Sample records for bap-diphtheria toxoid conjugate

  1. Antibody response to Haemophilus influenzae type b capsular polysaccharide conjugated to tetanus toxoid in preterm infants

    DEFF Research Database (Denmark)

    Kristensen, Kim; Gyhrs, A; Lausen, B;


    OBJECTIVE: To evaluate the antibody response to a Haemophilus influenzae type b capsular polysaccharide (HibCP) tetanus toxoid (TT) conjugate vaccine (HibCP-TT) in preterm infants. SUBJECTS: Thirty-five healthy preterm infants with gestational ages (GA) from 27 to 36 weeks and birth weights from...

  2. Preparation and immunochemical characterization of meningococcal group C polysaccharide-tetanus toxoid conjugates as a new generation of vaccines.


    Beuvery, E.C.; Miedema, F; Van Delft, R.; Haverkamp, J.


    Neisseria meningitidis group C polysaccharide-tetanus toxoid conjugates have been prepared by using high-molecular-weight polysaccharide and purified tetanus toxoid and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide as a coupling reagent. The influence of three conditions of preparation was studied. Biochemical assays, the enzyme-linked immunosorbent assay, and isopycnic CsCl gradient ultracentrifugation have been used to characterize the conjugates. The polysaccharide-to-protein ratios of th...

  3. Structural correlates of carrier protein recognition in tetanus toxoid-conjugated bacterial polysaccharide vaccines. (United States)

    Lockyer, Kay; Gao, Fang; Derrick, Jeremy P; Bolgiano, Barbara


    An analysis of structure-antibody recognition relationships in nine licenced polysaccharide-tetanus toxoid (TT) conjugate vaccines was performed. The panel of conjugates used included vaccine components to protect against disease caused by Haemophilus influenzae type b, Neisseria meningitidis groups A, C, W and Y and Streptococcus pneumoniae serotype 18C. Conformation and structural analysis included size exclusion chromatography with multi-angle light scattering to determine size, and intrinsic fluorescence spectroscopy and fluorescence quenching to evaluate the protein folding and exposure of Trp residues. A capture ELISA measured the recognition of TT epitopes in the conjugates, using four rat monoclonal antibodies: 2 localised to the HC domain, and 2 of which were holotoxoid conformation-dependent. The conjugates had a wide range of average molecular masses ranging from 1.8×10(6) g/mol to larger than 20×10(6) g/mol. The panel of conjugates were found to be well folded, and did not have spectral features typical of aggregated TT. A partial correlation was found between molecular mass and epitope recognition. Recognition of the epitopes either on the HC domain or the whole toxoid was not necessarily hampered by the size of the molecule. Correlation was also found between the accessibility of Trp side chains and polysaccharide loading, suggesting also that a higher level of conjugated PS does not necessarily interfere with toxoid accessibility. There were different levels of carrier protein Trp side-chain and epitope accessibility that were localised to the HC domain; these were related to the saccharide type, despite the conjugates being independently manufactured. These findings extend our understanding of the molecular basis for carrier protein recognition in TT conjugate vaccines.

  4. Meningococcal vaccine A,C,W135,Y: conjugated to tetanