further, as glasses with new functions to be proposed, the paper introduced transparent and high-strength glass used for houses and vehicles, light modulation glass which realizes energy saving and optical data processing, and environmentally functional glass which realizes environmental cleaning or high performance biosensor. An initial survey was also conducted on rights of intellectual property to be taken notice of in Japan and abroad in the present situation. Reports were summed up and introduced of Osaka National Research Institute, Electrotechnical Laboratory, and National Industrial Research Institute of Nagoya which are all carrying out leading studies of conjugate materials. 235 refs., 135 figs., 6 tabs.

  6. Conjugated polymer nanoparticles, methods of using, and methods of making

    KAUST Repository

    Habuchi, Satoshi

    2017-03-16

    Embodiments of the present disclosure provide for conjugated polymer nanoparticle, method of making conjugated polymer nanoparticles, method of using conjugated polymer nanoparticle, polymers, and the like.

  7. Conjugated polymer nanoparticles, methods of using, and methods of making

    KAUST Repository

    Habuchi, Satoshi; Piwonski, Hubert Marek; Michinobu, Tsuyoshi

    2017-01-01

    Embodiments of the present disclosure provide for conjugated polymer nanoparticle, method of making conjugated polymer nanoparticles, method of using conjugated polymer nanoparticle, polymers, and the like.

  8. Conjugated polymer zwitterions and solar cells comprising conjugated polymer zwitterions

    Science.gov (United States)

    Emrick, Todd; Russell, Thomas; Page, Zachariah; Liu, Yao

    2018-06-05

    A conjugated polymer zwitterion includes repeating units having structure (I), (II), or a combination thereof ##STR00001## wherein Ar is independently at each occurrence a divalent substituted or unsubstituted C3-30 arylene or heteroarylene group; L is independently at each occurrence a divalent C1-16 alkylene group, C6-30arylene or heteroarylene group, or alkylene oxide group; and R1 is independently at each occurrence a zwitterion. A polymer solar cell including the conjugated polymer zwitterion is also disclosed.

  9. Conjugal Pairing in Escherichia Coli

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 13; Issue 8. Conjugal Pairing in Escherichia Coli. Joshua Lederberg. Classics Volume 13 Issue 8 August 2008 pp 793-794. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/013/08/0793-0794 ...

  10. Persistence Mechanisms of Conjugative Plasmids

    DEFF Research Database (Denmark)

    Bahl, Martin Iain; Hansen, Lars H.; Sørensen, Søren Johannes

    2009-01-01

    Are plasmids selfish parasitic DNA molecules or an integrated part of the bacterial genome? This chapter reviews the current understanding of the persistence mechanisms of conjugative plasmids harbored by bacterial cells and populations. The diversity and intricacy of mechanisms affecting the suc...

  11. Orderings for conjugate gradient preconditionings

    Science.gov (United States)

    Ortega, James M.

    1991-01-01

    The effect of orderings on the rate of convergence of the conjugate gradient method with SSOR or incomplete Cholesky preconditioning is examined. Some results also are presented that help to explain why red/black ordering gives an inferior rate of convergence.

  12. Bacteriophytochromes control conjugation in Agrobacterium fabrum.

    Science.gov (United States)

    Bai, Yingnan; Rottwinkel, Gregor; Feng, Juan; Liu, Yiyao; Lamparter, Tilman

    2016-08-01

    Bacterial conjugation, the transfer of single stranded plasmid DNA from donor to recipient cell, is mediated through the type IV secretion system. We performed conjugation assays using a transmissible artificial plasmid as reporter. With this assay, conjugation in Agrobacterium fabrum was modulated by the phytochromes Agp1 and Agp2, photoreceptors that are most sensitive in the red region of visible light. In conjugation studies with wild-type donor cells carrying a pBIN-GUSINT plasmid as reporter that lacked the Ti (tumor inducing) plasmid, no conjugation was observed. When either agp1(-) or agp2(-) knockout donor strains were used, plasmid DNA was delivered to the recipient, indicating that both phytochromes suppress conjugation in the wild type donor. In the recipient strains, the loss of Agp1 or Agp2 led to diminished conjugation. When wild type cells with Ti plasmid and pBIN-GUS reporter plasmid were used as donor, a high rate of conjugation was observed. The DNA transfer was down regulated by red or far-red light by a factor of 3.5. With agp1(-) or agp2(-) knockout donor cells, conjugation in the dark was about 10 times lower than with the wild type donor, and with the double knockout donor no conjugation was observed. These results imply that the phytochrome system has evolved to inhibit conjugation in the light. The decrease of conjugation under different temperature correlated with the decrease of phytochrome autophosphorylation. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. REVIEW ARTICLE Conjugated Hyperbilirubinaemia in Early Infancy ...

    African Journals Online (AJOL)

    REVIEW ARTICLE Conjugated Hyperbilirubinaemia in Early Infancy. AOK Johnson. Abstract. Conjugated hyperbilirubinaemia exists when the conjugated serum bilirubin level is more than 2 mg/dl or more than 20 per cent of the total serum bilirubin. It is always pathological in early infancy. The causes are many and diverse ...

  14. Purification of SUMO conjugating enzymes and kinetic analysis of substrate conjugation

    Science.gov (United States)

    Yunus, Ali A.; Lima, Christopher D.

    2009-01-01

    SUMO conjugation to protein substrates requires the concerted action of a dedicated E2 ubiquitin conjugation enzyme (Ubc9) and associated E3 ligases. Although Ubc9 can directly recognize and modify substrate lysine residues that occur within a consensus site for SUMO modification, E3 ligases can redirect specificity and enhance conjugation rates during SUMO conjugation in vitro and in vivo. In this chapter, we will describe methods utilized to purify SUMO conjugating enzymes and model substrates which can be used for analysis of SUMO conjugation in vitro. We will also describe methods to extract kinetic parameters during E3-dependent or E3-independent substrate conjugation. PMID:19107417

  15. Extinction and recolonization of maritime Antarctica in the limpet Nacella concinna (Strebel, 1908) during the last glacial cycle: toward a model of Quaternary biogeography in shallow Antarctic invertebrates.

    Science.gov (United States)

    González-Wevar, C A; Saucède, T; Morley, S A; Chown, S L; Poulin, E

    2013-10-01

    Quaternary glaciations in Antarctica drastically modified geographical ranges and population sizes of marine benthic invertebrates and thus affected the amount and distribution of intraspecific genetic variation. Here, we present new genetic information in the Antarctic limpet Nacella concinna, a dominant Antarctic benthic species along shallow ice-free rocky ecosystems. We examined the patterns of genetic diversity and structure in this broadcast spawner along maritime Antarctica and from the peri-Antarctic island of South Georgia. Genetic analyses showed that N. concinna represents a single panmictic unit in maritime Antarctic. Low levels of genetic diversity characterized this population; its median-joining haplotype network revealed a typical star-like topology with a short genealogy and a dominant haplotype broadly distributed. As previously reported with nuclear markers, we detected significant genetic differentiation between South Georgia Island and maritime Antarctica populations. Higher levels of genetic diversity, a more expanded genealogy and the presence of more private haplotypes support the hypothesis of glacial persistence in this peri-Antarctic island. Bayesian Skyline plot and mismatch distribution analyses recognized an older demographic history in South Georgia. Approximate Bayesian computations did not support the persistence of N. concinna along maritime Antarctica during the last glacial period, but indicated the resilience of the species in peri-Antarctic refugia (South Georgia Island). We proposed a model of Quaternary Biogeography for Antarctic marine benthic invertebrates with shallow and narrow bathymetric ranges including (i) extinction of maritime Antarctic populations during glacial periods; (ii) persistence of populations in peri-Antarctic refugia; and (iii) recolonization of maritime Antarctica following the deglaciation process. © 2013 John Wiley & Sons Ltd.

  16. A polyvalent vaccine for high-risk prostate patients: "are more antigens better?"

    DEFF Research Database (Denmark)

    Slovin, Susan F; Ragupathi, Govind; Fernandez, Celina

    2007-01-01

    vaccine of synthetic "self" antigens broke immunologic tolerance against two or more antigens in all 30 vaccinated patients, was safe, but antibody titers against several of the antigens were lower than those seen in individual monovalent trials. No impact on PSA slope was detected. We address......We have shown the immunogenicity and safety of synthetic carbohydrate vaccines when conjugated to the carrier keyhole limpet hemocyanin (KLH) and given with the adjuvant, QS-21, in patients with biochemically relapsed prostate cancer. To determine whether immune response could be further enhanced...... and mixed with QS-21. Eight vaccinations were administered over 13 months. All 30 patients had significant elevations in antibody titers to at least two of the six antigens; 22 patients had increased reactivity with FACS. These serologic responses were lower than that seen previously in patients treated...

  17. Antigen-specific and nonspecific mediators of T cell/B cell cooperation. III. Characterization of the nonspecific mediator(s) from different sources.

    Science.gov (United States)

    Harwell, L; Kappler, J W; Marrack, P

    1976-05-01

    T cell-containing lymphoid populations produce a nonantigen-specific mediator(s) (NSM) which can replace T cell helper function in vitro in the response of B cells to sheep red blood cells (SRBC), but not to the hapten-protein conjugate, trinitrophenyl-keyhole limpet hemocyanin, (TNP-KLH). NSM produced under three conditions: 1) stimulation of KLH-primed cells with KLH; 2) allogeneic stimulation of normal spleen cells; and 3) stimulation of normal spleen cells with Con A (but not PHA) are indistinguishable on the basis of their biologic activity and m.w., estimated as 30 to 40,000 daltons by G-200 chromatography. Production of NSM is dependent on the presence of T cells. The action of NSM on B cells responding to SRBC in the presence of 2-mercaptoethanol is unaffected by severe macrophage depletion. Extensive absorption of NSM with SRBC failed to remove its activity, confirming its nonantigen-specific nature.

  18. Production of monoclonal antibodies for sandwich immunoassay detection of ciguatoxin 51-hydroxyCTX3C.

    Science.gov (United States)

    Tsumuraya, Takeshi; Fujii, Ikuo; Inoue, Masayuki; Tatami, Atsushi; Miyazaki, Keisuke; Hirama, Masahiro

    2006-09-01

    Every year, more than 50,000 people in subtropical and tropical regions suffer from ciguatera seafood poisoning. The extremely low level of the causative neurotoxins (ciguatoxins) in fish has hampered the preparation of antibodies for detection of the toxins. In this study, we produced a monoclonal antibody (8H4) against the right end of ciguatoxin CTX1B (1) and 51-hydroxyCTX3C (3) by immunizing mice with the keyhole limpet hemocyanin-conjugate of the synthetic HIJKLM ring fragment (10). We used 8H4 and another previously reported monoclonal antibody (10C9) that recognizes the left end of 3 to develop a sandwich enzyme-linked immunosorbent assay (ELISA) to detect 3. The assay could detect 3 down to the ppb level and lacked cross-reactivity with other related marine toxins, including brevetoxin A, brevetoxin B, okadaic acid, and maitotoxin.

  19. Effect of chlorphenesin on localized hemolysis in gel assay.

    Science.gov (United States)

    Fukui, G M; Berger, F M; Chandlee, G C; Goldenbaum, E G

    1968-10-01

    Chlorphenesin, a simple glycerol ether, when added to Jerne plates greatly reduced the number of hemolytic plaques. This effect appeared to be related to dose, and was clearly demonstrable with antibody-forming spleen cells from mice that had been immunized either with sheep red blood cells or with penicillin G conjugated with Keyhole limpet hemocyanin. Chlorphenesin did not affect the antigen, destroy complement, or interfere with the interaction of complement and the antigen-antibody complexes. Incubation of spleen cell suspensions with chlorphenesin prior to plating was more effective in reducing the number of plaques than was addition of the substance to the plates. It may act by reducing the ability of antibodies to react with antigens or by affecting the release of antibodies from the spleen cells.

  20. Structure Property Relationships in Organic Conjugated Systems

    OpenAIRE

    O'Neill, Luke

    2008-01-01

    A series of pi(п) conjugated oligomers containing 1 to 6 monomer units were studied by absorption and photoluminescence spectroscopies. The results are discussed and examined with regard to the variation of the optical properties with the increase of effective conjugation length. It was found that there was a linear relationship between the positioning of the absorption and photoluminescence maxima plotted against inverse conjugation length. The relationships are in good agreement with the si...

  1. Conjugated Polymers for Energy Production

    DEFF Research Database (Denmark)

    Livi, Francesco

    This dissertation is aimed at developing materials for flexible, large area, ITO-free polymer solar cells (PSCs) fully printed under ambient conditions. A large screening of conjugated polymers, both novel and well-known materials, has been carried out in order to find suitable candidates...... polymerization method for industrial production of polymers. Several DArP protocols have been employed for the synthesis of PPDTBT leading to polymers with high structural regularity and photovoltaic performances comparable with the same materials synthesized via Stille cross-coupling polymerization...

  2. Novel ?-cyclodextrin?eosin conjugates

    OpenAIRE

    Benkovics, G?bor; Afonso, Damien; Darcsi, Andr?s; B?ni, Szabolcs; Conoci, Sabrina; Fenyvesi, ?va; Szente, Lajos; Malanga, Milo; Sortino, Salvatore

    2017-01-01

    Eosin B (EoB) and eosin Y (EoY), two xanthene dye derivatives with photosensitizing ability were prepared in high purity through an improved synthetic route. The dyes were grafted to a 6-monoamino-β-cyclodextrin scaffold under mild reaction conditions through a stable amide linkage using the coupling agent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. The molecular conjugates, well soluble in aqueous medium, were extensively characterized by 1D and 2D NMR spectroscopy an...

  3. Test of charge conjugation invariance

    International Nuclear Information System (INIS)

    Nefkens, B.M.K.; Prakhov, S.; Gaardestig, A.; Clajus, M.; Marusic, A.; McDonald, S.; Phaisangittisakul, N.; Price, J.W.; Starostin, A.; Tippens, W.B.; Allgower, C.E.; Spinka, H.; Bekrenev, V.; Koulbardis, A.; Kozlenko, N.; Kruglov, S.; Lopatin, I.; Briscoe, W.J.; Shafi, A.; Comfort, J.R.

    2005-01-01

    We report on the first determination of upper limits on the branching ratio (BR) of η decay to π 0 π 0 γ and to π 0 π 0 π 0 γ. Both decay modes are strictly forbidden by charge conjugation (C) invariance. Using the Crystal Ball multiphoton detector, we obtained BR(η→π 0 π 0 γ) -4 at the 90% confidence level, in support of C invariance of isoscalar electromagnetic interactions of the light quarks. We have also measured BR(η→π 0 π 0 π 0 γ) -5 at the 90% confidence level, in support of C invariance of isovector electromagnetic interactions

  4. Conjugated polymers developed from alkynes

    Institute of Scientific and Technical Information of China (English)

    Yajing Liu; Jacky W.Y.Lam; Ben Zhong Tang

    2015-01-01

    The numerous merits of conjugated polymers(CPs) have encouraged scientists to develop a variety of synthetic routes to CPs with diverse structures and functionalities. Among the large scope of substrates,alkyne plays an important role in constructing polymers with conjugated backbones. In addition to some well-developed reactions including Glaser–Hay and Sonogashira coupling, azide/thiol-yne click reaction and cyclotrimerization, some novel alkyne-based reactions have also been explored such as oxidative polycoupling, decarbonylative polycoupling and multicomponent tandem polymerizations. his review focuses on the recent progress on the synthetic methodology of CPs in the last ive years using monomers with two or more triple bonds and some of their high-technological applications. Selected examples of materials properties of these CPs are given in this review, such as luorescence response to chemical or physical stimuli, magnetism, white light emission, cell imaging and bioprobing. Finally, a short perspective is raised in regard to the outlook of the preparation methodologies, functionalities as well as potential applications of CPs in the future.

  5. Subgap Absorption in Conjugated Polymers

    Science.gov (United States)

    Sinclair, M.; Seager, C. H.; McBranch, D.; Heeger, A. J; Baker, G. L.

    1991-01-01

    Along with X{sup (3)}, the magnitude of the optical absorption in the transparent window below the principal absorption edge is an important parameter which will ultimately determine the utility of conjugated polymers in active integrated optical devices. With an absorptance sensitivity of materials. We have used PDS to measure the optical absorption spectra of the conjugated polymers poly(1,4-phenylene-vinylene) (and derivitives) and polydiacetylene-4BCMU in the spectral region from 0.55 eV to 3 eV. Our spectra show that the shape of the absorption edge varies considerably from polymer to polymer, with polydiacetylene-4BCMU having the steepest absorption edge. The minimum absorption coefficients measured varied somewhat with sample age and quality, but were typically in the range 1 cm{sup {minus}1} to 10 cm{sup {minus}1}. In the region below 1 eV, overtones of C-H stretching modes were observed, indicating that further improvements in transparency in this spectral region might be achieved via deuteration of fluorination.

  6. Subgap absorption in conjugated polymers

    Energy Technology Data Exchange (ETDEWEB)

    Sinclair, M.; Seager, C.H. (Sandia National Labs., Albuquerque, NM (USA)); McBranch, D.; Heeger, A.J. (California Univ., Santa Barbara, CA (USA)); Baker, G.L. (Bell Communications Research, Inc., Red Bank, NJ (USA))

    1991-01-01

    Along with X{sup (3)}, the magnitude of the optical absorption in the transparent window below the principal absorption edge is an important parameter which will ultimately determine the utility of conjugated polymers in active integrated optical devices. With an absorptance sensitivity of < 10{sup {minus}5}, Photothermal Deflection Spectroscopy (PDS) is ideal for determining the absorption coefficients of thin films of transparent'' materials. We have used PDS to measure the optical absorption spectra of the conjugated polymers poly(1,4-phenylene-vinylene) (and derivitives) and polydiacetylene-4BCMU in the spectral region from 0.55 eV to 3 eV. Our spectra show that the shape of the absorption edge varies considerably from polymer to polymer, with polydiacetylene-4BCMU having the steepest absorption edge. The minimum absorption coefficients measured varied somewhat with sample age and quality, but were typically in the range 1 cm{sup {minus}1} to 10 cm{sup {minus}1}. In the region below 1 eV, overtones of C-H stretching modes were observed, indicating that further improvements in transparency in this spectral region might be achieved via deuteration of fluorination. 11 refs., 4 figs.

  7. Preconditioning the modified conjugate gradient method ...

    African Journals Online (AJOL)

    In this paper, the convergence analysis of the conventional conjugate Gradient method was reviewed. And the convergence analysis of the modified conjugate Gradient method was analysed with our extension on preconditioning the algorithm. Convergence of the algorithm is a function of the condition number of M-1A.

  8. DENDRIMER CONJUGATES FOR SELECTIVE OF PROTEIN AGGREGATES

    DEFF Research Database (Denmark)

    2004-01-01

    Dendrimer conjugates are presented, which are formed between a dendrimer and a protein solubilising substance. Such dendrimer conjugates are effective in the treatment of protein aggregate-related diseases (e.g. prion-related diseases). The protein solubilising substance and the dendrimer together...

  9. Tetrafullerene conjugates for all-organic photovoltaics

    NARCIS (Netherlands)

    Fernández, G.; Sánchez, L.; Veldman, D.; Wienk, M.M.; Atienza, C.M.; Guldi, D.M.; Janssen, R.A.J.; Martin, N.

    2008-01-01

    The synthesis of two new tetrafullerene nanoconjugates in which four C60 units are covalently connected through different -conjugated oligomers (oligo(p-phenylene ethynylene) and oligo(p-phenylene vinylene)) is described. The photovoltaic (PV) response of these C60-based conjugates was evaluated by

  10. CONJUGATED BLOCK-COPOLYMERS FOR ELECTROLUMINESCENT DIODES

    NARCIS (Netherlands)

    Hilberer, A; Gill, R.E; Herrema, J.K; Malliaras, G.G; Wildeman, J.; Hadziioannou, G

    In this article we review results obtained in our laboratory on the design and study of new light-emitting polymers. We are interested in the synthesis and characterisation of block copolymers with regularly alternating conjugated and non conjugated sequences. The blocks giving rise to luminescence

  11. The Conjugate Acid-Base Chart.

    Science.gov (United States)

    Treptow, Richard S.

    1986-01-01

    Discusses the difficulties that beginning chemistry students have in understanding acid-base chemistry. Describes the use of conjugate acid-base charts in helping students visualize the conjugate relationship. Addresses chart construction, metal ions, buffers and pH titrations, and the organic functional groups and nonaqueous solvents. (TW)

  12. Bio-Conjugates for Nanoscale Applications

    DEFF Research Database (Denmark)

    Villadsen, Klaus

    Bio-conjugates for Nanoscale Applications is the title of this thesis, which covers three different projects in chemical bio-conjugation research, namely synthesis and applications of: Lipidated fluorescent peptides, carbohydrate oxime-azide linkers and N-aryl O-R2 oxyamine derivatives. Lipidated...

  13. Class, Kinship Density, and Conjugal Role Segregation.

    Science.gov (United States)

    Hill, Malcolm D.

    1988-01-01

    Studied conjugal role segregation in 150 married women from intact families in working-class community. Found that, although involvement in dense kinship networks was associated with conjugal role segregation, respondents' attitudes toward marital roles and phase of family cycle when young children were present were more powerful predictors of…

  14. Misonidazole-glutathione conjugates in CHO cells

    International Nuclear Information System (INIS)

    Varghese, A.J.; Whitmore, G.F.

    1984-01-01

    Misonidazole, after reduction to the hydroxylamine derivative, reacts with glutathione (GSH) under physiological conditions. The reaction product has been identified as a mixture of two isomeric conjugates. When water soluble extracts of CHO cells exposed to misonidazole under hypoxic conditions are subjected to HPLC analysis, misonidazole derivatives, having the same chromatographic properties as the GSH-MISO conjugates, were detected. When CHO cells were incubated with misonidazole in the presence of added GSH, a substantial increase in the amount of the conjugate was detected. When extracts of CHO cells exposed to misonidazole under hypoxia were subsequently exposed to GSH, an increased formation of the conjugate was observed. A rearrangement product of the hydroxylamine derivative of misonidazole is postulated as the reactive intermediate responsible for the formation of the conjugate

  15. Approximate error conjugation gradient minimization methods

    Science.gov (United States)

    Kallman, Jeffrey S

    2013-05-21

    In one embodiment, a method includes selecting a subset of rays from a set of all rays to use in an error calculation for a constrained conjugate gradient minimization problem, calculating an approximate error using the subset of rays, and calculating a minimum in a conjugate gradient direction based on the approximate error. In another embodiment, a system includes a processor for executing logic, logic for selecting a subset of rays from a set of all rays to use in an error calculation for a constrained conjugate gradient minimization problem, logic for calculating an approximate error using the subset of rays, and logic for calculating a minimum in a conjugate gradient direction based on the approximate error. In other embodiments, computer program products, methods, and systems are described capable of using approximate error in constrained conjugate gradient minimization problems.

  16. Modelling conjugation with stochastic differential equations

    DEFF Research Database (Denmark)

    Philipsen, Kirsten Riber; Christiansen, Lasse Engbo; Hasman, Henrik

    2010-01-01

    Enterococcus faecium strains in a rich exhaustible media. The model contains a new expression for a substrate dependent conjugation rate. A maximum likelihood based method is used to estimate the model parameters. Different models including different noise structure for the system and observations are compared......Conjugation is an important mechanism involved in the transfer of resistance between bacteria. In this article a stochastic differential equation based model consisting of a continuous time state equation and a discrete time measurement equation is introduced to model growth and conjugation of two...... using a likelihood-ratio test and Akaike's information criterion. Experiments indicating conjugation on the agar plates selecting for transconjugants motivates the introduction of an extended model, for which conjugation on the agar plate is described in the measurement equation. This model is compared...

  17. Novel Aflatoxin Derivatives and Protein Conjugates

    Directory of Open Access Journals (Sweden)

    Reinhard Niessner

    2007-03-01

    Full Text Available Aflatoxins, a group of structurally related mycotoxins, are well known for their toxic and carcinogenic effects in humans and animals. Aflatoxin derivatives and protein conjugates are needed for diverse analytical applications. This work describes a reliable and fast synthesis of novel aflatoxin derivatives, purification by preparative HPLC and characterisation by ESI-MS and one- and two-dimensional NMR. Novel aflatoxin bovine serum albumin conjugates were prepared and characterised by UV absorption and MALDI-MS. These aflatoxin protein conjugates are potentially interesting as immunogens for the generation of aflatoxin selective antibodies with novel specificities.

  18. Evaluation of iodovinyl antibody conjugates: Comparison with a p-iodobenzoyl conjugate and direct radioiodination

    International Nuclear Information System (INIS)

    Hadley, S.W.; Wilbur, D.S.

    1990-01-01

    The preparations and conjugations of 2,3,5,6-tetrafluorophenyl 5-[125I/131I]iodo-4-pentenoate (7a) and 2,3,5,6-tetrafluorophenyl 3,3-dimethyl-5-[125I/131I]iodo-4-pentenoate (7b) to monoclonal antibodies are reported. Reagents 7a and 7b were prepared in high radiochemical yield by iododestannylation of their corresponding 5-tri-n-butylstannyl precursors. Radioiodinated antibody conjugates were prepared by reaction of 7a or 7b with the protein at basic pH. Evaluation of these conjugates by several in vitro procedures demonstrated that the radiolabel was attached to the antibody in a stable manner and that the conjugates maintained immunoreactivity. Comparative dual-isotope biodistribution studies of a monoclonal antibody Fab fragment conjugate of 7a and 7b with the same Fab fragment labeled with N-succinimidyl p-[131I]iodobenzoate (PIB, p-iodobenzoate, 2) or directly radioiodinated have been carried out in tumor-bearing nude mice. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 2 demonstrated that the biodistributions were similar in most organs, except the neck tissue (thyroid-containing) and the stomach, which contained substantially increased levels of the 7a label. Coinjection of the Fab conjugate of 7a with the Fab fragment radioiodinated by using the chloramine-T method demonstrated that the biodistributions were remarkably similar, suggesting roughly equivalent in vivo deiodination of these labeled antibody fragments. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 7b indicated that there was ∼ a 2-fold reduction in the amount of in vivo deiodination of the 7b conjugate as compared to the 7a conjugate

  19. Conjugate descent formulation of backpropagation error in ...

    African Journals Online (AJOL)

    nique of backpropagation was popularized in a paper by Rumelhart, et al. ... the training of a multilayer neural network using a gradient descent approach applied to a .... superior convergence of the conjugate descent method over a standard ...

  20. Soluble polymer conjugates for drug delivery.

    Science.gov (United States)

    Minko, Tamara

    2005-01-01

    The use of water-soluble polymeric conjugates as drug carriers offers several possible advantages. These advantages include: (1) improved drug pharmacokinetics; (2) decreased toxicity to healthy organs; (3) possible facilitation of accumulation and preferential uptake by targeted cells; (4) programmed profile of drug release. In this review, we will consider the main types of useful polymeric conjugates and their role and effectiveness as carriers in drug delivery systems.: © 2005 Elsevier Ltd . All rights reserved.

  1. Structure Property Relationships in Organic Conjugated Systems

    OpenAIRE

    O'Neill, Luke; Lynch, Patrick; McNamara, Mary

    2005-01-01

    A series of π conjugated oligomers were studied by absorption and photoluminescence spectroscopy. A linear relationship between the positioning of the absorption and photoluminescence maxima plotted against inverse conjugation length is observed. The relationships are in good agreement with the simple particle in a box method, one of the earliest descriptions of the properties of one-dimensional organic molecules. In addition to the electronic transition energies, it was observed that the Sto...

  2. Diffeomorphisms Holder conjugate to Anosov diffeomorphisms

    OpenAIRE

    Gogolev, Andrey

    2008-01-01

    We show by means of a counterexample that a $C^{1+Lip}$ diffeomorphism Holder conjugate to an Anosov diffeomorphism is not necessarily Anosov. The counterexample can bear higher smoothness up to $C^3$. Also we include a result from the 2006 Ph.D. thesis of T. Fisher: a $C^{1+Lip}$ diffeomorphism Holder conjugate to an Anosov diffeomorphism is Anosov itself provided that Holder exponents of the conjugacy and its inverse are sufficiently large.

  3. Rapid modification of retroviruses using lipid conjugates

    International Nuclear Information System (INIS)

    Mukherjee, Nimisha G; Le Doux, Joseph M; Andrew Lyon, L

    2009-01-01

    Methods are needed to manipulate natural nanoparticles. Viruses are particularly interesting because they can act as therapeutic cellular delivery agents. Here we examine a new method for rapidly modifying retroviruses that uses lipid conjugates composed of a lipid anchor (1,2-distearoyl-sn-glycero-3-phosphoethanolamine), a polyethylene glycol chain, and biotin. The conjugates rapidly and stably modified retroviruses and enabled them to bind streptavidin. The implication of this work for modifying viruses for gene therapy and vaccination protocols is discussed.

  4. Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma.

    Science.gov (United States)

    Heimberger, Amy B; Archer, Gary E; Crotty, Laura E; McLendon, Roger E; Friedman, Allan H; Friedman, Henry S; Bigner, Darell D; Sampson, John H

    2002-01-01

    Dendritic cells (DCs) are specialized cells of the immune system that are capable of generating potent immune responses that are active even within the "immunologically privileged" central nervous system. However, immune responses generated by DCs have also been demonstrated to produce clinically significant autoimmunity. Targeting the epidermal growth factor receptor variant III (EGFRvIII), which is a mutation specific to tumor tissue, could eliminate this risk. The purpose of this study was to demonstrate that DC-based immunizations directed solely against this tumor-specific antigen, which is commonly found on tumors that originate within or metastasize to the brain, could be efficacious. C3H mice were vaccinated with DCs mixed with a keyhole limpet hemocyanin conjugate of the tumor-specific peptide, PEP-3, which spans the EGFRvIII mutation, or the random-sequence peptide, PEP-1, and were intracerebrally challenged with a syngeneic melanoma expressing a murine homologue of EGFRvIII. Systemic immunization with DCs mixed with PEP-3-keyhole limpet hemocyanin generated antigen-specific immunity. Among mice challenged with intracerebral tumors, this resulted in an approximately 600% increase in the median survival time (>300 d, P < 0.0016), relative to control values. Sixty-three percent of mice treated with DCs mixed with the tumor-specific peptide survived in the long term and 100% survived rechallenge with tumor, indicating that antitumor immunological memory was also induced. In a murine melanoma model, immunization with DCs mixed with tumor-specific peptide results in an antigen-specific immunological response that recognizes the EGFRvIII mutation, has potent antitumor efficacy against intracerebral tumors that express EGFRvIII, and results in long-lasting antitumor immunity.

  5. Analytical characterization of polymer-drug conjugates

    International Nuclear Information System (INIS)

    Rizzo, V.; Gigli, M.; Pinciroli, V.

    1998-01-01

    A few polymeric conjugates of antitumor drugs have been recently developed in view of possible therapeutic advantages: solubilization of sparingly soluble drugs in water, improvement of therapeutic index, organ targeting through a second chemical species bound to the same polymeric chain. In this article it's described the analytical approach used in the characterization of the conjugates for chemical identity, purity and strength of the contained active ingredient. The techniques are: high field NMR and size exclusion chromatography with non-aqueous mobile phase for identity; selective hydrolysis and HPLC for strength and purity. A complete and reliable picture is thus obtained both for qualitative and for quantitative aspects. This is an important step forward in the direction of further development and marketing of polymer-drug conjugates [it

  6. Nonlinear conjugate gradient methods in micromagnetics

    Directory of Open Access Journals (Sweden)

    J. Fischbacher

    2017-04-01

    Full Text Available Conjugate gradient methods for energy minimization in micromagnetics are compared. The comparison of analytic results with numerical simulation shows that standard conjugate gradient method may fail to produce correct results. A method that restricts the step length in the line search is introduced, in order to avoid this problem. When the step length in the line search is controlled, conjugate gradient techniques are a fast and reliable way to compute the hysteresis properties of permanent magnets. The method is applied to investigate demagnetizing effects in NdFe12 based permanent magnets. The reduction of the coercive field by demagnetizing effects is μ0ΔH = 1.4 T at 450 K.

  7. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

    Science.gov (United States)

    Miller, Jacqueline M.; Mesaros, Narcisa; Van Der Wielen, Marie; Baine, Yaela

    2011-01-01

    Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT) designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles. PMID:21991444

  8. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

    Directory of Open Access Journals (Sweden)

    Jacqueline M. Miller

    2011-01-01

    Full Text Available Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles.

  9. 125I Radioimmunoassay of serum ursodeoxycholyl conjugates

    International Nuclear Information System (INIS)

    Hill, A.; Ross, P.E.; Bouchier, I.A.D.

    1983-01-01

    A radioimmunoassay for serum ursodeoxycholic conjugates using an iodine-125 ligand has been developed. The bile acid was present in normal fasting serum (0.19 +- SD 0.19 μmol/l, n=24) and 2-hour post-prandial serum (0.8 +- SD 0.8 μmol/l, n=16). Gallstone patients undergoing oral ursodeoxycholic acid therapy had significantly higher post-prandial serum levels (21.5 +- SD 14.0 μmol/l, n=15) by radioimmunoassay. Gas liquid chromatography analysis indicated that in normal serum ursodeoxycholic acid was totally conjugated, whereas sera from gallstone patients contained a proportion as the free bile acid (10.2 +- SD 8.1 μmol/l, n=15). Following an oral dose of ursodeoxycholic acid, both unconjugated and conjugated forms of the bile acid appeared in the serum of healthy individuals. (Auth.)

  10. Novel β-cyclodextrin–eosin conjugates

    Directory of Open Access Journals (Sweden)

    Gábor Benkovics

    2017-03-01

    Full Text Available Eosin B (EoB and eosin Y (EoY, two xanthene dye derivatives with photosensitizing ability were prepared in high purity through an improved synthetic route. The dyes were grafted to a 6-monoamino-β-cyclodextrin scaffold under mild reaction conditions through a stable amide linkage using the coupling agent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl-4-methylmorpholinium chloride. The molecular conjugates, well soluble in aqueous medium, were extensively characterized by 1D and 2D NMR spectroscopy and mass spectrometry. Preliminary spectroscopic investigations showed that the β-cyclodextrin–EoY conjugate retains both the fluorescence properties and the capability to photogenerate singlet oxygen of the unbound chromophore. In contrast, the corresponding β-cyclodextrin–EoB conjugate did not show either relevant emission or photosensitizing activity probably due to aggregation in aqueous medium, which precludes any response to light excitation.

  11. Novel β-cyclodextrin-eosin conjugates.

    Science.gov (United States)

    Benkovics, Gábor; Afonso, Damien; Darcsi, András; Béni, Szabolcs; Conoci, Sabrina; Fenyvesi, Éva; Szente, Lajos; Malanga, Milo; Sortino, Salvatore

    2017-01-01

    Eosin B (EoB) and eosin Y (EoY), two xanthene dye derivatives with photosensitizing ability were prepared in high purity through an improved synthetic route. The dyes were grafted to a 6-monoamino-β-cyclodextrin scaffold under mild reaction conditions through a stable amide linkage using the coupling agent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. The molecular conjugates, well soluble in aqueous medium, were extensively characterized by 1D and 2D NMR spectroscopy and mass spectrometry. Preliminary spectroscopic investigations showed that the β-cyclodextrin-EoY conjugate retains both the fluorescence properties and the capability to photogenerate singlet oxygen of the unbound chromophore. In contrast, the corresponding β-cyclodextrin-EoB conjugate did not show either relevant emission or photosensitizing activity probably due to aggregation in aqueous medium, which precludes any response to light excitation.

  12. Deciphering conjugative plasmid permissiveness in wastewater microbiomes

    DEFF Research Database (Denmark)

    Jacquiod, Samuel Jehan Auguste; Brejnrod, Asker Daniel; Milani, Stefan Morberg

    2017-01-01

    Wastewater treatment plants (WWTPs) are designed to robustly treat polluted water. They are characterized by ceaseless flows of organic, chemical and microbial matter, followed by treatment steps before environmental release. WWTPs are hotspots of horizontal gene transfer between bacteria via...... still remains largely uncharted. Furthermore, current in vitro methods used to assess conjugation in complex microbiomes do not include in situ behaviours of recipient cells, resulting in partial understanding of transfers. We investigated the in vitro conjugation capacities of WWTP microbiomes from...... inlet sewage and outlet treated water using the broad-host range IncP-1 conjugative plasmid, pKJK5. A thorough molecular approach coupling metagenomes to 16S rRNA DNA/cDNA amplicon sequencing was established to characterize microbiomes using the ecological concept of functional response groups. A broad...

  13. Conjugate gradient algorithms using multiple recursions

    Energy Technology Data Exchange (ETDEWEB)

    Barth, T.; Manteuffel, T.

    1996-12-31

    Much is already known about when a conjugate gradient method can be implemented with short recursions for the direction vectors. The work done in 1984 by Faber and Manteuffel gave necessary and sufficient conditions on the iteration matrix A, in order for a conjugate gradient method to be implemented with a single recursion of a certain form. However, this form does not take into account all possible recursions. This became evident when Jagels and Reichel used an algorithm of Gragg for unitary matrices to demonstrate that the class of matrices for which a practical conjugate gradient algorithm exists can be extended to include unitary and shifted unitary matrices. The implementation uses short double recursions for the direction vectors. This motivates the study of multiple recursion algorithms.

  14. METHOD OF CONJUGATED CIRCULAR ARCS TRACING

    Directory of Open Access Journals (Sweden)

    N. Ageyev Vladimir

    2017-01-01

    Full Text Available The geometric properties of conjugated circular arcs connecting two points on the plane with set directions of tan- gent vectors are studied in the work. It is shown that pairs of conjugated circular arcs with the same conditions in frontier points create one-parameter set of smooth curves tightly filling all the plane. One of the basic properties of this set is the fact that all coupling points of circular arcs are on the circular curve going through the initially given points. The circle radius depends on the direction of tangent vectors. Any point of the circle curve, named auxiliary in this work, determines a pair of conjugated arcs with given boundary conditions. One more condition of the auxiliary circle curve is that it divides the plane into two parts. The arcs going from the initial point are out of the circle limited by this circle curve and the arcs coming to the final point are inside it. These properties are the basis for the method of conjugated circular arcs tracing pro- posed in this article. The algorithm is rather simple and allows to fulfill all the needed plottings using only the divider and ruler. Two concrete examples are considered. The first one is related to the problem of tracing of a pair of conjugated arcs with the minimal curve jump when going through the coupling point. The second one demonstrates the possibility of trac- ing of the smooth curve going through any three points on the plane under condition that in the initial and final points the directions of tangent vectors are given. The proposed methods of conjugated circular arcs tracing can be applied in solving of a wide variety of problems connected with the tracing of cam contours, for example pattern curves in textile industry or in computer-aided-design systems when programming of looms with numeric control.

  15. Conjugated Polymers as Actuators: Modes of Actuation

    DEFF Research Database (Denmark)

    Skaarup, Steen

    2004-01-01

    The physical and chemical properties of conjugated polymers often depend very strongly on the degree of doping with anions or cations. The movement of ions in and out of the polymer matrix as it is redox cycled is also accompanied by mechanical changes. Both the volume and the stiffness can exhibit...... significant differences between the oxidized and reduced states. These effects form the basis of the use of conjugated polymers as actuators (or “artificial muscles”) controllable by a small (1-10 V) voltage. Three basic modes of actuation (bending, linear extension and stiffness change) have been proposed...

  16. Conjugated polymers as actuators: modes of actuation

    DEFF Research Database (Denmark)

    Skaarup, Steen

    2007-01-01

    The physical and chemical properties of conjugated polymers often depend very strongly on the degree of doping with anions or cations. The movement of ions in and out of the polymer matrix as it is redox cycled is also accompanied by mechanical changes. Both the volume and the stiffness can exhibit...... significant differences between the oxidized and reduced states. These effects form the basis of the use of conjugated polymers as actuators (or “artificial muscles”) controllable by a small (1-10 V) voltage. Three basic modes of actuation (bending, linear extension and stiffness change) have been proposed...

  17. Functionalized conjugated polyelectrolytes design and biomedical applications

    CERN Document Server

    Wang, Shu

    2014-01-01

    Functionalized Conjugated Polyelectrolytes presents a comprehensive review of these polyelectrolytes and their biomedical applications. Basic aspects like molecular design and optoelectronic properties are covered in the first chapter. Emphasis is placed on the various applications including sensing (chemical and biological), disease diagnosis, cell imaging, drug/gene delivery and disease treatment. This book explores a multi-disciplinary topic of interest to researchers working in the fields of chemistry, materials, biology and medicine. It also offers an integrated perspective on both basic research and application issues. Functionalized conjugated polyelectrolyte materials, which have already drawn considerable interest, will become a major new direction for biomedicine development.

  18. Plasmid transfer by conjugation in Xylella fastidiosa.

    Science.gov (United States)

    Recombination and horizontal gene transfer have been implicated in the adaption of Xylella fastidiosa (Xf) to infect a wide variety of different plant species. There is evidence that certain strains of Xf carry native plasmids equipped with transfer and mobilization genes, suggesting conjugation as ...

  19. Theory of periodic conjugate heat transfer

    CERN Document Server

    Zudin, Yuri B

    2016-01-01

    This book presents the theory of periodic conjugate heat transfer in detail. It offers a simplified description of the interaction between a solid body and a fluid as a boundary value problem of the heat conduction equation for the solid body.

  20. Conjugate Problems in Convective Heat Transfer: Review

    Directory of Open Access Journals (Sweden)

    Abram Dorfman

    2009-01-01

    Full Text Available A review of conjugate convective heat transfer problems solved during the early and current time of development of this modern approach is presented. The discussion is based on analytical solutions of selected typical relatively simple conjugate problems including steady-state and transient processes, thermal material treatment, and heat and mass transfer in drying. This brief survey is accompanied by the list of almost two hundred publications considering application of different more and less complex analytical and numerical conjugate models for simulating technology processes and industrial devices from aerospace systems to food production. The references are combined in the groups of works studying similar problems so that each of the groups corresponds to one of selected analytical solutions considered in detail. Such structure of review gives the reader the understanding of early and current situation in conjugate convective heat transfer modeling and makes possible to use the information presented as an introduction to this area on the one hand, and to find more complicated publications of interest on the other hand.

  1. Stochastic differential equations used to model conjugation

    DEFF Research Database (Denmark)

    Philipsen, Kirsten Riber; Christiansen, Lasse Engbo

    Stochastic differential equations (SDEs) are used to model horizontal transfer of antibiotic resis- tance by conjugation. The model describes the concentration of donor, recipient, transconjugants and substrate. The strength of the SDE model over the traditional ODE models is that the noise can...

  2. Immunogenicity of novel sulfadimethoxide conjugates | Chen ...

    African Journals Online (AJOL)

    Immunogenicity of novel sulfadimethoxide conjugates. L Chen, J Su, X Zhang, L Li, X He. Abstract. Sulfadimethoxine (SDM) is an antibiotic commonly added to animal feeds. Anti-SDM antibodies are useful for the detection of residual SDM in foods, feeds and biological fluids by ELISA. In this study, we show that SDM is ...

  3. Women experiencing the intergenerationality of conjugal violence

    Directory of Open Access Journals (Sweden)

    Gilvânia Patrícia do Nascimento Paixão

    2015-10-01

    Full Text Available Objective: to analyze the family relationship, in childhood and adolescence, of women who experience conjugal violence.Method: qualitative study. Interviews were held with 19 women, who were experiencing conjugal violence, and who were resident in a community in Salvador, Bahia, Brazil. The project was approved by the Research Ethics Committee (N. 42/2011.Results: the data was organized using the Discourse of the Collective Subject, identifying the summary central ideas: they witnessed violence between their parents; they suffered repercussions from the violence between their parents: they were angry about the mother's submission to her partner; and they reproduced the conjugal violence. The discourse showed that the women witnessed, in childhood and adolescence, violence between their parents, and were injured both physically and psychologically. As a result of the mother's submission, feelings of anger arose in the children. However, in the adult phase of their own lives, they noticed that their conjugal life resembled that of their parents, reproducing the violence.Conclusion: investment is necessary in strategies designed to break inter-generational violence, and the health professionals are important in this process, as it is a phenomenon with repercussions in health. Because they work in the Family Health Strategy, which focuses on the prevention of harm and illness, health promotion and interdepartmentality, the nurses are essential in the process of preventing and confronting this phenomenon.

  4. Integrated circuits based on conjugated polymer monolayer.

    Science.gov (United States)

    Li, Mengmeng; Mangalore, Deepthi Kamath; Zhao, Jingbo; Carpenter, Joshua H; Yan, Hongping; Ade, Harald; Yan, He; Müllen, Klaus; Blom, Paul W M; Pisula, Wojciech; de Leeuw, Dago M; Asadi, Kamal

    2018-01-31

    It is still a great challenge to fabricate conjugated polymer monolayer field-effect transistors (PoM-FETs) due to intricate crystallization and film formation of conjugated polymers. Here we demonstrate PoM-FETs based on a single monolayer of a conjugated polymer. The resulting PoM-FETs are highly reproducible and exhibit charge carrier mobilities reaching 3 cm 2  V -1  s -1 . The high performance is attributed to the strong interactions of the polymer chains present already in solution leading to pronounced edge-on packing and well-defined microstructure in the monolayer. The high reproducibility enables the integration of discrete unipolar PoM-FETs into inverters and ring oscillators. Real logic functionality has been demonstrated by constructing a 15-bit code generator in which hundreds of self-assembled PoM-FETs are addressed simultaneously. Our results provide the state-of-the-art example of integrated circuits based on a conjugated polymer monolayer, opening prospective pathways for bottom-up organic electronics.

  5. Conjugate problems in convective heat transfer

    CERN Document Server

    Dorfman, Abram S

    2009-01-01

    The conjugate heat transfer (CHT) problem takes into account the thermal interaction between a body and fluid flowing over or through it, a key consideration in both mechanical and aerospace engineering. Presenting more than 100 solutions of non-isothermal and CHT problems, this title considers the approximate solutions of CHT problems.

  6. Compositions for directed alignment of conjugated polymers

    Science.gov (United States)

    Kim, Jinsang; Kim, Bong-Gi; Jeong, Eun Jeong

    2016-04-19

    Conjugated polymers (CPs) achieve directed alignment along an applied flow field and a dichroic ratio of as high as 16.67 in emission from well-aligned thin films and fully realized anisotropic optoelectronic properties of CPs in field-effect transistor (FET).

  7. Conjugate Gradient Algorithms For Manipulator Simulation

    Science.gov (United States)

    Fijany, Amir; Scheid, Robert E.

    1991-01-01

    Report discusses applicability of conjugate-gradient algorithms to computation of forward dynamics of robotic manipulators. Rapid computation of forward dynamics essential to teleoperation and other advanced robotic applications. Part of continuing effort to find algorithms meeting requirements for increased computational efficiency and speed. Method used for iterative solution of systems of linear equations.

  8. Conjugated Polymer Actuators: Prospects and Limitations

    DEFF Research Database (Denmark)

    Skaarup, Steen

    2007-01-01

    Actuators constructed with a conjugated polymer as the active part have been predicted to have a number of highly desirable properties: Large mechanical strength, high power density, i.e. high actuation speeds possible, sufficient maximum strain values, high reversibility and safe, low voltages (1...

  9. Some aspects of geomagnetically conjugate phenomena

    Energy Technology Data Exchange (ETDEWEB)

    Rycroft, M.J.

    1987-12-01

    Both charged particles and waves convey information about the thermosphere, ionosphere and magnetosphere from the Northern to the Southern Hemisphere and vice versa, along geomagnetic flux tubes.The interhemispheric travel time of electrons or ions, being dependent upon L-value , pitch angle and energy (which may lie between less than or equal to 1 eV and greater than or equal to 1 MeV) may be many hours, ranging down to less than or equal to 1 s. However, the one-hop propagation time for magnetohydrodynamic or whistler mode waves generally lies between 10/sup 2/s and 1 s. Such times, therefore, give the time scales of transient phenomena that are geomagnetically conjugate and of changes in steady-state plasma processes occurring in geomagnetically conjugate regions. Contrasting examples are presented of conjugate physical phenomena, obtained using satellite, rocket, aircraft and ground-based observations; the latter capitalise upon the rather rare disposition of land - rather than ocean - at each end of a geophysically interesting flux tube. Particular attention is paid to the interactions between whistler mode waves and energetic electrons. Geomagnetic, radio, optical and plasma observations, taken together with model computations, provide a wealth of knowledge on conjugate phenomena and their dependence on conditions in the solar wind, substorms, L-value, etc... Finally, some suggestions are made for future lines of research.

  10. Cross-Conjugated n-Dopable Aromatic Polyketone

    NARCIS (Netherlands)

    Voortman, Thomas P.; Bartesaghi, Davide; Koster, L. Jan Anton; Chiechi, Ryan C.

    2015-01-01

    This paper describes the synthesis and characterization of a high molecular weight cross-conjugated polyketone synthesized via scalable Friedel Crafts chemistry. Cross-conjugated polyketones are precursors to conjugated polyions; they become orders of magnitude more conductive after a two-electron

  11. Bis-polymer lipid-peptide conjugates and nanoparticles thereof

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ting; Dong, He; Shu, Jessica; Dube, Nikhil

    2018-04-24

    The present invention provides bis-polymer lipid-peptide conjugates containing a hydrophobic block and headgroup containing a helical peptide and two polymer blocks. The conjugates can self-assemble to form helix bundle subunits, which in turn assemble to provide micellar nanocarriers for drug cargos and other agents. Particles containing the conjugates and methods for forming the particles are also disclosed.

  12. Development of a novel and automated fluorescent immunoassay for the analysis of beta-lactam antibiotics

    NARCIS (Netherlands)

    Benito-Pena, E.; Moreno-Bondi, M.C.; Orellana, G.; Maquieira, K.; Amerongen, van A.

    2005-01-01

    An automated immunosensor for the rapid and sensitive analysis of penicillin type -lactam antibiotics has been developed and optimized. An immunogen was prepared by coupling the common structure of the penicillanic -lactam antibiotics, i.e., 6-aminopenicillanic acid to keyhole limpet hemocyanin.

  13. Adoptive transfer of natural antibodies to non-immunized chickens affects subsequent antigen-specific humoral and cellular immune responses

    NARCIS (Netherlands)

    Lammers, A.; Klomp, M.E.V.; Nieuwland, M.G.B.; Savelkoul, H.F.J.; Parmentier, H.K.

    2004-01-01

    To determine a regulatory function of natural antibodies in the immune response of chickens, pooled plasma obtained from non-immunized (naive) 15 months old hens was subjected to keyhole limpet hemocyanin (KLH) antigen-affinity chromatography. Purified KLH-binding antibodies were adoptively

  14. Correlated effects of selection for immunity in White Leghorn chicken lines on natural antibodies and specific antibody responses to KLH and M. butyricum

    NARCIS (Netherlands)

    Minozzi, G.; Parmentier, H.K.; Mignon-Grasteau, S.; Nieuwland, M.G.B.; Bed'hom, B.; Gourichon, D.; Minvielle, F.; Pinard-van der Laan, M.H.

    2008-01-01

    Background - The effect of selection for three general immune response traits on primary antibody responses (Ab) to Mycobacterium butyricum or keyhole limpet hemocyanin (KLH) was studied in four experimental lines of White Leghorn chicken. Birds underwent 12 generations of selection for one of three

  15. Application of optical phase conjugation to plasma diagnostics (invited)

    International Nuclear Information System (INIS)

    Jahoda, F.C.; Anderson, B.T.; Forman, P.R.; Weber, P.G.

    1985-01-01

    Several possibilities for plasma diagnostics provided by optical phase conjugation and, in particular, self-pumped phase conjugation in barium titanate (BaTiO 3 ) are discussed. These include placing a plasma within a dye laser cavity equipped with a phase conjugate mirror for intracavity absorption measurements, time differential refractometry with high spatial resolution, and simplified real-time holographic interferometry. The principles of phase conjugation with particular reference to photorefractive media and the special advantages of self-pumped phase conjugation are reviewed prior to the discussion of the applications. Distinctions are made in the applications between those for which photorefractive conjugators are essential and those for which they only offer experimental simplification relative to other types of phase conjugators

  16. Stochastic Spectral and Conjugate Descent Methods

    KAUST Repository

    Kovalev, Dmitry

    2018-02-11

    The state-of-the-art methods for solving optimization problems in big dimensions are variants of randomized coordinate descent (RCD). In this paper we introduce a fundamentally new type of acceleration strategy for RCD based on the augmentation of the set of coordinate directions by a few spectral or conjugate directions. As we increase the number of extra directions to be sampled from, the rate of the method improves, and interpolates between the linear rate of RCD and a linear rate independent of the condition number. We develop and analyze also inexact variants of these methods where the spectral and conjugate directions are allowed to be approximate only. We motivate the above development by proving several negative results which highlight the limitations of RCD with importance sampling.

  17. Stochastic Spectral and Conjugate Descent Methods

    KAUST Repository

    Kovalev, Dmitry; Gorbunov, Eduard; Gasanov, Elnur; Richtarik, Peter

    2018-01-01

    The state-of-the-art methods for solving optimization problems in big dimensions are variants of randomized coordinate descent (RCD). In this paper we introduce a fundamentally new type of acceleration strategy for RCD based on the augmentation of the set of coordinate directions by a few spectral or conjugate directions. As we increase the number of extra directions to be sampled from, the rate of the method improves, and interpolates between the linear rate of RCD and a linear rate independent of the condition number. We develop and analyze also inexact variants of these methods where the spectral and conjugate directions are allowed to be approximate only. We motivate the above development by proving several negative results which highlight the limitations of RCD with importance sampling.

  18. Phase-conjugate optical coherence tomography

    International Nuclear Information System (INIS)

    Erkmen, Baris I.; Shapiro, Jeffrey H.

    2006-01-01

    Quantum optical coherence tomography (Q-OCT) offers a factor-of-2 improvement in axial resolution and the advantage of even-order dispersion cancellation when it is compared to conventional OCT (C-OCT). These features have been ascribed to the nonclassical nature of the biphoton state employed in the former, as opposed to the classical state used in the latter. Phase-conjugate OCT (PC-OCT) shows that nonclassical light is not necessary to reap Q-OCT's advantages. PC-OCT uses classical-state signal and reference beams, which have a phase-sensitive cross correlation, together with phase conjugation to achieve the axial resolution and even-order dispersion cancellation of Q-OCT with a signal-to-noise ratio that can be comparable to that of C-OCT

  19. Antibody conjugate radioimmunotherapy of superficial bladder cancer

    International Nuclear Information System (INIS)

    Perkins, Alan; Hopper, Melanie; Murray, Andrea; Frier, Malcolm; Bishop, Mike

    2002-01-01

    The administration of antibody conjugates for cancer therapy is now proving to be of clinical value. We are currently undertaking a programme of clinical studies using the monoclonal antibody C 595 (gG3) which reacts with the MUC1 glycoprotein antigen that is aberrantly expressed in a high proportion of bladder tumours. Radio immuno conjugates of the C 595 antibody have been produced with high radiolabelling efficiency and immuno reactivity using Tc-99 m and In-111 for diagnostic imaging, and disease staging and the cytotoxic radionuclides Cu-67 and Re-188 for therapy of superficial bladder cancer. A Phase I/II therapeutic trail involving the intravesical administration of antibody directly into the bladder has now begun. (author)

  20. Charge conjugation invariance of the spectator equations

    International Nuclear Information System (INIS)

    Gross, F.

    1999-01-01

    In response to recent criticism, the authors show how to define the spectator equations for negative energies so that charge conjugation invariance is preserved. The result, which emerges naturally from the application of spectator principles to systems of particles with negative energies, is to replace all factors of the external energies W iota by √ W 2 iota , insuring that the amplitudes are independent of the sign of the energies W iota

  1. Conjugated Linoleic Acid: good or bad nutrient

    Directory of Open Access Journals (Sweden)

    Gonçalves Daniela C

    2010-10-01

    Full Text Available Abstract Conjugated linoleic acid (CLA is a class of 28 positional and geometric isomers of linoleic acid octadecadienoic.Currently, it has been described many benefits related to the supplementation of CLA in animals and humans, as in the treatment of cancer, oxidative stress, in atherosclerosis, in bone formation and composition in obesity, in diabetes and the immune system. However, our results show that, CLA appears to be not a good supplement in patients with cachexia.

  2. Error Estimation in Preconditioned Conjugate Gradients

    Czech Academy of Sciences Publication Activity Database

    Strakoš, Zdeněk; Tichý, Petr

    2005-01-01

    Roč. 45, - (2005), s. 789-817 ISSN 0006-3835 R&D Projects: GA AV ČR 1ET400300415; GA AV ČR KJB1030306 Institutional research plan: CEZ:AV0Z10300504 Keywords : preconditioned conjugate gradient method * error bounds * stopping criteria * evaluation of convergence * numerical stability * finite precision arithmetic * rounding errors Subject RIV: BA - General Mathematics Impact factor: 0.509, year: 2005

  3. Conjugate gradient optimization programs for shuttle reentry

    Science.gov (United States)

    Powers, W. F.; Jacobson, R. A.; Leonard, D. A.

    1972-01-01

    Two computer programs for shuttle reentry trajectory optimization are listed and described. Both programs use the conjugate gradient method as the optimization procedure. The Phase 1 Program is developed in cartesian coordinates for a rotating spherical earth, and crossrange, downrange, maximum deceleration, total heating, and terminal speed, altitude, and flight path angle are included in the performance index. The programs make extensive use of subroutines so that they may be easily adapted to other atmospheric trajectory optimization problems.

  4. M-step preconditioned conjugate gradient methods

    Science.gov (United States)

    Adams, L.

    1983-01-01

    Preconditioned conjugate gradient methods for solving sparse symmetric and positive finite systems of linear equations are described. Necessary and sufficient conditions are given for when these preconditioners can be used and an analysis of their effectiveness is given. Efficient computer implementations of these methods are discussed and results on the CYBER 203 and the Finite Element Machine under construction at NASA Langley Research Center are included.

  5. [Relationship between family variables and conjugal adjustment].

    Science.gov (United States)

    Jiménez-Picón, Nerea; Lima-Rodríguez, Joaquín-Salvador; Lima-Serrano, Marta

    2018-04-01

    To determine whether family variables, such as type of relationship, years of marriage, existence of offspring, number of members of family, stage of family life cycle, transition between stages, perceived social support, and/or stressful life events are related to conjugal adjustment. A cross-sectional and correlational study using questionnaires. Primary care and hospital units of selected centres in the province of Seville, Spain. Consecutive stratified sampling by quotas of 369 heterosexual couples over 18years of age, who maintained a relationship, with or without children, living in Seville. A self-report questionnaire for the sociodemographic variables, and the abbreviated version of the Dyadic Adjustment Scale, Questionnaire MOS Perceived Social Support, and Social Readjustment Rating Scale, were used. Descriptive and inferential statistics were performed with correlation analysis and multivariate regression. Statistically significant associations were found between conjugal adjustment and marriage years (r=-10: Pfamily life cycle (F=2.65; Pfamily life cycle stage (mature-aged stage) on conjugal adjustment (R2=.21; F=9.9; df=356; Prelationship. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  6. Cancer Chemopreventive Ability of Conjugated Linolenic Acids

    Directory of Open Access Journals (Sweden)

    Kazuo Miyashita

    2011-11-01

    Full Text Available Conjugated fatty acids (CFA have received increased interest because of their beneficial effects on human health, including preventing cancer development. Conjugated linoleic acids (CLA are such CFA, and have been reviewed extensively for their multiple biological activities. In contrast to other types of CFAs including CLA that are found at low concentrations (less than 1% in natural products, conjugated linolenic acids (CLN are the only CFAs that occur in higher quantities in natural products. Some plant seeds contain a considerably high concentration of CLN (30 to 70 wt% lipid. Our research group has screened CLN from different plant seed oils to determine their cancer chemopreventive ability. This review describes the physiological functions of CLN isomers that occur in certain plant seeds. CLN are able to induce apoptosis through decrease of Bcl-2 protein in certain human cancer cell lines, increase expression of peroxisome proliferator-activated receptor (PPAR-γ, and up-regulate gene expression of p53. Findings in our preclinical animal studies have indicated that feeding with CLN resulted in inhibition of colorectal tumorigenesis through modulation of apoptosis and expression of PPARγ and p53. In this review, we summarize chemopreventive efficacy of CLN against cancer development, especially colorectal cancer.

  7. Dye linked conjugated homopolymers: using conjugated polymer electroluminescence to optically pump porphyrin-dye emission

    DEFF Research Database (Denmark)

    Nielsen, K.T.; Spanggaard, H.; Krebs, Frederik C

    2004-01-01

    . Electroluminescent devices of the homopolymer itself and of the zinc-porphyrin containing polymer were prepared and the nature of the electroluminescence was characterized. The homopolymer segments were found to optically pump the emission of the zinc-porphyrin dye moities. The homopolymer exhibits blue......Zinc-porphyrin dye molecules were incorporated into the backbone of a conjugated polymer material by a method, which allowed for the incorporation of only one zinc-porphyrin dye molecule into the backbone of each conjugated polymer molecule. The electronic properties of the homopolymer were...

  8. Co-conjugation vis-à-vis individual conjugation of α-amylase and glucoamylase for hydrolysis of starch.

    Science.gov (United States)

    Jadhav, Swati B; Singhal, Rekha S

    2013-10-15

    Two enzymes, α-amylase and glucoamylase have been individually and co-conjugated to pectin by covalent binding. Both the enzyme systems showed better thermal and pH stability over the free enzyme system with the complete retention of original activities. Mixture of individually conjugated enzymes showed lower inactivation rate constant with longer half life than the co-conjugated enzyme system. Individually conjugated enzymes showed an increase of 56.48 kJ/mole and 38.22 kJ/mole in activation energy for denaturation than the free enzymes and co-conjugated enzymes, respectively. Km as well as Vmax of individually and co-conjugated enzymes was found to be higher than the free enzymes. SDS-polyacrylamide gel electrophoresis confirmed the formation of conjugate and co-conjugate as evident by increased molecular weight. Both the enzyme systems were used for starch hydrolysis where individually conjugated enzymes showed highest release of glucose at 60 °C and pH 5.0 as compared to free and co-conjugated enzyme. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Structure and evolution of Panulirus interruptus Hemocyanin.

    NARCIS (Netherlands)

    Bak, Hendrikus Jacobus

    1987-01-01

    Hemocyaninies een koperbevattend zuurstof transporterend eiwit, dat vrij opgelost in de hemolymfe (bloed) van geleedpotige (arthropodene) en weekdieren (mollusken) voorkomt. Het is een van de drie types zuurstoftransporteurs die in de natuur voorkomen. Van de twee andere ademhalingspigmenten,

  10. Minimizing inner product data dependencies in conjugate gradient iteration

    Science.gov (United States)

    Vanrosendale, J.

    1983-01-01

    The amount of concurrency available in conjugate gradient iteration is limited by the summations required in the inner product computations. The inner product of two vectors of length N requires time c log(N), if N or more processors are available. This paper describes an algebraic restructuring of the conjugate gradient algorithm which minimizes data dependencies due to inner product calculations. After an initial start up, the new algorithm can perform a conjugate gradient iteration in time c*log(log(N)).

  11. Methotrexate and epirubicin conjugates as potential antitumor drugs

    Directory of Open Access Journals (Sweden)

    Szymon Wojciech Kmiecik

    2017-07-01

    Full Text Available Introduction: The use of hybrid molecules has become one of the most significant approaches in new cytotoxic drug design. This study describes synthesis and characterization of conjugates consisting of two well-known and characterized chemotherapeutic agents: methotrexate (MTX and epirubicin (EPR. The synthesized conjugates combine two significant anticancer strategies: combinatory therapy and targeted therapy. These two drugs were chosen because they have different mechanisms of action, which can increase the anticancer effect of the obtained conjugates. MTX, which is a folic acid analog, has high cytotoxic properties and can serve as a targeting moiety that can reach folate receptors (FRs overexpresing tumor cells. Combination of nonselective drugs such as EPR with MTX can increase the selectivity of the obtained conjugates, while maintaining the high cytotoxic properties.Materials and methods: Conjugates were purified by RP-HPLC and the structure was investigated by MS and MS/MS methods. The effect of the conjugates on proliferation of LoVo, LoVo/Dx, MCF-7 and MV-4-11 human cancer cell lines was determined by SRB or MTT assay.Results: The conjugation reaction results in the formation of monosubstituted (α, γ and disubstituted MTX derivatives. In vitro proliferation data demonstrate that the conjugates synthesized in our study show lower cytotoxic properties than both chemotherapeutics used alone.Discussion: Epirubicin cytotoxicity was not observed in obtained conjugates. Effective drugs release after internalization needs further investigation.

  12. Poly(2-oxazoline)-Antibiotic Conjugates with Penicillins.

    Science.gov (United States)

    Schmidt, Martin; Bast, Livia K; Lanfer, Franziska; Richter, Lena; Hennes, Elisabeth; Seymen, Rana; Krumm, Christian; Tiller, Joerg C

    2017-09-20

    The conjugation of antibiotics with polymers is rarely done, but it might be a promising alternative to low-molecular-weight derivatization. The two penicillins penicillin G (PenG) and penicillin V (PenV) were attached to the end groups of different water-soluble poly(2-oxazoline)s (POx) via their carboxylic acid function. This ester group was shown to be more stable against hydrolysis than the β-lactam ring of the penicillins. The conjugates are still antimicrobially active and up to 20 times more stable against penicillinase catalyzed hydrolysis. The antibiotic activity of the conjugates against Staphylococcus aureus in the presence of penicillinase is up to 350 times higher compared with the free antibiotics. Conjugates with a second antimicrobial function, a dodecyltrimethylammonium group (DDA-X), at the starting end of the PenG and PenV POx conjugates are more antimicrobially active than the conjugates without DDA-X and show high activity in the presence of penicillinase. For example, the conjugates DDA-X-PEtOx-PenG and DDA-X-PEtOx-PenV are 200 to 350 times more active against S. aureus in the presence of penicillinase and almost as effective as the penicillinase stable cloxacollin (Clox) under these conditions. These conjugates show even greater activity compared to cloxacollin without this enzyme present. Further, both conjugates kill Escherichia coli more effectively than PenG and Clox.

  13. Sources and Bioactive Properties of Conjugated Dietary Fatty Acids.

    Science.gov (United States)

    Hennessy, Alan A; Ross, Paul R; Fitzgerald, Gerald F; Stanton, Catherine

    2016-04-01

    The group of conjugated fatty acids known as conjugated linoleic acid (CLA) isomers have been extensively studied with regard to their bioactive potential in treating some of the most prominent human health malignancies. However, CLA isomers are not the only group of potentially bioactive conjugated fatty acids currently undergoing study. In this regard, isomers of conjugated α-linolenic acid, conjugated nonadecadienoic acid and conjugated eicosapentaenoic acid, to name but a few, have undergone experimental assessment. These studies have indicated many of these conjugated fatty acid isomers commonly possess anti-carcinogenic, anti-adipogenic, anti-inflammatory and immune modulating properties, a number of which will be discussed in this review. The mechanisms through which these bioactivities are mediated have not yet been fully elucidated. However, existing evidence indicates that these fatty acids may play a role in modulating the expression of several oncogenes, cell cycle regulators, and genes associated with energy metabolism. Despite such bioactive potential, interest in these conjugated fatty acids has remained low relative to the CLA isomers. This may be partly attributed to the relatively recent emergence of these fatty acids as bioactives, but also due to a lack of awareness regarding sources from which they can be produced. In this review, we will also highlight the common sources of these conjugated fatty acids, including plants, algae, microbes and chemosynthesis.

  14. Quantitative clinical uptake measurements using conjugate counting

    International Nuclear Information System (INIS)

    Lathrop, K.A.; Bartlett, R.D.; Chen, C.T.; Chou, J.S.; Faulhaber, P.F.; Harper, P.V.; Stark, V.J.

    1986-01-01

    While the use of conjugate counting for determination of organ uptake in human subjects has been extensively described, in the present study the determination of the organ uptake of ortho-iodohippurate presented several opportunities for validation of the in vivo counting data. Ortho-iodohippurate is distributed in the extracellular space, is largely extracted on each pass through the kidneys, and is not significantly deiodinated in vivo. Thus, the kidney uptake rate should be proportional to the blood level, the appearance rate of activity in the bladder is equal to the disappearance rate from the kidneys, and direct measurement of activity in the urine after voiding provides an internal standard for imaging measurements of bladder activity. Since the activity levels in the kidneys, bladder, and remainder of the body changed fairly rapidly, especially in the first 20 to 30 minutes following injection, posterior images of the trunk including kidneys and bladder were obtained continuously using a gamma camera fitted with a diverging collimator for 30 minutes and then at intervals for several hours. Simultaneous conjugate counting determinations were made using a whole body scanning system previously described at these meetings. Imaging data corrected for decay and adjacent background were fitted by least squares methods to curves representing a sum of exponentials, and the curves were normalized to the conjugate uptake measurements. The uptake curves of the kidneys and bladder matched well with the direct measurements of the urinary excretion. Data were collected in 16 normal subjects, and the estimated absorbed dose was calculated for the kidneys, the bladder and the remainder of the body for seven radioisotopes of iodine. 4 references, 6 figures, 2 tables

  15. Interplay of alternative conjugated pathways and steric interactions on the electronic and optical properties of donor-acceptor conjugated polymers

    KAUST Repository

    Lima, Igo T.; Risko, Chad; Aziz, Saadullah Gary; Da Silva Filho, Demé trio A Da Silva; Bredas, Jean-Luc

    2014-01-01

    Donor-acceptor π-conjugated copolymers are of interest for a wide range of electronic applications, including field-effect transistors and solar cells. Here, we present a density functional theory (DFT) study of the impact of varying the conjugation pathway on the geometric, electronic, and optical properties of donor-acceptor systems. We consider both linear ("in series"), traditional conjugation among the donor-acceptor moieties versus structures where the acceptor units are appended orthogonally to the linear, donor-only conjugated backbone. Long-range-corrected hybrid functionals are used in the investigation with the values of the tuned long-range separation parameters providing an estimate of the extent of conjugation as a function of the oligomer architecture. Considerable differences in the electronic and optical properties are determined as a function of the nature of the conjugation pathway, features that should be taken into account in the design of donor-acceptor copolymers.

  16. Conjugated polymer photovoltaic devices and materials

    International Nuclear Information System (INIS)

    Mozer, A.J.; Niyazi, Serdar Sariciftci

    2006-01-01

    The science and technology of conjugated polymer-based photovoltaic devices (bulk heterojunction solar cells) is highlighted focusing on three major issues, i.e. (i) nano-morphology optimization, (ii) improving charge carrier mobility, (iii) improving spectral sensitivity. Successful strategies towards improved photovoltaic performance are presented using various novel materials, including double-cable polymers, regioregular polymers and low bandgap polymers. The examples presented herein demonstrate that the bulk heterojunction concept is a viable approach towards developing photovoltaic systems by inexpensive solution-based fabrication technologies. (authors)

  17. Complex conjugate poles and parton distributions

    International Nuclear Information System (INIS)

    Tiburzi, B.C.; Detmold, W.; Miller, G.A.

    2003-01-01

    We calculate parton and generalized parton distributions in Minkowski space using a scalar propagator with a pair of complex conjugate poles. Correct spectral and support properties are obtained only after careful analytic continuation from Euclidean space. Alternately the quark distribution function can be calculated from modified cutting rules, which put the intermediate state on its complex mass shells. Distribution functions agree with those resulting from the model's Euclidean space double distribution which we calculate via nondiagonal matrix elements of twist-two operators. Thus one can use a wide class of analytic parametrizations of the quark propagator to connect Euclidean space Green functions to light-cone dominated amplitudes

  18. PET regularization by envelope guided conjugate gradients

    International Nuclear Information System (INIS)

    Kaufman, L.; Neumaier, A.

    1996-01-01

    The authors propose a new way to iteratively solve large scale ill-posed problems and in particular the image reconstruction problem in positron emission tomography by exploiting the relation between Tikhonov regularization and multiobjective optimization to obtain iteratively approximations to the Tikhonov L-curve and its corner. Monitoring the change of the approximate L-curves allows us to adjust the regularization parameter adaptively during a preconditioned conjugate gradient iteration, so that the desired solution can be reconstructed with a small number of iterations

  19. Rhenium 188 labelling of peptide conjugates

    International Nuclear Information System (INIS)

    Melendez-Alafort, Laura

    2001-01-01

    Many human tumours express high levels, of somatostatin receptors. In order to make possible a radiotherapeutic treatment of this kind for tumour a series of somatostatin analogues that can tightly chelate beta emitting isotopes have been developed in recent years. The work carried out for this thesis has been aimed towards development of a new therapeutic radiopharmaceutical for treatment of somatostatin receptor positive tumours. The first chapters describe work with technetium-99m to establish the labelling and analytical conditions for a somatostatin analogue, [Tyr 3 ]-octreotide (TOC), as a precursor to undertaking labelling studies with the beta emitter rhenium-188. 6-Hydrazinopyridine-3-carboxylic acid (HYNIC) was conjugated to TOC and labelled with 99m using different coligands. Then the stability, receptor binding and biodistribution of each complex were assessed. 99m Tc-HYNIC-TOC using EDDA as coligand showed the best characteristics, and was superior for tumour imaging in humans than the commercially available 111 In-DTPA-octreotide. The conditions for labelling the HYNIC-TOC conjugate with 188 Re were then optimised using tricine as a co-ligand. A labelling yield of ∼80% was achieved. After purification however, the stability of the complex was low. The use of other coligand systems which had proved useful for 99m Tc labelling was explored, but yields were very poor. Other chelators such as diethylenetriamine pentaacetic acid (DTPA), dimercaptosuccinic acid (DMSA) and mercaptoacetyltriglycine (MAG 3 ) were studied as potential co-ligand agents to label the HYNIC-TOC conjugate with 188 Re but, again low yields of the labelled peptide complexes were achieved. A novel 188 Re-HYNIC complex was prepared in high yields using N-N-disubstituted dithiocarbamates as coligands. However to date, the specific activities achieved with this system are relatively low. The use of the [ 99m Tc(CO) 3 (H 2 O) 3 ] complex to label the HYNIC-TOC conjugate was investigated

  20. In Vitro Evaluation of Third Generation PAMAM Dendrimer Conjugates

    Directory of Open Access Journals (Sweden)

    Mohammad Najlah

    2017-10-01

    Full Text Available The present study compares the use of high generation G3 and low generation G0 Polyamidoamine (PAMAM dendrimers as drug carriers of naproxen (NAP, a poorly water soluble drug. Naproxen was conjugated to G3 in different ratios and to G0 in a 1:1 ratio via a diethylene glycol linker. A lauroyl chain (L, a lipophilic permeability enhancer, was attached to G3 and G0 prodrugs. The G3 and G0 conjugates were more hydrophilic than naproxen as evaluated by the measurement of partitioning between 1-octanol and a phosphate buffer at pH 7.4 and pH 1.2. The unmodified surface PAMAM-NAP conjugates showed significant solubility enhancements of NAP at pH 1.2; however, with the number of NAP conjugated to G3, this was limited to 10 molecules. The lactate dehydrogenase (LDH assay indicated that the G3 dendrimer conjugates had a concentration dependent toxicity towards Caco-2 cells. Attaching naproxen to the surface of the dendrimer increased the IC50 of the resulting prodrugs towards Caco-2 cells. The lauroyl G3 conjugates showed the highest toxicity amongst the PAMAM dendrimer conjugates investigated and were significantly more toxic than the lauroyl-G0-naproxen conjugates. The permeability of naproxen across monolayers of Caco-2 cells was significantly increased by its conjugation to either G3 or G0 PAMAM dendrimers. Lauroyl-G0 conjugates displayed considerably lower cytotoxicity than G3 conjugates and may be preferable for use as a drug carrier for low soluble drugs such as naproxen.

  1. Antibody-Conjugated Nanoparticles for Biomedical Applications

    Directory of Open Access Journals (Sweden)

    Manuel Arruebo

    2009-01-01

    Full Text Available Nanoscience and Nanotechnology have found their way into the fields of Biotechnology and Medicine. Nanoparticles by themselves offer specific physicochemical properties that they do not exhibit in bulk form, where materials show constant physical properties regardless of size. Antibodies are nanosize biological products that are part of the specific immune system. In addition to their own properties as pathogens or toxin neutralizers, as well as in the recruitment of immune elements (complement, improving phagocytosis, cytotoxicity antibody dependent by natural killer cells, etc., they could carry several elements (toxins, drugs, fluorochroms, or even nanoparticles, etc. and be used in several diagnostic procedures, or even in therapy to destroy a specific target. The conjugation of antibodies to nanoparticles can generate a product that combines the properties of both. For example, they can combine the small size of nanoparticles and their special thermal, imaging, drug carrier, or magnetic characteristics with the abilities of antibodies, such as specific and selective recognition. The hybrid product will show versatility and specificity. In this review, we analyse both antibodies and nanoparticles, focusing especially on the recent developments for antibody-conjugated nanoparticles, offering the researcher an overview of the different applications and possibilities of these hybrid carriers.

  2. π-Clamp-mediated cysteine conjugation

    Science.gov (United States)

    Zhang, Chi; Welborn, Matthew; Zhu, Tianyu; Yang, Nicole J.; Santos, Michael S.; van Voorhis, Troy; Pentelute, Bradley L.

    2016-02-01

    Site-selective functionalization of complex molecules is one of the most significant challenges in chemistry. Typically, protecting groups or catalysts must be used to enable the selective modification of one site among many that are similarly reactive, and general strategies that selectively tune the local chemical environment around a target site are rare. Here, we show a four-amino-acid sequence (Phe-Cys-Pro-Phe), which we call the ‘π-clamp’, that tunes the reactivity of its cysteine thiol for site-selective conjugation with perfluoroaromatic reagents. We use the π-clamp to selectively modify one cysteine site in proteins containing multiple endogenous cysteine residues. These examples include antibodies and cysteine-based enzymes that would be difficult to modify selectively using standard cysteine-based methods. Antibodies modified using the π-clamp retained binding affinity to their targets, enabling the synthesis of site-specific antibody-drug conjugates for selective killing of HER2-positive breast cancer cells. The π-clamp is an unexpected approach to mediate site-selective chemistry and provides new avenues to modify biomolecules for research and therapeutics.

  3. The multigrid preconditioned conjugate gradient method

    Science.gov (United States)

    Tatebe, Osamu

    1993-01-01

    A multigrid preconditioned conjugate gradient method (MGCG method), which uses the multigrid method as a preconditioner of the PCG method, is proposed. The multigrid method has inherent high parallelism and improves convergence of long wavelength components, which is important in iterative methods. By using this method as a preconditioner of the PCG method, an efficient method with high parallelism and fast convergence is obtained. First, it is considered a necessary condition of the multigrid preconditioner in order to satisfy requirements of a preconditioner of the PCG method. Next numerical experiments show a behavior of the MGCG method and that the MGCG method is superior to both the ICCG method and the multigrid method in point of fast convergence and high parallelism. This fast convergence is understood in terms of the eigenvalue analysis of the preconditioned matrix. From this observation of the multigrid preconditioner, it is realized that the MGCG method converges in very few iterations and the multigrid preconditioner is a desirable preconditioner of the conjugate gradient method.

  4. Preparation and biodistribution study of 99Tcm labelled dextran conjugates

    International Nuclear Information System (INIS)

    Yang Chunhui; Li Hongyu; Liang Jixin; Lu Jia; Luo Hongyi; Zheng Deqiang; Sun Guiquan

    2012-01-01

    99 Tc m Mannosylated dextran conjugates were prepared through [ 99 Tc m (CO) 3 ] + precursor synthesized by carbonyl Isolink kit. The labelled conjugates were injected sub-dermally into the rear foots of the mice, and the patent blue solution was injected at the same site 10 min before sacrifice. The mice were killed at 1 h and 4 h postinjection, and the samples of different tissues including SLN, 2LN, injection site, liver, spleen, blood were dissected and counted. The uptake in terms was calculated. The results of biodistribution demonstrated that the SLN uptakes of radiopharmaceutical (without mannose in the molecules) were rather low and in vivo excretion of these conjugates were comparatively faster, and the uptake of injection site was also low; on the other hand, the SLN uptakes of radio pharmaceutical (with mannose in their molecules) were much higher than those of their corresponding dextran conjugates without mannose, but the retention in the injection site of these conjugates increased too. The results indicated that the affinity of mannosyl-dextran conjugates to the receptors on the surface of macrophages in the lymph node. In addition, the different relative molecular mass of dextran conjugates also cause different biodistribution results, the major one had higher SLN uptake, the difference was significant (P 99 Tc m (CO) 3 ] + labelled mannosylated dextran conjugates showed promising properties as SLN imaging agent and worth further investigation. (authors)

  5. PREPARATION OF CHEMICALLY WELL-DEFINED CARBOHYDRATE DENDRIMER CONJUGATES

    DEFF Research Database (Denmark)

    2004-01-01

    A method for the synthesis of dendrimer conjugates having a well-defined chemical structure, comprising one or more carbohydrate moieties and one or more immunomodulating substances coupled to a dendrimer, is presented. First, the carbohydrate is bound to the dendrimer in a chemoselective manner...... conjugates and their use in vaccination, production of antibodies, high throughput screening, diagnostic assays and libraries....

  6. Cross-conjugation and quantum interference: a general correlation?

    DEFF Research Database (Denmark)

    Valkenier, Hennie; Guedon, Constant M.; Markussen, Troels

    2014-01-01

    We discuss the relationship between the pi-conjugation pattern, molecular length, and charge transport properties of molecular wires, both from an experimental and a theoretical viewpoint. Specifically, we focus on the role of quantum interference in the conductance properties of cross-conjugated...

  7. The Synthesis of Substituted Piperazine-cholesterol Conjugates for ...

    African Journals Online (AJOL)

    A small library of cholesterol-piperazine conjugates were synthesized by the reaction of cholesteryl chloroformate with a set of substituted piperazines in dichloromethane at room temperature. The conjugates, all obtained in good to excellent yields, were synthesized to be key components of nucleic acid transfection ...

  8. New preconditioned conjugate gradient algorithms for nonlinear unconstrained optimization problems

    International Nuclear Information System (INIS)

    Al-Bayati, A.; Al-Asadi, N.

    1997-01-01

    This paper presents two new predilection conjugate gradient algorithms for nonlinear unconstrained optimization problems and examines their computational performance. Computational experience shows that the new proposed algorithms generally imp lone the efficiency of Nazareth's [13] preconditioned conjugate gradient algorithm. (authors). 16 refs., 1 tab

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

    NARCIS (Netherlands)

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

    1991-01-01

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

  10. Enhanced photodynamic efficacy of zinc phthalocyanine by conjugating to heptalysine.

    Science.gov (United States)

    Li, Linsen; Luo, Zhipu; Chen, Zhuo; Chen, Jincan; Zhou, Shanyong; Xu, Peng; Hu, Ping; Wang, Jundong; Chen, Naisheng; Huang, Jinling; Huang, Mingdong

    2012-11-21

    Zinc phthalocyanine (ZnPc) is a promising photosensitizer for photodynamic therapy, but faces some challenges: ZnPc is insoluble in water and thus requires either special formulation of ZnPc by, e.g., liposome or Cremophor EL, or chemical modification of Pc ring to enhance its bioavailability and photodynamic efficacy. Here, we conjugated monosubstituted ZnPc-COOH with a series of oligolysine moieties with different numbers of lysine residues (ZnPc-(Lys)(n) (n = 1, 3, 5, 7, 9) to improve the water solubility of the ZnPc conjugates. We measured the photosensitizing efficacies and the cellular uptakes of this series of conjugates on a normal and a cancerous cell line. In addition, we developed a sensitive in situ method to distinguish the difference in photodynamic efficacy among conjugates. Our results showed that ZnPc-(Lys)(7) has the highest photodynamic efficacy compared to the other conjugates investigated.

  11. Development of a monoclonal antibody against the left wing of ciguatoxin CTX1B: thiol strategy and detection using a sandwich ELISA.

    Science.gov (United States)

    Tsumuraya, Takeshi; Takeuchi, Katsutoshi; Yamashita, Shuji; Fujii, Ikuo; Hirama, Masahiro

    2012-09-01

    Ciguatera fish poisoning (CFP) is a form of food poisoning caused by the ingestion of a variety of reef fish that have accumulated trace amounts of ciguatoxins produced by dinoflagellates of the genus Gambierdiscus through the food chain. CFP affects more than 50,000 people each year. The extremely low level of the causative neurotoxins, ciguatoxins, in fish has hampered the preparation of antibodies for detecting the toxins. In this paper, we describe a thiol strategy for synthesizing a keyhole limpet hemocyanin (KLH)-conjugate (20) of the ABCDE-ring fragment of the Pacific ciguatoxins, CTX1B (1) and 54-deoxyCTX1B (4). We succeeded in producing a monoclonal antibody (3G8) against the left wings of these ciguatoxins by immunizing mice with the hapten-KLH conjugate (20) as the synthetic antigen. The most promising mAb, 3G8, does not cross-react with other related marine toxins. Sandwich enzyme-linked immunosorbent assay (ELISA) utilizing 3G8 and the previously prepared monoclonal antibody (8H4) enabled us to detect 1 specifically at less than 0.28 ng/mL. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Human glutathione S-transferase-mediated glutathione conjugation of curcumin and efflux of these conjugates in caco-2 cells

    NARCIS (Netherlands)

    Usta, M.; Wortelboer, H.M.; Vervoort, J.; Boersma, M.G.; Rietjens, I.M.C.M.; Bladeren, P.J. van; Cnubben, N.H.P.

    2007-01-01

    Curcumin, an α,β-unsaturated carbonyl compound, reacts with glutathione, leading to the formation of two monoglutathionyl curcumin conjugates. In the present study, the structures of both glutathione conjugates of curcumin were identified by LC-MS and one- and two-dimensional 1H NMR analysis, and

  13. Human glutathione S-transferase-mediated glutathione conjugation of curcumin and efflux of these conjugates in Caco-2 cells

    NARCIS (Netherlands)

    Usta, M.; Wortelboer, H.M.; Vervoort, J.J.M.; Boersma, M.G.; Rietjens, I.M.C.M.; Bladeren, van P.J.; Cnubben, N.H.P.

    2007-01-01

    Curcumin, an alpha,beta-unsaturated carbonyl compound, reacts with glutathione, leading to the formation of two monoglutathionyl curcumin conjugates. In the present study, the structures of both glutathione conjugates of curcumin were identified by LC-MS and one- and two-dimensional H-1 NMR

  14. Are conjugated linolenic acid isomers an alternative to conjugated linoleic acid isomers in obesity prevention?

    Science.gov (United States)

    Miranda, Jonatan; Arias, Noemi; Fernández-Quintela, Alfredo; del Puy Portillo, María

    2014-04-01

    Despite its benefits, conjugated linoleic acid (CLA) may cause side effects after long-term administration. Because of this and the controversial efficacy of CLA in humans, alternative biomolecules that may be used as functional ingredients have been studied in recent years. Thus, conjugated linolenic acid (CLNA) has been reported to be a potential anti-obesity molecule which may have additional positive effects related to obesity. According to the results reported in obesity, CLNA needs to be given at higher doses than CLA to be effective. However, because of the few studies conducted so far, it is still difficult to reach clear conclusions about the potential use of these CLNAs in obesity and its related changes (insulin resistance, dyslipidemia, or inflammation). Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  15. Conjugate Heat Transfer Study in Hypersonic Flows

    Science.gov (United States)

    Sahoo, Niranjan; Kulkarni, Vinayak; Peetala, Ravi Kumar

    2018-04-01

    Coupled and decoupled conjugate heat transfer (CHT) studies are carried out to imitate experimental studies for heat transfer measurement in hypersonic flow regime. The finite volume based solvers are used for analyzing the heat interaction between fluid and solid domains. Temperature and surface heat flux signals are predicted by both coupled and decoupled CHT analysis techniques for hypersonic Mach numbers. These two methodologies are also used to study the effect of different wall materials on surface parameters. Effectiveness of these CHT solvers has been verified for the inverse problem of wall heat flux recovery using various techniques reported in the literature. Both coupled and decoupled CHT techniques are seen to be equally useful for prediction of local temperature and heat flux signals prior to the experiments in hypersonic flows.

  16. A fast, preconditioned conjugate gradient Toeplitz solver

    Science.gov (United States)

    Pan, Victor; Schrieber, Robert

    1989-01-01

    A simple factorization is given of an arbitrary hermitian, positive definite matrix in which the factors are well-conditioned, hermitian, and positive definite. In fact, given knowledge of the extreme eigenvalues of the original matrix A, an optimal improvement can be achieved, making the condition numbers of each of the two factors equal to the square root of the condition number of A. This technique is to applied to the solution of hermitian, positive definite Toeplitz systems. Large linear systems with hermitian, positive definite Toeplitz matrices arise in some signal processing applications. A stable fast algorithm is given for solving these systems that is based on the preconditioned conjugate gradient method. The algorithm exploits Toeplitz structure to reduce the cost of an iteration to O(n log n) by applying the fast Fourier Transform to compute matrix-vector products. Matrix factorization is used as a preconditioner.

  17. Double diffusive conjugate heat transfer: Part I

    Science.gov (United States)

    Azeem, Soudagar, Manzoor Elahi M.

    2018-05-01

    The present work is undertaken to investigate the effect of solid wall being placed at left of square cavity filled with porous medium. The presence of a solid wall in the porous medium turns the situation into a conjugate heat transfer problem. The boundary conditions are such that the left vertical surface is maintained at highest temperature and concentration whereas right vertical surface at lowest temperature and concentration in the medium. The top and bottom surfaces are adiabatic. The additional conduction equation along with the regular momentum and energy equations of porous medium are solved in an iterative manner with the help of finite element method. It is seen that the heat and mass transfer rate is lesser due to smaller thermal and concentration gradients.

  18. Conjugated Polymers Atypically Prepared in Water

    Science.gov (United States)

    Invernale, Michael A.; Pendergraph, Samuel A.; Yavuz, Mustafa S.; Ombaba, Matthew; Sotzing, Gregory A.

    2010-01-01

    Processability remains a fundamental issue for the implementation of conducting polymer technology. A simple synthetic route towards processable precursors to conducting polymers (main chain and side chain) was developed using commercially available materials. These soluble precursor systems were converted to conjugated polymers electrochemically in aqueous media, offering a cheaper and greener method of processing. Oxidative conversion in aqueous and organic media each produced equivalent electrochromics. The precursor method enhances the yield of the electrochromic polymer obtained over that of electrodeposition, and it relies on a less corruptible electrolyte bath. However, electrochemical conversion of the precursor polymers often relies on organic salts and solvents. The ability to achieve oxidative conversion in brine offers a less costly and a more environmentally friendly processing step. It is also beneficial for biological applications. The electrochromics obtained herein were evaluated for electronic, spectral, and morphological properties. PMID:20959869

  19. Selective Covalent Conjugation of Phosphorothioate DNA Oligonucleotides with Streptavidin

    Directory of Open Access Journals (Sweden)

    Christof M. Niemeyer

    2011-08-01

    Full Text Available Protein-DNA conjugates have found numerous applications in the field of diagnostics and nanobiotechnology, however, their intrinsic susceptibility to DNA degradation by nucleases represents a major obstacle for many applications. We here report the selective covalent conjugation of the protein streptavidin (STV with phosphorothioate oligonucleotides (psDNA containing a terminal alkylthiolgroup as the chemically addressable linking unit, using a heterobifunctional NHS-/maleimide crosslinker. The psDNA-STV conjugates were synthesized in about 10% isolated yields. We demonstrate that the terminal alkylthiol group selectively reacts with the maleimide while the backbone sulfur atoms are not engaged in chemical conjugation. The novel psDNA-STV conjugates retain their binding capabilities for both biotinylated macromolecules and the complementary nucleic acid. Moreover, the psDNA-STV conjugate retained its binding capacity for complementary oligomers even after a nuclease digestion step, which effectively degrades deoxyribonucleotide oligomers and thus the binding capability of regular DNA-STV conjugates. The psDNA-STV therefore hold particular promise for applications e.g. in proteome research and novel biosensing devices, where interfering endogenous nucleic acids need to be removed from analytes by nuclease digestion.

  20. Preparation and immunological properties of procaine-protein conjugates

    International Nuclear Information System (INIS)

    Liakopoulou, A.

    1981-01-01

    Procaine was conjugated to BSA and rat and rabbit Gf using the carbodiimide method and 14 C-procaine as tracer. The composition of the conjugates could be varied depending on the time of incubation and the concentration of procaine in the reaction mixtures. Procaine-BSA conjugates were soluble in water or saline. However, procaine conjugates to rat or rabbit Gf were not readily soluble in saline. These conjugates were good for immunization purposes, but it was cumbersome to work with them when clear solutions were needed, as in the immunochemical procedures used in this study. The immunological properties of the conjugates were studied in rats and rabbits. Rats responded with production of IgGa and precipitating antibodies to the procaine group, but IgE antibodies to the immunogen could not be detected. Furthermore, precipitating antibodies towards the procaine group were raised in rabbits. When BSA was the protein carrier, antibodies to the carrier molecule were also detected in both rats and rabbits. The conjugates of procaine to rat or rabbit Gf did not elicit antibody response to the carrier molecule when used in the homologous species. Hapten inhibition studies suggested that, in the rabbit, antibodies were also produced with specificity directed towards the molecular configuration of the hapten-carrier bond. (author)

  1. Nanostructured conjugated polymers in chemical sensors: synthesis, properties and applications.

    Science.gov (United States)

    Correa, D S; Medeiros, E S; Oliveira, J E; Paterno, L G; Mattoso, Luiz C

    2014-09-01

    Conjugated polymers are organic materials endowed with a π-electron conjugation along the polymer backbone that present appealing electrical and optical properties for technological applications. By using conjugated polymeric materials in the nanoscale, such properties can be further enhanced. In addition, the use of nanostructured materials makes possible miniaturize devices at the micro/nano scale. The applications of conjugated nanostructured polymers include sensors, actuators, flexible displays, discrete electronic devices, and smart fabric, to name a few. In particular, the use of conjugated polymers in chemical and biological sensors is made feasible owning to their sensitivity to the physicochemical conditions of its surrounding environment, such as chemical composition, pH, dielectric constant, humidity or even temperature. Subtle changes in these conditions bring about variations on the electrical (resistivity and capacitance), optical (absorptivity, luminescence, etc.), and mechanical properties of the conjugated polymer, which can be precisely measured by different experimental methods and ultimately associated with a specific analyte and its concentration. The present review article highlights the main features of conjugated polymers that make them suitable for chemical sensors. An especial emphasis is given to nanostructured sensors systems, which present high sensitivity and selectivity, and find application in beverage and food quality control, pharmaceutical industries, medical diagnosis, environmental monitoring, and homeland security, and other applications as discussed throughout this review.

  2. IRDye78 Conjugates for Near-Infrared Fluorescence Imaging

    Directory of Open Access Journals (Sweden)

    Atif Zaheer

    2002-10-01

    Full Text Available The detection of human malignancies by near-infrared (NIR fluorescence will require the conjugation of cancer-specific ligands to NIR fluorophores that have optimal photoproperties and pharmacokinetics. IRDye78, a tetra-sulfonated heptamethine indocyanine NIR fluorophore, meets most of the criteria for an in vivo imaging agent, and is available as an N-hydroxysuccinimide ester for conjugation to low-molecular-weight ligands. However, IRDye78 has a high charge-to-mass ratio, complicating purification of conjugates. It also has a potentially labile linkage between fluorophore and ligand. We have developed an ion-pairing purification strategy for IRDye78 that can be performed with a standard C18 column under neutral conditions, thus preserving the stability of fluorophore, ligand, and conjugate. By employing parallel evaporative light scatter and absorbance detectors, all reactants and products are identified, and conjugate purity is maximized. We describe reversible and irreversible conversions of IRDye78 that can occur during sample purification, and describe methods for preserving conjugate stability. Using seven ligands, spanning several classes of small molecules and peptides (neutral, charged, and/or hydrophobic, we illustrate the robustness of these methods, and confirm that IRDye78 conjugates so purified retain bioactivity and permit NIR fluorescence imaging of specific targets.

  3. Synthesis and antimicrobial activity of gold nanoparticle conjugates with cefotaxime

    Science.gov (United States)

    Titanova, Elena O.; Burygin, Gennady L.

    2016-04-01

    Gold nanoparticles (GNPs) have attracted significant interest as a novel platform for various applications to nanobiotechnology and biomedicine. The conjugates of GNPs with antibiotics and antibodies were also used for selective photothermal killing of protozoa and bacteria. Also the conjugates of some antibiotics with GNPs decreased the number of bacterial growing cells. In this work was made the procedure optimization for conjugation of cefotaxime (a third-generation cephalosporin antibiotic) with GNPs (15 nm) and we examined the antimicrobial properties of this conjugate to bacteria culture of E. coli K-12. Addition of cefotaxime solution to colloidal gold does not change their color and extinction spectrum. For physiologically active concentration of cefotaxime (3 μg/mL), it was shown that the optimum pH for the conjugation was more than 9.5. A partial aggregation of the GNPs in saline medium was observed at pH 6.5-7.5. The optimum concentration of K2CO3 for conjugation cefotaxime with GNPs-15 was 5 mM. The optimum concentration of cefotaxime was at 0.36 μg/mL. We found the inhibition of the growth of E. coli K12 upon application cefotaxime-GNP conjugates.

  4. Modern methods for the synthesis of peptide-oligonucleotide conjugates

    International Nuclear Information System (INIS)

    Zubin, Evgenii M; Oretskaya, Tat'yana S; Romanova, Elena A

    2002-01-01

    The published data on the methods of chemical solution and solid-phase synthesis of peptide-oligonucleotide conjugates are reviewed. The known methods are systematised and their advantages and disadvantages are considered. The approaches to the solution synthesis of peptide-oligonucleotide conjugates are systematised according to the type of chemical bonds between the fragments, whereas those to the solid-phase synthesis are classified according to the procedure used for the preparation of conjugates, viz., stepwise elongation of oligonucleotide and peptide chains on the same polymeric support or solid-phase condensation of two presynthesised fragments. The bibliography includes 141 references.

  5. Lipid-peptide-polymer conjugates and nanoparticles thereof

    Science.gov (United States)

    Xu, Ting; Dong, He; Shu, Jessica

    2015-06-02

    The present invention provides a conjugate having a peptide with from about 10 to about 100 amino acids, wherein the peptide adopts a helical structure. The conjugate also includes a first polymer covalently linked to the peptide, and a hydrophobic moiety covalently linked to the N-terminus of the peptide, wherein the hydrophobic moiety comprises a second polymer or a lipid moiety. The present invention also provides helix bundles form by self-assembling the conjugates, and particles formed by self-assembling the helix bundles. Methods of preparing the helix bundles and particles are also provided.

  6. Conjugation vs hyperconjugation in molecular structure of acrolein

    Science.gov (United States)

    Shishkina, Svitlana V.; Slabko, Anzhelika I.; Shishkin, Oleg V.

    2013-01-01

    Analysis of geometric parameters of butadiene and acrolein reveals the contradiction between the Csp2-Csp2 bond length in acrolein and classical concept of conjugation degree in the polarized molecules. In this Letter the reasons of this contradiction have been investigated. It is concluded that the Csp2-Csp2 bond length in acrolein is determined by influence of the bonding for it π-π conjugation and antibonding n → σ∗ hyperconjugation between the oxygen lone pair and the antibonding orbital of the single bond. It was shown also this bond length depends on the difference in energy of conjugative and hyperconjugative interactions.

  7. Perfect lensing with phase-conjugating surfaces: toward practical realization

    International Nuclear Information System (INIS)

    Maslovski, Stanislav; Tretyakov, Sergei

    2012-01-01

    It is theoretically known that a pair of phase-conjugating surfaces can function as a perfect lens, focusing propagating waves and enhancing evanescent waves. However, the known experimental approaches based on thin sheets of nonlinear materials cannot fully realize the required phase conjugation boundary condition. In this paper, we show that the ideal phase-conjugating surface is, in principle, physically realizable and investigate the necessary properties of nonlinear and nonreciprocal particles which can be used to build a perfect lens system. The physical principle of the lens operation is discussed in detail and directions of possible experimental realizations are outlined. (paper)

  8. CONJUGATED POLYMERS AND POLYELECTROLYTES IN SOLAR PHOTOCONVERSION, Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Schanze, Kirk S [University of Florida

    2014-08-05

    This DOE-supported program investigated the fundamental properties of conjugated polyelectrolytes, with emphasis placed on studies of excited state energy transport, self-assembly into conjugated polyelectroyte (CPE) based films and colloids, and exciton transport and charge injection in CPE films constructed atop wide bandgap semiconductors. In the most recent grant period we have also extended efforts to examine the properties of low-bandgap donor-acceptor conjugated polyelectrolytes that feature strong visible light absorption and the ability to adsorb to metal-oxide interfaces.

  9. Preparation, structural analysis and bioactivity of ribonuclease A-albumin conjugate: tetra-conjugation or PEG as the linker.

    Science.gov (United States)

    Li, Chunju; Lin, Qixun; Wang, Jun; Shen, Lijuan; Ma, Guanghui; Su, Zhiguo; Hu, Tao

    2012-12-31

    Ribonuclease A (RNase A) is a therapeutic enzyme with cytotoxic action against tumor cells. Its clinical application is limited by the short half-life and insufficient stability. Conjugation of albumin can overcome the limitation, whereas dramatically decrease the enzymatic activity of RNase A. Here, three strategies were proposed to prepare the RNase A-bovine serum albumin (BSA) conjugates. R-SMCC-B (a conjugate of four RNase A attached with one BSA) and R-PEG-B (a mono-conjugate) were prepared using Sulfo-SMCC (a short bifunctional linker) and mal-PEG-NHS (a bifunctional PEG), respectively. Mal-PEG-NHS and hexadecylamine (HDA) were used to prepare the mono-conjugate, R-HDA-B, where HDA was adopted to bind BSA. The PEG linker can elongate the proximity between RNase A and BSA. In contrast, four RNase A were closely located on BSA in R-SMCC-B. R-SMCC-B showed the lowest K(m) and the highest relative enzymatic activity and k(cat)/K(m) in the three conjugates. Presumably, the tetravalent interaction of RNase A in R-SMCC-B can increase the binding affinity to its substrate. In addition, the slow release of BSA from R-HDA-B may increase the enzymatic activity of R-HDA-B. Our study is expected to provide strategies to develop protein-albumin conjugate with high therapeutic potential. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Conjugated Polymers and Oligomers: Structural and Soft Matter Aspects

    DEFF Research Database (Denmark)

    This book identifies modern topics and current trends of structural and soft matter aspects of conjugated polymers and oligomers. Each chapter recognizes an active research line where structural perspective dominates research and therefore the book covers fundamental aspects of persistent...

  11. Synthesis of Mikto-Arm Star Peptide Conjugates.

    Science.gov (United States)

    Koo, Jin Mo; Su, Hao; Lin, Yi-An; Cui, Honggang

    2018-01-01

    Mikto-arm star peptide conjugates are an emerging class of self-assembling peptide-based structural units that contain three or more auxiliary segments of different chemical compositions and/or functionalities. This group of molecules exhibit interesting self-assembly behavior in solution due to their chemically asymmetric topology. Here we describe the detailed procedure for synthesis of an ABC Mikto-arm star peptide conjugate in which two immiscible entities (a saturated hydrocarbon and a hydrophobic and lipophobic fluorocarbon) are conjugated onto a short β-sheet forming peptide sequence, GNNQQNY, derived from the Sup35 prion, through a lysine junction. Automated and manual Fmoc-solid phase synthesis techniques are used to synthesize the Mikto-arm star peptide conjugates, followed by HPLC purification. We envision that this set of protocols can afford a versatile platform to synthesize a new class of peptidic building units for diverse applications.

  12. Guanidinylated polyethyleneimine-polyoxypropylene-polyoxyethylene conjugates as gene transfection agents.

    Science.gov (United States)

    Bromberg, Lev; Raduyk, Svetlana; Hatton, T Alan; Concheiro, Angel; Rodriguez-Valencia, Cosme; Silva, Maite; Alvarez-Lorenzo, Carmen

    2009-05-20

    Conjugates of linear and branched polyethyleneimine (PEI) and monoamine polyether Jeffamine M-2070 (PO/EO mol ratio 10/31, 2000 Da) were synthesized through polyether activation by cyanuric chloride followed by attachment to PEI and guanidinylation by 1H-pyrazole-carboxamidine hydrochloride. The resulting guanidinylated PEI-polyether conjugates (termed gPEI-Jeffamine) efficiently complexed plasmid DNA, and their polyplexes possessed enhanced colloidal stability in the presence of serum proteins. In vitro studies with mammalian CHO-1, 3T3, and Cos-7 cell lines demonstrated improved transfection efficiency of the pCMVbeta-gal plasmid/gPEI-Jeffamine polyplexes. The guanidinylation of the amino groups of PEI and the conjugation of PEI with the Jeffamine polyether enhanced the conjugates' interaction with genetic material and reduced the cytotoxicity of the polyplexes in experiments with the L929 cell line.

  13. Two novel plasma diagnostic tools: fiber sensors and phase conjugation

    International Nuclear Information System (INIS)

    Jahoda, F.C.

    1985-01-01

    A rapidly developing technology (single-mode optical fiber sensors) and recent fundamental research in nonlinear optics (phase conjugation) both offer opportunities for novel plasma diagnostics. Single-mode fiber sensors can replace electrical wire probes for current and magnetic field measurements with advantages in voltage insulation requirements, electromagnetic noise immunity, much greater bandwidth, and some configuration flexibility. Faraday rotation measurements through fibers wound on the ZT-40M RFP have demonstrated quantitative results, but competing linear birefringence effects still hinder independent interpretation. Twisted fiber may solve this problem. Optical phase conjugation (in which a phase reversed copy of a laser beam is generated) allows real time distortion corrections in laser diagnostics. Self-pumped phase conjugation in BaTiO 3 improves the quality of phase conjugation imagery and greatly simplifies experimentation directed toward plasma diagnostics. Our initial applications are a) time-differential refractometry with high spatial resolution and b) intracavity absorption Zeeman spectroscopy

  14. On conjugate points and the Leitmann equivalent problem approach

    NARCIS (Netherlands)

    Wagener, F.O.O.

    2009-01-01

    This article extends the Leitmann equivalence method to a class of problems featuring conjugate points. The class is characterised by the requirement that the set of indifference points of a given problem forms a finite stratification.

  15. Enantioselective conjugate addition of hydroxylamines to pyrazolidinone acrylamides.

    Science.gov (United States)

    Sibi, M P; Liu, M

    2001-12-27

    Chiral relay templates provide amplification of selectivity in conjugate addition reactions. Reversal of stereochemistry of the product isoxazolidinones has also been demonstrated by a simple change of the Lewis acid. [reaction: see text

  16. Site-Selective Conjugation of Native Proteins with DNA

    DEFF Research Database (Denmark)

    Trads, Julie Brender; Tørring, Thomas; Gothelf, Kurt Vesterager

    2017-01-01

    Conjugation of DNA to proteins is increasingly used in academia and industry to provide proteins with tags for identification or handles for hybridization to other DNA strands. Assay technologies such as immuno-PCR and proximity ligation and the imaging technology DNA-PAINT require DNA-protein....... The introduction of a bioorthogonal handle at a specific position of a protein by recombinant techniques provides an excellent approach to site-specific conjugation, but for many laboratories and for applications where several proteins are to be labeled, the expression of recombinant proteins may be cumbersome...... conjugates. In DNA nanotechnology, the DNA handle is exploited to precisely position proteins by self-assembly. For these applications, site-selective conjugation is almost always desired because fully functional proteins are required to maintain the specificity of antibodies and the activity of enzymes...

  17. Conjugal conflict and violence: a review and theoretical paradigm.

    Science.gov (United States)

    Smilkstein, G; Aspy, C B; Quiggins, P A

    1994-02-01

    Conjugal violence has been described as having multiple etiologies. The variables are so numerous that intervention and research protocols are difficult to effect. This paper proposes a paradigm that establishes conjugal conflict and violence as separate entities. According to the paradigm, conjugal conflict is viewed as "an inevitable part of human association," whereas conjugal violence is determined to be a learned behavioral tactic that is employed as a coping strategy when an individual's conflict threshold potential is exceeded. Evidence will be offered that violence is learned from family of origin and from observing what is common or accepted practice in the community. Use of this paradigm would give primacy to community education programs that advance the concept of conflict resolution through rational discourse.

  18. Modeling of SBS Phase Conjugation in Multimode Step Index Fibers

    National Research Council Canada - National Science Library

    Spring, Justin B

    2008-01-01

    ... limited, double-pass high-power amplifiers or coherent beam combination. Little modeling of such a fiber-based phase-conjugator has been done, making it difficult to make decisions about the right fiber to use...

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

    NARCIS (Netherlands)

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

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

  20. Intergenic and intragenic conjugal transfer of multiple antibiotic ...

    African Journals Online (AJOL)

    Conjugation process was conducted to determine the means of transferring ... In this study, it was surprisingly observed that tetracycline resistant gene was ... among pathogenic bacteria, particularly since antibiotics are indiscriminately used in ...

  1. Conjugated Polymers for Flexible Energy Harvesting and Storage.

    Science.gov (United States)

    Zhang, Zhitao; Liao, Meng; Lou, Huiqing; Hu, Yajie; Sun, Xuemei; Peng, Huisheng

    2018-03-01

    Since the discovery of conjugated polymers in the 1970s, they have attracted considerable interest in light of their advantages of having a tunable bandgap, high electroactivity, high flexibility, and good processability compared to inorganic conducting materials. The above combined advantages make them promising for effective energy harvesting and storage, which have been widely studied in recent decades. Herein, the key advancements in the use of conjugated polymers for flexible energy harvesting and storage are reviewed. The synthesis, structure, and properties of conjugated polymers are first summarized. Then, their applications in flexible polymer solar cells, thermoelectric generators, supercapacitors, and lithium-ion batteries are described. The remaining challenges are then discussed to highlight the future direction in the development of conjugated polymers. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Fullerene-biomolecule conjugates and their biomedicinal applications.

    Science.gov (United States)

    Yang, Xinlin; Ebrahimi, Ali; Li, Jie; Cui, Quanjun

    2014-01-01

    Fullerenes are among the strongest antioxidants and are characterized as "radical sponges." The research on biomedicinal applications of fullerenes has achieved significant progress since the landmark publication by Friedman et al in 1993. Fullerene-biomolecule conjugates have become an important area of research during the past 2 decades. By a thorough literature search, we attempt to update the information about the synthesis of different types of fullerene-biomolecule conjugates, including fullerene-containing amino acids and peptides, oligonucleotides, sugars, and esters. Moreover, we also discuss in this review recently reported data on the biological and pharmaceutical utilities of these compounds and some other fullerene derivatives of biomedical importance. While within the fullerene-biomolecule conjugates, in which fullerene may act as both an antioxidant and a carrier, specific targeting biomolecules conjugated to fullerene will undoubtedly strengthen the delivery of functional fullerenes to sites of clinical interest.

  3. Factors contributing to the immunogenicity of meningococcal conjugate vaccines

    Science.gov (United States)

    Bröker, Michael; Berti, Francesco; Costantino, Paolo

    2016-01-01

    ABSTRACT Various glycoprotein conjugate vaccines have been developed for the prevention of invasive meningococcal disease, having significant advantages over pure polysaccharide vaccines. One of the most important features of the conjugate vaccines is the induction of a T-cell dependent immune response, which enables both the induction of immune memory and a booster response after repeated immunization. The nature of the carrier protein to which the polysaccharides are chemically linked, is often regarded as the main component of the vaccine in determining its immunogenicity. However, other factors can have a significant impact on the vaccine's profile. In this review, we explore the physico-chemical properties of meningococcal conjugate vaccines, which can significantly contribute to the vaccine's immunogenicity. We demonstrate that the carrier is not the sole determining factor of the vaccine's profile, but, moreover, that the conjugate vaccine's immunogenicity is the result of multiple physico-chemical structures and characteristics. PMID:26934310

  4. Side Chain Engineering in Solution-Processable Conjugated Polymers

    KAUST Repository

    Mei, Jianguo; Bao, Zhenan

    2014-01-01

    Side chains in conjugated polymers have been primarily utilized as solubilizing groups. However, these side chains have roles that are far beyond. We advocate using side chain engineering to tune a polymer's physical properties, including absorption

  5. Gold Nanoparticle Conjugation Enhances the Antiacanthamoebic Effects of Chlorhexidine

    Science.gov (United States)

    Aqeel, Yousuf; Siddiqui, Ruqaiyyah; Anwar, Ayaz; Shah, Muhammad Raza

    2015-01-01

    Acanthamoeba keratitis is a serious infection with blinding consequences and often associated with contact lens wear. Early diagnosis, followed by aggressive topical application of drugs, is a prerequisite in successful treatment, but even then prognosis remains poor. Several drugs have shown promise, including chlorhexidine gluconate; however, host cell toxicity at physiologically relevant concentrations remains a challenge. Nanoparticles, subcolloidal structures ranging in size from 10 to 100 nm, are effective drug carriers for enhancing drug potency. The overall aim of the present study was to determine whether conjugation with gold nanoparticles enhances the antiacanthamoebic potential of chlorhexidine. Gold-conjugated chlorhexidine nanoparticles were synthesized. Briefly, gold solution was mixed with chlorhexidine and reduced by adding sodium borohydride, resulting in an intense deep red color, indicative of colloidal gold-conjugated chlorhexidine nanoparticles. The synthesis was confirmed using UV-visible spectrophotometry that shows a plasmon resonance peak of 500 to 550 nm, indicative of gold nanoparticles. Further characterization using matrix-assisted laser desorption ionization-mass spectrometry showed a gold-conjugated chlorhexidine complex at m/z 699 ranging in size from 20 to 100 nm, as determined using atomic force microscopy. To determine the amoebicidal and amoebistatic effects, amoebae were incubated with gold-conjugated chlorhexidine nanoparticles. For controls, amoebae also were incubated with gold and silver nanoparticles alone, chlorhexidine alone, neomycin-conjugated nanoparticles, and neomycin alone. The findings showed that gold-conjugated chlorhexidine nanoparticles exhibited significant amoebicidal and amoebistatic effects at 5 μM. Amoebicidal effects were observed by parasite viability testing using a Trypan blue exclusion assay and flow-cytometric analysis using propidium iodide, while amoebistatic effects were observed using growth

  6. Occurrence of Conjugated Linolenic Acids in Purified Soybean Oil

    OpenAIRE

    Kinami, Tomohisa; Horii, Naoto; Narayan, Bhaskar; Arato, Shingo; Hosokawa, Masashi; Miyashita, Kazuo; Negishi, Hironori; Ikuina, Junichi; Noda, Ryuji; Shirasawa, Seiichi

    2007-01-01

    A high-performance liquid chromatographic (HPLC) method is described for the determination of conjugated linoleic acids (CLA) and conjugated linolenic acids (CLN). Methyl esters prepared from purified lipid fractions of soybean oil were analyzed using an HPLC system equipped with photodiode-array detector to detect peaks having maximum absorption around 233 and 275 nm. These peaks were concentrated by AgNO3-silicic acid column chromatography and reversed-phase HPLC. The structural analysis, o...

  7. Ways to Optimize Therapy of Prolonged Conjugation Jaundice in Infants

    Directory of Open Access Journals (Sweden)

    O.G. Shadrin

    2015-09-01

    Full Text Available The article is devoted to the optimization of the treatment of prolonged conjugation jaundice. Inclusion of ursodeoxycholic acid in the treatment of neonatal prolonged conjugation jaundice in a dose of 15–20 mg/kg of body mass per day increases the terms of regression of clinical and paraclinical signs of jaundice as much as 2 times and leads to cytolysis normalization. The preparation has a sufficient level of safety, there were not revealed side effects whilst its application.

  8. Information properties of a hologram of mutually conjugate waves

    International Nuclear Information System (INIS)

    Rubanov, A.S.; Serebryakova, L.M.

    1995-01-01

    A theoretical study of information properties of a correlation response to a fragment of an image of a thin referenceless hologram of mutually conjugate waves that is recorded with a phase-conjugating (PC) mirror is reported. It is shown that this hologram reconstructs a full image in reflected light and can be used as an associative storage device and as a selective PC mirror. 7 refs., 1 fig

  9. New Conjugacy Conditions and Related Nonlinear Conjugate Gradient Methods

    International Nuclear Information System (INIS)

    Dai, Y.-H.; Liao, L.-Z.

    2001-01-01

    Conjugate gradient methods are a class of important methods for unconstrained optimization, especially when the dimension is large. This paper proposes a new conjugacy condition, which considers an inexact line search scheme but reduces to the old one if the line search is exact. Based on the new conjugacy condition, two nonlinear conjugate gradient methods are constructed. Convergence analysis for the two methods is provided. Our numerical results show that one of the methods is very efficient for the given test problems

  10. Several Guaranteed Descent Conjugate Gradient Methods for Unconstrained Optimization

    Directory of Open Access Journals (Sweden)

    San-Yang Liu

    2014-01-01

    Full Text Available This paper investigates a general form of guaranteed descent conjugate gradient methods which satisfies the descent condition gkTdk≤-1-1/4θkgk2  θk>1/4 and which is strongly convergent whenever the weak Wolfe line search is fulfilled. Moreover, we present several specific guaranteed descent conjugate gradient methods and give their numerical results for large-scale unconstrained optimization.

  11. Conjugated linoleic acid in ewe milk fat.

    Science.gov (United States)

    Luna, Pilar; Fontecha, Javier; Juárez, Manuela; de la Fuente, Miguel Angel

    2005-11-01

    Ewe milk fat from five different herds was studied to determine the content of conjugated linoleic acid (CLA) isomers. Research was carried out by combining gas chromatography-mass spectrometry (GC-MS) of fatty acid methyl esters (FAME) and 4,4-dimethyloxazolyne derivatives (DMOX) with silver ion-high performance liquid chromatography (Ag+-HPLC). Reconstructed mass spectral profiles of CLA characteristic ions from DMOX were used to identify positional isomers and Ag+-HPLC to quantify them. Total CLA content varied from 0.57 to 0.97 g/100 g of total fatty acids. FAME and DMOX were separated into a complex mixture of minor isomers and major rumenic acid (9-cis 11-trans C18:2) by GC-MS using a 100-m polar capillary column. Rumenic acid would represent more than 75% of total CLA. 11-trans 13-trans, 11-13 cis/trans plus trans/cis and 7-9 cis/trans plus trans/cis were the main CLA isomers after rumenic acid. Minor amounts of 8-10 and 10-12 C18:2 isomers were also found. Although most of the isomers were present in each herd's milk, differences in content were observed for some CLA species.

  12. Microfluidic Fabrication of Conjugated Polymer Sensor Fibers

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Imsung; Song, Simon [Hanyang University, Seoul (Korea, Republic of)

    2014-10-15

    We propose a fabrication method for polydiacetylene (PDA)-embedded hydrogel microfibers on a microfluidic chip. These fibers can be applied to the detection of cyclodextrines (CDs), which are a family of sugar and aluminum ions. PDA, a family of conjugated polymers, has unique characteristics when used for a sensor, because it undergoes a blue-to-red color transition and nonfluorescence-to-fluorescence transition in response to environmental stimulation. PDAs have different sensing characteristics depending on the head group of PCDA. By taking advantage of ionic crosslinking-induced hydrogel formation and the 3D hydrodynamic focusing effect on a microfluidic chip, PCDA-EDEA-derived diacetylene (DA) monomer-embedded microfibers were successfully fabricated. UV irradiation of the fibers afforded blue-colored PDA, and the resulting blue PDA fibers underwent a phase transition to red and emitted red fluorescence upon exposure to CDs and aluminum ions. Their fluorescence intensity varied depending on the CDs and aluminum ion concentrations. This phase transition was also observed when the fibers were dried.

  13. Theory of Periodic Conjugate Heat Transfer

    CERN Document Server

    Zudin, Yuri B

    2012-01-01

    This book presents the theory of periodic conjugate heat transfer in a detailed way. The effects of thermophysical properties and geometry of a solid body on the commonly used and experimentally determined heat transfer coefficient are analytically presented from a general point of view. The main objective of the book is a simplified description of the interaction between a solid body and a fluid as a boundary value problem of the heat conduction equation for the solid body. At the body surface, the true heat transfer coefficient is composed of two parts: the true mean value resulting from the solution of the steady state heat transfer problem and a periodically variable part, the periodic time and length to describe the oscillatory hydrodynamic effects. The second edition is extended by (i) the analysis of stability boundaries in helium flow at supercritical conditions in a heated channel with respect to the interaction between a solid body and a fluid; (ii) a periodic model and a method of heat transfer sim...

  14. Photodynamic tissue adhesion with chlorin(e6) protein conjugates.

    Science.gov (United States)

    Khadem, J; Veloso, A A; Tolentino, F; Hasan, T; Hamblin, M R

    1999-12-01

    To test the hypothesis that a photodynamic laser-activated tissue solder would perform better in sealing scleral incisions when the photosensitizer was covalently linked to the protein than when it was noncovalently mixed. Conjugates and mixtures were prepared between the photosensitizer chlorin(e6) and various proteins (albumin, fibrinogen, and gelatin) in different ratios and used to weld penetrating scleral incisions made in human cadaveric eyes. A blue-green (488-514 nm) argon laser activated the adhesive, and the strength of the closure was measured by increasing the intraocular pressure until the wound showed leakage. Both covalent conjugates and noncovalent mixtures showed a light dose-dependent increase in leaking pressure. A preparation of albumin chlorin(e6) conjugate with additional albumin added (2.5 protein to chlorin(e6) molar ratio) showed significantly higher weld strength than other protein conjugates and mixtures. This is the first report of dye-protein conjugates as tissue solders. These conjugates may have applications in ophthalmology.

  15. Intense correlation between brain infarction and protein-conjugated acrolein.

    Science.gov (United States)

    Saiki, Ryotaro; Nishimura, Kazuhiro; Ishii, Itsuko; Omura, Tomohiro; Okuyama, Shigeru; Kashiwagi, Keiko; Igarashi, Kazuei

    2009-10-01

    We recently found that increases in plasma levels of protein-conjugated acrolein and polyamine oxidases, enzymes that produce acrolein, are good markers for stroke. The aim of this study was to determine whether the level of protein-conjugated acrolein is increased and levels of spermine and spermidine, the substrates of acrolein production, are decreased at the locus of infarction. A unilateral infarction was induced in mouse brain by photoinduction after injection of Rose Bengal. The volume of the infarction was analyzed using the public domain National Institutes of Health image program. The level of protein-conjugated acrolein at the locus of infarction and in plasma was measured by Western blotting and enzyme-linked immunosorbent assay, respectively. The levels of polyamines at the locus of infarction and in plasma were measured by high-performance liquid chromatography. The level of protein-conjugated acrolein was greatly increased, and levels of spermine and spermidine were decreased at the locus of infarction at 24 hours after the induction of stroke. The size of infarction was significantly decreased by N-acetylcysteine, a scavenger of acrolein. It was also found that the increases in the protein-conjugated acrolein, polyamines, and polyamine oxidases in plasma were observed after the induction of stroke. The results indicate that the induction of infarction is well correlated with the increase in protein-conjugated acrolein at the locus of infarction and in plasma.

  16. O:2-CRM(197) conjugates against Salmonella Paratyphi A.

    Science.gov (United States)

    Micoli, Francesca; Rondini, Simona; Gavini, Massimiliano; Lanzilao, Luisa; Medaglini, Donata; Saul, Allan; Martin, Laura B

    2012-01-01

    Enteric fevers remain a common and serious disease, affecting mainly children and adolescents in developing countries. Salmonella enterica serovar Typhi was believed to cause most enteric fever episodes, but several recent reports have shown an increasing incidence of S. Paratyphi A, encouraging the development of a bivalent vaccine to protect against both serovars, especially considering that at present there is no vaccine against S. Paratyphi A. The O-specific polysaccharide (O:2) of S. Paratyphi A is a protective antigen and clinical data have previously demonstrated the potential of using O:2 conjugate vaccines. Here we describe a new conjugation chemistry to link O:2 and the carrier protein CRM(197), using the terminus 3-deoxy-D-manno-octulosonic acid (KDO), thus leaving the O:2 chain unmodified. The new conjugates were tested in mice and compared with other O:2-antigen conjugates, synthesized adopting previously described methods that use CRM(197) as carrier protein. The newly developed conjugation chemistry yielded immunogenic conjugates with strong serum bactericidal activity against S. Paratyphi A.

  17. O:2-CRM(197 conjugates against Salmonella Paratyphi A.

    Directory of Open Access Journals (Sweden)

    Francesca Micoli

    Full Text Available Enteric fevers remain a common and serious disease, affecting mainly children and adolescents in developing countries. Salmonella enterica serovar Typhi was believed to cause most enteric fever episodes, but several recent reports have shown an increasing incidence of S. Paratyphi A, encouraging the development of a bivalent vaccine to protect against both serovars, especially considering that at present there is no vaccine against S. Paratyphi A. The O-specific polysaccharide (O:2 of S. Paratyphi A is a protective antigen and clinical data have previously demonstrated the potential of using O:2 conjugate vaccines. Here we describe a new conjugation chemistry to link O:2 and the carrier protein CRM(197, using the terminus 3-deoxy-D-manno-octulosonic acid (KDO, thus leaving the O:2 chain unmodified. The new conjugates were tested in mice and compared with other O:2-antigen conjugates, synthesized adopting previously described methods that use CRM(197 as carrier protein. The newly developed conjugation chemistry yielded immunogenic conjugates with strong serum bactericidal activity against S. Paratyphi A.

  18. Protein carriers of conjugate vaccines: characteristics, development, and clinical trials.

    Science.gov (United States)

    Pichichero, Michael E

    2013-12-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products.

  19. Comparison of the pharmacological and biological properties of HPMA copolymer-pirarubicin conjugates: A single-chain copolymer conjugate and its biodegradable tandem-diblock copolymer conjugate

    Czech Academy of Sciences Publication Activity Database

    Etrych, Tomáš; Tsukigawa, K.; Nakamura, H.; Chytil, Petr; Fang, J.; Ulbrich, Karel; Otagiri, M.; Maeda, H.

    2017-01-01

    Roč. 106, 30 August (2017), s. 10-19 ISSN 0928-0987 R&D Projects: GA ČR(CZ) GA15-02986S; GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Grant - others:AV ČR,Japan Society for the Promotion of Science(CZ) JSPS-16-05 Program:Bilaterální spolupráce Institutional support: RVO:61389013 Keywords : pirarubicin * PHPMA conjugate * tandem-diblock PHPMA conjugate Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Pharmacology and pharmacy Impact factor: 3.756, year: 2016

  20. Fast optimal wavefront reconstruction for multi-conjugate adaptive optics using the Fourier domain preconditioned conjugate gradient algorithm.

    Science.gov (United States)

    Vogel, Curtis R; Yang, Qiang

    2006-08-21

    We present two different implementations of the Fourier domain preconditioned conjugate gradient algorithm (FD-PCG) to efficiently solve the large structured linear systems that arise in optimal volume turbulence estimation, or tomography, for multi-conjugate adaptive optics (MCAO). We describe how to deal with several critical technical issues, including the cone coordinate transformation problem and sensor subaperture grid spacing. We also extend the FD-PCG approach to handle the deformable mirror fitting problem for MCAO.

  1. Multivalent peptidic linker enables identification of preferred sites of conjugation for a potent thialanstatin antibody drug conjugate.

    Directory of Open Access Journals (Sweden)

    Sujiet Puthenveetil

    Full Text Available Antibody drug conjugates (ADCs are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads beyond the mictotubule inhibitors and DNA damaging agents has led us to the recent discovery of an mRNA splicing inhibitor, thailanstatin, as a potent ADC payload. In our previous work, we observed that the potency of this payload was uniquely tied to the method of conjugation, with lysine conjugates showing much superior potency as compared to cysteine conjugates. However, the ADC field is rapidly shifting towards site-specific ADCs due to their advantages in manufacturability, characterization and safety. In this work we report the identification of a highly efficacious site-specific thailanstatin ADC. The site of conjugation played a critical role on both the in vitro and in vivo potency of these ADCs. During the course of this study, we developed a novel methodology of loading a single site with multiple payloads using an in situ generated multi-drug carrying peptidic linker that allowed us to rapidly screen for optimal conjugation sites. Using this methodology, we were able to identify a double-cysteine mutant ADC delivering four-loaded thailanstatin that was very efficacious in a gastric cancer xenograft model at 3mg/kg and was also shown to be efficacious against T-DM1 resistant and MDR1 overexpressing tumor cell lines.

  2. Multivalent peptidic linker enables identification of preferred sites of conjugation for a potent thialanstatin antibody drug conjugate.

    Science.gov (United States)

    Puthenveetil, Sujiet; He, Haiyin; Loganzo, Frank; Musto, Sylvia; Teske, Jesse; Green, Michael; Tan, Xingzhi; Hosselet, Christine; Lucas, Judy; Tumey, L Nathan; Sapra, Puja; Subramanyam, Chakrapani; O'Donnell, Christopher J; Graziani, Edmund I

    2017-01-01

    Antibody drug conjugates (ADCs) are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads beyond the mictotubule inhibitors and DNA damaging agents has led us to the recent discovery of an mRNA splicing inhibitor, thailanstatin, as a potent ADC payload. In our previous work, we observed that the potency of this payload was uniquely tied to the method of conjugation, with lysine conjugates showing much superior potency as compared to cysteine conjugates. However, the ADC field is rapidly shifting towards site-specific ADCs due to their advantages in manufacturability, characterization and safety. In this work we report the identification of a highly efficacious site-specific thailanstatin ADC. The site of conjugation played a critical role on both the in vitro and in vivo potency of these ADCs. During the course of this study, we developed a novel methodology of loading a single site with multiple payloads using an in situ generated multi-drug carrying peptidic linker that allowed us to rapidly screen for optimal conjugation sites. Using this methodology, we were able to identify a double-cysteine mutant ADC delivering four-loaded thailanstatin that was very efficacious in a gastric cancer xenograft model at 3mg/kg and was also shown to be efficacious against T-DM1 resistant and MDR1 overexpressing tumor cell lines.

  3. Chemical de-conjugation for investigating the stability of small molecule drugs in antibody-drug conjugates.

    Science.gov (United States)

    Chen, Tao; Su, Dian; Gruenhagen, Jason; Gu, Christine; Li, Yi; Yehl, Peter; Chetwyn, Nik P; Medley, Colin D

    2016-01-05

    Antibody-drug conjugates (ADCs) offer new therapeutic options for advanced cancer patients through precision killing with fewer side effects. The stability and efficacy of ADCs are closely related, emphasizing the urgency and importance of gaining a comprehensive understanding of ADC stability. In this work, a chemical de-conjugation approach was developed to investigate the in-situ stability of the small molecule drug while it is conjugated to the antibody. This method involves chemical-mediated release of the small molecule drug from the ADC and subsequent characterization of the released small molecule drug by HPLC. The feasibility of this technique was demonstrated utilizing a model ADC containing a disulfide linker that is sensitive to the reducing environment within cancer cells. Five reducing agents were screened for use in de-conjugation; tris(2-carboxyethyl) phosphine (TCEP) was selected for further optimization due to its high efficiency and clean impurity profile. The optimized de-conjugation assay was shown to have excellent specificity and precision. More importantly, it was shown to be stability indicating, enabling the identification and quantification of the small molecule drug and its degradation products under different formulation pHs and storage temperatures. In summary, the chemical de-conjugation strategy demonstrated here offers a powerful tool to assess the in-situ stability of small molecule drugs on ADCs and the resulting information will shed light on ADC formulation/process development and storage condition selection. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Identification of excited states in conjugated polymers

    International Nuclear Information System (INIS)

    Hartwell, Lewis John

    2003-01-01

    This thesis reports quasi steady state photoinduced absorption measurements from three conjugated polymers: polypyridine (PPy), polyfluorene (PFO) and the emeraldine base (EB) form of polyaniline. The aim of these experiments was to determine the nature of the photoexcited states existing in these materials in the millisecond time domain, as this has important consequences for the operation of real devices manufactured using these materials. The results from the photoinduced absorption experiments are closely compared with published results from pulse radiolysis experiments. In all cases there is very good correspondence between the two data sets, which has enabled the photoexcited states to be assigned with a high degree of confidence. Quasi steady-state photoinduced absorption involves the measurement of the change in absorption of a material in response to optical excitation with a laser beam. The changes in absorption are small, so a dedicated instrument was developed and optimised for each different sample. Lock-in techniques were used to recover the small signals from the samples. The samples involved were thin films of the polymer spin coated onto sapphire substrates in the cases of PPy and EB. Solution state experiments were conducted on EB. The experiments on PFO were conducted on aligned and unaligned thin films provided by Sony. In the case of the aligned PFO samples, the photoinduced absorption spectrometer was modified to enable polarisation-sensitive data collection. In PPy, both triplet excitons and polarons have been shown to be long-lived photoexcitations, with photoinduced absorption features at 2.29 eV (triplet exciton transition), 1.5 eV and 0.8 eV (polaron transitions). In PFO, the one observed photoinduced band at 1.52 eV is assigned to a triplet exciton. Two photoinduced absorption bands are observed in EB, at 1.4 eV and 0.8 eV. These are assigned to a self-trapped CT singlet exciton and triplet exciton, respectively. (author)

  5. Four-wave mixing and phase conjugation in plasmas

    International Nuclear Information System (INIS)

    Federici, J.F.

    1989-01-01

    Nonlinear optical effects such as Stimulated Brillouin Scattering, Stimulated Raman Scattering, self-focusing, wave-mixing, parametric mixing, etc., have a long history in plasma physics. Recently, four-wave mixing in plasmas and its applications to phase conjugation has been extensively studied. Although four-wave mixing (FWM), using various nonlinear mediums, has many practical applications in the visible regime, no successful attempt has been made to study or demonstrate FWM for wavelengths longer than 10μm. Plasmas as phase conjugate mirrors have received considerable attention since they become more efficient at longer wavelengths (far-infrared to microwave). The purpose of this thesis is to study various fundamental issues which concern the suitability of plasmas for four-wave mixing and phase conjugation. The major contributions of this thesis are the identification and study of thermal and ionization nonlinearities as potential four-wave mixing and phase conjugation mechanisms and the study of the affect of density inhomogeneities on the FWM process. Using a fluid description for the plasma, this thesis demonstrates that collisional heating generates a thermal force which substantially enhances the phase conjugate reflectivity. The prospect of using a novel ionization nonlinearity in weakly ionized plasmas for wave-mixing and phase conjugation is discussed. The ionization nonlinearity arises from localized heating of the plasma by the beat-wave. Wherever, the local temperature is increased, a plasma density grating is produced due to increased electron-impact ionization. Numerical estimates of the phase conjugate reflectivity indicate reflectivities in the range of 10 -4 -10 -3 are possible in a weakly ionized steady-state gas discharge plasma

  6. Optical observations geomagnetically conjugate to sprite-producing lightning discharges

    Directory of Open Access Journals (Sweden)

    R. A. Marshall

    2005-09-01

    Full Text Available Theoretical studies have predicted that large positive cloud-to-ground discharges can trigger a runaway avalanche process of relativistic electrons, forming a geomagnetically trapped electron beam. The beam may undergo pitch angle and energy scattering during its traverse of the Earth's magnetosphere, with a small percentage of electrons remaining in the loss cone and precipitating in the magnetically conjugate atmosphere. In particular, N2 1P and N2+1N optical emissions are expected to be observable. In July and August 2003, an attempt was made to detect these optical emissions, called "conjugate sprites", in correlation with sprite observations in Europe near . Sprite observations were made from the Observatoire du Pic du Midi (OMP in the French Pyrenées, and VLF receivers were installed in Europe to detect causative sferics and ionospheric disturbances associated with sprites. In the Southern Hemisphere conjugate region, the Wide-angle Array for Sprite Photometry (WASP was deployed at the South African Astronomical Observatory (SAAO, near Sutherland, South Africa, to observe optical emissions with a field-of-view magnetically conjugate to the Northern Hemisphere observing region. Observations at OMP revealed over 130 documented sprites, with WASP observations covering the conjugate region successfully for 30 of these events. However, no incidences of optical emissions in the conjugate hemisphere were found. Analysis of the conjugate optical data from SAAO, along with ELF energy measurements from Palmer Station, Antarctica, and charge-moment analysis, show that the lightning events during the course of this experiment likely had insufficient intensity to create a relativistic beam.

    Keywords. Ionosphere (Ionsophere-magnetosphere interactions; Ionospheric disturbances; Instruments and techniques

  7. Recent Advances in Conjugated Polymers for Light Emitting Devices

    Science.gov (United States)

    AlSalhi, Mohamad Saleh; Alam, Javed; Dass, Lawrence Arockiasamy; Raja, Mohan

    2011-01-01

    A recent advance in the field of light emitting polymers has been the discovery of electroluminescent conjugated polymers, that is, kind of fluorescent polymers that emit light when excited by the flow of an electric current. These new generation fluorescent materials may now challenge the domination by inorganic semiconductor materials of the commercial market in light-emitting devices such as light-emitting diodes (LED) and polymer laser devices. This review provides information on unique properties of conjugated polymers and how they have been optimized to generate these properties. The review is organized in three sections focusing on the major advances in light emitting materials, recent literature survey and understanding the desirable properties as well as modern solid state lighting and displays. Recently, developed conjugated polymers are also functioning as roll-up displays for computers and mobile phones, flexible solar panels for power portable equipment as well as organic light emitting diodes in displays, in which television screens, luminous traffic, information signs, and light-emitting wallpaper in homes are also expected to broaden the use of conjugated polymers as light emitting polymers. The purpose of this review paper is to examine conjugated polymers in light emitting diodes (LEDs) in addition to organic solid state laser. Furthermore, since conjugated polymers have been approved as light-emitting organic materials similar to inorganic semiconductors, it is clear to motivate these organic light-emitting devices (OLEDs) and organic lasers for modern lighting in terms of energy saving ability. In addition, future aspects of conjugated polymers in LEDs were also highlighted in this review. PMID:21673938

  8. Optical observations geomagnetically conjugate to sprite-producing lightning discharges

    Directory of Open Access Journals (Sweden)

    R. A. Marshall

    2005-09-01

    Full Text Available Theoretical studies have predicted that large positive cloud-to-ground discharges can trigger a runaway avalanche process of relativistic electrons, forming a geomagnetically trapped electron beam. The beam may undergo pitch angle and energy scattering during its traverse of the Earth's magnetosphere, with a small percentage of electrons remaining in the loss cone and precipitating in the magnetically conjugate atmosphere. In particular, N2 1P and N2+1N optical emissions are expected to be observable. In July and August 2003, an attempt was made to detect these optical emissions, called "conjugate sprites", in correlation with sprite observations in Europe near . Sprite observations were made from the Observatoire du Pic du Midi (OMP in the French Pyrenées, and VLF receivers were installed in Europe to detect causative sferics and ionospheric disturbances associated with sprites. In the Southern Hemisphere conjugate region, the Wide-angle Array for Sprite Photometry (WASP was deployed at the South African Astronomical Observatory (SAAO, near Sutherland, South Africa, to observe optical emissions with a field-of-view magnetically conjugate to the Northern Hemisphere observing region. Observations at OMP revealed over 130 documented sprites, with WASP observations covering the conjugate region successfully for 30 of these events. However, no incidences of optical emissions in the conjugate hemisphere were found. Analysis of the conjugate optical data from SAAO, along with ELF energy measurements from Palmer Station, Antarctica, and charge-moment analysis, show that the lightning events during the course of this experiment likely had insufficient intensity to create a relativistic beam. Keywords. Ionosphere (Ionsophere-magnetosphere interactions; Ionospheric disturbances; Instruments and techniques

  9. Nacellidae limpets of the southern end of South America: taxonomy and distribution Lapas Nacellidae del extremo sur de Sudamérica: taxonomía y distribución

    Directory of Open Access Journals (Sweden)

    CLAUDIO VALDOVINOS

    2005-09-01

    Full Text Available Taxonomically, the Mollusca of the southern end of South America are moderately well known, but the literature is scattered, there is little information on their habitats, and distributional records are scarce for the Chilean archipelago lying between Chiloé Island (42° S and Tierra del Fuego (55° S. Although much is known about the biology and ecology of of some species of Nacellidae, the taxonomy of the group have been partially neglected, particularly in remote areas of the world such as the Chilean fjords. Therefore, this study aims to clarify the nomenclatural status, and establish the morphological characteristics and distribution of the Chilean Nacellidae. Especially, the following three objectives are pursued: (i to clarify the correct identity of existing species; (ii to describe of morphological details, highlighting the clear diagnostic characters of each species, and (iii to delimitate and discuss their geographical range in Chile. The examination of the Nacellidae of the Chilean fiords has resulted in the recognition of one species of Nacella (Nacella and seven species of Nacella (Patinigera, wherein the principal specific differences are in the shell (shape, thickness and color and in radular teeth morphology. The genus Nacella and its subgenus Patinigera are cold-water limpets, and are exclusively inhabitants of Subantarctic and Antarctic waters. The greater part of their range being subantarctic, but extending to the Antarctic by way of the Scotia Arc, and also ranging northward up the Chilean coast to at least Valparaiso at 33° S (only N. (P. clypeater. They apparently have their centre of distribution in the Magellanic Province of southern South America, corresponding to an area with a high degree of diversification (N. (N. mytilina, N. (P. chiloensis, N. (P. deaurata, N. (P. delicatissima, N. (P. flammea, N. (P. magellanica, N. (P. venosa, wherefrom the species tends to spread eastward, with a larval transport probably

  10. 6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines.

    Science.gov (United States)

    Liao, Guochao; Zhou, Zhifang; Liao, Jun; Zu, Luning; Wu, Qiuye; Guo, Zhongwu

    2016-02-12

    With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. These glycoconjugates were proved to elicit strong IgG antibody responses in mice. It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. Moreover, antibodies induced by the synthetic oligosaccharide-KLH conjugates were able to recognize and bind to natural β-glucans and fungal cells. Most importantly, these conjugates elicited effective protection against systemic Candida albicans infection in mice. Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates.

  11. New heparin–indomethacin conjugate with an ester linkage: Synthesis, self aggregation and drug delivery behavior

    Energy Technology Data Exchange (ETDEWEB)

    Li, Nan-Nan; Zheng, Bing-Na [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Lin, Jian-Tao [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Guangdong Medical College, Dongguan 523808 (China); Zhang, Li-Ming, E-mail: ceszhlm@mail.sysu.edu.cn [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China)

    2014-01-01

    New heparin–indomethacin conjugate with an ester linkage was prepared by the carbodiimide-mediated condensation reaction, and then characterized by FTIR and {sup 1}HNMR analyses. Due to its amphiphilic character, such a conjugate could self-aggregate into spherical nanoparticles in aqueous system, as confirmed by fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. By the in vitro drug release tests, the resultant conjugate nanoparticles were found to have a sustained and esterase-sensitive release behavior for conjugated indomethacin. In addition, the uptake of these conjugate nanoparticles into human nasopharyngeal carcinoma CNE1 cells was confirmed by fluorescence microscopy. - Highlights: • New heparin–indomethacin conjugate with an ester linkage was prepared. • Such a conjugate could self-aggregate into spherical nanoparticles in aqueous system. • The resultant conjugate nanoparticles exhibited an esterase-sensitive drug release behavior. • The resultant conjugate nanoparticles showed the cellular uptake ability in CNE1 cells.

  12. Social behaviour and decision making in bacterial conjugation

    Directory of Open Access Journals (Sweden)

    Günther eKoraimann

    2014-04-01

    Full Text Available Bacteria frequently acquire novel genes by HGT (horizontal gene transfer. HGT through the process of bacterial conjugation is highly efficient and depends on the presence of conjugative plasmids (CPs or integrated conjugative elements (ICEs that provide the necessary genes for DNA transmission. This review focuses on recent advancements in our understanding of ssDNA transfer systems and regulatory networks ensuring timely and spatially controlled DNA transfer (tra gene expression. As will become obvious by comparing different systems, by default, tra genes are shut off in cells in which conjugative elements are present. Only when conditions are optimal, donor cells – through epigenetic alleviation of negatively acting roadblocks and direct stimulation of DNA transfer genes – become transfer competent. These transfer competent cells have developmentally transformed into specialized cells capable of secreting ssDNA via a T4S (type IV secretion complex directly into recipient cells. Intriguingly, even under optimal conditions, only a fraction of the population undergoes this transition, a finding that indicates specialization and cooperative, social behavior. Thereby, at the population level, the metabolic burden and other negative consequences of tra gene expression are greatly reduced without compromising the ability to horizontally transfer genes to novel bacterial hosts. This undoubtedly intelligent strategy may explain why conjugative elements – CPs and ICEs – have been successfully kept in and evolved with bacteria to constitute a major driving force of bacterial evolution.

  13. Conjugation of Inulin Improves Anti-Biofilm Activity of Chitosan.

    Science.gov (United States)

    Zhang, Guiqiang; Liu, Jing; Li, Ruilian; Jiao, Siming; Feng, Cui; Wang, Zhuo A; Du, Yuguang

    2018-05-04

    Bacteria biofilm helps bacteria prevent phagocytosis during infection and increase resistance to antibiotics. Staphylococcus aureus is a Gram-positive pathogenic bacterium and is tightly associated with biofilm-related infections, which have led to great threat to human health. Chitosan, the only cationic polysaccharide in nature, has been demonstrated to have antimicrobial and anti-biofilm activities, which, however, require a relative high dosage of chitosan. Moreover, poor water solubility further restricts its applications on anti-infection therapy. Inulins are a group of polysaccharides produced by many types of plants, and are widely used in processed foods. Compared to chitosan, inulin is very soluble in water and possesses a mild antibacterial activity against certain pathogenic bacteria. In order to develop an effective strategy to treat biofilm-related infections, we introduce a method by covalent conjugation of inulin to chitosan. The physicochemical characterization of the inulin⁻chitosan conjugate was assayed, and the anti-biofilm activity was evaluated against S. aureus biofilm. The results indicated that, as compared to chitosan, this novel polysaccharide⁻polysaccharide conjugate significantly enhanced activities against S. aureus either in a biofilm or planktonic state. Of note, the conjugate also showed a broad spectrum anti-biofilm activity on different bacteria strains and low cellular toxicity to mammalian cells. These results suggested that chitosan conjugation of inulin was a viable strategy for treatment against biofilm-related infections. This finding may further spread the application of natural polysaccharides on treatments of infectious disease.

  14. Quantum dot-polymer conjugates for stable luminescent displays.

    Science.gov (United States)

    Ghimire, Sushant; Sivadas, Anjaly; Yuyama, Ken-Ichi; Takano, Yuta; Francis, Raju; Biju, Vasudevanpillai

    2018-05-23

    The broad absorption of light in the UV-Vis-NIR region and the size-based tunable photoluminescence color of semiconductor quantum dots make these tiny crystals one of the most attractive antennae in solar cells and phosphors in electrooptical devices. One of the primary requirements for such real-world applications of quantum dots is their stable and uniform distribution in optically transparent matrices. In this work, we prepare transparent thin films of polymer-quantum dot conjugates, where CdSe/ZnS quantum dots are uniformly distributed at high densities in a chitosan-polystyrene copolymer (CS-g-PS) matrix. Here, quantum dots in an aqueous solution are conjugated to the copolymer by a phase transfer reaction. With the stable conjugation of quantum dots to the copolymer, we prevent undesired phase separation between the two and aggregation of quantum dots. Furthermore, the conjugate allows us to prepare transparent thin films in which quantum dots are uniformly distributed at high densities. The CS-g-PS copolymer helps us in not only preserving the photoluminescence properties of quantum dots in the film but also rendering excellent photostability to quantum dots at the ensemble and single particle levels, making the conjugate a promising material for photoluminescence-based devices.

  15. Antibody-radioisotope conjugates for tumor localization and treatment

    International Nuclear Information System (INIS)

    Larson, S.M.; Carrasquillo, J.A.

    1985-01-01

    In principle, anti-tumor antibodies can be used to carry radioactivity to tumors for in-vivo diagnosis and treatment of cancer. First, for diagnostic purposes, an antibody that targets a specific antigen (for example, the p97 antigen of human melanoma tumor), is labeled with a tracer amount of radioactivity. When this antibody-radioisotope conjugate is injected into the blood stream, the antibody carries the radioactivity throughout the body and in time, percolates through all the tissues of the body. Because the tumor has specific antigens to which the antibody can bind, the antibody conjugate progressively accumulates in the tumor. Using conventional nuclear medicine imaging equipment, the body of the patient is scanned for radioactivity content, and a map of the distribution of the radioactivity is displayed on photographic film. The tumor shows up as a dense area of radio-activity. These same antibody-radioisotope conjugates may be used for therapy of tumors, except that in this case large amounts of radioactivity are loaded on the antibody. After localization of the conjugate there is sufficient radiation deposited in the tumor of radiotherapy. The success of this approach in the clinic is determined in large measure by the concentration gradient that can be achieved between tissue antibody conjugate in tumor versus normal tissue

  16. Free and conjugated dopamine in human ventricular fluid

    International Nuclear Information System (INIS)

    Sharpless, N.S.; Thal, L.J.; Wolfson, L.I.; Tabaddor, K.; Tyce, G.M.; Waltz, J.M.

    1981-01-01

    Free dopamine and an acid hydrolyzable conjugate of dopamine were measured in human ventricular fluid specimens with a radioenzymatic assay and by high performance liquid chromatography (HPLC) with electrochemical detection. Only trace amounts of free norepinephrine and dopamine were detected in ventricular fluid from patients with movement disorders. When the ventricular fluid was hydrolyzed by heating in HClO 4 or by lyophilization in dilute HClO 4 , however, a substantial amount of free dopamine was released. Values for free plus conjugated dopamine in ventricular fluid from patients who had never taken L-DOPA ranged from 139 to 340 pg/ml when determined by HPLC and from 223 to 428 pg/ml when measured radioenzymatically. The correlation coefficient for values obtained by the two methods in the same sample of CSF was 0.94 (P<0.001). Patients who had been treated with L-DOPA had higher levels of conjugated dopamine in their ventricular CSF which correlated inversely with the time between the last dose of L-DOPA and withdrawal of the ventricular fluid. Additionally, one patient with acute cerebral trauma had elevated levels of free norepinephrine and both free and conjugated dopamine in his ventricular fluid. Conjugation may be an important inactivation pathway for released dopamine in man. (Auth.)

  17. Comparative evaluation of cytotoxicity of a glucosamine-TBA conjugate and a chitosan-TBA conjugate.

    Science.gov (United States)

    Guggi, Davide; Langoth, Nina; Hoffer, Martin H; Wirth, Michael; Bernkop-Schnürch, Andreas

    2004-07-08

    D-glucosamine and chitosan were modified by the immobilization of thiol groups utilizing 2-iminothiolane. The toxicity profile of the resulting D-glucosamine-TBA (4-thiobutylamidine) conjugate, of chitosan-TBA conjugate and of the corresponding unmodified controls was evaluated in vitro. On the one hand, the cell membrane damaging effect of 0.025% solutions of the test compounds was investigated via red blood cell lysis test. On the other hand, the cytotoxity of 0.025, 0.25 and 0.5% solutions of the test compounds was evaluated on L-929 mouse fibroblast cells utilizing two different bioassays: the MTT assay (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide), which assess the mitochondrial metabolic activity of the cells, and the BrdU-based enzyme-linked immunosorbent assay, which measures the incorporation in the DNA of 5-bromo-2'-deoxyuridine and consequently the cell proliferation. Results of the red blood cell lysis test showed that both thiolated compounds displayed a lower membrane damaging effect causing a significantly lower haemoglobine release than the unmodified compounds. Data obtained by the MTT assay and the BrdU assay revealed a concentration dependent relative cytotoxicity for all tested compounds. The covalent linkage of the TBA-substructure to D-glucosamine did not cause a significant increase in cytotoxicity, whereas at higher concentrations a slightly enhanced cytotoxic effect was caused by the derivatisation of chitosan. In conclusion, the -TBA derivatives show a comparable toxicity profile to the corresponding unmodified compounds, which should not compromise their future use as save pharmaceutical excipients.

  18. Conjugated Linoleic Triacylglycerols Exhibit Superior Lymphatic Absorption Than Free Conjugate Linoleic Acids and Have Antiobesity Properties.

    Science.gov (United States)

    Woo, Hyunjoon; Chung, Min-Yu; Kim, Juyeon; Kong, Daecheol; Min, Jinyoung; Choi, Hee-Don; Choi, In-Wook; Kim, In-Hwan; Noh, Sang K; Kim, Byung Hee

    2016-05-01

    This study aimed to compare lymphatic absorption of conjugated linoleic acids (CLAs) in the triacylglycerol (TAG) or free fatty acid (FFA) form and to examine the antiobesity effects of different doses of CLAs in the TAG form in animals. Conjugated linoleic TAGs (containing 70.3 wt% CLAs; CLA-TAG) were prepared through lipase-catalyzed esterification of glycerol with commercial CLA mixtures (CLA-FFA). Lymphatic absorption of CLA-TAG and CLA-FFA was compared in a rat model of lymphatic cannulation. Greater amounts of cis-9,trans-11 and trans-10,cis-12 CLAs were detected in the collected lymph from a lipid emulsion containing CLA-TAG. This result suggests that CLA-TAG has greater capacity for lymphatic absorption than does CLA-FFA. The antiobesity efficacy of CLA-TAG at different doses was examined in mice with diet-induced obesity. A high-fat diet (HFD) for 12 weeks caused a significant increase in body weight and epididymal and retroperitoneal fat weights, which were significantly decreased by 2% dietary supplementation (w/w) with CLA-TAG. CLA-TAG at 2% significantly attenuated the HFD-induced upregulation of serum TAG, but led to hepatomegaly and exacerbated HFD-induced hypercholesterolemia. CLA-TAG at 1% significantly attenuated upregulation of retroperitoneal fat weight and significantly increased liver weight, which was decreased by the HFD. Nonetheless, the liver weight in group "HFD +1% CLA-TAG" was not significantly different from that of normal diet controls. CLA-TAG at 1% significantly reduced serum TAG levels and did not exacerbate HFD-induced hypercholesterolemia. Thus, 1% dietary supplementation with CLA-TAG reduces retroperitoneal fat weight without apparent hepatomegaly, a known side-effect of CLAs in mouse models of obesity.

  19. Conjugates of a Photoactivated Rhodamine with Biopolymers for Cell Staining

    Science.gov (United States)

    Zaitsev, Sergei Yu.; Shaposhnikov, Mikhail N.; Solovyeva, Daria O.; Solovyeva, Valeria V.; Rizvanov, Albert A.

    2014-01-01

    Conjugates of the photoactivated rhodamine dyes with biopolymers (proteins, polysaccharides, and nucleic acids) are important tools for microscopic investigation of biological tissue. In this study, a precursor of the photoactivated fluorescent dye (PFD) has been successfully used for staining of numerous mammalian cells lines and for conjugate formation with chitosan (“Chitosan-PFD”) and histone H1 (“Histone H1.3-PFD”). The intensive fluorescence has been observed after photoactivation of these conjugates inside cells (A431, HaCaT, HEK239, HBL-100, and MDCK). Developed procedures and obtained data are important for further application of novel precursors of fluorescent dyes (“caged” dyes) for microscopic probing of biological objects. Thus, the synthesized “Chitosan-PFD” and “Histone H1-PFD” have been successfully applied in this study for intracellular transport visualization by fluorescent microscopy. PMID:25383365

  20. Scintillation Reduction using Conjugate-Plane Imaging (Abstract)

    Science.gov (United States)

    Vander Haagen, G. A.

    2017-12-01

    (Abstract only) All observatories are plagued by atmospheric turbulence exhibited as star scintillation or "twinkle" whether a high altitude adaptive optics research or a 30-cm amateur telescope. It is well known that these disturbances are caused by wind and temperature-driven refractive gradients in the atmosphere and limit the ultimate photometric resolution of land-based facilities. One approach identified by Fuchs (1998) for scintillation noise reduction was to create a conjugate image space at the telescope and focus on the dominant conjugate turbulent layer within that space. When focused on the turbulent layer little or no scintillation exists. This technique is described whereby noise reductions of 6 to 11/1 have been experienced with mathematical and optical bench simulations. Discussed is a proof-of-principle conjugate optical train design for an 80-mm, f7 telescope.

  1. /sup 125/I Radioimmunoassay of serum ursodeoxycholyl conjugates

    Energy Technology Data Exchange (ETDEWEB)

    Hill, A.; Ross, P.E.; Bouchier, I.A.D. (Ninewells Hospital and Medical School, Dundee (UK))

    1983-02-07

    A radioimmunoassay for serum ursodeoxycholic conjugates using an iodine-125 ligand has been developed. The bile acid was present in normal fasting serum (0.19 +- SD 0.19 ..mu..mol/l, n=24) and 2-hour post-prandial serum (0.8 +- SD 0.8 ..mu..mol/l, n=16). Gallstone patients undergoing oral ursodeoxycholic acid therapy had significantly higher post-prandial serum levels (21.5 +- SD 14.0 ..mu..mol/l, n=15) by radioimmunoassay. Gas liquid chromatography analysis indicated that in normal serum ursodeoxycholic acid was totally conjugated, whereas sera from gallstone patients contained a proportion as the free bile acid (10.2 +- SD 8.1 ..mu..mol/l, n=15). Following an oral dose of ursodeoxycholic acid, both unconjugated and conjugated forms of the bile acid appeared in the serum of healthy individuals.

  2. Intracellular trafficking of new anticancer therapeutics: antibody–drug conjugates

    Science.gov (United States)

    Kalim, Muhammad; Chen, Jie; Wang, Shenghao; Lin, Caiyao; Ullah, Saif; Liang, Keying; Ding, Qian; Chen, Shuqing; Zhan, Jinbiao

    2017-01-01

    Antibody–drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs. PMID:28814834

  3. Intracellular trafficking of new anticancer therapeutics: antibody-drug conjugates.

    Science.gov (United States)

    Kalim, Muhammad; Chen, Jie; Wang, Shenghao; Lin, Caiyao; Ullah, Saif; Liang, Keying; Ding, Qian; Chen, Shuqing; Zhan, Jinbiao

    2017-01-01

    Antibody-drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs.

  4. Small angle scattering from protein/sugar conjugates

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, Andrew [Research School of Chemistry, Australian National University, Canberra, ACT 0200 (Australia)]. E-mail: ajj@nist.gov; White, John [Research School of Chemistry, Australian National University, Canberra, ACT 0200 (Australia)

    2006-11-15

    The Maillard reaction between free amine groups on proteins and sugars is well known. We have examined the effect of the reaction of the casein group of milk proteins with sugars on their nanoscale structure and aggregation. The small angle neutron scattering from beta casein and sodium caseinate and their sugar conjugates have been studied as a function of solution concentration. At high conjugate concentration (greater than ca. 5mg/ml) the addition of sugar reduces supra-micellar aggregation of the protein whilst at lower concentration, where the protein is expected to be deaggregated already, little effect is seen. Guinier analysis of the scattering data show a radius of gyration of around 75A-bar for beta casein in solution and around 80A-bar for the sucrose conjugate.

  5. Small angle scattering from protein/sugar conjugates

    International Nuclear Information System (INIS)

    Jackson, Andrew; White, John

    2006-01-01

    The Maillard reaction between free amine groups on proteins and sugars is well known. We have examined the effect of the reaction of the casein group of milk proteins with sugars on their nanoscale structure and aggregation. The small angle neutron scattering from beta casein and sodium caseinate and their sugar conjugates have been studied as a function of solution concentration. At high conjugate concentration (greater than ca. 5mg/ml) the addition of sugar reduces supra-micellar aggregation of the protein whilst at lower concentration, where the protein is expected to be deaggregated already, little effect is seen. Guinier analysis of the scattering data show a radius of gyration of around 75A-bar for beta casein in solution and around 80A-bar for the sucrose conjugate

  6. Preparation of conjugated polymer suspensions by using ultrasonic atomizer

    Energy Technology Data Exchange (ETDEWEB)

    Tada, Kazuya, E-mail: tada@eng.u-hyogo.ac.jp; Onoda, Mitsuyoshi

    2010-11-30

    The electrophoretic deposition is a method useful to prepare conjugated polymer films for electronic devices. This method provides high material recovery rate on the substrate from the suspension, in contrast to the conventional spin-coating in which most of the material placed on the substrate is blown away. Although manual reprecipitation technique successfully yields suspensions of various conjugated polymers including polyfluorene derivatives, it is favorable to control the preparation process of suspensions. In this context, this paper reports preliminary results on the preparation of suspension of conjugated polymer by using an ultrasonic atomizer. While the resultant films do not show particular difference due to the preparation methods of the suspension, the electric current profiles during the electrophoretic deposition suggests that the ultrasonic atomization of polymer solution prior to be mixed with poor solvent results in smaller and less uniform colloidal particles than the conventional manual pouring method.

  7. Principles of conjugating quantum dots to proteins via carbodiimide chemistry

    International Nuclear Information System (INIS)

    Song Fayi; Chan, Warren C W

    2011-01-01

    The covalent coupling of nanomaterials to bio-recognition molecules is a critical intermediate step in using nanomaterials for biology and medicine. Here we investigate the carbodiimide-mediated conjugation of fluorescent quantum dots to different proteins (e.g., immunoglobulin G, bovine serum albumin, and horseradish peroxidase). To enable these studies, we developed a simple method to isolate quantum dot bioconjugates from unconjugated quantum dots. The results show that the reactant concentrations and protein type will impact the overall number of proteins conjugated onto the surfaces of the quantum dots, homogeneity of the protein–quantum dot conjugate population, quantum efficiency, binding avidity, and enzymatic kinetics. We propose general principles that should be followed for the successful coupling of proteins to quantum dots.

  8. Recent advances in the construction of antibody-drug conjugates

    Science.gov (United States)

    Chudasama, Vijay; Maruani, Antoine; Caddick, Stephen

    2016-02-01

    Antibody-drug conjugates (ADCs) comprise antibodies covalently attached to highly potent drugs using a variety of conjugation technologies. As therapeutics, they combine the exquisite specificity of antibodies, enabling discrimination between healthy and diseased tissue, with the cell-killing ability of cytotoxic drugs. This powerful and exciting class of targeted therapy has shown considerable promise in the treatment of various cancers with two US Food and Drug Administration approved ADCs currently on the market (Adcetris and Kadcyla) and approximately 40 currently undergoing clinical evaluation. However, most of these ADCs exist as heterogeneous mixtures, which can result in a narrow therapeutic window and have major pharmacokinetic implications. In order for ADCs to deliver their full potential, sophisticated site-specific conjugation technologies to connect the drug to the antibody are vital. This Perspective discusses the strategies currently used for the site-specific construction of ADCs and appraises their merits and disadvantages.

  9. Progress towards meningitis prevention in the conjugate vaccines era

    Directory of Open Access Journals (Sweden)

    Cristina Aparecida Borges Laval

    Full Text Available Acute bacterial meningitis is an important cause of morbidity and mortality among children less than five years old. Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis are the most important agents of bacterial meningitis in developing countries. The development of the conjugate vaccines in the beginning of the 90's, especially type b H. influenzae (Hib, and more recently the heptavalent pneumococcal and the serogroup C meningococcal vaccines, have contributed directly to changes in the epidemiological profile of these invasive diseases (direct effect and of their carriage status (indirect effect. We review the impact of the Hib conjugate vaccine in Latin American countries, where this vaccine has been implemented, and the potential of pneumococcal and meningococcal conjugate vaccines for the reduction of meningitis worldwide. We also address constraints for the development and delivery of these vaccines and review new candidate state-of-the-art vaccines. The greatest challenge, undoubtedly, is to implement these vaccines worldwide, especially in the developing regions.

  10. Experiments with conjugate gradient algorithms for homotopy curve tracking

    Science.gov (United States)

    Irani, Kashmira M.; Ribbens, Calvin J.; Watson, Layne T.; Kamat, Manohar P.; Walker, Homer F.

    1991-01-01

    There are algorithms for finding zeros or fixed points of nonlinear systems of equations that are globally convergent for almost all starting points, i.e., with probability one. The essence of all such algorithms is the construction of an appropriate homotopy map and then tracking some smooth curve in the zero set of this homotopy map. HOMPACK is a mathematical software package implementing globally convergent homotopy algorithms with three different techniques for tracking a homotopy zero curve, and has separate routines for dense and sparse Jacobian matrices. The HOMPACK algorithms for sparse Jacobian matrices use a preconditioned conjugate gradient algorithm for the computation of the kernel of the homotopy Jacobian matrix, a required linear algebra step for homotopy curve tracking. Here, variants of the conjugate gradient algorithm are implemented in the context of homotopy curve tracking and compared with Craig's preconditioned conjugate gradient method used in HOMPACK. The test problems used include actual large scale, sparse structural mechanics problems.

  11. Small angle scattering from protein/sugar conjugates

    Science.gov (United States)

    Jackson, Andrew; White, John

    2006-11-01

    The Maillard reaction between free amine groups on proteins and sugars is well known. We have examined the effect of the reaction of the casein group of milk proteins with sugars on their nanoscale structure and aggregation. The small angle neutron scattering from beta casein and sodium caseinate and their sugar conjugates have been studied as a function of solution concentration. At high conjugate concentration (greater than ca. 5 mg/ml) the addition of sugar reduces supra-micellar aggregation of the protein whilst at lower concentration, where the protein is expected to be deaggregated already, little effect is seen. Guinier analysis of the scattering data show a radius of gyration of around 75 A˚ for beta casein in solution and around 80 A˚ for the sucrose conjugate.

  12. Repercussions of imprisonment for conjugal violence: discourses of men

    Directory of Open Access Journals (Sweden)

    Anderson Reis de Sousa

    Full Text Available ABSTRACT Objective: to know the consequences that men experience related to incarceration by conjugal violence. Methods: qualitative study on 20 men in jail and indicted in criminal processes related to conjugal violence in a Court specialized in Family and Domestic Violence against women. The interviews were classified based on Collective Subject Discourse method, using NVIVO(r software. Results: the collective discourse shows that the experience of preventive imprisonment starts a process of family dismantling, social stigma, financial hardship and psycho-emotional symptoms such as phobia, depression, hypertension, and headaches. Conclusion: due to the physical, mental and social consequences of the conjugal violence-related imprisonment experience, it is urgent to look carefully into the somatization process as well as to the prevention strategies regarding this process.

  13. The extended regulatory networks of SXT/R391 integrative and conjugative elements and IncA/C conjugative plasmids.

    Science.gov (United States)

    Poulin-Laprade, Dominic; Carraro, Nicolas; Burrus, Vincent

    2015-01-01

    Nowadays, healthcare systems are challenged by a major worldwide drug resistance crisis caused by the massive and rapid dissemination of antibiotic resistance genes and associated emergence of multidrug resistant pathogenic bacteria, in both clinical and environmental settings. Conjugation is the main driving force of gene transfer among microorganisms. This mechanism of horizontal gene transfer mediates the translocation of large DNA fragments between two bacterial cells in direct contact. Integrative and conjugative elements (ICEs) of the SXT/R391 family (SRIs) and IncA/C conjugative plasmids (ACPs) are responsible for the dissemination of a broad spectrum of antibiotic resistance genes among diverse species of Enterobacteriaceae and Vibrionaceae. The biology, diversity, prevalence and distribution of these two families of conjugative elements have been the subject of extensive studies for the past 15 years. Recently, the transcriptional regulators that govern their dissemination through the expression of ICE- or plasmid-encoded transfer genes have been described. Unrelated repressors control the activation of conjugation by preventing the expression of two related master activator complexes in both types of elements, i.e., SetCD in SXT/R391 ICEs and AcaCD in IncA/C plasmids. Finally, in addition to activating ICE- or plasmid-borne genes, these master activators have been shown to specifically activate phylogenetically unrelated mobilizable genomic islands (MGIs) that also disseminate antibiotic resistance genes and other adaptive traits among a plethora of pathogens such as Vibrio cholerae and Salmonella enterica.

  14. The extended regulatory networks of SXT/R391 integrative and conjugative elements and IncA/C conjugative plasmids.

    Directory of Open Access Journals (Sweden)

    Dominic ePoulin-Laprade

    2015-08-01

    Full Text Available Nowadays, healthcare systems are challenged by a major worldwide drug resistance crisis caused by the massive and rapid dissemination of antibiotic resistance genes and associated emergence of multidrug resistant pathogenic bacteria, in both clinical and environmental settings. Conjugation is the main driving force of gene transfer among microorganisms. This mechanism of horizontal gene transfer mediates the translocation of large DNA fragments between two bacterial cells in direct contact. Integrative and conjugative elements (ICEs of the SXT/R391 family (SRIs and IncA/C conjugative plasmids (ACPs are responsible for the dissemination of a broad spectrum of antibiotic resistance genes among diverse species of Enterobacteriaceae and Vibrionaceae. The biology, diversity, prevalence and distribution of these two families of conjugative elements have been the subject of extensive studies for the past 15 years. Recently, the transcriptional regulators that govern their dissemination through the expression of ICE- or plasmid-encoded transfer genes have been described. Unrelated repressors control the activation of conjugation by preventing the expression of two related master activator complexes in both types of elements, i.e. SetCD in SXT/R391 ICEs and AcaCD in IncA/C plasmids. Finally, in addition to activating ICE- or plasmid-borne genes, these master activators have been shown to specifically activate phylogenetically unrelated mobilizable genomic islands (MGIs that also disseminate antibiotic resistance genes and other adaptive traits among a plethora of pathogens such as Vibrio cholerae and Salmonella enterica.

  15. Development of Immunoassay Based on Monoclonal Antibody Reacted with the Neonicotinoid Insecticides Clothianidin and Dinotefuran

    Directory of Open Access Journals (Sweden)

    Seiji Iwasa

    2012-11-01

    Full Text Available Enzyme-linked immunosorbent assay (ELISA based on a monoclonal antibody (MoAb was developed for the neonicotinoid insecticide clothianidin. A new clothianidin hapten (3-[5-(3-methyl-2-nitroguanidinomethyl-1,3-thiazol-2-ylthio] propionic acid was synthesized and conjugated to keyhole limpet hemocyanin, and was used for monoclonal antibody preparation. The resulting MoAb CTN-16A3-13 was characterized by a direct competitive ELISA (dc-ELISA. The 50% of inhibition concentration value with clothianidin was 4.4 ng/mL, and the working range was 1.5–15 ng/mL. The antibody showed high cross-reactivity (64% to dinotefuran among the structurally related neonicotinoid insecticides. The recovery examinations of clothianidin for cucumber, tomato and apple showed highly agreement with the spiked concentrations; the recovery rate was between 104% and 124% and the coefficient of variation value was between 1.8% and 15%. Although the recovery rate of the dc-ELISA was slightly higher than that of HPLC analysis, the difference was small enough to accept the dc-ELISA as a useful method for residue analysis of clothianidin in garden crops.

  16. Production and characterization of polyclonal antibody against a synthetic peptide from β-actin protein

    Directory of Open Access Journals (Sweden)

    Nazila Amini

    2014-06-01

    Full Text Available Objective(s:Antibodies against actin, as one of the most widely studied structural and multifunctional housekeeping proteins in eukaryotic cells, are used as internal loading controls in western blot analyses. The aim of this study was to produce polyclonal antibody against a synthetic peptide derived from N-terminal region of β-actin protein to be used as a protein loading control in western blot and other assay systems. Materials and Methods: A synthetic peptide derived from β-actin protein was designed and conjugated to Keyhole limpet hemocyanin (KLH (and used to immunize a white New Zealand rabbit. The antibody was purified from serum by affinity chromatography column. The purity of the antibody was determined by SDS-PAGE and its ability to recognize the immunizing peptide was measured by ELISA. The reactivity of the antibody with β-actin protein in a panel of different cell lysates was then evaluated by western blot. In addition, the reactivity of the antibody with the corresponding protein was also evaluated by Immunocytochemistry and Immunohistochemistry in different samples. Results: The antibody could recognize the immunizing peptide in ELISA. It could also recognize            β-actin protein in western blot as well as in immunocytochemistry and immunohistochemistry. Conclusion: Our data suggest that this antibody may be used as an internal control in western blot analyses as well as in other immunological applications such as ELISA,immunocytochemistry and immunohistochemistry.

  17. Solid-phase classical complement activation by C-reactive protein (CRP) is inhibited by fluid-phase CRP-C1q interaction

    International Nuclear Information System (INIS)

    Sjoewall, Christopher; Wetteroe, Jonas; Bengtsson, Torbjoern; Askendal, Agneta; Almroth, Gunnel; Skogh, Thomas; Tengvall, Pentti

    2007-01-01

    C-reactive protein (CRP) interacts with phosphorylcholine (PC), Fcγ receptors, complement factor C1q and cell nuclear constituents, yet its biological roles are insufficiently understood. The aim was to characterize CRP-induced complement activation by ellipsometry. PC conjugated with keyhole limpet hemocyanin (PC-KLH) was immobilized to cross-linked fibrinogen. A low-CRP serum with different amounts of added CRP was exposed to the PC-surfaces. The total serum protein deposition was quantified and deposition of IgG, C1q, C3c, C4, factor H, and CRP detected with polyclonal antibodies. The binding of serum CRP to PC-KLH dose-dependently triggered activation of the classical pathway. Unexpectedly, the activation was efficiently down-regulated at CRP levels >150 mg/L. Using radial immunodiffusion, CRP-C1q interaction was observed in serum samples with high CRP concentrations. We propose that the underlying mechanism depends on fluid-phase interaction between C1q and CRP. This might constitute another level of complement regulation, which has implications for systemic lupus erythematosus where CRP is often low despite flare-ups

  18. Development of immunoassay based on monoclonal antibody reacted with the neonicotinoid insecticides clothianidin and dinotefuran.

    Science.gov (United States)

    Uchigashima, Mikiko; Watanabe, Eiki; Ito, Shigekazu; Iwasa, Seiji; Miyake, Shiro

    2012-11-15

    Enzyme-linked immunosorbent assay (ELISA) based on a monoclonal antibody (MoAb) was developed for the neonicotinoid insecticide clothianidin. A new clothianidin hapten (3-[5-(3-methyl-2-nitroguanidinomethyl)-1,3-thiazol-2-ylthio] propionic acid) was synthesized and conjugated to keyhole limpet hemocyanin, and was used for monoclonal antibody preparation. The resulting MoAb CTN-16A3-13 was characterized by a direct competitive ELISA (dc-ELISA). The 50% of inhibition concentration value with clothianidin was 4.4 ng/mL, and the working range was 1.5–15 ng/mL. The antibody showed high cross-reactivity (64%) to dinotefuran among the structurally related neonicotinoid insecticides. The recovery examinations of clothianidin for cucumber, tomato and apple showed highly agreement with the spiked concentrations; the recovery rate was between 104% and 124% and the coefficient of variation value was between 1.8% and 15%. Although the recovery rate of the dc-ELISA was slightly higher than that of HPLC analysis, the difference was small enough to accept the dc-ELISA as a useful method for residue analysis of clothianidin in garden crops.

  19. Preclinical Evaluation of the Synthetic Adjuvant SQS-21 and its Constituent Isomeric Saponins

    Science.gov (United States)

    Ragupathi, Govind; Damani, Payal; Deng, Kai; Adams, Michelle M.; Hang, Jianfeng; George, Constantine; Livingston, Philip O.; Gin, David Y.

    2010-01-01

    The saponin fraction QS-21 from Quillaja saponaria has been demonstrated to be a potent immunological adjuvant when mixed with keyhole limpet hemocyanin conjugate vaccines, as well as with other classes of subunit antigen vaccines. QS-21 adjuvant is composed of two isomers that include the apiose and xylose forms in a ratio of 65:35, respectively. The chemical syntheses of these two isomers in pure form have recently been disclosed. Herein we describe detailed in vivo immunological evaluations of these synthetic QS-21 isomeric constituents, employing the GD3-KLH melanoma antigen. With this vaccine construct, high antibody titers against GD3 ganglioside and KLH were elicited when GD3-KLH was co-administered with adjuvant, either as the individual separate synthetic QS-21 isomers (SQS-21-Api or SQS-21-Xyl), or as its reconstituted 65:35 isomeric mixture (SQS-21). These antibody titer levels were comparable to that elicited by vaccinations employing naturally derived QS-21 (PQS-21). Moreover, toxicities of the synthetic saponin adjuvants were also found to be comparable to that of naturally derived PQS-21. These findings demonstrate unequivocally that the adjuvant activity of QS-21 resides in these two principal isomeric forms, and not in trace contaminants within the natural extracts. This lays the foundation for future exploration of structure-function correlations to enable the discovery of novel saponins with increased potency, enhanced stability, and attenuated toxicity. PMID:20450868

  20. Active immunization with the peptide epitope vaccine Aβ3-10-KLH induces a Th2-polarized anti-Aβ antibody response and decreases amyloid plaques in APP/PS1 transgenic mice.

    Science.gov (United States)

    Ding, Li; Meng, Yuan; Zhang, Hui-Yi; Yin, Wen-Chao; Yan, Yi; Cao, Yun-Peng

    2016-11-10

    Active amyloid-β (Aβ) immunotherapy is effective in preventing Aβ deposition, facilitating plaque clearance, and improving cognitive functions in mouse models of Alzheimer's disease (AD). Developing a safe and effective AD vaccine requires a delicate balance between inducing adequate humoral immune responses and avoiding T cell-mediated autoimmune responses. In this study, we designed 2 peptide epitope vaccines, Aβ3-10-KLH and 5Aβ3-10, prepared respectively by coupling Aβ3-10 to the immunogenic carrier protein keyhole limpet hemocyanin (KLH) or by joining 5 Aβ3-10 epitopes linearly in tandem. Young APP/PS1 mice were immunized subcutaneously with Aβ3-10-KLH or 5Aβ3-10 mixed with Freund's adjuvant, and the immunopotencies of these Aβ3-10 peptide vaccines were tested. Aβ3-10-KLH elicited a robust Th2-polarized anti-Aβ antibody response and inhibited Aβ deposition in APP/PS1 mice. However, 5Aβ3-10 did not induce an effective humoral immune response. These results indicated that Aβ3-10-KLH may be a safe and efficient vaccine for AD and that conjugating the antigen to a carrier protein may be more effective than linking multiple peptide antigens in tandem in applications for antibody production and vaccine preparation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Tumor Necrosis Factor-Alpha Targeting Can Protect against Arthritis with Low Sensitization to Infection

    Directory of Open Access Journals (Sweden)

    Nadia Belmellat

    2017-11-01

    Full Text Available Tumor necrosis factor-alpha (TNF-α blockade is an effective treatment for rheumatoid arthritis (RA and other inflammatory diseases, but in patients, it is associated with reduced resistance to the infectious agents Mycobacterium tuberculosis and Listeria monocytogenes, among others. Our goal was to model infection and arthritis in mice and to compare etanercept, a currently used anti-TNF-α inhibitor, to an anti-TNF-α vaccine. We developed a murine surrogate of the TNF-α kinoid and produced an anti-murine TNF-α vaccine (TNFKi composed of keyhole limpet hemocyanin conjugated to TNF-α, which resulted in anti-TNF-α antibody production in mice. We also used etanercept (a soluble receptor of TNF commonly used to treat RA as a control of TNF neutralization. In a mouse model of collagen-induced arthritis, TNFKi protected against inflammation similar to etanercept. In a mouse model of acute L. monocytogenes infection, all TNFKi-treated mice showed cleared bacterial infection and survived, whereas etanercept-treated mice showed large liver granulomas and quickly died. Moreover, TNFKi mice infected with the virulent H37Rv M. tuberculosis showed resistance to infection, in contrast with etanercept-treated mice or controls. Depending on the TNF-α blockade strategy, treating arthritis with a TNF-α inhibitor could result in a different profile of infection suceptibility. Our TNFKi vaccine allowed for a better remaining host defense than did etanercept.

  2. Solar multi-conjugate adaptive optics performance improvement

    Science.gov (United States)

    Zhang, Zhicheng; Zhang, Xiaofang; Song, Jie

    2015-08-01

    In order to overcome the effect of the atmospheric anisoplanatism, Multi-Conjugate Adaptive Optics (MCAO), which was developed based on turbulence correction by means of several deformable mirrors (DMs) conjugated to different altitude and by which the limit of a small corrected FOV that is achievable with AO is overcome and a wider FOV is able to be corrected, has been widely used to widen the field-of-view (FOV) of a solar telescope. With the assistance of the multi-threaded Adaptive Optics Simulator (MAOS), we can make a 3D reconstruction of the distorted wavefront. The correction is applied by one or more DMs. This technique benefits from information about atmospheric turbulence at different layers, which can be used to reconstruct the wavefront extremely well. In MAOS, the sensors are either simulated as idealized wavefront gradient sensors, tip-tilt sensors based on the best Zernike fit, or a WFS using physical optics and incorporating user specified pixel characteristics and a matched filter pixel processing algorithm. Only considering the atmospheric anisoplanatism, we focus on how the performance of a solar MCAO system is related to the numbers of DMs and their conjugate heights. We theoretically quantify the performance of the tomographic solar MCAO system. The results indicate that the tomographic AO system can improve the average Strehl ratio of a solar telescope by only employing one or two DMs conjugated to the optimum altitude. And the S.R. has a significant increase when more deformable mirrors are used. Furthermore, we discuss the effects of DM conjugate altitude on the correction achievable by the MCAO system, and present the optimum DM conjugate altitudes.

  3. Conjugate adaptive optics with remote focusing in multiphoton microscopy

    Science.gov (United States)

    Tao, Xiaodong; Lam, Tuwin; Zhu, Bingzhao; Li, Qinggele; Reinig, Marc R.; Kubby, Joel

    2018-02-01

    The small correction volume for conventional wavefront shaping methods limits their application in biological imaging through scattering media. In this paper, we take advantage of conjugate adaptive optics (CAO) and remote focusing (CAORF) to achieve three-dimensional (3D) scanning through a scattering layer with a single correction. Our results show that the proposed system can provide 10 times wider axial field of view compared with a conventional conjugate AO system when 16,384 segments are used on a spatial light modulator. We demonstrate two-photon imaging with CAORF through mouse skull. The fluorescent microspheres embedded under the scattering layers can be clearly observed after applying the correction.

  4. Ketopantoyl lactone reductase is a conjugated polyketone reductase.

    Science.gov (United States)

    Hata, H; Shimizu, S; Hattori, S; Yamada, H

    1989-03-01

    Ketopantoyl lactone reductase (EC 1.1.1.168) of Saccharomyces cerevisiae was found to catalyze the reduction of a variety of natural and unnatural conjugated polyketone compounds and quinones, such as isatin, ninhydrin, camphorquinone and beta-naphthoquinone in the presence of NADPH. 5-Bromoisatin is the best substrate for the enzyme (Km = 3.1 mM; Vmax = 650 mumol/min/mg). The enzyme is inhibited by quercetin, and several polyketones. These results suggest that ketopantoyl lactone reductase is a carbonyl reductase which specifically catalyzes the reduction of conjugated polyketones.

  5. Conjugate heat and mass transfer in heat mass exchanger ducts

    CERN Document Server

    Zhang, Li-Zhi

    2013-01-01

    Conjugate Heat and Mass Transfer in Heat Mass Exchanger Ducts bridges the gap between fundamentals and recent discoveries, making it a valuable tool for anyone looking to expand their knowledge of heat exchangers. The first book on the market to cover conjugate heat and mass transfer in heat exchangers, author Li-Zhi Zhang goes beyond the basics to cover recent advancements in equipment for energy use and environmental control (such as heat and moisture recovery ventilators, hollow fiber membrane modules for humidification/dehumidification, membrane modules for air purification, desi

  6. Conjugate dynamical systems: classical analogue of the quantum energy translation

    International Nuclear Information System (INIS)

    Torres-Vega, Gabino

    2012-01-01

    An aspect of quantum mechanics that has not been fully understood is the energy shift generated by the time operator. In this study, we introduce the use of the eigensurfaces of dynamical variables and commutators in classical mechanics to study the classical analogue of the quantum translation of energy. We determine that there is a conjugate dynamical system that is conjugate to Hamilton's equations of motion, and then we generate the analogue of the time operator and use it in the translation of points along the energy direction, i.e. the classical analogue of the Pauli theorem. The theory is illustrated with a nonlinear oscillator model. (paper)

  7. Side Chain Engineering in Solution-Processable Conjugated Polymers

    KAUST Repository

    Mei, Jianguo

    2014-01-14

    Side chains in conjugated polymers have been primarily utilized as solubilizing groups. However, these side chains have roles that are far beyond. We advocate using side chain engineering to tune a polymer\\'s physical properties, including absorption, emission, energy level, molecular packing, and charge transport. To date, numerous flexible substituents suitable for constructing side chains have been reported. In this Perspective article, we advocate that the side chain engineering approach can advance better designs for next-generation conjugated polymers. © 2013 American Chemical Society.

  8. Peptide π-Electron Conjugates: Organic Electronics for Biology?

    Science.gov (United States)

    Ardoña, Herdeline Ann M; Tovar, John D

    2015-12-16

    Highly ordered arrays of π-conjugated molecules are often viewed as a prerequisite for effective charge-transporting materials. Studies involving these materials have traditionally focused on organic electronic devices, with more recent emphasis on biological systems. In order to facilitate the transition to biological environments, biomolecules that can promote hierarchical ordering and water solubility are often covalently appended to the π-electron unit. This review highlights recent work on π-conjugated systems bound to peptide moieties that exhibit self-assembly and aims to provide an overview on the development and emerging applications of peptide-based supramolecular π-electron systems.

  9. Imaging GABAc Receptors with Ligand-Conjugated Quantum Dots

    Directory of Open Access Journals (Sweden)

    Ian D. Tomlinson

    2007-01-01

    Full Text Available We report a methodology for labeling the GABAc receptor on the surface membrane of intact cells. This work builds upon our earlier work with serotonin-conjugated quantum dots and our studies with PEGylated quantum dots to reduce nonspecific binding. In the current approach, a PEGylated derivative of muscimol was synthesized and attached via an amide linkage to quantum dots coated in an amphiphilic polymer derivative of a modified polyacrylamide. These conjugates were used to image GABAC receptors heterologously expressed in Xenopus laevis oocytes.

  10. Conjugation of colloidal clusters and chains by capillary condensation.

    Science.gov (United States)

    Li, Fan; Stein, Andreas

    2009-07-29

    Capillary condensation was used to establish connections in colloidal clusters and 1D colloidal chains with high regional selectivity. This vapor-phase process produced conjugated clusters and chains with anisotropic functionality. The capillary condensation method is simple and can be applied to a wide range of materials. It can tolerate geometric variations and even permits conjugation of spatially separated particles. The selective deposition was also used to modulate the functionality on the colloid surfaces, producing tip-tethered nanosized building blocks that may be suitable for further assembly via directional interactions.

  11. Combining CPT-conjugate neutrino channels at Fermilab

    International Nuclear Information System (INIS)

    Jansson, Andreas; Parke, Stephen; Saoulidou, Niki; Mena, Olga

    2008-01-01

    We explore an alternative strategy to determine the neutrino mass hierarchy by making use of possible future neutrino facilities at Fermilab. Here, we use CPT-conjugate neutrino channels, exploiting a ν μ beam from the NuMI beamline and a ν e beam from a beta-beam experimental setup. Both experiments are performed at approximately the same /L. We present different possible accelerator scenarios for the beta-beam neutrino setup and fluxes. This CPT-conjugate neutrino channel scenario can extract the neutrino mass hierarchy down to sin 2 2θ 13 ≅0.02.

  12. A feasible DY conjugate gradient method for linear equality constraints

    Science.gov (United States)

    LI, Can

    2017-09-01

    In this paper, we propose a feasible conjugate gradient method for solving linear equality constrained optimization problem. The method is an extension of the Dai-Yuan conjugate gradient method proposed by Dai and Yuan to linear equality constrained optimization problem. It can be applied to solve large linear equality constrained problem due to lower storage requirement. An attractive property of the method is that the generated direction is always feasible and descent direction. Under mild conditions, the global convergence of the proposed method with exact line search is established. Numerical experiments are also given which show the efficiency of the method.

  13. Conjugate gradient heat bath for ill-conditioned actions.

    Science.gov (United States)

    Ceriotti, Michele; Bussi, Giovanni; Parrinello, Michele

    2007-08-01

    We present a method for performing sampling from a Boltzmann distribution of an ill-conditioned quadratic action. This method is based on heat-bath thermalization along a set of conjugate directions, generated via a conjugate-gradient procedure. The resulting scheme outperforms local updates for matrices with very high condition number, since it avoids the slowing down of modes with lower eigenvalue, and has some advantages over the global heat-bath approach, compared to which it is more stable and allows for more freedom in devising case-specific optimizations.

  14. A Modified Conjugacy Condition and Related Nonlinear Conjugate Gradient Method

    Directory of Open Access Journals (Sweden)

    Shengwei Yao

    2014-01-01

    Full Text Available The conjugate gradient (CG method has played a special role in solving large-scale nonlinear optimization problems due to the simplicity of their very low memory requirements. In this paper, we propose a new conjugacy condition which is similar to Dai-Liao (2001. Based on this condition, the related nonlinear conjugate gradient method is given. With some mild conditions, the given method is globally convergent under the strong Wolfe-Powell line search for general functions. The numerical experiments show that the proposed method is very robust and efficient.

  15. Electronic states of emodin and its conjugate base

    DEFF Research Database (Denmark)

    Nguyen, Son Chi; Hansen, Bjarke Knud Vilster; Hoffmann, Søren Vrønning

    2008-01-01

    The electronic transitions of emodin (1,3,8-trihydroxy-6-methyl-9,10-anthraquinone, E) and its conjugate base (3-oxido-6-methyl-1,8-dihydroxy-9,10-anthraquinone, Ecb) were investigated by UV-Vis linear dichroism (LD) spectroscopy on molecular samples aligned in stretched poly(vinylalcohol). The e......The electronic transitions of emodin (1,3,8-trihydroxy-6-methyl-9,10-anthraquinone, E) and its conjugate base (3-oxido-6-methyl-1,8-dihydroxy-9,10-anthraquinone, Ecb) were investigated by UV-Vis linear dichroism (LD) spectroscopy on molecular samples aligned in stretched poly...

  16. Assessment of immunotoxic effects of environmental contamination using a cotton rat model

    International Nuclear Information System (INIS)

    Zhang, Z.R.; Propst, T.L.; McMurry, S.T.; Lochmiller, R.L.; McBee, K.; Quails, C.W. Jr.; Burks, S.L.

    1993-01-01

    Adult National Institute of Health inbred cotton rats (Sigmodon hispidus) were housed in six terrestrial mesocosms on or near an abandoned oil refinery in central Oklahoma for 56 days. Exposure sites included three mesocosms located on sites judged to be contaminated with a variety of complex mixtures of contaminants and three matched reference mesocosm. In addition, wild cotton rats were collected from contaminated and reference areas near the mesocosm sites. Peripheral leukocyte and erythrocyte variables, secondary lymphoid organ weight and cellularity, proliferative response of splenocytes to mitogens, lymphocyte subpopulations, delayed-type hypersensitivity response, 24 h hypersensitivity, antibody response to keyhole limpet hemocyanin, NK cell activity, macrophage metabolic functions, and complement activity were measures as a comprehensive screen of immunocompetence. According to current data analysis, peripheral leukocyte numbers, mitogenic response of splenocytes, antibody response to keyhole limpet hemocyanin, delayed-type sensitivity and 24 h hypersensitivity were altered by contaminant exposure

  17. Threshold couplings of phase-conjugate mirrors with two interaction regions.

    Science.gov (United States)

    Beli, M; Petrovi, M; Sandfuchs, O; Kaiser, F

    1998-03-01

    Using the grating-action method, we determine the threshold coupling strengths of three generic examples of phase-conjugate mirrors with two interaction regions: the cat conjugator, the mutually incoherent beam coupler, and the interconnected ring mirror.

  18. Synthesis, characterization and in vitro cytotoxicity evaluation of polyamidoamine conjugate containing pamidronate and platinum drug

    CSIR Research Space (South Africa)

    Ndamase, AS

    2018-02-01

    Full Text Available Bisphosphonates have been found to be effective when combined with anticancer drugs for chemotherapy. In this paper, pamidronate and platinum complexes were conjugated to linear poly(amidoamine)s (PAMAM) to improve the drug efficacy. The conjugates...

  19. Metal chelate conjugated monoclonal antibodies, wherein the metal is an α emitter

    International Nuclear Information System (INIS)

    Gansow, O.A.; Strand, M.

    1984-01-01

    Methods of manufacturing and purifying metal chelate conjugated monoclonal antibodies are described, wherein the chelated metal emits alpha radiation. The conjugates are suited for therapeutic uses being substantially free of nonchelated radiometal. (author)

  20. Synthesis, characterization and the release kinetics of antiproliferative agents from polyamidoamine conjugates

    CSIR Research Space (South Africa)

    Aderibigbe, BA

    2015-01-01

    Full Text Available Polyamidoamine conjugates containing curcumin and bisphosphonate were synthesized via a one-pot aqueous phase Michael addition reaction. In the design of the conjugate, bisphosphonate formed an integral part of the polymer carrier backbone. Curcumin...

  1. Realization of large area flexible fullerene - conjugated polymer photocells: a route to plastic solar cells

    NARCIS (Netherlands)

    Brabec, C.J.; Padinger, F.; Hummelen, J.C.; Janssen, R.A.J.; Sariciftci, N.S.

    1999-01-01

    Bulk donor — acceptor heterojunctions between conjugated polymers and fullerenes have been utilized for photovoltaic devices with quantum efficiencies of around 1%. These devices are based on the photoinduced, ultrafast electron transfer between non degenerate ground state conjugated polymers and

  2. Novel Curcumin Diclofenac Conjugate Enhanced Curcumin Bioavailability and Efficacy in Streptococcal Cell Wall-induced Arthritis

    OpenAIRE

    Jain, S. K.; Gill, M. S.; Pawar, H. S.; Suresh, Sarasija

    2014-01-01

    Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; st...

  3. Demonstration of conjugated dopamine in monkey CSF by gas chromatography-mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Elchisak, M A; Powers, K H; Ebert, M H

    1982-09-01

    A method for measuring unconjugated and conjugated dopamine in body tissues and fluids is described. Conjugated dopamine was hydrolyzed in acid to unconjugated dopamine, separated from the sample matrix by alumina chromatography, and assayed by gas chromatography-mass spectrometry. Conjugated dopamine was detected in greater concentrations than unconjugated dopamine in CSF taken from lateral ventricle or thecal sac of the Rhesus monkey. Haloperidol administration did not increase the levels of conjugated dopamine in lumbar CSF.

  4. [Role of proton-motive force in the conjugative DNA transport in Staphylococci].

    Science.gov (United States)

    Gavriliuk, V G; Vinnikov, A I

    1997-01-01

    Sensitivity of the conjugative process in staphylococci to the action of uncouplers of oxidative phosphorylation and inhibitors of electron transport systems have been proved, that testifies to the energy-dependent character of conjugative transport of DNA. Proceeding of the conjugation process depends upon the generation of delta microH+ on the membrane of both the donor and recipient cells. contribution of protonmotive forces to providing for the transfer of plasmids during conjugation to staphylococci has been defined.

  5. Morphological Priming by Itself: A Study of Portuguese Conjugations

    Science.gov (United States)

    Verissimo, Joao; Clahsen, Harald

    2009-01-01

    Does the language processing system make use of abstract grammatical categories and representations that are not directly visible from the surface form of a linguistic expression? This study examines stem-formation processes and conjugation classes, a case of "pure" morphology that provides insight into the role of grammatical structure in…

  6. Structure and function of nanoparticle-protein conjugates

    International Nuclear Information System (INIS)

    Aubin-Tam, M-E; Hamad-Schifferli, K

    2008-01-01

    Conjugation of proteins to nanoparticles has numerous applications in sensing, imaging, delivery, catalysis, therapy and control of protein structure and activity. Therefore, characterizing the nanoparticle-protein interface is of great importance. A variety of covalent and non-covalent linking chemistries have been reported for nanoparticle attachment. Site-specific labeling is desirable in order to control the protein orientation on the nanoparticle, which is crucial in many applications such as fluorescence resonance energy transfer. We evaluate methods for successful site-specific attachment. Typically, a specific protein residue is linked directly to the nanoparticle core or to the ligand. As conjugation often affects the protein structure and function, techniques to probe structure and activity are assessed. We also examine how molecular dynamics simulations of conjugates would complete those experimental techniques in order to provide atomistic details on the effect of nanoparticle attachment. Characterization studies of nanoparticle-protein complexes show that the structure and function are influenced by the chemistry of the nanoparticle ligand, the nanoparticle size, the nanoparticle material, the stoichiometry of the conjugates, the labeling site on the protein and the nature of the linkage (covalent versus non-covalent)

  7. Conjugal gene transfer between bacteria in soil and rhizosphere

    NARCIS (Netherlands)

    Smit, E.

    1994-01-01

    The extent of possible conjugal transfer of recombinant DNA present in genetically engineered microorganisms (GEMs) was studied. Occurrence of transfer of recombinant DNA is only one of the concerns regarding the use of GEMs (Chapter 2). Other potential hazards preventing the application of

  8. Plasmid Conjugation in E. coli and Drug Resistance | Igwe ...

    African Journals Online (AJOL)

    This study aimed at determining the antibiotics susceptibility pattern of E. coli isolates claimed to be multidrug resistance using disc diffusion method. It also determined the presence of transferable resistance plasmids through conjugation and evaluated the medical significance of plasmid encoding E. coli and drug ...

  9. Hybrid zinc oxide conjugated polymer bulk heterojunction solar cells

    NARCIS (Netherlands)

    Beek, W.J.E.; Wienk, M.M.; Kemerink, M.; Yang, X.N.; Janssen, R.A.J.

    2005-01-01

    Bulk heterojunction photovoltaic devices based on blends of a conjugated polymer poly[2-methoxy-5-(3‘,7‘-dimethyloctyloxy)-1,4-phenylenevinylene] (MDMO-PPV) as electron donor and crystalline ZnO nanoparticles (nc-ZnO) as electron acceptor have been studied. Composite nc-ZnO:MDMO-PPV films were cast

  10. QM/MM-MD simulations of conjugated polyelectrolytes

    DEFF Research Database (Denmark)

    Sjöqvist, Jonas; Linares, Mathieu; Mikkelsen, Kurt Valentin

    2014-01-01

    A methodological development is reported for the study of luminescence properties of conjugated polyelectrolytes, encompassing systems in which dihedral rotational barriers are easily overcome at room temperature. The components of the model include (i) a molecular mechanics (MM) force field desc...

  11. Scanning-tunneling spectroscopy on conjugated polymer films

    NARCIS (Netherlands)

    Kemerink, M.; Alvarado, S.F.; Koenraad, P.M.; Janssen, R.A.J.; Salemink, H.W.M.; Wolter, J.H.; Blom, P.W.M.

    2003-01-01

    Scanning-tunneling spectroscopy experiments have been performed on conjugated polymer films and have been compared to a three-dimensional numerical model for charge injection and transport. It is found that field enhancement near the tip apex leads to significant changes in the injected current,

  12. Direct measurement of the microscale conductivity of conjugated polymer monolayers

    DEFF Research Database (Denmark)

    Bøggild, Peter; Grey, Francois; Hassenkam, T.

    2000-01-01

    The in-plane conductivity of conjugated polymer monolayers is mapped here for the first time on the microscale using a novel scanning micro four-point probe (see Figure). The probe allows the source, drain, and voltage electrodes to be positioned within the same domain and the mapping results...

  13. Synthesis of regioregular pentacene-containing conjugated polymers

    KAUST Repository

    Okamoto, Toshihiro; Jiang, Ying; Becerril, Hector A.; Hong, Sanghyun; Senatore, Michelle L.; Tang, Ming L.; Toney, Michael F.; Siegrist, Theo; Bao, Zhenan

    2011-01-01

    We report the synthesis and characterization of a new class of regioregular pentacene-containing conjugated polymers via our synthetic routes reported previously. We found that our regioregular pentacene polymers showed improved ordering than their regiorandom counterpart as well as ambipolar OFET performance. © 2011 The Royal Society of Chemistry.

  14. Conjugated material self-assembly : towards supramolecular electronics

    NARCIS (Netherlands)

    Leclère, P.E.L.G.; Surin, M.; Cavallini, M.; Jonkheijm, P.; Henze, O.; Schenning, A.P.H.J.; Biscarini, F.; Grimsdale, A.C.; Feast, W.J.; Meijer, E.W.; Müllen, K.; Brédas, J.L.; Lazzaroni, R.

    2004-01-01

    Properties of organic electronic materials in solid-state are determined as individual molecules and molecular assembly. It is essential to optimize conjugated materials to control performance of molecular assembly that constitute electronic devices such as light-emitting diodes and solar cells, and

  15. Maternal Conjugal Multiplicity and Child Development in Rural Jamaica

    Science.gov (United States)

    Dreher, Melanie; Hudgins, Rebekah

    2010-01-01

    Using field-based observations and standardized measures of the home environment and child development, the authors followed 59 rural Jamaican women and their offspring from birth to age 5. The findings suggest that conjugal multiplicity, a female reproductive pattern characterized by multiple unions, maternal unmarried status, and absent father,…

  16. Zero-energy modes, charge conjugation, and fermion number

    International Nuclear Information System (INIS)

    Sudarshan, E.C.G.; Yajnik, U.A.

    1986-01-01

    States with a half-integer fermion number occur when a fermionic field coupled to a soliton possesses a zero mode. This paper spells out the circumstances under which one can retain an integer fermion number as also a charge-conjugation-invariant ground state. It is necessary to make the representation reducible but it is kept irreducible by introducing an additional operator

  17. Lanthanide Lewis acid-mediated enantioselective conjugate radical additions.

    Science.gov (United States)

    Sibi, Mukund P; Manyem, Shankar

    2002-08-22

    [reaction: see text] Lanthanide triflates along with proline-derived ligands have been found to be efficient catalysts for enantioselective conjugate addition of nucleophilic radicals to enoates. N-Acyl oxazolidinones, when used as achiral additives, gave meaningful enhancements in the ees for the product.

  18. Evaluation of mutagenic/antimutagenic activity of conjugated linoleic ...

    African Journals Online (AJOL)

    Jane

    2011-10-12

    Oct 12, 2011 ... INTRODUCTION. Conjugated linoleic acid (CLA) is a dietary adjuvant for its ... who found unidentified anticarcinogenic factors in fried ground beef. ..... products decreases rectum cancer in 13% and colon cancer in 34%. .... alters mammary gland morphogenesis and reduces cancer risk in rats. J. Nutr.

  19. Synthesis, characterisation and biomedical applications of curcumin conjugated chitosan microspheres.

    Science.gov (United States)

    Saranya, T S; Rajan, V K; Biswas, Raja; Jayakumar, R; Sathianarayanan, S

    2018-04-15

    Curcumin is a diaryl heptanoid of curcuminoids class obtained from Curcuma longa. It possesses various biological activities like anti-inflammatory, hypoglycemic, antioxidant, wound-healing, and antimicrobial activities. Chitosan is a biocompatible, biodegradable and non-toxic natural polymer which enhances the adhesive property of the skin. Chemical conjugation will leads to sustained release action and to enhance the bioavailability. This study aims to synthesis and characterize biocompatible curcumin conjugated chitosan microspheres for bio-medical applications. The Schiff base reaction was carried out for the preparation of curcumin conjugated chitosan by microwave method and it was characterised using FTIR and NMR. Curcumin conjugated chitosan microspheres (CCCMs) were prepared by wet milling solvent evaporation method. SEM analysis showed these CCCMs were 2-5μm spherical particles. The antibacterial activities of the prepared CCCMs were studied against Staphylococcus aureus and Escherichia coli, the zone of inhibition was 28mm and 23mm respectively. Antioxidant activity of the prepared CCCMs was also studied by DPPH and H 2 O 2 method it showed IC 50 esteem value of 216μg/ml and 228μg/ml, and anti-inflammatory activity results showed that CCCMs having IC 50 value of 45μg/ml. The results conclude that the CCCMs having a good antibacterial, antioxidant and anti-inflammatory activities. This, the prepared CCCMs have potential application in preventing skin infections. Copyright © 2017. Published by Elsevier B.V.

  20. Nanobody-photosensitizer conjugates for targeted photodynamic therapy

    NARCIS (Netherlands)

    Heukers, Raimond; van Bergen en Henegouwen, P; Oliveira, Sabrina

    2014-01-01

    Photodynamic therapy (PDT) induces cell death through light activation of a photosensitizer (PS). Targeted delivery of PS via monoclonal antibodies has improved tumor selectivity. However, these conjugates have long half-lives, leading to relatively long photosensitivity in patients. In an attempt

  1. Bispecific small molecule-antibody conjugate targeting prostate cancer.

    Science.gov (United States)

    Kim, Chan Hyuk; Axup, Jun Y; Lawson, Brian R; Yun, Hwayoung; Tardif, Virginie; Choi, Sei Hyun; Zhou, Quan; Dubrovska, Anna; Biroc, Sandra L; Marsden, Robin; Pinstaff, Jason; Smider, Vaughn V; Schultz, Peter G

    2013-10-29

    Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 ~ 100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors.

  2. Bispecific small molecule–antibody conjugate targeting prostate cancer

    Science.gov (United States)

    Kim, Chan Hyuk; Axup, Jun Y.; Lawson, Brian R.; Yun, Hwayoung; Tardif, Virginie; Choi, Sei Hyun; Zhou, Quan; Dubrovska, Anna; Biroc, Sandra L.; Marsden, Robin; Pinstaff, Jason; Smider, Vaughn V.; Schultz, Peter G.

    2013-01-01

    Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 ∼100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors. PMID:24127589

  3. Adaptive Regularization of Neural Networks Using Conjugate Gradient

    DEFF Research Database (Denmark)

    Goutte, Cyril; Larsen, Jan

    1998-01-01

    Andersen et al. (1997) and Larsen et al. (1996, 1997) suggested a regularization scheme which iteratively adapts regularization parameters by minimizing validation error using simple gradient descent. In this contribution we present an improved algorithm based on the conjugate gradient technique........ Numerical experiments with feedforward neural networks successfully demonstrate improved generalization ability and lower computational cost...

  4. Synthesis and characterization of nido-carborane-cobalamin conjugates

    International Nuclear Information System (INIS)

    Hogenkamp, Harry P.C.; Collins, Douglas A.; Live, David; Benson, Linda M.; Naylor, Stephen

    2000-01-01

    Three vitamin B 12 (cyanocobalamin) conjugates bearing one nido-carborane molecule or two nido-carborane molecules linked to the propionamide side chains via a four carbon linker have been synthesized. Reaction of o-carboranoylchloride with 1,4-diaminobutane in pyridine produced nido-carboranoyl(4-amidobutyl)amine, which was linked to the b- and d-monocarboxylic acids and the b,d-dicarboxylic acid of cyanocobalamin. Mass spectrometry analysis as well as 11 B nuclear magnetic resonance demonstrated that during the reaction of o-carboranonylchloride with diaminobutane one of the boron atoms was eliminated. In vitro biological activity of the cyanocobalamin-nido-carborane conjugates was assessed by the unsaturated vitamin B 12 binding capacity assay. When compared with 57 Co cyanocobalamin, the biological activity of cyanocobalamin-b-nido-carborane, cyanocobalamin-d-nido-carborane, and cyanocobalamin-b-d-bis-nido-carborane conjugates were 92.93%, 35.75%, and 37.02%, respectively. These findings suggest that the 10 B cobalamin conjugates might be useful agents in treating malignant tumors via neutron capture therapy

  5. Phase conjugation of gap solitons: A numerical study

    Indian Academy of Sciences (India)

    We study the effect of a nearby phase-conjugate mirror (PCM) on the gap soliton of a. Kerr non-linear ... They are characterized by a sech field distribution corresponding to the ... It is a generalization of the earlier model proposed by Jose et.

  6. Two novel conjugative plasmids from a single strain of Sulfolobus

    NARCIS (Netherlands)

    Erauso, G.; Stedman, K.M.; Werken, van de H.J.G.; Zillig, W.; Oost, van der J.

    2006-01-01

    Two conjugative plasmids (CPs) were isolated and characterized from the same 'Sulfolobus islandicus' strain, SOG2/4, The plasmids were separated from each other and transferred into Sulfolobus soltataricus. One has a high copy number and is not stable (pSOG1) whereas the other has a low copy number

  7. Self-assembly behaviour of conjugated terthiophene surfactants in water

    NARCIS (Netherlands)

    van Rijn, Patrick; Janeliunas, Dainius; Brizard, Aurelie M.; Stuart, Marc C. A.; Koper, Ger J. M.; Eelkema, Rienk; van Esch, Jan H.

    2011-01-01

    Conjugated self-assembled systems in water are of great interest because of their potential application in biocompatible supramolecular electronics, but so far their supramolecular chemistry remains almost unexplored. Here we present amphiphilic terthiophenes as a general self-assembling platform

  8. Accurate conjugate gradient methods for families of shifted systems

    NARCIS (Netherlands)

    Eshof, J. van den; Sleijpen, G.L.G.

    2003-01-01

    We consider the solution of the linear system (ATA + σI)xσ = ATb, for various real values of σ. This family of shifted systems arises, for example, in Tikhonov regularization and computations in lattice quantum chromodynamics. For each single shift σ this system can be solved using the conjugate

  9. Homology among tet determinants in conjugative elements of streptococci

    Energy Technology Data Exchange (ETDEWEB)

    Smith, M.D.; Hazum, S.; Guild, W.R.

    1981-10-01

    A mutation to tetracycline sensitivity in a resistant strain of Streptococcus pneumoniae was shown by several criteria to be due to a point mutation in the conjugative o(cat-tet) element found in the chromosomes of strains derived from BM6001, a clinical strain resistant to tetracycline and chloramphenicol. Strains carrying the mutation were transformed back to tetracycline resistance with the high efficiency of a point marker by donor deoxyribonucleic acids from its ancestral strain and from nine other clinical isolates of pneumococcus and by deoxyribonucleic acids from Group D Streptococcus faecalis and Group B Streptococcus agalactiae strains that also carry conjugative tet elements in their chromosomes. It was not transformed to resistance by tet plasmid deoxyribonucleic acids from either gram-negative or gram-positive species, except for one that carried transposon TN916, the conjugative tet element present in the chromosomes of some S. faecalis strains. The results showed that the tet determinants in conjugative elements of several streptococcal species share a high degree of deoxyribonucleic acid sequence homology and suggested that they differ from other tet genes.

  10. Fullerene–biomolecule conjugates and their biomedicinal applications

    Directory of Open Access Journals (Sweden)

    Yang X

    2013-12-01

    Full Text Available Xinlin Yang,1 Ali Ebrahimi,1 Jie Li,1,2 Quanjun Cui11Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA; 2School of Materials Science, Beijing Institute of Technology, Beijing, People's Republic of ChinaAbstract: Fullerenes are among the strongest antioxidants and are characterized as "radical sponges." The research on biomedicinal applications of fullerenes has achieved significant progress since the landmark publication by Friedman et al in 1993. Fullerene–biomolecule conjugates have become an important area of research during the past 2 decades. By a thorough literature search, we attempt to update the information about the synthesis of different types of fullerene–biomolecule conjugates, including fullerene-containing amino acids and peptides, oligonucleotides, sugars, and esters. Moreover, we also discuss in this review recently reported data on the biological and pharmaceutical utilities of these compounds and some other fullerene derivatives of biomedical importance. While within the fullerene–biomolecule conjugates, in which fullerene may act as both an antioxidant and a carrier, specific targeting biomolecules conjugated to fullerene will undoubtedly strengthen the delivery of functional fullerenes to sites of clinical interest.Keywords: fullerene, amino acid, peptide, oligonucleotide, sugar, ester

  11. Computing several eigenpairs of Hermitian problems by conjugate gradient iterations

    International Nuclear Information System (INIS)

    Ovtchinnikov, E.E.

    2008-01-01

    The paper is concerned with algorithms for computing several extreme eigenpairs of Hermitian problems based on the conjugate gradient method. We analyse computational strategies employed by various algorithms of this kind reported in the literature and identify their limitations. Our criticism is illustrated by numerical tests on a set of problems from electronic structure calculations and acoustics

  12. Conjugate-Gradient Algorithms For Dynamics Of Manipulators

    Science.gov (United States)

    Fijany, Amir; Scheid, Robert E.

    1993-01-01

    Algorithms for serial and parallel computation of forward dynamics of multiple-link robotic manipulators by conjugate-gradient method developed. Parallel algorithms have potential for speedup of computations on multiple linked, specialized processors implemented in very-large-scale integrated circuits. Such processors used to stimulate dynamics, possibly faster than in real time, for purposes of planning and control.

  13. Deflation in preconditioned conjugate gradient methods for Finite Element Problems

    NARCIS (Netherlands)

    Vermolen, F.J.; Vuik, C.; Segal, A.

    2002-01-01

    We investigate the influence of the value of deflation vectors at interfaces on the rate of convergence of preconditioned conjugate gradient methods applied to a Finite Element discretization for an elliptic equation. Our set-up is a Poisson problem in two dimensions with continuous or discontinuous

  14. Implementing the conjugate gradient algorithm on multi-core systems

    NARCIS (Netherlands)

    Wiggers, W.A.; Bakker, Vincent; Kokkeler, Andre B.J.; Smit, Gerardus Johannes Maria; Nurmi, J.; Takala, J.; Vainio, O.

    2007-01-01

    In linear solvers, like the conjugate gradient algorithm, sparse-matrix vector multiplication is an important kernel. Due to the sparseness of the matrices, the solver runs relatively slow. For digital optical tomography (DOT), a large set of linear equations have to be solved which currently takes

  15. Accurate conjugate gradient methods for families of shifted systems

    NARCIS (Netherlands)

    Eshof, J. van den; Sleijpen, G.L.G.

    We present an efficient and accurate variant of the conjugate gradient method for solving families of shifted systems. In particular we are interested in shifted systems that occur in Tikhonov regularization for inverse problems since these problems can be sensitive to roundoff errors. The

  16. Accurate reanalysis of structures by a preconditioned conjugate gradient method

    Czech Academy of Sciences Publication Activity Database

    Kirsch, U.; Kočvara, Michal; Zowe, J.

    2002-01-01

    Roč. 55, č. 2 (2002), s. 233-251 ISSN 0029-5981 R&D Projects: GA AV ČR IAA1075005 Grant - others:BMBF(DE) 03ZOM3ER Institutional research plan: CEZ:AV0Z1075907 Keywords : preconditioned conjugate gradient s * structural reanalysis Subject RIV: BA - General Mathematics Impact factor: 1.468, year: 2002

  17. Parallel conjugate gradient algorithms for manipulator dynamic simulation

    Science.gov (United States)

    Fijany, Amir; Scheld, Robert E.

    1989-01-01

    Parallel conjugate gradient algorithms for the computation of multibody dynamics are developed for the specialized case of a robot manipulator. For an n-dimensional positive-definite linear system, the Classical Conjugate Gradient (CCG) algorithms are guaranteed to converge in n iterations, each with a computation cost of O(n); this leads to a total computational cost of O(n sq) on a serial processor. A conjugate gradient algorithms is presented that provide greater efficiency using a preconditioner, which reduces the number of iterations required, and by exploiting parallelism, which reduces the cost of each iteration. Two Preconditioned Conjugate Gradient (PCG) algorithms are proposed which respectively use a diagonal and a tridiagonal matrix, composed of the diagonal and tridiagonal elements of the mass matrix, as preconditioners. Parallel algorithms are developed to compute the preconditioners and their inversions in O(log sub 2 n) steps using n processors. A parallel algorithm is also presented which, on the same architecture, achieves the computational time of O(log sub 2 n) for each iteration. Simulation results for a seven degree-of-freedom manipulator are presented. Variants of the proposed algorithms are also developed which can be efficiently implemented on the Robot Mathematics Processor (RMP).

  18. The Lanczos and Conjugate Gradient Algorithms in Finite Precision Arithmetic

    Czech Academy of Sciences Publication Activity Database

    Meurant, G.; Strakoš, Zdeněk

    2006-01-01

    Roč. 15, - (2006), s. 471-542 ISSN 0962-4929 R&D Projects: GA AV ČR 1ET400300415 Institutional research plan: CEZ:AV0Z10300504 Keywords : Lanczos method * conjugate gradient method * finite precision arithmetic * numerical stability * iterative methods Subject RIV: BA - General Mathematics

  19. Rapid, facile synthesis of conjugated polymer zwitterions in ionic liquids

    Energy Technology Data Exchange (ETDEWEB)

    Page, Zachariah A. [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA; Liu, Feng [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA; Russell, Thomas P. [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA; Emrick, Todd [Polymer Science & Engineering Department; Conte Center for Polymer Research; University of Massachusetts; Amherst, USA

    2014-01-01

    Ionic liquids (ILs) were utilized for the rapid air-stable Suzuki polymerization of polar zwitterionic thiophene monomers, precluding the need for volatile organic solvents, phosphine ligands and phase transfer catalysts typically used in conjugated polymer synthesis.

  20. Chiral amides via copper-catalysed enantioselective conjugate addition

    NARCIS (Netherlands)

    Schoonen, Anne K.; Fernández-Ibáñez, M. Ángeles; Fañanás-Mastral, Martín; Teichert, Johannes F.; Feringa, Bernard

    2014-01-01

    A highly enantioselective one pot procedure for the synthesis of beta-substituted amides was developed starting from the corresponding alpha,beta-unsaturated esters. This new methodology is based on the copper-catalysed enantioselective conjugate addition of Grignard reagents to

  1. Excitons in conjugated polymers: Do we need a paradigma change?

    Energy Technology Data Exchange (ETDEWEB)

    Beenken, Wichard J.D. [Department of Theoretical Physics I, Ilmenau University of Thechnology (Germany)

    2009-12-15

    We have previously shown that both, polymer conformation and dynamics are crucial for the exciton transport in conjugated polymers. Thereby we found that the usual Foerster-type hopping transfer model - even if one applies the line-dipole approximation - falls short in one crucial aspect: the nature of the sites the excitons are transferred between is still unclear. We found that the simple model of spectroscopic units defined as segments of the polymer chains separated by structural defects breaking the {pi}-conjugation is only justified for chemical defects like hydrogenated double bonds, or extreme gauche (90 ) torsions between the monomers. Both defects are far too rare in a well-prepared conjugated polymer to explain the mean spectroscopic-unit length of typically 6-7 monomers. Meanwhile, also the concept of dynamical formation of the spectroscopic units, we had previously suggested, has also failed. Thus the question of a paradigma change concerning the exciton transport in conjugated polymers appears on the agenda. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

  2. Propargylamine-isothiocyanate reaction: efficient conjugation chemistry in aqueous media

    DEFF Research Database (Denmark)

    Viart, Helene Marie-France; Larsen, T. S.; Tassone, Chiara

    2014-01-01

    A coupling reaction between secondary propargyl amines and isothiocyanates in aqueous media is described. The reaction is high-yielding and affords cyclized products within 2-24 h. A functionalized ether lipid was synthesized in 8 steps, formulated as liposomes with POPC and conjugated to FITC un...

  3. A nanodiamond-fluorescein conjugate for cell studies

    Science.gov (United States)

    Pedroso-Santana, Seidy; Fleitas-Salazar, Noralvis; Sarabia-Sainz, Andrei; Silva-Campa, Erika; Burgara-Estrella, Alexel; Angulo-Molina, Aracely; Melendrez, Rodrigo; Pedroza-Montero, Martin; Riera, Raul

    2018-03-01

    The use of nanodiamonds in studies with living systems generally involves the modification of their surfaces with functional groups. Fluorescent molecules can be attached to these groups, so that one can know the exact position of the particles in each moment of the interaction with the cells. Here we modify the surface of detonation nanodiamonds and nitrogen-vacancy center nanodiamonds using carboxylation and hydroxylation procedures. Subsequent reactions with silicates and cysteine, before addition of fluorescein allow to obtain fluorescent nano-conjugates. We used confocal microscopy to observe the position of nanodiamonds interacting with HeLa cells. At 3 h post-incubation the green fluorescence is localized in extracellular rounded like-vesicles assemblies while at 24 h the conjugates can be observed inside the cells. The measurement of the fluorescence emitted by both conjugates allowed to find an enhanced emission of fluorescein isothiocyanate (FITC) when the nitrogen-vacancy center is present. We propose the existence of a fluorescence enhancement by electron transference process. The procedure described in this work allows the functionalization of nanodiamonds with FITC and other molecules using functional surface groups and small size mediators. Also, as was proved in our work, the nanodiamond-fluorescein conjugates can be used to track nanoparticles position within the cell. Localization studies are particularly important for drug delivery applications of nanodiamonds.

  4. Target binding improves relaxivity in aptamer-gadolinium conjugates.

    Science.gov (United States)

    Bernard, Elyse D; Beking, Michael A; Rajamanickam, Karunanithi; Tsai, Eve C; Derosa, Maria C

    2012-12-01

    MRI contrast agents (CA) have been heavily used over the past several decades to enhance the diagnostic value of the obtained images. From a design perspective, two avenues to improve the efficacy of contrast agents are readily evident: optimization of magnetic properties of the CA, and optimization of the pharmacokinetics and distribution of the CA in the patient. Contrast agents consisting of DNA aptamer-gadolinium(III) conjugates provide a single system in which these factors can be addressed simultaneously. In this proof-of-concept study, the 15mer thrombin aptamer was conjugated to diethylenetriaminepentaacetic (DTPA) dianhydride to form a monoamide derivative of the linear open-chain chelate present in the commonly used contrast agent Magnevist(®). The stability of the conjugated DNA aptamer-DTPA-Gd(III) chelate in a transmetallation study using Zn(II) was found to be similar to that reported for DTPA-Gd(III). Relaxivity enhancements of 35 ± 4 and 20 ± 1 % were observed in the presence of thrombin compared to a control protein at fields of 9.4 and 1.5 T, respectively. The inclusion of spacers between the aptamer and the DTPA to eliminate possible steric effects was also investigated but not found to improve the relaxation enhancement achieved in comparison to the unaltered aptamer conjugate.

  5. A Glycoform of Immunoglobulin G (IgG) as an Early Biomarker of Exposure to Nonhuman Substances

    Science.gov (United States)

    2012-12-01

    the usual closed conformation adopted by immunoglobulin CH2 domains, which are known to deny all glycan access. 15. SUBJECT TERMS Aleuria aurantia...reactive IgG in the closed conformation and AAL-reactive IgG, or primebody, in the flip-out conformation .....................15 TABLES...adjuvant b IP, intraperitoneal injection c KLH, keyhole limpet hemocyanin d N/A, not applicable e CFA, complete Freund’s adjuvant f RV, rabies

  6. Plant antigens cross-react with rat polyclonal antibodies against

    Czech Academy of Sciences Publication Activity Database

    Oulehlová, Denisa; Hála, Michal; Potocký, Martin; Žárský, Viktor; Cvrčková, F.

    2009-01-01

    Roč. 33, č. 1 (2009), s. 113-118 ISSN 1065-6995 R&D Projects: GA AV ČR KJB600380601; GA ČR GA204/05/0268; GA MŠk(CZ) LC06004; GA MŠk(CZ) LC06034 Institutional research plan: CEZ:AV0Z50380511 Keywords : Keyhole limpet hemocyanin * Rat antisera * Synthetic peptides Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.800, year: 2009

  7. 78 FR 18999 - Prospective Grant of Start-Up Exclusive License: Photosensitizing Antibody-Fluorophore Conjugates...

    Science.gov (United States)

    2013-03-28

    ...-Up Exclusive License: Photosensitizing Antibody-Fluorophore Conjugates for Photoimmunotherapy AGENCY...-205-2010/0-US-01), and entitled ``Photosensitizing Antibody- Fluorophore Conjugates,'' to Aspyrian... invention. The field of use may be limited to ``use of photosensitizing antibody-fluorophore conjugate by...

  8. Technology of DTPA and immunoglobulins conjugation and their attachment to 90Y and 177Lu radionuclides

    International Nuclear Information System (INIS)

    Rekova, M.; Jedinakova-Krizova, V.

    2010-01-01

    The aim of the study of labeling of ligand-antibody conjugates was to find optimal conditions of preparing of these conjugates and appropriate radioactivity of selected nuclide for applications in nuclear medicine. Conjugation of the γ-immunoglobulin G (human or bovine IgG, polyclonal antibodies) and bifunctional chelating agent, diethylenetriaminepentaacetic acid dianhydride (cDTPAA), was carried out. Various values of the cDTPAA/antibody ratio, the weight concentration of polyclonal or monoclonal antibodies (MEM-97) and buffers were used. Further, the labeling conditions of the DTPA-IgG conjugate by radionuclides 90 Y and 177 Lu were optimized, and the labeling yield and the conjugation ratio of prepared radionuclide-DTPA-IgG conjugates was determined. Optimal incubation time of the immunoglobulin conjugation was obtained at 30 min from mixing of individual components. The labeling yield of radionuclide-DTPA-antibody conjugate higher than 95% was achieved. Higher values of conjugation ratio of radionuclide-DTPA-antibody conjugate were achieved in 0.1 mol L -1 carbonate buffer, pH 8.5, and the 0.1 mol L -1 carbonate buffer is suitable for studied conjugation systems. This study showed that the labeling yield as well as the conjugation ratio of tested systems depend on the amount of antibody substance, bifunctional chelating agent/antibody molar ratio and pH value of the buffer used. (author)

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

    NARCIS (Netherlands)

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

    1983-01-01

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

  10. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Urinary bilirubin and its conjugates... Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative) test system. (a) Identification. A urinary bilirubin and its conjugates (nonquantitative) test system is a...

  11. Diclofenac in Arabidopsis cells: Rapid formation of conjugates.

    Science.gov (United States)

    Fu, Qiuguo; Ye, Qingfu; Zhang, Jianbo; Richards, Jaben; Borchardt, Dan; Gan, Jay

    2017-03-01

    Pharmaceutical and personal care products (PPCPs) are continuously introduced into the soil-plant system, through practices such as agronomic use of reclaimed water and biosolids containing these trace contaminants. Plants may accumulate PPCPs from soil, serving as a conduit for human exposure. Metabolism likely controls the final accumulation of PPCPs in plants, but is in general poorly understood for emerging contaminants. In this study, we used diclofenac as a model compound, and employed 14 C tracing, and time-of-flight (TOF) and triple quadruple (QqQ) mass spectrometers to unravel its metabolism pathways in Arabidopsis thaliana cells. We further validated the primary metabolites in Arabidopsis seedlings. Diclofenac was quickly taken up into A. thaliana cells. Phase I metabolism involved hydroxylation and successive oxidation and cyclization reactions. However, Phase I metabolites did not accumulate appreciably; they were instead rapidly conjugated with sulfate, glucose, and glutamic acid through Phase II metabolism. In particular, diclofenac parent was directly conjugated with glutamic acid, with acyl-glutamatyl-diclofenac accounting for >70% of the extractable metabolites after 120-h incubation. In addition, at the end of incubation, >40% of the spiked diclofenac was in the non-extractable form, suggesting extensive sequestration into cell matter. The rapid formation of non-extractable residue and dominance of diclofenac-glutamate conjugate uncover previously unknown metabolism pathways for diclofenac. In particular, the rapid conjugation of parent highlights the need to consider conjugates of emerging contaminants in higher plants, and their biological activity and human health implications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Generic method for the absolute quantification of glutathione S-conjugates : Application to the conjugates of acetaminophen, clozapine and diclofenac

    NARCIS (Netherlands)

    den Braver, Michiel W.; Vermeulen, Nico P.E.; Commandeur, Jan N.M.

    2017-01-01

    Modification of cellular macromolecules by reactive drug metabolites is considered to play an important role in the initiation of tissue injury by many drugs. Detection and identification of reactive intermediates is often performed by analyzing the conjugates formed after trapping by glutathione

  13. A conserved helicase processivity factor is needed for conjugation and replication of an integrative and conjugative element.

    Directory of Open Access Journals (Sweden)

    Jacob Thomas

    Full Text Available Integrative and conjugative elements (ICEs are agents of horizontal gene transfer and have major roles in evolution and acquisition of new traits, including antibiotic resistances. ICEs are found integrated in a host chromosome and can excise and transfer to recipient bacteria via conjugation. Conjugation involves nicking of the ICE origin of transfer (oriT by the ICE-encoded relaxase and transfer of the nicked single strand of ICE DNA. For ICEBs1 of Bacillus subtilis, nicking of oriT by the ICEBs1 relaxase NicK also initiates rolling circle replication. This autonomous replication of ICEBs1 is critical for stability of the excised element in growing cells. We found a conserved and previously uncharacterized ICE gene that is required for conjugation and replication of ICEBs1. Our results indicate that this gene, helP (formerly ydcP, encodes a helicase processivity factor that enables the host-encoded helicase PcrA to unwind the double-stranded ICEBs1 DNA. HelP was required for both conjugation and replication of ICEBs1, and HelP and NicK were the only ICEBs1 proteins needed for replication from ICEBs1 oriT. Using chromatin immunoprecipitation, we measured association of HelP, NicK, PcrA, and the host-encoded single-strand DNA binding protein Ssb with ICEBs1. We found that NicK was required for association of HelP and PcrA with ICEBs1 DNA. HelP was required for association of PcrA and Ssb with ICEBs1 regions distal, but not proximal, to oriT, indicating that PcrA needs HelP to progress beyond nicked oriT and unwind ICEBs1. In vitro, HelP directly stimulated the helicase activity of the PcrA homologue UvrD. Our findings demonstrate that HelP is a helicase processivity factor needed for efficient unwinding of ICEBs1 for conjugation and replication. Homologues of HelP and PcrA-type helicases are encoded on many known and putative ICEs. We propose that these factors are essential for ICE conjugation, replication, and genetic stability.

  14. Less is More: A Comparison of Antibody-Gold Nanoparticle Conjugates of Different Ratios.

    Science.gov (United States)

    Byzova, Nadezhda A; Safenkova, Irina V; Slutskaya, Elvira S; Zherdev, Anatoly V; Dzantiev, Boris B

    2017-11-15

    This comprehensive study is related to gold nanoparticles (GNPs) conjugated with antibodies. The goal of the study is to determine the minimal concentration of antibodies for conjugate synthesis when the conjugates have high antigen-capturing activity. Two systems were studied: gold nanoparticles conjugated with monoclonal antibodies (mAb-GNP) specific to Helicobacter pylori and gold nanoparticles conjugated with polyclonal antibodies (pAb-GNP) specific to mouse immunoglobulins. Several conjugates were synthesized with different GNP-to-antibody molar ratios (from 1:1 to 1:245) through nondirectional and noncovalent immobilization on a surface of GNPs with a diameter of 25.3 ± 4.6 nm. The maximal antigen-capturing activities and equilibrium constants of the conjugates correlate with the formation of a constant hydrodynamic radius of the conjugates for mAb-GNP (GNP to antibody molar ratio 1:58) and with the stabilizing concentration by flocculation curves for pAb-GNP (GNP to antibody molar ratio 1:116). The application of the conjugates to the lateral flow immunoassay shows that the antibody concentrations used for the conjugation can be reduced (below the stabilizing concentration) without losing activity for the mAb-GNP conjugates. The findings highlight that the optimal concentration of antibodies immobilized on the surface of GNPs is not always equal to the stabilizing concentration determined by the flocculation curve.

  15. HER2 specific delivery of methotrexate by dendrimer conjugated anti-HER2 mAb

    International Nuclear Information System (INIS)

    Shukla, Rameshwer; Thomas, Thommey P; Desai, Ankur M; Kotlyar, Alina; Park, Steve J; Baker, James R Jr

    2008-01-01

    Herceptin, a humanized monoclonal antibody that binds to human growth factor receptor-2 (HER2), was covalently attached to a fifth-generation (G5) polyamidoamine dendrimer containing the cytotoxic drug methotrexate. The specific binding and internalization of this conjugate labeled with FITC was clearly demonstrated in cell lines overexpressing HER2 by flow cytometry as well as confocal microscopic analysis. In addition, binding and uptake of antibody conjugated dendrimers was completely blocked by excess non-conjugated herceptin. The dendrimer conjugate was also shown to inhibit the dihydrofolate reductase with similar activity to methotrexate. Co-localization experiments with lysotracker red indicate that antibody conjugate, although internalized efficiently into cells, has an unusually long residence time in the lysosome. Somewhat lower cytotoxicity of the conjugate in comparison to free methotrexate was attributed to the slow release of methotrexate from the conjugate and its long retention in the lysosomal pocket

  16. PSMA-targeted bispecific Fab conjugates that engage T cells.

    Science.gov (United States)

    Patterson, James T; Isaacson, Jason; Kerwin, Lisa; Atassi, Ghazi; Duggal, Rohit; Bresson, Damien; Zhu, Tong; Zhou, Heyue; Fu, Yanwen; Kaufmann, Gunnar F

    2017-12-15

    Bioconjugate formats provide alternative strategies for antigen targeting with bispecific antibodies. Here, PSMA-targeted Fab conjugates were generated using different bispecific formats. Interchain disulfide bridging of an αCD3 Fab enabled installation of either the PSMA-targeting small molecule DUPA (SynFab) or the attachment of an αPSMA Fab (BisFab) by covalent linkage. Optimization of the reducing conditions was critical for selective interchain disulfide reduction and good bioconjugate yield. Activity of αPSMA/CD3 Fab conjugates was tested by in vitro cytotoxicity assays using prostate cancer cell lines. Both bispecific formats demonstrated excellent potency and antigen selectivity. Copyright © 2017. Published by Elsevier Ltd.

  17. Radioimmunoassay for the determination of free and conjugated abscisic acid

    International Nuclear Information System (INIS)

    Weiler, E.W.

    1979-01-01

    The characterization and application of a radioimmunoassay specific for free and conjugated abscisic acid (ABA) is reported, The antibodies produced against a bovine serum albumin-(+-)-ABA conjugate have a high affinity for ABA (Ka= 1.3 x 10 9 l mol -1 ). Trans, trans-ABA and related compounds, such as xanthoxin, phaseic acid, dihydrophaseic acid, vomifoliol or violaxanthin do not interfere with the assay. The detection limit of this method is 0.25 x 10 -12 mol ABA, the measuring range extends to 20 x 10 -12 mol, and average recoveries are 103%. Because of the high specificity of this immunoassay, no extract purification steps are required prior to analysis. Several hundred plants can be analyzed per day in a semi-automatic assay performance. ABA has been detected in all higher plant families examined, but was absent in the blue-green alga, Spirulina platensis, the liverwort Marchantia polymorpha, and two species of fungi. (orig.) [de

  18. Optimised deconjugation of androgenic steroid conjugates in bovine urine

    DEFF Research Database (Denmark)

    Pedersen, Mikael; Frandsen, Henrik Lauritz; Andersen, Jens Hinge

    2017-01-01

    and glucuronidase resulting in free steroids in the extract. It is well known that some sulphates are not deconjugated using aryl sulphatase; instead, for example, solvolysis can be used for deconjugation of these aliphatic sulphates. The effectiveness of solvolysis on androgenic steroid sulphates was tested......After administration of steroids to animals the steroids are partially metabolised in the liver and kidney to phase 2 metabolites, i.e., glucuronic acid or sulphate conjugates. During analysis these conjugated metabolites are normally deconjugated enzymatically with aryl sulphatase...... with selected aliphatic steroid sulphates (boldenone sulphate, nortestosteron sulphate and testosterone sulphate), and the method was validated for analysis of androgenic steroids in bovine urine using free steroids, steroid sulphates and steroid glucuronides as standards. Glucuronidase and sulphuric acid...

  19. [The profile of female victims of conjugal violence].

    Science.gov (United States)

    Vasseur, Philippe

    2004-12-18

    To define the profile of female victims of conjugal violence examined in the Legal Medicine emergency unit of the Hotel-Dieu hospital in Paris. A self-administered questionnaire with 15 questions was distributed to 100 victims. The 100 victims replied: 86 cases of violence took place usually in the home, 78 episodes of violence were multiple and complaints were rarely lodged after the first episodes. Mental and sexual violence were severe and unrecognized. Eighty women interviewed suffered from mental violence. In 43 cases, alcohol played a determining role in the onset of such violence. Female victims of conjugal violence do not have a specific profile. The law of silence persists, but the increase in the number of complaints from North African and African women is encouraging for the future.

  20. Polythiophenes Comprising Conjugated Pendants for Polymer Solar Cells: A Review

    Directory of Open Access Journals (Sweden)

    Hsing-Ju Wang

    2014-03-01

    Full Text Available Polythiophene (PT is one of the widely used donor materials for solution-processable polymer solar cells (PSCs. Much progress in PT-based PSCs can be attributed to the design of novel PTs exhibiting intense and broad visible absorption with high charge carrier mobility to increase short-circuit current density (Jsc, along with low-lying highest occupied molecular orbital (HOMO levels to achieve large open circuit voltage (Voc values. A promising strategy to tailor the photophysical properties and energy levels via covalently attaching electron donor and acceptor pendants on PTs backbone has attracted much attention recently. The geometry, electron-donating capacity, and composition of conjugated pendants are supposed to be the crucial factors in adjusting the conformation, energy levels, and photovoltaic performance of PTs. This review will go over the most recent approaches that enable researchers to obtain in-depth information in the development of PTs comprising conjugated pendants for PSCs.

  1. Non-classical light emission from single conjugated polymers

    Science.gov (United States)

    Hollars, Christopher; Lane, Stephen; Huser, Thomas

    2002-03-01

    Photon-antibunching from single, isolated molecules of collapsed-chain poly[2-methoxy,5-(2’-ethyl-hexyloxy)-p-phenylene-vinylene] (MEH-PPV) has been observed using confocal microscopy techniques. Efficient inter-segment energy transfer in collapsed-chain conjugated polymers leads to emission from an average of only 2-3 active sites on a polymer chain that is composed of hundreds of quasi-chromophores. These few centers consist of the segments with the lowest excitation energy and are supplied by the efficient light-harvesting and energy transfer of the surrounding higher-energy segments. This effect depends on the conformation of the polymer molecules, which is controlled by solvent polarity. These results provide new insight into the controversial photophysics of conjugated polymers and their application in optoelectronic devices.

  2. All solid-state SBS phase conjugate mirror

    Science.gov (United States)

    Dane, C.B.; Hackel, L.A.

    1999-03-09

    A stimulated Brillouin scattering (SBS) phase conjugate laser mirror uses a solid-state nonlinear gain medium instead of the conventional liquid or high pressure gas medium. The concept has been effectively demonstrated using common optical-grade fused silica. An energy threshold of 2.5 mJ and a slope efficiency of over 90% were achieved, resulting in an overall energy reflectivity of >80% for 15 ns, 1 um laser pulses. The use of solid-state materials is enabled by a multi-pass resonant architecture which suppresses transient fluctuations that would otherwise result in damage to the SBS medium. This all solid state phase conjugator is safer, more reliable, and more easily manufactured than prior art designs. It allows nonlinear wavefront correction to be implemented in industrial and defense laser systems whose operating environments would preclude the introduction of potentially hazardous liquids or high pressure gases. 8 figs.

  3. Exploring the origin of high optical absorption in conjugated polymers

    KAUST Repository

    Vezie, Michelle S.

    2016-05-16

    The specific optical absorption of an organic semiconductor is critical to the performance of organic optoelectronic devices. For example, higher light-harvesting efficiency can lead to higher photocurrent in solar cells that are limited by sub-optimal electrical transport. Here, we compare over 40 conjugated polymers, and find that many different chemical structures share an apparent maximum in their extinction coefficients. However, a diketopyrrolopyrrole-thienothiophene copolymer shows remarkably high optical absorption at relatively low photon energies. By investigating its backbone structure and conformation with measurements and quantum chemical calculations, we find that the high optical absorption can be explained by the high persistence length of the polymer. Accordingly, we demonstrate high absorption in other polymers with high theoretical persistence length. Visible light harvesting may be enhanced in other conjugated polymers through judicious design of the structure.

  4. Quantum dot conjugates in a sub-micrometer fluidic channel

    Science.gov (United States)

    Stavis, Samuel M.; Edel, Joshua B.; Samiee, Kevan T.; Craighead, Harold G.

    2010-04-13

    A nanofluidic channel fabricated in fused silica with an approximately 500 nm square cross section was used to isolate, detect and identify individual quantum dot conjugates. The channel enables the rapid detection of every fluorescent entity in solution. A laser of selected wavelength was used to excite multiple species of quantum dots and organic molecules, and the emission spectra were resolved without significant signal rejection. Quantum dots were then conjugated with organic molecules and detected to demonstrate efficient multicolor detection. PCH was used to analyze coincident detection and to characterize the degree of binding. The use of a small fluidic channel to detect quantum dots as fluorescent labels was shown to be an efficient technique for multiplexed single molecule studies. Detection of single molecule binding events has a variety of applications including high throughput immunoassays.

  5. Exploring the origin of high optical absorption in conjugated polymers

    KAUST Repository

    Vezie, Michelle S.; Few, Sheridan; Meager, Iain; Pieridou, Galatia; Dö rling, Bernhard; Ashraf, Raja Shahid; Goñ i, Alejandro R.; Bronstein, Hugo; McCulloch, Iain; Hayes, Sophia C.; Campoy-Quiles, Mariano; Nelson, Jenny

    2016-01-01

    The specific optical absorption of an organic semiconductor is critical to the performance of organic optoelectronic devices. For example, higher light-harvesting efficiency can lead to higher photocurrent in solar cells that are limited by sub-optimal electrical transport. Here, we compare over 40 conjugated polymers, and find that many different chemical structures share an apparent maximum in their extinction coefficients. However, a diketopyrrolopyrrole-thienothiophene copolymer shows remarkably high optical absorption at relatively low photon energies. By investigating its backbone structure and conformation with measurements and quantum chemical calculations, we find that the high optical absorption can be explained by the high persistence length of the polymer. Accordingly, we demonstrate high absorption in other polymers with high theoretical persistence length. Visible light harvesting may be enhanced in other conjugated polymers through judicious design of the structure.

  6. Discovery of a conjugative megaplasmid in Bifidobacterium breve.

    Science.gov (United States)

    Bottacini, Francesca; O'Connell Motherway, Mary; Casey, Eoghan; McDonnell, Brian; Mahony, Jennifer; Ventura, Marco; van Sinderen, Douwe

    2015-01-01

    Bifidobacterium breve is a common and sometimes very abundant inhabitant of the human gut. Genome sequencing of B. breve JCM 7017 revealed the presence of an extrachromosomal element, designated pMP7017 consisting of >190 kb, thus representing the first reported bifidobacterial megaplasmid. In silico characterization of this element revealed several genomic features supporting a stable establishment of the megaplasmid in its host, illustrated by predicted CRISPR-Cas functions that are known to protect the host against intrusion of foreign DNA. Interestingly, pMP7017 is also predicted to encode a conjugative DNA transfer apparatus and, consistent with this notion, we demonstrate here the conjugal transfer of pMP7017 to representative strains of B. breve and B. longum subsp. longum. We also demonstrate the presence of a megaplasmid with homology to pMP7017 in three B. longum subsp. longum strains. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Discovery of a Conjugative Megaplasmid in Bifidobacterium breve

    Science.gov (United States)

    Bottacini, Francesca; O'Connell Motherway, Mary; Casey, Eoghan; McDonnell, Brian; Mahony, Jennifer; Ventura, Marco

    2014-01-01

    Bifidobacterium breve is a common and sometimes very abundant inhabitant of the human gut. Genome sequencing of B. breve JCM 7017 revealed the presence of an extrachromosomal element, designated pMP7017 consisting of >190 kb, thus representing the first reported bifidobacterial megaplasmid. In silico characterization of this element revealed several genomic features supporting a stable establishment of the megaplasmid in its host, illustrated by predicted CRISPR-Cas functions that are known to protect the host against intrusion of foreign DNA. Interestingly, pMP7017 is also predicted to encode a conjugative DNA transfer apparatus and, consistent with this notion, we demonstrate here the conjugal transfer of pMP7017 to representative strains of B. breve and B. longum subsp. longum. We also demonstrate the presence of a megaplasmid with homology to pMP7017 in three B. longum subsp. longum strains. PMID:25326305

  8. Conjugated Molecules for the Smart Filtering of Intense Radiations

    Directory of Open Access Journals (Sweden)

    Danilo Dini

    2003-04-01

    Full Text Available Abstract: The practical realization of smart optical filters, i.e. devices which change their optical transmission in a suitable way to keep a working state for a general light sensitive element , can involve the use of conjugated molecules whose light absorption properties are light- intensity dependent (nonlinear optical effect. The verification of optical limiting displayed by some particular conjugated molecules, e.g. phthalocyanines, is quite noteworthy and can be successfully exploited for the realization of such smart optical devices. In the present contribution the analysis of the relevant molecular feature of a phthalocyanine are analyzed with the aim of determining useful correlations between optical limiting performance and phthalocyanine chemical structure. In particular , the electronic nature of the substituent is considered as a key factor for the explanation of some observed optical limiting trends.

  9. Wavelet methods in multi-conjugate adaptive optics

    International Nuclear Information System (INIS)

    Helin, T; Yudytskiy, M

    2013-01-01

    The next generation ground-based telescopes rely heavily on adaptive optics for overcoming the limitation of atmospheric turbulence. In the future adaptive optics modalities, like multi-conjugate adaptive optics (MCAO), atmospheric tomography is the major mathematical and computational challenge. In this severely ill-posed problem, a fast and stable reconstruction algorithm is needed that can take into account many real-life phenomena of telescope imaging. We introduce a novel reconstruction method for the atmospheric tomography problem and demonstrate its performance and flexibility in the context of MCAO. Our method is based on using locality properties of compactly supported wavelets, both in the spatial and frequency domains. The reconstruction in the atmospheric tomography problem is obtained by solving the Bayesian MAP estimator with a conjugate-gradient-based algorithm. An accelerated algorithm with preconditioning is also introduced. Numerical performance is demonstrated on the official end-to-end simulation tool OCTOPUS of European Southern Observatory. (paper)

  10. Facial expressions of emotion and the course of conjugal bereavement.

    Science.gov (United States)

    Bonanno, G A; Keltner, D

    1997-02-01

    The common assumption that emotional expression mediates the course of bereavement is tested. Competing hypotheses about the direction of mediation were formulated from the grief work and social-functional accounts of emotional expression. Facial expressions of emotion in conjugally bereaved adults were coded at 6 months post-loss as they described their relationship with the deceased; grief and perceived health were measured at 6, 14, and 25 months. Facial expressions of negative emotion, in particular anger, predicted increased grief at 14 months and poorer perceived health through 25 months. Facial expressions of positive emotion predicted decreased grief through 25 months and a positive but nonsignificant relation to perceived health. Predictive relations between negative and positive emotional expression persisted when initial levels of self-reported emotion, grief, and health were statistically controlled, demonstrating the mediating role of facial expressions of emotion in adjustment to conjugal loss. Theoretical and clinical implications are discussed.

  11. Conjugate schema and basis representation of crossover and mutation operators.

    Science.gov (United States)

    Kazadi, S T

    1998-01-01

    In genetic search algorithms and optimization routines, the representation of the mutation and crossover operators are typically defaulted to the canonical basis. We show that this can be influential in the usefulness of the search algorithm. We then pose the question of how to find a basis for which the search algorithm is most useful. The conjugate schema is introduced as a general mathematical construct and is shown to separate a function into smaller dimensional functions whose sum is the original function. It is shown that conjugate schema, when used on a test suite of functions, improves the performance of the search algorithm on 10 out of 12 of these functions. Finally, a rigorous but abbreviated mathematical derivation is given in the appendices.

  12. Quantum dot conjugates in a sub-micrometer fluidic channel

    Science.gov (United States)

    Stavis, Samuel M [Ithaca, NY; Edel, Joshua B [Brookline, MA; Samiee, Kevan T [Ithaca, NY; Craighead, Harold G [Ithaca, NY

    2008-07-29

    A nanofluidic channel fabricated in fused silica with an approximately 500 nm square cross section was used to isolate, detect and identify individual quantum dot conjugates. The channel enables the rapid detection of every fluorescent entity in solution. A laser of selected wavelength was used to excite multiple species of quantum dots and organic molecules, and the emission spectra were resolved without significant signal rejection. Quantum dots were then conjugated with organic molecules and detected to demonstrate efficient multicolor detection. PCH was used to analyze coincident detection and to characterize the degree of binding. The use of a small fluidic channel to detect quantum dots as fluorescent labels was shown to be an efficient technique for multiplexed single molecule studies. Detection of single molecule binding events has a variety of applications including high throughput immunoassays.

  13. Preparation of Conjugates of Cytotoxic Lupane Triterpenes with Biotin.

    Science.gov (United States)

    Soural, Miroslav; Hodon, Jiri; Dickinson, Niall J; Sidova, Veronika; Gurska, Sona; Dzubak, Petr; Hajduch, Marian; Sarek, Jan; Urban, Milan

    2015-12-16

    To better understand the mechanism of action of antitumor triterpenes, we are developing methods to identify their molecular targets. A promising method is based on combination of quantitative proteomics with SILAC and uses active compounds anchored to magnetic beads via biotin-streptavidin interaction. We developed a simple and fast solid-phase synthetic technique to connect terpenes to biotin through a linker. Betulinic acid was biotinylated from three different conjugation sites for use as a standard validation tool since many molecular targets of this triterpene are already known. Then, a set of four other cytotoxic triterpenoids was biotinylated. Biotinylated terpenes were similarly cytotoxic to their nonbiotinylated parents, which suggests that the target identification should not be influenced by linker or biotin. The developed solid-phase synthetic approach is the first attempt to use solid-phase synthesis to connect active triterpenes to biotin and is applicable as a general procedure for routine conjugation of triterpenes with other molecules of choice.

  14. Pomeron-Quark Coupling from Charge Conjugation Invariance

    International Nuclear Information System (INIS)

    Zhou Lijuan; Wu Qing; Ma Weixing; Gu Yunting

    2006-01-01

    Based on the charge conjugation invariance and the vacuum property of the Pomeron, we point out that the commonly used vector vertex of the Pomeron coupling to quark is incorrect since it contradicts with the Pomeron property. We also claim that the soft Pomeron could be a tensor glueball ξ(2230) with quantum numbers I G J PC = 0 + 2 ++ and total decay width Γ tot ≅100 MeV, which lies on the soft Pomeron trajectory α p = 1.08+0.20t. Therefore, the coupling vertex of the soft Pomeron to quark should be tensorial which is invariant under the charge conjugation and can explain why the inadequate vector coupling, γ μ , of the soft Pomeron to quark is successful in dealing with Pomeron physics.

  15. Two New PRP Conjugate Gradient Algorithms for Minimization Optimization Models.

    Directory of Open Access Journals (Sweden)

    Gonglin Yuan

    Full Text Available Two new PRP conjugate Algorithms are proposed in this paper based on two modified PRP conjugate gradient methods: the first algorithm is proposed for solving unconstrained optimization problems, and the second algorithm is proposed for solving nonlinear equations. The first method contains two aspects of information: function value and gradient value. The two methods both possess some good properties, as follows: 1 βk ≥ 0 2 the search direction has the trust region property without the use of any line search method 3 the search direction has sufficient descent property without the use of any line search method. Under some suitable conditions, we establish the global convergence of the two algorithms. We conduct numerical experiments to evaluate our algorithms. The numerical results indicate that the first algorithm is effective and competitive for solving unconstrained optimization problems and that the second algorithm is effective for solving large-scale nonlinear equations.

  16. Application of Conjugate Gradient methods to tidal simulation

    Science.gov (United States)

    Barragy, E.; Carey, G.F.; Walters, R.A.

    1993-01-01

    A harmonic decomposition technique is applied to the shallow water equations to yield a complex, nonsymmetric, nonlinear, Helmholtz type problem for the sea surface and an accompanying complex, nonlinear diagonal problem for the velocities. The equation for the sea surface is linearized using successive approximation and then discretized with linear, triangular finite elements. The study focuses on applying iterative methods to solve the resulting complex linear systems. The comparative evaluation includes both standard iterative methods for the real subsystems and complex versions of the well known Bi-Conjugate Gradient and Bi-Conjugate Gradient Squared methods. Several Incomplete LU type preconditioners are discussed, and the effects of node ordering, rejection strategy, domain geometry and Coriolis parameter (affecting asymmetry) are investigated. Implementation details for the complex case are discussed. Performance studies are presented and comparisons made with a frontal solver. ?? 1993.

  17. Modified conjugate gradient method for diagonalizing large matrices.

    Science.gov (United States)

    Jie, Quanlin; Liu, Dunhuan

    2003-11-01

    We present an iterative method to diagonalize large matrices. The basic idea is the same as the conjugate gradient (CG) method, i.e, minimizing the Rayleigh quotient via its gradient and avoiding reintroducing errors to the directions of previous gradients. Each iteration step is to find lowest eigenvector of the matrix in a subspace spanned by the current trial vector and the corresponding gradient of the Rayleigh quotient, as well as some previous trial vectors. The gradient, together with the previous trial vectors, play a similar role as the conjugate gradient of the original CG algorithm. Our numeric tests indicate that this method converges significantly faster than the original CG method. And the computational cost of one iteration step is about the same as the original CG method. It is suitable for first principle calculations.

  18. Fourier domain preconditioned conjugate gradient algorithm for atmospheric tomography.

    Science.gov (United States)

    Yang, Qiang; Vogel, Curtis R; Ellerbroek, Brent L

    2006-07-20

    By 'atmospheric tomography' we mean the estimation of a layered atmospheric turbulence profile from measurements of the pupil-plane phase (or phase gradients) corresponding to several different guide star directions. We introduce what we believe to be a new Fourier domain preconditioned conjugate gradient (FD-PCG) algorithm for atmospheric tomography, and we compare its performance against an existing multigrid preconditioned conjugate gradient (MG-PCG) approach. Numerical results indicate that on conventional serial computers, FD-PCG is as accurate and robust as MG-PCG, but it is from one to two orders of magnitude faster for atmospheric tomography on 30 m class telescopes. Simulations are carried out for both natural guide stars and for a combination of finite-altitude laser guide stars and natural guide stars to resolve tip-tilt uncertainty.

  19. Two New PRP Conjugate Gradient Algorithms for Minimization Optimization Models.

    Science.gov (United States)

    Yuan, Gonglin; Duan, Xiabin; Liu, Wenjie; Wang, Xiaoliang; Cui, Zengru; Sheng, Zhou

    2015-01-01

    Two new PRP conjugate Algorithms are proposed in this paper based on two modified PRP conjugate gradient methods: the first algorithm is proposed for solving unconstrained optimization problems, and the second algorithm is proposed for solving nonlinear equations. The first method contains two aspects of information: function value and gradient value. The two methods both possess some good properties, as follows: 1) βk ≥ 0 2) the search direction has the trust region property without the use of any line search method 3) the search direction has sufficient descent property without the use of any line search method. Under some suitable conditions, we establish the global convergence of the two algorithms. We conduct numerical experiments to evaluate our algorithms. The numerical results indicate that the first algorithm is effective and competitive for solving unconstrained optimization problems and that the second algorithm is effective for solving large-scale nonlinear equations.

  20. Extending the construct validity of dependency among conjugally bereaved adults.

    Science.gov (United States)

    Denckla, Christy A; Bornstein, Robert F; Mancini, Anthony D; Bonanno, George A

    2015-06-01

    The Relationship Profile Test is a widely used measure of dependency, detachment, and healthy dependency that has been examined in both clinical and nonclinical settings, though researchers have yet to validate this measure among conjugally bereaved adults. The present study examines the construct validity of a three-facet model of dependency-detachment by comparing relationships among self-report, semistructured interview-rated, and knowledgeable informant-rated functioning among conjugally bereaved adults. Participants (N = 112) included bereaved adults (M = 51.1 years; SD = 9.7) who had experienced the loss of a spouse 1.5 to 3 years prior to taking part in this study. Findings indicate adequate psychometric properties and theoretically expected associations with various measures of wellness and health including satisfaction with life, coping flexibility, somatic complaints, and ego resiliency. Results draw attention to adaptive correlates of dependency, suggesting potentially beneficial mental health interventions. © The Author(s) 2014.

  1. MILC staggered conjugate gradient performance on Intel KNL

    OpenAIRE

    DeTar, Carleton; Doerfler, Douglas; Gottlieb, Steven; Jha, Ashish; Kalamkar, Dhiraj; Li, Ruizi; Toussaint, Doug

    2016-01-01

    We review our work done to optimize the staggered conjugate gradient (CG) algorithm in the MILC code for use with the Intel Knights Landing (KNL) architecture. KNL is the second gener- ation Intel Xeon Phi processor. It is capable of massive thread parallelism, data parallelism, and high on-board memory bandwidth and is being adopted in supercomputing centers for scientific research. The CG solver consumes the majority of time in production running, so we have spent most of our effort on it. ...

  2. Functional conjugated pyridines via main-group element tuning.

    Science.gov (United States)

    Stolar, Monika; Baumgartner, Thomas

    2018-03-29

    Pyridine-based materials have seen widespread attention for the development of n-type organic materials. In recent years, the incorporation of main-group elements has also explored significant advantages for the development and tunability of organic conjugated materials. The unique chemical and electronic structure of main-group elements has led to several enhancements in conventional organic materials. This Feature article highlights recent main-group based pyridine materials by discussing property enhancements and application in organic electronics.

  3. Invasive pneumococcal infection despite 7-valent conjugated vaccine

    Directory of Open Access Journals (Sweden)

    Sebastien Joye

    2013-03-01

    Full Text Available Despite good cover with 7-valent vaccination, invasive pneumococcal infections may still be misdiagnosed and may lead to lifethreatening situations or death in young children. New serotypes are emerging and, therefore, clinicians must keep a high level of suspicion in young children regardless of their vaccination status. We report three cases of invasive pneumococcal infection due to new serotypes not covered by the 7-valent conjugated vaccine, two of which led children to death.

  4. Enantioselective conjugate radical addition to alpha'-hydroxy enones.

    Science.gov (United States)

    Lee, Sunggi; Lim, Chae Jo; Kim, Sunggak; Subramaniam, Rajesh; Zimmerman, Jake; Sibi, Mukund P

    2006-09-14

    Enantioselective conjugate radical addition to alpha'-hydroxy alpha,beta-unsaturated ketones, compounds containing bidentate donors, has been investigated. It has been found that radical additions to alpha'-hydroxy alpha,beta-unsaturated ketones in the presence of Mg(NTf2)2 and bisoxazoline ligand 5a proceeded cleanly, yielding the addition products in high chemical yields and good enantiomeric excesses.

  5. Antimicrobial Peptide-PNA Conjugates Selectively Targeting Bacterial Genes

    Science.gov (United States)

    2013-07-22

    antibacterial therapy. Initial publications suggest that conjugates of cell penetrating peptides and PNA’s can overcome the barrier in transporting ...Zhou, Y., Hou, Z., Meng, J., and Luo, X. Targeting RNA polymerase primary σ70 as a therapeutic strategy against methicillin - resistant ... Staphylococcus aureus by antisense peptide nucleic acid. PLoS One. 2012; 7(1):e29886. 2. Good, L., Sandberg, R., Larsson, O., Nielsen, P.E., and Wahlestedt, C

  6. Conjugate Image Theory Applied on Capacitive Wireless Power Transfer

    OpenAIRE

    Ben Minnaert; Nobby Stevens

    2017-01-01

    Wireless power transfer using a magnetic field through inductive coupling is steadily entering the market in a broad range of applications. However, for certain applications, capacitive wireless power transfer using electric coupling might be preferable. In order to obtain a maximum power transfer efficiency, an optimal compensation network must be designed at the input and output ports of the capacitive wireless link. In this work, the conjugate image theory is applied to determine this opti...

  7. Conjugated equine estrogen enhances rats' cognitive, anxiety, and social behavior

    OpenAIRE

    Walf, Alicia A.; Frye, Cheryl A.

    2008-01-01

    The ovarian hormone, 17β-estradiol (E2), has numerous targets in the body and brain, and can influence cognitive, affective, and social behavior. However, functional effects of commonly prescribed E2-based hormone therapies are less known. The effects of conjugated equine estrogen (CEE) on middle-aged female rats for cognitive (object recognition), anxiety (open field, plus maze), and social (social interaction, lordosis) behavior were compared-with vehicle. Our hypothesis that CEE would enha...

  8. A stereo-controlled route to conjugated E-enediynes

    Institute of Scientific and Technical Information of China (English)

    ZHOU Lei; JIANG Huanfeng

    2007-01-01

    3-Ene-1,5-diynes are important components of many enediyne antitumor agents and luminescent materials.A stereo-controlled approach to the synthesis of E-enediynes was developed,and it consists of the following two steps:(1)a mild and economical synthesis of dihalo vinyl derivatives via addition of CuBr2 to alkynes;(2) the Sonogashira coupling reaction of the dihalo vinyl derivatives with terminal alkynes to form conjugated enediynes.

  9. Calcium(ii)-catalyzed enantioselective conjugate additions of amines.

    Science.gov (United States)

    Uno, Brice E; Dicken, Rachel D; Redfern, Louis R; Stern, Charlotte M; Krzywicki, Greg G; Scheidt, Karl A

    2018-02-14

    The direct enantioselective chiral calcium(ii)·phosphate complex (Ca[CPA] 2 )-catalyzed conjugate addition of unprotected alkyl amines to maleimides was developed. This mild catalytic system represents a significant advance towards the general convergent asymmetric amination of α,β-unsaturated electrophiles, providing medicinally relevant chiral aminosuccinimide products in high yields and enantioselectivities. Furthermore, the catalyst can be reused directly from a previously chromatographed reaction and still maintain both high yield and selectivity.

  10. Regioselectivity of conjugate additions to monoalkyl-1,4-benzoquinones

    Directory of Open Access Journals (Sweden)

    SNEZANA TRIFUNOVIC

    2002-09-01

    Full Text Available The regioselectivity of the reaction of conjugate addition of thiols, amines, methanol and hydrogen chloride with the monoalkyl-1,4-benzoquinones avarone and 2-tert-butyl-1,4-benzoquinone was investigated. It was shown that the regioselectivity of the reaction is influenced by the electrophilicity of position 5 in unprotonated 2-alkylquinones, the increased electrophilicity of position 6 in acidic medium, and by the acidity of the intermediate hydroquinones.

  11. Some biological actions of PEG-conjugated RNase A oligomers

    Czech Academy of Sciences Publication Activity Database

    Poučková, P.; Škvor, J.; Gotte, G.; Vottariello, F.; Slavík, Tomáš; Matoušek, Josef; Laurents, D. V.; Libonati, M.; Souček, J.

    2006-01-01

    Roč. 53, č. 1 (2006), s. 79-85 ISSN 0028-2685 R&D Projects: GA ČR GA523/04/0755; GA MZd NR8233 Grant - others:Spanish Ministerio de Ciencia y Technologia BQU2003-05227 Institutional research plan: CEZ:AV0Z50450515 Keywords : RNase A oligomers * polyethylene glycol conjugates * anti-tumour activity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.247, year: 2006

  12. Comparison of genetic algorithms with conjugate gradient methods

    Science.gov (United States)

    Bosworth, J. L.; Foo, N. Y.; Zeigler, B. P.

    1972-01-01

    Genetic algorithms for mathematical function optimization are modeled on search strategies employed in natural adaptation. Comparisons of genetic algorithms with conjugate gradient methods, which were made on an IBM 1800 digital computer, show that genetic algorithms display superior performance over gradient methods for functions which are poorly behaved mathematically, for multimodal functions, and for functions obscured by additive random noise. Genetic methods offer performance comparable to gradient methods for many of the standard functions.

  13. Gadolinium burnable absorber optimization by the method of conjugate gradients

    International Nuclear Information System (INIS)

    Drumm, C.R.; Lee, J.C.

    1987-01-01

    The optimal axial distribution of gadolinium burnable poison in a pressurized water reactor is determined to yield an improved power distribution. The optimization scheme is based on Pontryagin's maximum principle, with the objective function accounting for a target power distribution. The conjugate gradients optimization method is used to solve the resulting Euler-Lagrange equations iteratively, efficiently handling the high degree of nonlinearity of the problem

  14. A Spectral Conjugate Gradient Method for Unconstrained Optimization

    International Nuclear Information System (INIS)

    Birgin, E. G.; Martinez, J. M.

    2001-01-01

    A family of scaled conjugate gradient algorithms for large-scale unconstrained minimization is defined. The Perry, the Polak-Ribiere and the Fletcher-Reeves formulae are compared using a spectral scaling derived from Raydan's spectral gradient optimization method. The best combination of formula, scaling and initial choice of step-length is compared against well known algorithms using a classical set of problems. An additional comparison involving an ill-conditioned estimation problem in Optics is presented

  15. A partitioned conjugate gradient algorithm for lattice Green functions

    International Nuclear Information System (INIS)

    Bowler, K.C.; Kenway, R.D.; Pawley, G.S.; Wallace, D.J.

    1984-01-01

    Partitioning reduces by one the dimensionality of the lattice on which a propagator need be calculated using, for example, the conjugate gradient algorithm. Thus the quark propagator in lattice QCD may be determined by a computation on a single spatial hyperplane. For free fermions on a 16 3 x N lattice 2N-bit accuracy in the propagator is required to avoid rounding errors. (orig.)

  16. In vitro results of conjugation of arabinagalactan and pegulated avidin

    International Nuclear Information System (INIS)

    Lichtenstein, L.; Salehi, N.; Doukarellis, C.

    1998-01-01

    Full text: The principles of avidin - biotin tumor targeting system were described at the Society of Nuclear Medicine in 1995. The preparation and use of the pegulated avidin to prolong circulation of avidin and therefore its uptake into tumour was reported in 1997. The biodistribution of radioactivity, tumour to blood, liver and bone T: B1 = 6.3, T: Li - 0.32 and T: B - 10.9 showed that the pegulation ( PEG) of avidin increased its circulation time which resulted in the high activity in the blood circulation and that the Dextran - Biotin conjugate was used to aggregate the PEG - Avidin, failed to facilitate its desired clearance out of the blood pool. Aim: We attempted to couple the 9 KDa fragment of 37 KDa polysaccharide arabinogalactan ( AG 37 KDa) with pegulated avidin to facilitate its hepatic clearance and thus increase the uptake of radiolabelled Tc - 99m - DTPA - Biocytinamide in all tissues including tumour. Method: AG (9 KDa) fragment was isolated from AG (37 KDa) by autoclaving at 121deg C and separated using a 10 KDa centricon ultrafiltration membrane. The average molecular weight was determined by HPLC at UV absorbance 280 nm. The AG 9kDa sample was oxidised by adding NaIO4, 30 minutes after incubation the solution was purified and coupled to Biotin - Hydrazide at (1:1) molar ratio, 2hrs after incubation, the coupled agent was radiolabelled with Tc-99m. The instant thin - layer chromatography (ITLC strips), with M.E.K and N.S. as eluants showed a LE = 91 %. The radiolabelled product was coupled to pegulated avidin at (1:1) for 1 hr at RT. The conjugated agent was separated by using 50 KDa ultrafiltration membrane. Results: > 95 % of AG - Biotin - Tc -99m- pegulated avidin remained unfiltered hence conjugated Conclusion: The results obtained from in vitro conjugation is encouraging and will be experimented for in vivo studies

  17. Moving force identification based on modified preconditioned conjugate gradient method

    Science.gov (United States)

    Chen, Zhen; Chan, Tommy H. T.; Nguyen, Andy

    2018-06-01

    This paper develops a modified preconditioned conjugate gradient (M-PCG) method for moving force identification (MFI) by improving the conjugate gradient (CG) and preconditioned conjugate gradient (PCG) methods with a modified Gram-Schmidt algorithm. The method aims to obtain more accurate and more efficient identification results from the responses of bridge deck caused by vehicles passing by, which are known to be sensitive to ill-posed problems that exist in the inverse problem. A simply supported beam model with biaxial time-varying forces is used to generate numerical simulations with various analysis scenarios to assess the effectiveness of the method. Evaluation results show that regularization matrix L and number of iterations j are very important influence factors to identification accuracy and noise immunity of M-PCG. Compared with the conventional counterpart SVD embedded in the time domain method (TDM) and the standard form of CG, the M-PCG with proper regularization matrix has many advantages such as better adaptability and more robust to ill-posed problems. More importantly, it is shown that the average optimal numbers of iterations of M-PCG can be reduced by more than 70% compared with PCG and this apparently makes M-PCG a preferred choice for field MFI applications.

  18. Nano-assembly of nanodiamonds by conjugation to actin filaments.

    Science.gov (United States)

    Bradac, Carlo; Say, Jana M; Rastogi, Ishan D; Cordina, Nicole M; Volz, Thomas; Brown, Louise J

    2016-03-01

    Fluorescent nanodiamonds (NDs) are remarkable objects. They possess unique mechanical and optical properties combined with high surface areas and controllable surface reactivity. They are non-toxic and hence suited for use in biological environments. NDs are also readily available and commercially inexpensive. Here, the exceptional capability of controlling and tailoring their surface chemistry is demonstrated. Small, bright diamond nanocrystals (size ˜30 nm) are conjugated to protein filaments of actin (length ˜3-7 µm). The conjugation to actin filaments is extremely selective and highly target-specific. These unique features, together with the relative simplicity of the conjugation-targeting method, make functionalised nanodiamonds a powerful and versatile platform in biomedicine and quantum nanotechnologies. Applications ranging from using NDs as superior biological markers to, potentially, developing novel bottom-up approaches for the fabrication of hybrid quantum devices that would bridge across the bio/solid-state interface are presented and discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Meeting the challenge: prevention of pneumococcal disease with conjugate vaccines

    Directory of Open Access Journals (Sweden)

    Echániz-Avilés Irma Gabriela

    2001-01-01

    Full Text Available Streptococcus pneumoniae is one of the leading causes of both invasive and noninvasive diseases in the pediatric population and continues to represent a significant public health burden worldwide. The increasing incidence of antibioticresistant strains of the pathogen has complicated treatment and management of the various pneumococcal disease manifestations. Thus, the best management strategy may be the prevention of pneumococcal diseases through vaccination. Although several pneumococcal conjugate vaccines have been clinically studied in infants and children, only a 7-valent conjugate vaccine (PNCRM7; Prevnar®/Prevenar® is currently approved for the prevention of invasive disease. Vaccination with PNCRM7 is safe and effective in infants and young children. Routine vaccination with the conjugate vaccine could improve outcomes by safeguarding against the development of antibiotic-resistant strains of S. pneumoniae, thus simplifying the management of pneumococcal disease. Additionally, the overall costs associated with the treatment of pneumococcal diseases could be substantially reduced, particularly in developing countries. The time has come for fully applying this new advancement against S. pneumoniae, to benefit the children of the world. The Spanish version of this paper is available at: http://www.insp.mx/salud/index.html

  20. Human platelet as an independent unit for sulfate conjugation

    International Nuclear Information System (INIS)

    Khoo, B.Y.; Sit, K.H.; Wong, K.P.

    1988-01-01

    The human platelets possess a full complement of enzymes capable of synthesizing N-acetyldopamine (NADA) 35 sulfate from ATP, Mg ++ and sodium 35 sulfate. The pH optimum for this three-step overall sulfate conjugation (comprising of the ATP sulfurylase, APS kinase and phenolsulfotransferase reactions) is 8.6 and the reactions proceeded progressively for several hours. Both ATP and Mg ++ ions, above their respective optimal concentrations of 5 and 7 mM, inhibited the sulfate conjugation of NADA. The apparent Km values for NADA as determined by the phenolsulfotransferase (PST) and overall reactions were similar in magnitude being 2.6 and 4.8 μM, respectively, while that for sodium 35 sulfate was 202 μM. A comparison of these two activities in 62 platelet preparations of normal subjects showed that the rate of the PST reaction was generally higher than the overall reaction even though the PST assay was carried out at suboptimal concentration of PAPS. There was a positive correlation (r=0.82) between the two sets of data, suggesting that the PST reaction probably has some control over the rate of overall sulfate conjugation

  1. An Integrated Solution for Performing Thermo-fluid Conjugate Analysis

    Science.gov (United States)

    Kornberg, Oren

    2009-01-01

    A method has been developed which integrates a fluid flow analyzer and a thermal analyzer to produce both steady state and transient results of 1-D, 2-D, and 3-D analysis models. The Generalized Fluid System Simulation Program (GFSSP) is a one dimensional, general purpose fluid analysis code which computes pressures and flow distributions in complex fluid networks. The MSC Systems Improved Numerical Differencing Analyzer (MSC.SINDA) is a one dimensional general purpose thermal analyzer that solves network representations of thermal systems. Both GFSSP and MSC.SINDA have graphical user interfaces which are used to build the respective model and prepare it for analysis. The SINDA/GFSSP Conjugate Integrator (SGCI) is a formbase graphical integration program used to set input parameters for the conjugate analyses and run the models. The contents of this paper describes SGCI and its thermo-fluids conjugate analysis techniques and capabilities by presenting results from some example models including the cryogenic chill down of a copper pipe, a bar between two walls in a fluid stream, and a solid plate creating a phase change in a flowing fluid.

  2. Collagen-Gold Nanoparticle Conjugates for Versatile Biosensing

    Directory of Open Access Journals (Sweden)

    Sarah Unser

    2017-02-01

    Full Text Available Integration of noble metal nanoparticles with proteins offers promising potential to create a wide variety of biosensors that possess both improved selectivity and versatility. The multitude of functionalities that proteins offer coupled with the unique optical properties of noble metal nanoparticles can allow for the realization of simple, colorimetric sensors for a significantly larger range of targets. Herein, we integrate the structural protein collagen with 10 nm gold nanoparticles to develop a protein-nanoparticle conjugate which possess the functionality of the protein with the desired colorimetric properties of the nanoparticles. Applying the many interactions that collagen undergoes in the extracellular matrix, we are able to selectively detect both glucose and heparin with the same collagen-nanoparticle conjugate. Glucose is directly detected through the cross-linking of the collagen fibrils, which brings the attached nanoparticles into closer proximity, leading to a red-shift in the LSPR frequency. Conversely, heparin is detected through a competition assay in which heparin-gold nanoparticles are added to solution and compete with heparin in the solution for the binding sites on the collagen fibrils. The collagen-nanoparticle conjugates are shown to detect both glucose and heparin in the physiological range. Lastly, glucose is selectively detected in 50% mouse serum with the collagen-nanoparticle devices possessing a linear range of 3–25 mM, which is also within the physiologically relevant range.

  3. NGR-peptide-drug conjugates with dual targeting properties.

    Directory of Open Access Journals (Sweden)

    Kata Nóra Enyedi

    Full Text Available Peptides containing the asparagine-glycine-arginine (NGR motif are recognized by CD13/aminopeptidase N (APN receptor isoforms that are selectively overexpressed in tumor neovasculature. Spontaneous decomposition of NGR peptides can result in isoAsp derivatives, which are recognized by RGD-binding integrins that are essential for tumor metastasis. Peptides binding to CD13 and RGD-binding integrins provide tumor-homing, which can be exploited for dual targeted delivery of anticancer drugs. We synthesized small cyclic NGR peptide-daunomycin conjugates using NGR peptides of varying stability (c[KNGRE]-NH2, Ac-c[CNGRC]-NH2 and the thioether bond containing c[CH2-CO-NGRC]-NH2, c[CH2-CO-KNGRC]-NH2. The cytotoxic effect of the novel cyclic NGR peptide-Dau conjugates were examined in vitro on CD13 positive HT-1080 (human fibrosarcoma and CD13 negative HT-29 (human colon adenocarcinoma cell lines. Our results confirm the influence of structure on the antitumor activity and dual acting properties of the conjugates. Attachment of the drug through an enzyme-labile spacer to the C-terminus of cyclic NGR peptide resulted in higher antitumor activity on both CD13 positive and negative cells as compared to the branching versions.

  4. Conjugal intimacy, gender and modernity in contemporary China.

    Science.gov (United States)

    Liu, Jieyu; Bell, Eona; Zhang, Jiayu

    2017-12-15

    The new generation of modernity theorists have forecast the democratization of gender relations within intimate relationships in late-modern times. Chinese society has undergone rapid and dramatic changes in its unique trajectory of political, social and economic reform. Using China as an example of a region which has been largely ignored in contemporary social theory, this article enters the debate to contest the extent to which conjugal relationships are democratized in line with modernity. We further test the assertion that modern marriages are characterized by increased self-disclosure and communication between partners. Data from a national survey on Chinese families is analysed in relation to the level of self-disclosure between husbands and wives; gender division of housework; household decision-making; and home ownership. We highlight the impact of gender, cohort and location (urban, rural or migrant) on experiences of modernity and draw attention to the material, social and cultural factors which continue to shape conjugal relations in contemporary Chinese society. Based on our findings, we contest the argument that disclosing intimacy between intimate partners is a defining characteristic of modern relationships, and suggest that other social factors may condition degrees of self-disclosure in marriage. Similarly, we question the extent to which heterosexual conjugal equality is attained: the cultural practices and values of patrilineal family organization, together with material circumstances, continue to influence marital relations in China. © London School of Economics and Political Science 2017.

  5. Development of antibacterial conjugates using sulfamethoxazole with monocyclic terpenes: A systematic medicinal chemistry based computational approach.

    Science.gov (United States)

    Swain, Shasank S; Paidesetty, Sudhir K; Padhy, Rabindra N

    2017-03-01

    To develop 6 conjugate agents of the moribund antibiotic sulfamethoxazole (SMZ) joined to 6 individual monoterpenes, followed by protocols of medicinal chemistry as potent antibacterials, against multidrug resistant (MDR) human gruesome pathogenic bacteria. Antibacterial activities of the proposed conjugates were ascertained by the 'prediction of activity spectra of substances' (PASS) program. Drug-likeness parameters and toxicity profiles of conjugates were standardized with the Lipinski rule of five, using cheminformatic tools, Molsoft, molinspiration, OSIRIS and ProTox. Antibacterial activities of individual chemicals and conjugates were examined by targeting the bacterial folic acid biosynthesis enzyme, dihydropteroate synthases (DHPSs) of bacteria, Bacillus anthracis, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae and Mycobacterium tuberculosis, with 3D structures of DHPSs from protein data bank. According to the PASS program, biological spectral values of conjugate-2, conjugate-5 and conjugate-6 were ascertained effective with 'probably active' or 'Pa' value > 0.5, for anti-infective and antituberculosic activities. Using molecular docking against 5 cited bacterial DHPSs, effective docking scores of 6 monoterpenes in the specified decreasing order (kcal/mol): -9.72 (eugenol against B. anthracis), -9.61 (eugenol against S. pneumoniae), -9. 42 (safrol, against B. anthracis), -9.39 (thymol, against M. tuberculosis), -9.34 (myristicin, against S. pneumoniae) and -9.29 (thymol, against B. anthracis); whereas the lowest docking score of SMZ was -8.46kcal/mol against S. aureus DHPS. Similarly, effective docking scores of conjugates were as specified (kcal/mol.): -10.80 (conjugate-4 consisting SMZ+safrol, against M. tuberculosis), -10.78 (conjugate-5 consisting SMZ+thymol, against M. tuberculosis), -10.60 (conjugate-5 against B. anthracis), -10.26 (conjugate-2 consisting SMZ+ eugenol, against M. tuberculosis), -10.25 (conjugate-5, against S

  6. Bioanalysis of antibody-drug conjugates: American Association of Pharmaceutical Scientists Antibody-Drug Conjugate Working Group position paper.

    Science.gov (United States)

    Gorovits, Boris; Alley, Stephen C; Bilic, Sanela; Booth, Brian; Kaur, Surinder; Oldfield, Phillip; Purushothama, Shobha; Rao, Chetana; Shord, Stacy; Siguenza, Patricia

    2013-05-01

    Antibody-drug conjugates (ADCs) typically consist of a cytotoxic drug covalently bound to an antibody by a linker. These conjugates have the potential to substantially improve efficacy and reduce toxicity compared with cytotoxic small-molecule drugs. Since ADCs are generally complex heterogeneous mixtures of multiple species, these novel therapeutic products present unique bioanalytical challenges. The growing number of ADCs being developed across the industry suggests the need for alignment of the bioanalytical methods or approaches used to assess the multiple species and facilitate consistent interpretation of the bioanalytical data. With limited clinical data, the current strategies that can be used to provide insight into the relationship between the multiple species and the observed clinical safety and efficacy are still evolving. Considerations of the bioanalytical strategies for ADCs based on the current industry practices that take into account the complexity and heterogeneity of ADCs are discussed.

  7. Self-Assembly and Crystallization of Conjugated Block Copolymers

    Science.gov (United States)

    Davidson, Emily Catherine

    This dissertation demonstrates the utility of molecular design in conjugated polymers to create diblock copolymers that robustly self-assemble in the melt and confine crystallization upon cooling. This work leverages the model conjugated polymer poly(3-(2'-ethyl)hexylthiophene) (P3EHT), which features a branched side chain, resulting in a dramatically reduced melting temperature (Tm 80°C) relative to the widely-studied poly(3-hexylthiophene) (P3HT) (Tm 200°C). This reduced melting temperature permits an accessible melt phase, without requiring that the segregation strength (chiN) be dramatically increased. Thus, diblock copolymers containing P3EHT demonstrate robust diblock copolymer self-assembly in the melt over a range of compositions and morphologies. Furthermore, confined crystallization in the case of both glassy (polystyrene (PS) matrix block) and soft (polymethylacrylate (PMA) matrix block) confinement is studied, with the finding that even in soft confinement, crystallization is constrained within the diblock microdomains. This success demonstrates the strategy of leveraging molecular design to decrease the driving force for crystallization as a means to achieving robust self-assembly and confined crystallization in conjugated block copolymers. Importantly, despite the relatively flexible nature of P3EHT in the melt, the diblock copolymer phase behavior appears to be significantly impacted by the stiffness (persistence length of 3 nm) of the P3EHT chain compared to the coupled amorphous blocks (persistence length 0.7 nm). In particular, it is shown that the synthesized morphologies are dominated by a very large composition window for lamellar geometries (favored at high P3EHT volume fractions); cylindrical geometries are favored when P3EHT is the minority fraction. This asymmetry of the composition window is attributed to impact of conformational asymmetry (the difference in chain stiffness, as opposed to shape) between conjugated and amorphous blocks

  8. Optimization of condition for conjugation of enrofloxacin to enzymes in chemiluminescence enzyme immunoassay

    Science.gov (United States)

    Yu, Songcheng; Yu, Fei; Zhang, Hongquan; Qu, Lingbo; Wu, Yongjun

    2014-06-01

    In this study, in order to find out a proper method for conjugation of enrofloxacin to label enzymes, two methods were compared and carbodiimide condensation was proved to be better. The results showed that the binding ratio of enrofloxacin and alkaline phosphatase (ALP) was 8:1 and that of enrofloxacin and horseradish peroxidase (HRP) was 5:1. This indicated that conjugate synthesized by carbodiimide condensation was fit for chemiluminescence enzyme immunoassay (CLEIA). Furthermore, data revealed that dialysis time was an important parameter for conjugation and 6 days was best. Buffer to dilute conjugate had little effect on CLEIA. The storage condition for conjugates was also studied and it was shown that the conjugate was stable at 4 °C with no additive up to 30 days. These data were valuable for establishing CLEIA to quantify enrofloxacin.

  9. Systemic aspects of conjugal resilience in couples with a child facing cancer and marrow transplantation.

    Science.gov (United States)

    Martin, Julie; Péloquin, Katherine; Vachon, Marie-France; Duval, Michel; Sultan, Serge

    The negative impact of paediatric cancer on parents is well known and is even greater when intensive treatments are used. This study aimed to describe how couples whose child has received a transplant for the treatment of leukaemia view conjugal resilience and to evaluate the role of we-ness as a precursor of conjugal adjustment. Four parental couples were interviewed. Interviews were analysed in two ways: inductive thematic analysis and rating of verbal content with the We-ness Coding Scale . Participants report that conjugal resilience involves the identification of the couple as a team and cohesion in the couple. Being a team generates certain collaborative interactions that lead to conjugal resilience. A sense of we-ness in parents is associated with fluctuation in the frequency of themes. Participants' vision of conjugal resilience introduced novel themes. The sense of we-ness facilitates cohesion and the process of conjugal resilience.

  10. Systemic aspects of conjugal resilience in couples with a child facing cancer and marrow transplantation

    Directory of Open Access Journals (Sweden)

    Julie Martin

    2016-09-01

    Full Text Available Introduction: The negative impact of paediatric cancer on parents is well known and is even greater when intensive treatments are used. This study aimed to describe how couples whose child has received a transplant for the treatment of leukaemia view conjugal resilience and to evaluate the role of we-ness as a precursor of conjugal adjustment. Methods: Four parental couples were interviewed. Interviews were analysed in two ways: inductive thematic analysis and rating of verbal content with the We-ness Coding Scale. Results: Participants report that conjugal resilience involves the identification of the couple as a team and cohesion in the couple. Being a team generates certain collaborative interactions that lead to conjugal resilience. A sense of we-ness in parents is associated with fluctuation in the frequency of themes. Discussion: Participants’ vision of conjugal resilience introduced novel themes. The sense of we-ness facilitates cohesion and the process of conjugal resilience.

  11. Preparation of bioconjugates by solid-phase conjugation to ion exchange matrix-adsorbed carrier proteins

    DEFF Research Database (Denmark)

    Houen, G.; Olsen, D.T.; Hansen, P.R.

    2003-01-01

    A solid-phase conjugation method utilizing carrier protein bound to an ion exchange matrix was developed. Ovalbumin was adsorbed to an anion exchange matrix using a batch procedure, and the immobilized protein was then derivatized with iodoacetic acid N-hydroxysuccinimid ester. The activated......, and immunization experiments with the eluted conjugates showed that the more substituted conjugates gave rise to the highest titers of glutathione antibodies. Direct immunization with the conjugates adsorbed to the ion exchange matrix was possible and gave rise to high titers of glutathione antibodies. Conjugates...... of ovalbumin and various peptides were prepared in a similar manner and used for production of peptide antisera by direct immunization with the conjugates bound to the ion exchanger. Advantages of the method are its solid-phase nature, allowing fast and efficient reactions and intermediate washings...

  12. Design and biological activity of β-sheet breaker peptide conjugates

    International Nuclear Information System (INIS)

    Rocha, Sandra; Cardoso, Isabel; Boerner, Hans; Pereira, Maria Carmo; Saraiva, Maria Joao; Coelho, Manuel

    2009-01-01

    The sequence LPFFD (iAβ 5 ) prevents amyloid-β peptide (Aβ) fibrillogenesis and neurotoxicity, hallmarks of Alzheimer's disease (AD), as previously demonstrated. In this study iAβ 5 was covalently linked to poly(ethylene glycol) (PEG) and the activity of conjugates was assessed and compared to the activity of the peptide alone by in vitro studies. The conjugates were characterized by MALDI-TOF. Competition binding assays established that conjugates retained the ability to bind Aβ with similar strength as iAβ 5 . Transmission electron microscopy analysis showed that iAβ 5 conjugates inhibited amyloid fibril formation, which is in agreement with binding properties observed for the conjugates towards Aβ. The conjugates were also able to prevent amyloid-induced cell death, as evaluated by activation of caspase 3. These results demonstrated that the biological activity of iAβ 5 is not affected by the pegylation process.

  13. A penalized linear and nonlinear combined conjugate gradient method for the reconstruction of fluorescence molecular tomography.

    Science.gov (United States)

    Shang, Shang; Bai, Jing; Song, Xiaolei; Wang, Hongkai; Lau, Jaclyn

    2007-01-01

    Conjugate gradient method is verified to be efficient for nonlinear optimization problems of large-dimension data. In this paper, a penalized linear and nonlinear combined conjugate gradient method for the reconstruction of fluorescence molecular tomography (FMT) is presented. The algorithm combines the linear conjugate gradient method and the nonlinear conjugate gradient method together based on a restart strategy, in order to take advantage of the two kinds of conjugate gradient methods and compensate for the disadvantages. A quadratic penalty method is adopted to gain a nonnegative constraint and reduce the illposedness of the problem. Simulation studies show that the presented algorithm is accurate, stable, and fast. It has a better performance than the conventional conjugate gradient-based reconstruction algorithms. It offers an effective approach to reconstruct fluorochrome information for FMT.

  14. Seismic evidence of conjugate normal faulting: The 1994 Devil Canyon earthquake sequence near Challis, Idaho

    International Nuclear Information System (INIS)

    Jackson, S.M.

    1994-08-01

    In this study, the term ''conjugate'' refers to faults that occur in two intersecting sets and coordinated kinematically, with each set being distinctive in both orientation and sense of shear (Davis, 1984). Contemporaneous activity along the conjugate faults is defined as occurring within the time frame of the mainshock-aftershock sequence (three weeks for this sequence and generally less than one month in other observed cases). Detailed recordings of microearthquakes from a dense array of temporary analog seismic stations are analyzed. The focal mechanisms and hypocenter spatial and temporal characteristics are combined with geological information to assess the style, geometry, timing, kinematics, and mechanics of conjugate normal faulting. The characteristics of conjugate normal faulting observed in the Devil Canyon sequence are compared to other conjugate normal faulting sequences, and strike-slip and thrust conjugate sequences worldwide

  15. Optical phase conjugation for time-domain undoing of dispersive self-phase-modulation effects

    International Nuclear Information System (INIS)

    Fisher, R.A.; Suydam, B.R.; Yevick, D.

    1983-01-01

    We show that the temporal distortion and spectral broadening of a pulse generated by the combined effects of group-velocity dispersion and self-phase modulation is removed by reflection of a cw-pumped, broadband, unity-reflecting Kerr-like optical phase conjugator followed by retraversal of the nonlinear medium. We also examine numerically the effects of finite linear loss in the material, of nonunity conjugate reflectivity, and of finite conjugator thickness

  16. Phase conjugation with random fields and with deterministic and random scatterers

    International Nuclear Information System (INIS)

    Gbur, G.; Wolf, E.

    1999-01-01

    The theory of distortion correction by phase conjugation, developed since the discovery of this phenomenon many years ago, applies to situations when the field that is conjugated is monochromatic and the medium with which it interacts is deterministic. In this Letter a generalization of the theory is presented that applies to phase conjugation of partially coherent waves interacting with either deterministic or random weakly scattering nonabsorbing media. copyright 1999 Optical Society of America

  17. Enzymatic degradation behavior and cytocompatibility of silk fibroin-starch-chitosan conjugate membranes

    Energy Technology Data Exchange (ETDEWEB)

    Baran, Erkan T., E-mail: erkantur@metu.edu.tr; Tuzlakoglu, Kadriye, E-mail: kadriye@dep.uminho.pt; Mano, Joao F., E-mail: jmano@dep.uminho.pt; Reis, Rui L., E-mail: rgreis@dep.uminho.pt

    2012-08-01

    The objective of this study was to investigate the influence of silk fibroin and oxidized starch conjugation on the enzymatic degradation behavior and the cytocompatability of chitosan based biomaterials. The tensile stress of conjugate membranes, which was at 50 Megapascal (MPa) for the lowest fibroin and starch composition (10 weight percent (wt.%)), was decreased significantly with the increased content of fibroin and starch. The weight loss of conjugates in {alpha}-amylase was more notable when the starch concentration was the highest at 30 wt.%. The conjugates were resistant to the degradation by protease and lysozyme except for the conjugates with the lowest starch concentration. After 10 days of cell culture, the proliferation of osteoblast-like cells (SaOS-2) was stimulated significantly by higher fibroin compositions and the DNA synthesis on the conjugate with the highest fibroin (30 wt.%) was about two times more compared to the native chitosan. The light microscopy and the image analysis results showed that the cell area and the lengths were decreased significantly with higher fibroin/chitosan ratio. The study proved that the conjugation of fibroin and starch with the chitosan based biomaterials by the use of non-toxic reductive alkylation crosslinking significantly improved the cytocompatibility and modulated the biodegradation, respectively. - Highlights: Black-Right-Pointing-Pointer Silk fibroin, starch and chitosan conjugates were prepared by reductive alkylation. Black-Right-Pointing-Pointer The enzymatic biodegradation and the cytocompatibility of conjugates were tested. Black-Right-Pointing-Pointer The conjugate with 30% starch composition was degraded by {alpha}-amylase significantly. Black-Right-Pointing-Pointer Higher starch composition in conjugates prevented protease and lysozyme degradation. Black-Right-Pointing-Pointer Fibroin incorporation effectively increased the cell proliferation of conjugates.

  18. Degradable conjugated polymers for the selective sorting of semiconducting carbon nanotubes

    Science.gov (United States)

    Gopalan, Padma; Arnold, Michael Scott; Kansiusarulsamy, Catherine Kanimozhi; Brady, Gerald Joseph; Shea, Matthew John

    2018-04-10

    Conjugated polymers composed of bi-pyridine units linked to 9,9-dialkyl fluorenyl-2,7-diyl units via imine linkages along the polymer backbone are provided. Also provided are semiconducting single-walled carbon nanotubes coated with the conjugated polymers and methods of sorting and separating s-SWCNTs from a sample comprising a mixture of s-SWCNTs and metallic single-walled carbon nanotubes using the conjugated polymers.

  19. Particle-in-a-box model of exciton absorption and electroabsorption in conjugated polymers

    Science.gov (United States)

    Pedersen, Thomas G.

    2000-12-01

    The recently proposed particle-in-a-box model of one-dimensional excitons in conjugated polymers is applied in calculations of optical absorption and electroabsorption spectra. It is demonstrated that for polymers of long conjugation length a superposition of single exciton resonances produces a line shape characterized by a square-root singularity in agreement with experimental spectra near the absorption edge. The effects of finite conjugation length on both absorption and electroabsorption spectra are analyzed.

  20. Nonlinear propagation of phase-conjugate focused sound beams in water

    Science.gov (United States)

    Brysev, A. P.; Krutyansky, L. M.; Preobrazhensky, V. L.; Pyl'nov, Yu. V.; Cunningham, K. B.; Hamilton, M. F.

    2000-07-01

    Nonlinear propagation of phase-conjugate, focused, ultrasound beams is studied. Measurements are presented of harmonic amplitudes along the axis and in the focal plane of the conjugate beam, and of the waveform and spectrum at the focus. A maximum peak pressure of 3.9 MPa was recorded in the conjugate beam. The measurements are compared with simulations based on the KZK equation, and satisfactory agreement is obtained.

  1. Repercussions of imprisonment for conjugal violence: discourses of men.

    Science.gov (United States)

    Sousa, Anderson Reis de; Pereira, Álvaro; Paixão, Gilvânia Patrícia do Nascimento; Pereira, Nadirlene Gomes; Campos, Luana Moura; Couto, Telmara Menezes

    2016-12-08

    to know the consequences that men experience related to incarceration by conjugal violence. qualitative study on 20 men in jail and indicted in criminal processes related to conjugal violence in a Court specialized in Family and Domestic Violence against women. The interviews were classified based on Collective Subject Discourse method, using NVIVO(r) software. the collective discourse shows that the experience of preventive imprisonment starts a process of family dismantling, social stigma, financial hardship and psycho-emotional symptoms such as phobia, depression, hypertension, and headaches. due to the physical, mental and social consequences of the conjugal violence-related imprisonment experience, it is urgent to look carefully into the somatization process as well as to the prevention strategies regarding this process. conhecer as repercussões da prisão por violência conjugal para os homens. estudo qualitativo com 20 homens que foram presos e respondem a processo criminal por violência conjugal em uma Vara de Violência Doméstica e Familiar contra a Mulher. As entrevistas foram categorizadas com base no método do Discurso do Sujeito Coletivo, com auxílio do software NVIVO(r). o discurso coletivo revela que a vivência da prisão preventiva desencadeia desagregação familiar, estigma social, dificuldades financeiras e sintomatologia de caráter psicoemocional, como fobia, depressão, hipertensão e cefaleia. diante das repercussões físicas, mentais e sociais de experienciar a prisão em decorrência de violência conjugal, urge um olhar acerca do processo de somatização do vivido, da mesma maneira que estratégias de prevenção do fenômeno. conocer las repercusiones de prisión, por violencia conyugal, en los hombres. estudio cualitativo con 20 hombres que fueron presos y responden por caso criminal de violencia conyugal, en una Juzgado de Violencia Doméstica y Familiar contra la Mujer. Las entrevistas fueron categorizadas con base en el m

  2. Doxorubicin conjugated to D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS): conjugation chemistry, characterization, in vitro and in vivo evaluation.

    Science.gov (United States)

    Cao, Na; Feng, Si-Shen

    2008-10-01

    To develop a polymer-anticancer drug conjugate, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was employed as a carrier of doxorubicin (DOX) to enhance its therapeutic effects and reduce its side effects. Doxorubicin was chemically conjugated to TPGS. The molecular structure, drug loading efficiency, drug release kinetics and stability of the conjugate were characterized. The cellular uptake, intracellular distribution, and cytotoxicity were accessed by using MCF-7 breast cancer cells and C6 glioma cells as in vitro cell model. The conjugate showed higher cellular uptake efficiency and broader distribution within the cells. Judged by IC(50), the conjugate was found 31.8, 69.6, 84.1% more effective with MCF-7 cells and 43.9, 87.7, 42.2% more effective with C6 cells than the parent drug after 24, 48, 72 h culture, respectively. The in vivo pharmacokinetics and biodistribution were investigated after an i.v. administration at 5 mg DOX/kg body weight in rats. Promisingly, 4.5-fold increase in the half-life and 24-fold increase in the area-under-the-curve (AUC) of DOX were achieved for the TPGS-DOX conjugate compared with the free DOX. The drug level in heart, gastric and intestine was significantly reduced, which is an indication of reduced side effects. Our TPGS-DOX conjugate showed great potential to be a prodrug of higher therapeutic effects and fewer side effects than DOX itself.

  3. Cholesterol-conjugated supramolecular assemblies of low generations polyamidoamine dendrimers for enhanced EGFP plasmid DNA transfection

    Energy Technology Data Exchange (ETDEWEB)

    Golkar, Nasim; Samani, Soliman Mohammadi; Tamaddon, Ali Mohammad, E-mail: amtamadon@gmail.com [Shiraz University of Medical Sciences, Department of Pharmaceutics, School of Pharmacy (Iran, Islamic Republic of)

    2016-05-15

    Aimed to prepare an enhanced gene delivery system with low cytotoxicity and high transfection efficiency, various cholesterol-conjugated derivates of low generation polyamidoamine (PAMAM) dendrimers were prepared. The conjugates were characterized by TNBS assay, FTIR, and {sup 1}H-NMR spectroscopy. Self-assembly of the dendrimer conjugates (G1-Chol, G2-Chol, and G3-Chol) was investigated by pyrene assay. Following formation of the complexes between enhanced green fluorescence protein plasmid and the dendrimer conjugates at various N (primary amine)/P (phosphate) mole ratios, plasmid condensation, biologic stability, cytotoxicity, and protein expression were investigated. The conjugates self-assembled into micellar dispersions with the critical micelle concentration values (<50 µg/ml) depending on the dendrimer generation and cholesterol/amine mole ratio. Cholesterol conjugation resulted in higher resistance of the condensed plasmid DNA in a competition assay with heparin sulfate. Also, the transfection efficiency was determined higher for the cholesterol conjugates than unmodified dendrimers in HepG2 cells, showing the highest for G2-Chol at 40 % degree of cholesterol modification (G2-Chol{sub 40 %}) among various dendrimer generations. Interestingly, such conjugate showed a complete protection of plasmid against serum nucleases. Our results confirmed that the cholesterol conjugation to PAMAM dendrimers of low generations bearing little cytotoxicity improves their several physicochemical and biological characteristics required for an enhanced delivery of plasmid DNA into cells.

  4. Conjugate Etalon Spectral Imager (CESI) & Scanning Etalon Methane Mapper (SEMM), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The Conjugate Etalon Spectral Imaging (CESI) concept enables the development of miniature instruments with high spectral resolution, suitable for LEO missions aboard...

  5. Efficient conjugate gradient algorithms for computation of the manipulator forward dynamics

    Science.gov (United States)

    Fijany, Amir; Scheid, Robert E.

    1989-01-01

    The applicability of conjugate gradient algorithms for computation of the manipulator forward dynamics is investigated. The redundancies in the previously proposed conjugate gradient algorithm are analyzed. A new version is developed which, by avoiding these redundancies, achieves a significantly greater efficiency. A preconditioned conjugate gradient algorithm is also presented. A diagonal matrix whose elements are the diagonal elements of the inertia matrix is proposed as the preconditioner. In order to increase the computational efficiency, an algorithm is developed which exploits the synergism between the computation of the diagonal elements of the inertia matrix and that required by the conjugate gradient algorithm.

  6. Multifunctional adhesive polymers: Preactivated thiolated chitosan-EDTA conjugates.

    Science.gov (United States)

    Netsomboon, Kesinee; Suchaoin, Wongsakorn; Laffleur, Flavia; Prüfert, Felix; Bernkop-Schnürch, Andreas

    2017-02-01

    The aim of this study was to synthesis preactivated thiolated chitosan-EDTA (Ch-EDTA-cys-2MNA) conjugates exhibiting in particular high mucoadhesive, cohesive and chelating properties. Thiol groups were coupled with chitosan by carbodiimide reaction and further preactivated by attachment with 2-mercaptonicotinic acid (2MNA) via disulfide bond formation. Determinations of primary amino and sulfhydryl groups were performed by TNBS and Ellman's tests, respectively. Cytotoxicity was screened by resazurin assay in Caco-2 cells. Mucoadhesive properties and bivalent cation binding capacity with Mg 2+ and Ca 2+ in comparison to chitosan-EDTA (Ch-EDTA) and thiolated Ch-EDTA (Ch-EDTA-cys) were evaluated. Determination of 2MNA and total sulfhydryl groups indicated that 80% of thiol groups were preactivated. The results from cytotoxicity studies demonstrated that Ch-EDTA-cys and Ch-EDTA-cys-2MNA were not toxic to the cells at the polymer test concentration of 0.25% (w/v) while cell viability decreased by increasing the concentration of Ch-EDTA. Although EDTA molecule was modified by thiolation and preactivation, approximately 50% of chelating properties of the conjugates were maintained compared to Ch-EDTA. Ch-EDTA-cys-2MNA adhered on freshly excised porcine intestinal mucosa up to 6h while Ch-EDTA adhered for just 1h. According to the combination of mucoadhesive and chelating properties of the conjugates synthesized in this study, Ch-EDTA-cys-2MNA might be useful for various mucosal drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Numerical Modeling of Conjugate Heat Transfer in Fluid Network

    Science.gov (United States)

    Majumdar, Alok

    2004-01-01

    Fluid network modeling with conjugate heat transfer has many applications in Aerospace engineering. In modeling unsteady flow with heat transfer, it is important to know the variation of wall temperature in time and space to calculate heat transfer between solid to fluid. Since wall temperature is a function of flow, a coupled analysis of temperature of solid and fluid is necessary. In cryogenic applications, modeling of conjugate heat transfer is of great importance to correctly predict boil-off rate in propellant tanks and chill down of transfer lines. In TFAWS 2003, the present author delivered a paper to describe a general-purpose computer program, GFSSP (Generalized Fluid System Simulation Program). GFSSP calculates flow distribution in complex flow circuit for compressible/incompressible, with or without heat transfer or phase change in all real fluids or mixtures. The flow circuit constitutes of fluid nodes and branches. The mass, energy and specie conservation equations are solved at the nodes where as momentum conservation equations are solved at the branches. The proposed paper describes the extension of GFSSP to model conjugate heat transfer. The network also includes solid nodes and conductors in addition to fluid nodes and branches. The energy conservation equations for solid nodes solves to determine the temperatures of the solid nodes simultaneously with all conservation equations governing fluid flow. The numerical scheme accounts for conduction, convection and radiation heat transfer. The paper will also describe the applications of the code to predict chill down of cryogenic transfer line and boil-off rate of cryogenic propellant storage tank.

  8. Peptide/protein-polymer conjugates: synthetic strategies and design concepts.

    Science.gov (United States)

    Gauthier, Marc A; Klok, Harm-Anton

    2008-06-21

    This feature article provides a compilation of tools available for preparing well-defined peptide/protein-polymer conjugates, which are defined as hybrid constructs combining (i) a defined number of peptide/protein segments with uniform chain lengths and defined monomer sequences (primary structure) with (ii) a defined number of synthetic polymer chains. The first section describes methods for post-translational, or direct, introduction of chemoselective handles onto natural or synthetic peptides/proteins. Addressed topics include the residue- and/or site-specific modification of peptides/proteins at Arg, Asp, Cys, Gln, Glu, Gly, His, Lys, Met, Phe, Ser, Thr, Trp, Tyr and Val residues and methods for producing peptides/proteins containing non-canonical amino acids by peptide synthesis and protein engineering. In the second section, methods for introducing chemoselective groups onto the side-chain or chain-end of synthetic polymers produced by radical, anionic, cationic, metathesis and ring-opening polymerization are described. The final section discusses convergent and divergent strategies for covalently assembling polymers and peptides/proteins. An overview of the use of chemoselective reactions such as Heck, Sonogashira and Suzuki coupling, Diels-Alder cycloaddition, Click chemistry, Staudinger ligation, Michael's addition, reductive alkylation and oxime/hydrazone chemistry for the convergent synthesis of peptide/protein-polymer conjugates is given. Divergent approaches for preparing peptide/protein-polymer conjugates which are discussed include peptide synthesis from synthetic polymer supports, polymerization from peptide/protein macroinitiators or chain transfer agents and the polymerization of peptide side-chain monomers.

  9. Labeling of monoclonal antibody conjugates with 90Y

    International Nuclear Information System (INIS)

    Motta-Hennessy, Cecilia; Sharkey, R.M.; Goldenberg, D.M.

    1991-01-01

    An anti-carcinoembryonic antigen (CEA) antibody, NP-4, was labeled with 90 Y using p-isothiocyanatobenzyl DTPA (SCN-Bz-DTPA) and its derivatives 1-(p-isothiocyanatobenzyl)-3-methyl-DTPA (1B3M), 2-(p-isothiocyanatobenzyl)-4-methyl-DTPA (1M3B), 1-(2)-methyl-4-isothiocyanatobenzyl-DTPA (MX-DTPA) as the chelating agents. The 90 Y conjugates were purified from unbound 90 Y by two different methods, HPLC or acrylamide size exclusion gel chromatography, in order to evaluate the best purification method. Labeling efficiency, reaction kinetics and immunoreactivity were compared to the same antibodies labeled with [ 111 In]citrate. Labeling efficiency, as determined by either HPLC or ITLC (instant thin layer chromatography), was consistently higher by ITLC than HPLC for 90 Y-labeled MAb, but equal for 111 In-labeled MAbs. Discrepancies between the 2 methods were linked to impurities in the 90 Y that remained at the origin of ITLC plates. After purification by acrylamide gel filtration, recovery was 50-60% of loaded 90 Y activity, but was more than 87% for the 111 In compounds. Using HPLC, the recovery measured 85% for 90 Y-labeled MAb and more than 93% for 111 In-labeled conjugates. Immunoreactivity of the [ 90 Y]MAb was comparable to the 111 In-labeled conjugates. These studies indicate that HPLC purification of the [ 90 Y] MAbs improves recovery of activity, and suggests that impurities found in the 90 Y and metal-binding properties of acrylamide may have contributed to the poor recoveries from acrylamide gels. (author)

  10. Solving large mixed linear models using preconditioned conjugate gradient iteration.

    Science.gov (United States)

    Strandén, I; Lidauer, M

    1999-12-01

    Continuous evaluation of dairy cattle with a random regression test-day model requires a fast solving method and algorithm. A new computing technique feasible in Jacobi and conjugate gradient based iterative methods using iteration on data is presented. In the new computing technique, the calculations in multiplication of a vector by a matrix were recorded to three steps instead of the commonly used two steps. The three-step method was implemented in a general mixed linear model program that used preconditioned conjugate gradient iteration. Performance of this program in comparison to other general solving programs was assessed via estimation of breeding values using univariate, multivariate, and random regression test-day models. Central processing unit time per iteration with the new three-step technique was, at best, one-third that needed with the old technique. Performance was best with the test-day model, which was the largest and most complex model used. The new program did well in comparison to other general software. Programs keeping the mixed model equations in random access memory required at least 20 and 435% more time to solve the univariate and multivariate animal models, respectively. Computations of the second best iteration on data took approximately three and five times longer for the animal and test-day models, respectively, than did the new program. Good performance was due to fast computing time per iteration and quick convergence to the final solutions. Use of preconditioned conjugate gradient based methods in solving large breeding value problems is supported by our findings.

  11. Labeling of monoclonal antibody conjugates with sup 90 Y

    Energy Technology Data Exchange (ETDEWEB)

    Motta-Hennessy, Cecilia; Sharkey, R.M.; Goldenberg, D.M. (Center for Molecular Medicine and Immunology, Newark, NJ (USA))

    1991-01-01

    An anti-carcinoembryonic antigen (CEA) antibody, NP-4, was labeled with {sup 90}Y using p-isothiocyanatobenzyl DTPA (SCN-Bz-DTPA) and its derivatives 1-(p-isothiocyanatobenzyl)-3-methyl-DTPA (1B3M), 2-(p-isothiocyanatobenzyl)-4-methyl-DTPA (1M3B), 1-(2)-methyl-4-isothiocyanatobenzyl-DTPA (MX-DTPA) as the chelating agents. The {sup 90}Y conjugates were purified from unbound {sup 90}Y by two different methods, HPLC or acrylamide size exclusion gel chromatography, in order to evaluate the best purification method. Labeling efficiency, reaction kinetics and immunoreactivity were compared to the same antibodies labeled with ({sup 111}In)citrate. Labeling efficiency, as determined by either HPLC or ITLC (instant thin layer chromatography), was consistently higher by ITLC than HPLC for {sup 90}Y-labeled MAb, but equal for {sup 111}In-labeled MAbs. Discrepancies between the 2 methods were linked to impurities in the {sup 90}Y that remained at the origin of ITLC plates. After purification by acrylamide gel filtration, recovery was 50-60% of loaded {sup 90}Y activity, but was more than 87% for the {sup 111}In compounds. Using HPLC, the recovery measured 85% for {sup 90}Y-labeled MAb and more than 93% for {sup 111}In-labeled conjugates. Immunoreactivity of the ({sup 90}Y)MAb was comparable to the {sup 111}In-labeled conjugates. These studies indicate that HPLC purification of the ({sup 90}Y) MAbs improves recovery of activity, and suggests that impurities found in the {sup 90}Y and metal-binding properties of acrylamide may have contributed to the poor recoveries from acrylamide gels. (author).

  12. Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant.

    Science.gov (United States)

    MacLean, G D; Reddish, M; Koganty, R R; Wong, T; Gandhi, S; Smolenski, M; Samuel, J; Nabholtz, J M; Longenecker, B M

    1993-01-01

    We have synthesized various formulations that have potential for active specific immunotherapy (ASI) of human cancers. Sialyl-Tn (STn) is a potentially important target structure for ASI because its expression on mucins is a strong, independent predictor of poor prognosis, suggesting that it may have functional significance in the metastatic process. In this first pilot study of synthetic sialyl-Tn hapten conjugated to keyhole limpet hemocyanin (STn-KLH), with Detox adjuvant, toxicity and humoral immunogenicity were assessed in 12 patients with metastatic breast cancer. Toxicity was minimal, restricted to local cutaneous reactions (apart from transient nausea and vomiting following single low-dose cyclophosphamide treatment). Using STn-conjugated human serum albumin in a solid-phase enzyme-linked immunosorbent assay, it was shown that all patients developed IgM and IgG specific for the synthetic STn hapten. Following immunization, most patients were shown to develop increased titres of complement-mediated cytotoxic antibodies, partially inhibited by synthetic STn hapten, but not by the related TF hapten. We also detected IgM and IgG antibodies reactive with natural STn determinants expressed on ovine submaxillary mucin, the STn specificity of this reactivity being confirmed by hapten inhibition. Evaluation of clinical efficacy in a small pilot study is difficult. Five patients are alive 12 or more months after entry, and another 4 patients are alive 6 or more months after entry into the study. All 3 patients with known widespread bulky disease progressed despite ASI, 2 having died from widespread cancer. Two patients had partial responses, each lasting 6 months. While several patients had disease stability for 3-10 months, 1 patient with pulmonary metastases remains stable 15 months after entry into the program.

  13. Conjugated hyperbilirubinemia in infancy associated with parenteral alimentation.

    Science.gov (United States)

    Bernstein, J; Chang, C H; Brough, A J; Heidelberger, K P

    1977-03-01

    Liver biopsy was performed to exclude anatomic obstruction of the biliary tract in five prematurely born infants who had developed conjugated hyperbilirubinemia during intravenous alimentation with a protein hydrolysate. Each was being treated after having undergone a segmental intestinal resection for necrotizing enterocolitis. Bacterial and viral infections, metabolic disorders, and isoimmune hemolytic disease were excluded as possible causes of jaundice. Light microscopic and ultrastructural analysis disclosed cholestasis and hepatocellular injury without significant inflammatory reaction. Jaundice abated following permanent discontinuation of parenteral alimentation. The jaundice and cholestasis are interpreted to be hepatotoxic effects because of (1) their temporal relationship to the treatment and (2) the presence of hepatocellular damage.

  14. Recombinogenic engineering of conjugative plasmids with fluorescent marker cassettes

    DEFF Research Database (Denmark)

    Reisner, A.; Molin, Søren; Zechner, E.L.

    2002-01-01

    An efficient approach for the insertion of fluorescent marker genes with sequence specificity into conjugative plasmids in Escherichia coli is described. For this purpose, homologous recombination of linear double-stranded targeting DNA was mediated by the bacteriophage lambda recombination...... resistance genes and fluorescent markers. The choice of 5' non-homologous extensions in primer pairs used for amplifying the marker cassettes determines the site specificity of the targeting DNA. This methodology is applicable to the modification of all plasmids that replicate in E coli and is not restricted...

  15. Determination of conjugated linoleic acid (CLA) concentrations in milk chocolate.

    Science.gov (United States)

    Hurst, W J; Tarka, S M; Dobson, G; Reid, C M

    2001-03-01

    The fatty acids from a series of milk-chocolate-based confectionery samples were analyzed as methyl esters by GC to determine the presence and amount of conjugated linoleic acid (CLA). A single peak corresponding to the 9-cis,11-trans isomer and ranging from less than 0.1% to nearly 0.2% of the total fatty acids, corresponding to up to 0.3 mg per g of chocolate, was observed. One of the chocolate extracts and a milk extract were subjected to silver ion HPLC and GC-MS in order to confirm the identity of the major isomer and tentatively identity minor isomers.

  16. Program generator for the Incomplete Cholesky Conjugate Gradient (ICCG) method

    International Nuclear Information System (INIS)

    Kuo-Petravic, G.; Petravic, M.

    1978-04-01

    The Incomplete Cholesky Conjugate Gradient (ICCG) method has been found very effective for the solution of sparse systems of linear equations. Its implementation on a computer, however, requires a considerable amount of careful coding to achieve good machine efficiency. Furthermore, the resulting code is necessarily inflexible and cannot be easily adapted to different problems. We present in this paper a code generator GENIC which, given a small amount of information concerning the sparsity pattern and size of the system of equations, generates a solver package. This package, called SOLIC, is tailor made for a particular problem and can be easily incorporated into any user program

  17. Self-Adjuvanting Glycopeptide Conjugate Vaccine against Disseminated Candidiasis

    Science.gov (United States)

    Xin, Hong; Cartmell, Jonathan; Bailey, Justin J.; Dziadek, Sebastian; Bundle, David R.; Cutler, Jim E.

    2012-01-01

    Our research on pathogenesis of disseminated candidiasis led to the discovery that antibodies specific for Candida albicans cell surface β-1, 2–mannotriose [β-(Man)3] protect mice. A 14 mer peptide Fba, which derived from the N-terminal portion of the C. albicans cytosolic/cell surface protein fructose-bisphosphate aldolase, was used as the glycan carrier and resulted in a novel synthetic glycopeptide vaccine β-(Man)3-Fba. By a dendritic cell-based immunization approach, this conjugate induced protective antibody responses against both the glycan and peptide parts of the vaccine. In this report, we modified the β-(Man)3-Fba conjugate by coupling it to tetanus toxoid (TT) in order to improve immunogenicity and allow for use of an adjuvant suitable for human use. By new immunization procedures entirely compatible with human use, the modified β-(Man)3-Fba-TT was administered either alone or as a mixture made with alum or monophosphoryl lipid A (MPL) adjuvants and given to mice by a subcutaneous (s.c.) route. Mice vaccinated with or, surprisingly, without adjuvant responded well by making robust antibody responses. The immunized groups showed a high degree of protection against a lethal challenge with C. albicans as evidenced by increased survival times and reduced kidney fungal burden as compared to control groups that received only adjuvant or DPBS buffer prior to challenge. To confirm that induced antibodies were protective, sera from mice immunized against the β-(Man)3-Fba-TT conjugate transferred protection against disseminated candidiasis to naïve mice, whereas C. albicans-absorbed immune sera did not. Similar antibody responses and protection induced by the β-(Man)3-Fba-TT vaccine was observed in inbred BALB/c and outbred Swiss Webster mice. We conclude that addition of TT to the glycopeptide conjugate results in a self-adjuvanting vaccine that promotes robust antibody responses without the need for additional adjuvant, which is novel and represents a

  18. Data on atherosclerosis specific antibody conjugation to nanoemulsions

    Directory of Open Access Journals (Sweden)

    Geoffrey Prévot

    2017-12-01

    Full Text Available This article present data related to the publication entitled “Iron oxide core oil-in-water nanoemulsion as tracer for atherosclerosis MPI and MRI imaging” (Prévot et al., 2017 [1]. Herein we describe the engineering in the baculovirus-insect cell system and purification processes of the human scFv-Fc TEG4-2C antibody, specific of platelets within the atheroma plaque. For molecular targeting purpose, atheroma specific antibody was conjugated to nanoemulsions (NEs using a heterobifunctional linker (DSPE-PEG-maleimide. Atheroma labelling was assayed by immunochemistry on arterial sections from rabbits.

  19. Synthesis and in-vitro cytotoxicity of dendrimer cytostatic conjugates

    OpenAIRE

    Scutaru, Ana Maria

    2011-01-01

    Bendamustine and melphalan are nitrogen mustard derivatives from the group of alkylating agents and are used for the treatment of various cancers such as chronic lymphocytic leukemia (CLL) or breast cancer. However their use is limited by numerous side effects. Therefore, 1,3,5-tris(3-aminopropyl)benzene (G0) and the G1 analogous 1,3,5-tris[3,5-bis(3-aminopropyl)-N-propylbenzamide]benzene were chosen to synthesize cytostatic-dendrimer conjugates and to achieve ‘tumor targeting' through the EP...

  20. DNA-Conjugated Organic Chromophores in DNA Stacking Interactions

    DEFF Research Database (Denmark)

    Filichev, Vyacheslav V.; Pedersen, Erik Bjerregaard

    2009-01-01

    Since the discovery of the intercalation of acridine derivatives into DNA (1961), chemists have synthesized many intercalators tethered to DNA. Advances in the chemical synthesis of modified nucleosides along with progress in oligonucleotide synthesis have made it possible to introduce organic ch...... review presents those efforts in the design of intercalators/organic chromophores as oligonucleotide conjugates that form a foundation for the generation of novel nucleic acid architectures......Since the discovery of the intercalation of acridine derivatives into DNA (1961), chemists have synthesized many intercalators tethered to DNA. Advances in the chemical synthesis of modified nucleosides along with progress in oligonucleotide synthesis have made it possible to introduce organic...

  1. Conjugate gradient coupled with multigrid for an indefinite problem

    Science.gov (United States)

    Gozani, J.; Nachshon, A.; Turkel, E.

    1984-01-01

    An iterative algorithm for the Helmholtz equation is presented. This scheme was based on the preconditioned conjugate gradient method for the normal equations. The preconditioning is one cycle of a multigrid method for the discrete Laplacian. The smoothing algorithm is red-black Gauss-Seidel and is constructed so it is a symmetric operator. The total number of iterations needed by the algorithm is independent of h. By varying the number of grids, the number of iterations depends only weakly on k when k(3)h(2) is constant. Comparisons with a SSOR preconditioner are presented.

  2. Parallel preconditioned conjugate gradient algorithm applied to neutron diffusion problem

    International Nuclear Information System (INIS)

    Majumdar, A.; Martin, W.R.

    1992-01-01

    Numerical solution of the neutron diffusion problem requires solving a linear system of equations such as Ax = b, where A is an n x n symmetric positive definite (SPD) matrix; x and b are vectors with n components. The preconditioned conjugate gradient (PCG) algorithm is an efficient iterative method for solving such a linear system of equations. In this paper, the authors describe the implementation of a parallel PCG algorithm on a shared memory machine (BBN TC2000) and on a distributed workstation (IBM RS6000) environment created by the parallel virtual machine parallelization software

  3. A finite element conjugate gradient FFT method for scattering

    Science.gov (United States)

    Collins, Jeffery D.; Ross, Dan; Jin, J.-M.; Chatterjee, A.; Volakis, John L.

    1991-01-01

    Validated results are presented for the new 3D body of revolution finite element boundary integral code. A Fourier series expansion of the vector electric and mangnetic fields is employed to reduce the dimensionality of the system, and the exact boundary condition is employed to terminate the finite element mesh. The mesh termination boundary is chosen such that is leads to convolutional boundary operatores of low O(n) memory demand. Improvements of this code are discussed along with the proposed formulation for a full 3D implementation of the finite element boundary integral method in conjunction with a conjugate gradiant fast Fourier transformation (CGFFT) solution.

  4. Weighted graph based ordering techniques for preconditioned conjugate gradient methods

    Science.gov (United States)

    Clift, Simon S.; Tang, Wei-Pai

    1994-01-01

    We describe the basis of a matrix ordering heuristic for improving the incomplete factorization used in preconditioned conjugate gradient techniques applied to anisotropic PDE's. Several new matrix ordering techniques, derived from well-known algorithms in combinatorial graph theory, which attempt to implement this heuristic, are described. These ordering techniques are tested against a number of matrices arising from linear anisotropic PDE's, and compared with other matrix ordering techniques. A variation of RCM is shown to generally improve the quality of incomplete factorization preconditioners.

  5. Synthesis and study of conjugated polymers containing Di- or Triphenylamine

    Energy Technology Data Exchange (ETDEWEB)

    Sukwattanasinitt, M.

    1996-06-21

    This thesis consists of two separate parts. The first part addresses the synthesis and study of conjugated polymers containing di- or triphenylamine. Two types of polymers: linear polymers and dendrimers, were synthesized. The polymers were characterized by NMR, IR, UV, GPC, TGA and DSC. Electronic and optical properties of the polymers were studied through the conductivity measurements and excitation- emission spectra. the second part of this thesis deals with a reaction of electron-rich acetylenes with TCNE. The discovery of the reaction from charge transfer complex studies and the investigation of this reaction on various electron-rich acetylenes are presented.

  6. Gd(III)-nanodiamond conjugates for MRI contrast enhancement

    Science.gov (United States)

    Manus, Lisa M.; Mastarone, Daniel J.; Waters, Emily A.; Zhang, Xue-Qing; Schultz-Sikma, Elise A.; MacRenaris, Keith W.; Ho, Dean

    2010-01-01

    A Gd(III)-nanodiamond conjugate [Gd(III)-ND] was prepared and characterized, enabling detection of nanodiamonds by MR imaging. The Gd(III)-ND particles significantly reduced the T1 of water protons with a per-Gd(III) relaxivity of 58.82 ± 1.18 mM−1s−1 at 1.5 Tesla (60 MHz). This represents a tenfold increase compared to the monomer Gd(III) complex (r1 = 5.42 ± 0.20 mM−1s−1) and is among the highest per-Gd(III) relaxivities reported. PMID:20038088

  7. Treatment with Cefotaxime Affects Expression of Conjugation Associated Proteins and Conjugation Transfer Frequency of an IncI1 Plasmid in Escherichia coli

    DEFF Research Database (Denmark)

    Møller, Thea S B; Liu, Gang; Boysen, Anders

    2017-01-01

    research suggests that the effect of antibiotic treatment on plasmid conjugation frequencies, and hence the spread of resistance plasmids, may have been overestimated. We addressed the question by quantifying transfer proteins and conjugation frequencies of a blaCTX-M-1 encoding IncI1 resistance plasmid....... The frequency of plasmid conjugation, measured in an antibiotic free environment, increased significantly when the donor was pre-grown in broth containing CTX compared to growth without this drug, regardless of whether blaCTX-M-1 was located on the plasmid or in trans on the chromosome. The results shows...

  8. Prevenção da violência conjugal contra a mulher Prevention of conjugal violence against women

    OpenAIRE

    Mara Aparecida Alves Cabral

    1999-01-01

    Este trabalho visa a realizar uma revisão bibliográfica da literatura médica, psicológica, psiquiátrica e sociológica, concernente ao combate à violência conjugal contra a mulher. Analisa criticamente as medidas preventivas propostas em países com alto índice de desenvolvimento humano, como é o caso do Canadá e da França, tomando por base a aplicabilidade e eficácia dessas medidas. Compara esta aplicação com o que é realizado no Brasil neste momento. Levanta a bibliografia, principalmente des...

  9. Coherent chirped pulse laser network with Mickelson phase conjugator.

    Science.gov (United States)

    Okulov, A Yu

    2014-04-10

    The mechanisms of nonlinear phase-locking of a large fiber amplifier array are analyzed. The preference is given to the most suitable configuration for a coherent coupling of thousands of fundamental spatial mode fiber beams into a single smooth beam ready for chirped pulse compression. It is shown that a Michelson phase-conjugating configuration with double passage through an array of fiber amplifiers has the definite advantage compared to a one-way fiber array coupled in a Mach-Zehnder configuration. Regardless of the amount of synchronized fiber amplifiers, the Michelson phase-conjugating interferometer is expected to do a perfect compensation of the phase-piston errors and collimation of backwardly amplified fiber beams on an entrance/output beam splitter. In both configurations, the nonlinear transformation of the stretched pulse envelope, due to gain saturation, is capable of randomizing the position of chirp inside an envelope; thus it may reduce the visibility of the interference pattern at an output beam splitter. Certain advantages are inherent to the sech-form temporal envelope because of the exponential precursor and self-similar propagation in gain medium. The Gaussian envelope is significantly compressed in a deep gain saturation regime, and the frequency chirp position inside pulse envelope is more deformed.

  10. Conjugate Compressible Fluid Flow and Heat Transfer in Ducts

    Science.gov (United States)

    Cross, M. F.

    2011-01-01

    A computational approach to modeling transient, compressible fluid flow with heat transfer in long, narrow ducts is presented. The primary application of the model is for analyzing fluid flow and heat transfer in solid propellant rocket motor nozzle joints during motor start-up, but the approach is relevant to a wide range of analyses involving rapid pressurization and filling of ducts. Fluid flow is modeled through solution of the spatially one-dimensional, transient Euler equations. Source terms are included in the governing equations to account for the effects of wall friction and heat transfer. The equation solver is fully-implicit, thus providing greater flexibility than an explicit solver. This approach allows for resolution of pressure wave effects on the flow as well as for fast calculation of the steady-state solution when a quasi-steady approach is sufficient. Solution of the one-dimensional Euler equations with source terms significantly reduces computational run times compared to general purpose computational fluid dynamics packages solving the Navier-Stokes equations with resolved boundary layers. In addition, conjugate heat transfer is more readily implemented using the approach described in this paper than with most general purpose computational fluid dynamics packages. The compressible flow code has been integrated with a transient heat transfer solver to analyze heat transfer between the fluid and surrounding structure. Conjugate fluid flow and heat transfer solutions are presented. The author is unaware of any previous work available in the open literature which uses the same approach described in this paper.

  11. Concanavalin A conjugated biodegradable nanoparticles for oral insulin delivery

    Science.gov (United States)

    Hurkat, Pooja; Jain, Aviral; Jain, Ashish; Shilpi, Satish; Gulbake, Arvind; Jain, Sanjay K.

    2012-11-01

    Major research issues in oral protein delivery include the stabilization of protein in delivery devices which could increase its oral bioavailability. The study deals with development of oral insulin delivery system utilizing biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles and modifying its surface with Concanavalin A to increase lymphatic uptake. Surface-modified PLGA nanoparticles were characterized for conjugation efficiency of ligand, shape and surface morphology, particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro drug release. Stability of insulin in the developed formulation was confirmed by SDS-PAGE, and integrity of entrapped insulin was assessed using circular dichroism spectrum. Ex vivo study was performed on Wistar rats, which exhibited the higher intestinal uptake of Con A conjugated nanoparticles. In vivo study performed on streptozotocin-induced diabetic rats which indicate that a surface-modified nanoparticle reduces blood glucose level effectively within 4 h of its oral administration. In conclusion, the present work resulted in successful production of Con A NPs bearing insulin with sustained release profile, and better absorption and stability. The Con A NPs showed high insulin uptake, due to its relative high affinity for non-reducing carbohydrate residues i.e., fucose present on M cells and have the potential for oral insulin delivery in effective management of Type 1 diabetes condition.

  12. Guanidinylated Neomycin Conjugation Enhances Intranasal Enzyme Replacement in the Brain.

    Science.gov (United States)

    Tong, Wenyong; Dwyer, Chrissa A; Thacker, Bryan E; Glass, Charles A; Brown, Jillian R; Hamill, Kristina; Moremen, Kelley W; Sarrazin, Stéphane; Gordts, Philip L S M; Dozier, Lara E; Patrick, Gentry N; Tor, Yitzhak; Esko, Jeffrey D

    2017-12-06

    Iduronidase (IDUA)-deficient mice accumulate glycosaminoglycans in cells and tissues and exhibit many of the same neuropathological symptoms of patients suffering from Mucopolysaccharidosis I. Intravenous enzyme-replacement therapy for Mucopolysaccharidosis I ameliorates glycosaminoglycan storage and many of the somatic aspects of the disease but fails to treat neurological symptoms due to poor transport across the blood-brain barrier. In this study, we examined the delivery of IDUA conjugated to guanidinoneomycin (GNeo), a molecular transporter. GNeo-IDUA and IDUA injected intravenously resulted in reduced hepatic glycosaminoglycan accumulation but had no effect in the brain due to fast clearance from the circulation. In contrast, intranasally administered GNeo-IDUA entered the brain rapidly. Repetitive intranasal treatment with GNeo-IDUA reduced glycosaminoglycan storage, lysosome size and number, and neurodegenerative astrogliosis in the olfactory bulb and primary somatosensory cortex, whereas IDUA was less effective. The enhanced efficacy of GNeo-IDUA was not the result of increased nose-to-brain delivery or enzyme stability, but rather due to more efficient uptake into neurons and astrocytes. GNeo conjugation also enhanced glycosaminoglycan clearance by intranasally delivered sulfamidase to the brain of sulfamidase-deficient mice, a model of Mucopolysaccharidosis IIIA. These findings suggest the general utility of the guanidinoglycoside-based delivery system for restoring missing lysosomal enzymes in the brain. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  13. Effect of disorder on exciton dissociation in conjugated polymers

    International Nuclear Information System (INIS)

    Feng Yuwen; Zhao Hui; Chen Yuguang; Yan Yonghong

    2017-01-01

    By using a multi-configurational time-dependent Hartree–Fock (MCTDHF) method for the time-dependent Schrödinger equation and a Newtonian equation of motion for lattice, we investigate the disorder effects on the dissociation process of excitons in conjugated polymer chains. The simulations are performed within the framework of an extended version of the Su–Schrieffer–Heeger model modified to include on-site disorder, off-diagonal, electron–electron interaction, and an external electric field. Our results show that Coulomb correlation effects play an important role in determining the exciton dissociation process. The electric field required to dissociate an exciton can practically impossibly occur in a pure polymer chain, especially in the case of triplet exciton. However, when the on-site disorder effects are taken into account, this leads to a reduction in mean dissociation electric fields. As the disorder strength increases, the dissociation field decreases effectively. On the contrary, the effects of off-diagonal disorder are negative in most cases. Moreover, the dependence of exciton dissociation on the conjugated length is also discussed. (paper)

  14. Dielectrophoresis of gold nanoparticles conjugated to DNA origami structures

    Directory of Open Access Journals (Sweden)

    Anja Henning-Knechtel

    2016-07-01

    Full Text Available DNA nanostructures are promising construction materials to bridge the gap between self-assembly of functional molecules and conventional top-down fabrication methods in nanotechnology. Their positioning onto specific locations of a microstructured substrate is an important task towards this aim. Here we study manipulation and positioning of pristine and of gold nanoparticle-conjugated tubular DNA origami structures using ac dielectrophoresis. The dielectrophoretic behavior was investigated employing fluorescence microscopy. For the pristine origami, a significant dielectrophoretic response was found to take place in the megahertz range, whereas, due to the higher polarizability of the metallic nanoparticles, the nanoparticle/DNA hybrid structures required a lower electrical field strength and frequency for a comparable trapping at the edges of the electrode structure. The nanoparticle conjugation additionally resulted in a remarkable alteration of the DNA structure arrangement. The growth of linear, chain-like structures in between electrodes at applied frequencies in the megahertz range was observed. The long-range chain formation is caused by a local, gold nanoparticle-induced field concentration along the DNA nanostructures, which in turn, creates dielectrophoretic forces that enable the observed self-alignment of the hybrid structures.

  15. Liposomal Conjugates for Drug Delivery to the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Frieder Helm

    2015-04-01

    Full Text Available Treatments of central nervous system (CNS diseases often fail due to the blood–brain barrier. Circumvention of this obstacle is crucial for any systemic treatment of such diseases to be effective. One approach to transfer drugs into the brain is the use of colloidal carrier systems—amongst others, liposomes. A prerequisite for successful drug delivery by colloidal carriers to the brain is the modification of their surface, making them invisible to the reticuloendothelial system (RES and to target them to specific surface epitopes at the blood–brain barrier. This study characterizes liposomes conjugated with cationized bovine serum albumin (cBSA as transport vectors in vitro in porcine brain capillary endothelial cells (PBCEC and in vivo in rats using fluorescently labelled liposomes. Experiments with PBCEC showed that sterically stabilized (PEGylated liposomes without protein as well as liposomes conjugated to native bovine serum albumin (BSA were not taken up. In contrast, cBSA-liposomes were taken up and appeared to be concentrated in intracellular vesicles. Uptake occurred in a concentration and time dependent manner. Free BSA and free cBSA inhibited uptake. After intravenous application of cBSA-liposomes, confocal fluorescence microscopy of brain cryosections from male Wistar rats showed fluorescence associated with liposomes in brain capillary surrounding tissue after 3, 6 and 24 h, for liposomes with a diameter between 120 and 150 nm, suggesting successful brain delivery of cationized-albumin coupled liposomes.

  16. Genetic engineering and chemical conjugation of potato virus X.

    Science.gov (United States)

    Lee, Karin L; Uhde-Holzem, Kerstin; Fischer, Rainer; Commandeur, Ulrich; Steinmetz, Nicole F

    2014-01-01

    Here we report the genetic engineering and chemical modification of potato virus X (PVX) for the presentation of various peptides, proteins, and fluorescent dyes, or other chemical modifiers. Three different ways of genetic engineering are described and by these means, peptides are successfully expressed not only when the foot and mouth disease virus (FMDV) 2A sequence or a flexible glycine-serine linker is included, but also when the peptide is fused directly to the PVX coat protein. When larger proteins or unfavorable peptide sequences are presented, a partial fusion via the FMDV 2A sequence is preferable. When these PVX chimeras retain the ability to assemble into viral particles and are thus able to infect plants systemically, they can be utilized to inoculate susceptible plants for isolation of sufficient amounts of virus particles for subsequent chemical modification. Chemical modification is required for the display of nonbiological ligands such as fluorophores, polymers, and small drug compounds. We present three methods of chemical bioconjugation. For direct conjugation of small chemical modifiers to solvent exposed lysines, N-hydroxysuccinimide chemistry can be applied. Bio-orthogonal reactions such as copper-catalyzed azide-alkyne cycloaddition or hydrazone ligation are alternatives to achieve more efficient conjugation (e.g., when working with high molecular weight or insoluble ligands). Furthermore, hydrazone ligation offers an attractive route for the introduction of pH-cleavable cargos (e.g., therapeutic molecules).

  17. Smaller Counter Cation for Higher Transconductance in Anionic Conjugated Polyelectrolytes

    KAUST Repository

    Schmidt, Martina M.

    2017-12-11

    Conjugated polyelectrolytes (CPEs) are a focus of research because combine their inherent electrical conductivity and the ability to interact with ions in aqueous solutions or biological systems. However, it is still not understood to what degree the counter ion in CPEs influences the properties of the CPE itself and the performance of electronic transducers. In order to investigate this, three different conjugated polyelectrolytes, poly(6-(thiophen-3-yl)hexane-1-sulfonate)s (PTHS−X+), are synthesized, which have the same polythiophene backbone but different X+ counter ions: the bulky tetrabutylammonium (TBA+), tetraethylammonium (TEA+), and the smallest tetramethylammonium (TMA+). At the interface with biological systems, thin CPE films have to be stable in an aqueous environment and should allow the inward and outward flow of ions from the electrolyte. Since the studied PTHS−X+ have different solubilities in water, the optical properties of pristine PTHS−X+ as well as of crosslinked PTHS−X+ via UV–vis absorption spectroscopy are investigated additionally. PTHS−TMA+ exhibits better aggregation, fast interdiffusion of ions, and fast recovery from the oxidized state. Additionally, spectroelectrochemical and cyclic voltammetric as well as electrochemical capacitance investigations show that PTHS−TMA+ can be oxidized to a higher degree. This leads to a better performance of PTHS−TMA+-based organic electrochemical transistors.

  18. Concanavalin A conjugated biodegradable nanoparticles for oral insulin delivery

    Energy Technology Data Exchange (ETDEWEB)

    Hurkat, Pooja; Jain, Aviral; Jain, Ashish; Shilpi, Satish; Gulbake, Arvind; Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour Vishwavidyalaya, Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

    2012-11-15

    Major research issues in oral protein delivery include the stabilization of protein in delivery devices which could increase its oral bioavailability. The study deals with development of oral insulin delivery system utilizing biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles and modifying its surface with Concanavalin A to increase lymphatic uptake. Surface-modified PLGA nanoparticles were characterized for conjugation efficiency of ligand, shape and surface morphology, particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro drug release. Stability of insulin in the developed formulation was confirmed by SDS-PAGE, and integrity of entrapped insulin was assessed using circular dichroism spectrum. Ex vivo study was performed on Wistar rats, which exhibited the higher intestinal uptake of Con A conjugated nanoparticles. In vivo study performed on streptozotocin-induced diabetic rats which indicate that a surface-modified nanoparticle reduces blood glucose level effectively within 4 h of its oral administration. In conclusion, the present work resulted in successful production of Con A NPs bearing insulin with sustained release profile, and better absorption and stability. The Con A NPs showed high insulin uptake, due to its relative high affinity for non-reducing carbohydrate residues i.e., fucose present on M cells and have the potential for oral insulin delivery in effective management of Type 1 diabetes condition.

  19. Conjugate pair of non-extensive statistics in quantum scattering

    International Nuclear Information System (INIS)

    Ion, D.B.; Ion, M.L.D.

    1999-01-01

    In this paper, by defining the Fourier transform of the scattering amplitudes as a bounded linear mapping from the space L 2p to the space L 2q when 1/(2p)+1/(2q)=1, we introduced a new concept in quantum physics in terms of Tsallis-like entropies S J (p) and S θ (q), namely, that of conjugate pair of non-extensive statistics. This new concept is experimentally illustrated by using 88 + 49 sets of pion-nucleon and pion-nucleus phase shifts. From the experimental determination of the (p,q) - non-extensivity indices by choosing the pairs for which the [χ L 2 (p) + χ θ 2 (q min )] - optimal - test function is minimum we get the conjugate pair of [(p min ,J),(q min , θ)]- non-extensive statistics with 0.50 ≤ p min ≤ 0.60. This new non-extensive statistical effect is experimentally evidenced with high degree of accuracy (CL≥ 99%). Moreover, it is worth to mention that the modification of the statistics has been more efficient than the modification of the PMD-SQS-optimum principle in obtaining the best overall fitting to the experimental data. (authors)

  20. Self-Consistent Study of Conjugated Aromatic Molecular Transistors

    International Nuclear Information System (INIS)

    Jing, Wang; Yun-Ye, Liang; Hao, Chen; Peng, Wang; Note, R.; Mizuseki, H.; Kawazoe, Y.

    2010-01-01

    We study the current through conjugated aromatic molecular transistors modulated by a transverse field. The self-consistent calculation is realized with density function theory through the standard quantum chemistry software Gaussian03 and the non-equilibrium Green's function formalism. The calculated I – V curves controlled by the transverse field present the characteristics of different organic molecular transistors, the transverse field effect of which is improved by the substitutions of nitrogen atoms or fluorine atoms. On the other hand, the asymmetry of molecular configurations to the axis connecting two sulfur atoms is in favor of realizing the transverse field modulation. Suitably designed conjugated aromatic molecular transistors possess different I – V characteristics, some of them are similar to those of metal-oxide-semiconductor field-effect transistors (MOSFET). Some of the calculated molecular devices may work as elements in graphene electronics. Our results present the richness and flexibility of molecular transistors, which describe the colorful prospect of next generation devices. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  1. Material Selection for Microchannel Heatsink: Conjugate Heat Transfer Simulation

    Science.gov (United States)

    Uday Kumar, A.; Javed, Arshad; Dubey, Satish K.

    2018-04-01

    Heat dissipation during the operation of electronic devices causes rise in temperature, which demands an effective thermal management for their performance, life and reliability. Single phase liquid cooling in microchannels is an effective and proven technology for electronics cooling. However, due to the ongoing trends of miniaturization and developments in the microelectronics technology, the future needs of heat flux dissipation rate are expected to rise to 1 kW/cm2. Air cooled systems are unable to meet this demand. Hence, liquid cooled heatsinks are preferred. This paper presents conjugate heat transfer simulation of single phase flow in microchannels with application to electronic cooling. The numerical model is simulated for different materials: copper, aluminium and silicon as solid and water as liquid coolant. The performances of microchannel heatsink are analysed for mass flow rate range of 20-40 ml/min. The investigation has been carried out on same size of electronic chip and heat flux in order to have comparative study of different materials. This paper is divided into two sections: fabrication techniques and numerical simulation for different materials. In the first part, a brief discussion of fabrication techniques of microchannel heatsink have been presented. The second section presents conjugate heat transfer simulation and parametric investigation for different material microchannel heatsink. The presented study and findings are useful for selection of materials for microchannel heatsink.

  2. Fluorescent nanodiamond-bacteriophage conjugates maintain host specificity.

    Science.gov (United States)

    Trinh, Jimmy T; Alkahtani, Masfer H; Rampersaud, Isaac; Rampersaud, Arfaan; Scully, Marlan; Young, Ryland F; Hemmer, Philip; Zeng, Lanying

    2018-06-01

    Rapid identification of specific bacterial strains within clinical, environmental, and food samples can facilitate the prevention and treatment of disease. Fluorescent nanodiamonds (FNDs) are being developed as biomarkers in biology and medicine, due to their excellent imaging properties, ability to accept surface modifications, and lack of toxicity. Bacteriophages, the viruses of bacteria, can have exquisite specificity for certain hosts. We propose to exploit the properties of FNDs and phages to develop phages conjugated with FNDs as long-lived fluorescent diagnostic reagents. In this study, we develop a simple procedure to create such fluorescent probes by functionalizing the FNDs and phages with streptavidin and biotin, respectively. We find that the FND-phage conjugates retain the favorable characteristics of the individual components and can discern their proper host within a mixture. This technology may be further explored using different phage/bacteria systems, different FND color centers and alternate chemical labeling schemes for additional means of bacterial identification and new single-cell/virus studies. © 2018 Wiley Periodicals, Inc.

  3. Assessment of gold nanoparticles as a size-dependent vaccine carrier for enhancing the antibody response against synthetic foot-and-mouth disease virus peptide

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yu-Shiun [Department of Materials Science and Engineering, National Chiao Tung University, 1001 University Road, EE137, Hsinchu 300, Taiwan (China); Hung, Yao-Ching [Department of Obstetrics and Gynecology, School of Medicine, China Medical University and Hospital, 91 Hsueh-Shih Road, Taichung 40402, Taiwan (China); Lin, Wei-Hsu [Institute of Nanotechnology, National Chiao Tung University, 1001 University Road, Hsinchu 300, Taiwan (China); Huang, Guewha Steven, E-mail: gstevehuang@mail.nctu.edu.tw [Department of Materials Science and Engineering, Institute of Nanotechnology, National Chiao Tung University, 1001 University Road, Hsinchu 300, Taiwan, Republic of China (China)

    2010-05-14

    To assess the ability of gold nanoparticles (GNPs) to act as a size-dependent carrier, a synthetic peptide resembling foot-and-mouth disease virus (FMDV) protein was conjugated to GNPs ranging from 2 to 50 nm in diameter (2, 5, 8, 12, 17, 37, and 50 nm). An extra cysteine was added to the C-terminus of the FMDV peptide (pFMDV) to ensure maximal conjugation to the GNPs, which have a high affinity for sulfhydryl groups. The resultant pFMDV-GNP conjugates were then injected into BALB/c mice. Immunization with pFMDV-keyhole limpet hemocyanin (pFMDV-KLH) conjugate was also performed as a control. Blood was obtained from the mice after 4, 6, 8, and 10 weeks and antibody titers against both pFMDV and the carriers were measured. For the pFMDV-GNP immunization, specific antibodies against the synthetic peptide were detected in the sera of mice injected with 2, 5, 8, 12, and 17 nm pFMDV-GNP conjugates. Maximal antibody binding was noted for GNPs of diameter 8-17 nm. The pFMDV-GNPs induced a three-fold increase in the antibody response compared to the response to pFMDV-KLH. However, sera from either immunized mouse group did not exhibit an antibody response to GNPs, while the sera from pFMDV-KLH-immunized mice presented high levels of binding activity against KLH. Additionally, the uptake of pFMDV-GNP in the spleen was examined by inductively coupled plasma mass spectroscopy (ICP-MS) and transmission electron microscopy (TEM). The quantity of GNPs that accumulated in the spleen correlated to the magnitude of the immune response induced by pFMDV-GNP. In conclusion, we demonstrated the size-dependent immunogenic properties of pFMDV-GNP conjugates. Furthermore, we established that GNPs ranging from 8 to 17 nm in diameter may be ideal for eliciting a focused antibody response against a synthetic pFMDV peptide.

  4. Assessment of gold nanoparticles as a size-dependent vaccine carrier for enhancing the antibody response against synthetic foot-and-mouth disease virus peptide

    Science.gov (United States)

    Chen, Yu-Shiun; Hung, Yao-Ching; Lin, Wei-Hsu; Huang, Guewha Steven

    2010-05-01

    To assess the ability of gold nanoparticles (GNPs) to act as a size-dependent carrier, a synthetic peptide resembling foot-and-mouth disease virus (FMDV) protein was conjugated to GNPs ranging from 2 to 50 nm in diameter (2, 5, 8, 12, 17, 37, and 50 nm). An extra cysteine was added to the C-terminus of the FMDV peptide (pFMDV) to ensure maximal conjugation to the GNPs, which have a high affinity for sulfhydryl groups. The resultant pFMDV-GNP conjugates were then injected into BALB/c mice. Immunization with pFMDV-keyhole limpet hemocyanin (pFMDV-KLH) conjugate was also performed as a control. Blood was obtained from the mice after 4, 6, 8, and 10 weeks and antibody titers against both pFMDV and the carriers were measured. For the pFMDV-GNP immunization, specific antibodies against the synthetic peptide were detected in the sera of mice injected with 2, 5, 8, 12, and 17 nm pFMDV-GNP conjugates. Maximal antibody binding was noted for GNPs of diameter 8-17 nm. The pFMDV-GNPs induced a three-fold increase in the antibody response compared to the response to pFMDV-KLH. However, sera from either immunized mouse group did not exhibit an antibody response to GNPs, while the sera from pFMDV-KLH-immunized mice presented high levels of binding activity against KLH. Additionally, the uptake of pFMDV-GNP in the spleen was examined by inductively coupled plasma mass spectroscopy (ICP-MS) and transmission electron microscopy (TEM). The quantity of GNPs that accumulated in the spleen correlated to the magnitude of the immune response induced by pFMDV-GNP. In conclusion, we demonstrated the size-dependent immunogenic properties of pFMDV-GNP conjugates. Furthermore, we established that GNPs ranging from 8 to 17 nm in diameter may be ideal for eliciting a focused antibody response against a synthetic pFMDV peptide.

  5. Assessment of gold nanoparticles as a size-dependent vaccine carrier for enhancing the antibody response against synthetic foot-and-mouth disease virus peptide

    International Nuclear Information System (INIS)

    Chen, Yu-Shiun; Hung, Yao-Ching; Lin, Wei-Hsu; Huang, Guewha Steven

    2010-01-01

    To assess the ability of gold nanoparticles (GNPs) to act as a size-dependent carrier, a synthetic peptide resembling foot-and-mouth disease virus (FMDV) protein was conjugated to GNPs ranging from 2 to 50 nm in diameter (2, 5, 8, 12, 17, 37, and 50 nm). An extra cysteine was added to the C-terminus of the FMDV peptide (pFMDV) to ensure maximal conjugation to the GNPs, which have a high affinity for sulfhydryl groups. The resultant pFMDV-GNP conjugates were then injected into BALB/c mice. Immunization with pFMDV-keyhole limpet hemocyanin (pFMDV-KLH) conjugate was also performed as a control. Blood was obtained from the mice after 4, 6, 8, and 10 weeks and antibody titers against both pFMDV and the carriers were measured. For the pFMDV-GNP immunization, specific antibodies against the synthetic peptide were detected in the sera of mice injected with 2, 5, 8, 12, and 17 nm pFMDV-GNP conjugates. Maximal antibody binding was noted for GNPs of diameter 8-17 nm. The pFMDV-GNPs induced a three-fold increase in the antibody response compared to the response to pFMDV-KLH. However, sera from either immunized mouse group did not exhibit an antibody response to GNPs, while the sera from pFMDV-KLH-immunized mice presented high levels of binding activity against KLH. Additionally, the uptake of pFMDV-GNP in the spleen was examined by inductively coupled plasma mass spectroscopy (ICP-MS) and transmission electron microscopy (TEM). The quantity of GNPs that accumulated in the spleen correlated to the magnitude of the immune response induced by pFMDV-GNP. In conclusion, we demonstrated the size-dependent immunogenic properties of pFMDV-GNP conjugates. Furthermore, we established that GNPs ranging from 8 to 17 nm in diameter may be ideal for eliciting a focused antibody response against a synthetic pFMDV peptide.

  6. Specific bile acid radioimmunoassays for separate determinations of unconjugated cholic acid, conjugated cholic acid and conjugated deoxycholic acid in serum and their clinical application

    International Nuclear Information System (INIS)

    Matern, S.; Gerok, W.

    1977-01-01

    Specific radioimmunoassays for separate determinations of serum unconjugated cholic, conjugated cholic and conjugated deoxycholic acids have been developed. Prior to the radioimmunoassay, extraction of serum bile acids was performed with Amberlite XAD-2. Unconjugated cholic acid was separated from glyco- and taurocholic acids by thin-layer chromatography. At 50% displacement of bound labeled glyco[ 3 H]cholic acid using antiserum obtained after immunization with cholic acid-bovine serum albumin-conjugate the cross-reactivity of taurocholic acid was 100%, cholic acid 80%, glycochenodeoxycholic acid 10%, chenodeoxycholic acid 7%, conjugated deoxycholic acid 3%, and conjugated lithocholic acid 3 H]cholic acid was linear on a logit-log plot from 5 to 80 pmol of unlabeled glycocholic acid. Fasting serum conjugated cholic acid in healthy subjects was 0.68 +- 0.34 μmol/l. Unconjugated cholic acid was determined by a solid phase radioimmunoassay using the cholic acid antibody chemically bound to Sepharose. The displacement curve of [ 3 H]cholic acid in the solid phase radioimmunoassay was linear on a logit-log plot from 5 to 200 pmol of unlabeled cholic acid. The coefficient of variation between samples was 5%. Fasting serum conjugated deoxycholic acid concentrations in 10 healthy subjects ranged from 0.18 to 0.92 μmol/l determined by a radioimmunoassay using antiserum obtained after immunization with deoxycholic acid-bovine serum albumin-conjugate. The clinical application of these bile acid radioimmunoassays is shown by an 'oral cholate tolerance test' as a sensitive indicator of liver function and by an 'oral cholyglycine tolerance test' as a useful test for bile acid absorption. (orig.) [de

  7. Molecules with linear pi-conjugated pathways between all substituents : Omniconjugation

    NARCIS (Netherlands)

    van der Veen, M.H.; Rispens, M.T; Jonkman, H.T.; Hummelen, J.C.

    In this paper, omniconjugation is introduced as a topological phenomenon in pi-conjugated systems. Omniconjugated molecules are defined by the fact that they provide direct and fully pi-conjugated pathways between all subdstituents attached to them. Surprisingly, until now such topologies have never

  8. Molecules with Linear π-Conjugated Pathways between All Substituents : Omniconjugation

    NARCIS (Netherlands)

    Veen, Marleen H. van der; Rispens, Minze T.; Jonkman, Harry T.; Hummelen, Jan C.

    2004-01-01

    In this paper, omniconjugation is introduced as a topological phenomenon in π-conjugated systems. Omniconjugated molecules are defined by the fact that they provide direct and fully π-conjugated pathways between all substituents attached to them. Surprisingly, until now such topologies have never

  9. Fiber nonlinearity compensation of an 8-channel WDM PDM-QPSK signal using multiple phase conjugations

    DEFF Research Database (Denmark)

    Hu, Hao; Jopson, R. M.; Dinu, M.

    2013-01-01

    We demonstrate compensation of fiber nonlinearities using optical phase conjugation of an 8-chamiel WDM 32-Gbaud PDM QPSK signal. Conjugating phase every 600 km in a fiber loop enabled a 6000 km transmission over True Wave fiber. © 2013 Optical Society of America....

  10. Substituted Polyacetylenes Prepared with Rh Catalysts: From Linear to Network-Type Conjugated Polymers

    Czech Academy of Sciences Publication Activity Database

    Sedláček, J.; Balcar, Hynek

    2017-01-01

    Roč. 57, č. 1 (2017), s. 31-51 ISSN 1558-3724 Institutional support: RVO:61388955 Keywords : conjugated polymers * polyacetylenes * conjugated polymer networks Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Polymer science Impact factor: 6.459, year: 2016

  11. Mutagenicity and cytotoxicity of two regioisomeric mercapturic acids and cysteine S-conjugates of trichloroethylene.

    NARCIS (Netherlands)

    Commandeur, J.N.M.; Boogaard, P.J.; Mulder, G.J.; Vermeulen, N.P.E.

    1991-01-01

    The mutagenicity, cytotoxicity and metabolism of two regioisomic l-cysteine- and N-acetyl-l-cysteine-S-conjugates of trichloroethylene were studied. The 1,2-dichlorovinyl(1,2-DCV) isomers of both the cysteine conjugate and the mercapturate were much stronger mutagens in the Ames test with Salmonella

  12. Pump induced normal mode splittings in phase conjugation in a Kerr ...

    Indian Academy of Sciences (India)

    Abstract. Phase conjugation in a Kerr nonlinear waveguide is studied with counter-propagating normally incident pumps and a probe beam at an arbitrary angle of incidence. Detailed numerical results for the specular and phase conjugated reflectivities are obtained with full account of pump depletion. For sufficient ...

  13. Immunological characterization of conjugated Haemophilus influenzae type b vaccine failure in infants

    NARCIS (Netherlands)

    Breukels, M. A.; Spanjaard, L.; Sanders, L. A.; Rijkers, G. T.

    2001-01-01

    Infant vaccination with conjugated Haemophilus influenzae type b (Hib) vaccine is highly effective in protecting against invasive Hib infections, but vaccine failures do occur. Twenty-one vaccine failures are reported since the introduction of the Hib conjugate vaccine in The Netherlands. Of the 14

  14. Conjugal plasmid transfer (pAM beta 1) in Lactobacillus plantarum.

    OpenAIRE

    Shrago, A W; Chassy, B M; Dobrogosz, W J

    1986-01-01

    The streptococcal plasmid pAM beta 1 (erythromycin resistance) was transferred via conjugation from Streptococcus faecalis to Lactobacillus plantarum and was transferred among L. plantarum strains. Streptococcus sanguis Challis was transformed with pAM beta 1 isolated from these transconjugants, and transformants harboring intact pAM beta 1 could conjugate the plasmid back to L. plantarum.

  15. A Scanning Hologram Recorded by Phase Conjugate Property of Nonlinear Crystals

    DEFF Research Database (Denmark)

    Zi-Liang, Ping; Dalsgaard, Erik

    1996-01-01

    A methode of recording a scanning hologram with phase conjugate property of nonlinear crystal is provided. The principle of recording, setup and experiments are given.......A methode of recording a scanning hologram with phase conjugate property of nonlinear crystal is provided. The principle of recording, setup and experiments are given....

  16. Improvement of Emulsifying Properties of Wheat Gluten Hydrolysate λ-Carrageenan Conjugates

    Directory of Open Access Journals (Sweden)

    Jin-Shui Wang

    2006-01-01

    Full Text Available Gluten hydrolysate was prepared through limited enzymatic hydrolysis of wheat gluten resulting from the byproducts of wheat starch. The enzyme applied in the present study was Protamex. Response surface methodology was used to investigate the effects of pH, gluten hydrolysate (GHPλ-carrageenan (C ratio and reaction time on emulsifying properties of the GHP-C conjugate. The regression model for emulsion activity index (EAI was significant at p=0.001, while reaction time had a significant effect on EAI of the conjugate with regression coefficient of 4.25. The interactions of pH and GHP/ C ratio, and GHP/C ratio and reaction time significantly affected the EAI of the conjugate. Both the emulsifying property and nitrogen solubility index (NSI of GHP-C conjugate prepared under the optimal conditions increased more remarkably, compared to the control. The denaturation temperature of GHP-C conjugate obviously increased compared to wheat gluten. The addition of GHP-C conjugate had different effects on dough characteristics. Moreover, this conjugate can delay the increase in the bread crumb firmness during storage. It demonstrated that this conjugate couldimprove the dough characteristics and had anti-staling properties of bread.

  17. Characterization of fus1 of Schizosaccharomyces pombe: a developmentally controlled function needed for conjugation

    DEFF Research Database (Denmark)

    Petersen, J; Weilguny, D; Egel, R

    1995-01-01

    In Schizosaccharomyces pombe, the fus1 mutation blocks conjugation at a point after cell contact and agglutination. The cell walls separating the mating partners are not degraded, which prevents cytoplasmic fusion. In order to investigate the molecular mechanism of conjugation, we cloned the fus1...

  18. HYDROGELS BASED ON POLYMERS OF DEXTRAN TYRAMINE AND TYRAMINE CONJUGATES OF NATURAL POLYMERS

    NARCIS (Netherlands)

    Feijen, Jan; Karperien, Marcel; Jin, R.; Moreira Teixeira, Liliana; Dijkstra, Pieter J.

    2012-01-01

    The invention relates to composition comprising a dextran-tyramine conjugate and a conjugate selected from the group consisting of chondroitin sulphate-tyramine, collagen-tyramine, chitosan-tyramine, chitosan-phloretic acid, gelatine-tyramine, heparan sulphate-tyramine, keratin sulphate-tyramine,

  19. Functional properties of nisin–carbohydrate conjugates formed by radiation induced Maillard reaction

    International Nuclear Information System (INIS)

    Muppalla, Shobita R.; Sonavale, Rahul; Chawla, Surinder P.; Sharma, Arun

    2012-01-01

    Nisin–carbohydrate conjugates were prepared by irradiating nisin either with glucose or dextran. Increase in browning and formation of intermediate products was observed with a concomitant decrease in free amino and reducing sugar groups indicating occurrence of the Maillard reaction catalyzed by irradiation. Nisin–carbohydrate conjugates showed a broad spectrum antibacterial activity against Gram negative bacteria (Escherichia coli, Pseudomonas fluorescence) as well as Gram positive bacteria (Staphylococcus aureus, Bacillus cereus). Results of antioxidant assays, including that of DPPH radical-scavenging activity and reducing power, showed that the nisin–dextran conjugates possessed better antioxidant potential than nisin–glucose conjugate. These results suggested that it was possible to enhance the functional properties of nisin by preparing radiation induced conjugates suitable for application in food industry. - Highlights: ► Nisin–carbohydrate conjugates were prepared using radiation induced Maillard reaction. ► Conjugation of nisin with dextran/glucose resulted in improvement of antibacterial spectrum. ► Conjugates of nisin with dextran/glucose had significant radical scavenging activity.

  20. HYDROGELS BASED ON POLYMERS OF DEXTRAN TYRAMINE AND TYRAMINE CONJUGATES OF NATURAL POLYMERS

    NARCIS (Netherlands)

    Karperien, H.B.J.; Jin, R.; Moreira Teixeira, Liliana; Feijen, Jan; Dijkstra, Pieter J.

    2011-01-01

    The invention relates to composition comprising a dextran-tyramine conjugate and a conjugate selected from the group consisting of chondroitin sulphate-tyramine, collagen-tyramine, chitosan-tyramine, chitosan-phloretic acid, gelatine-tyramine, heparan sulphate-tyramine, keratin sulphate tyramine,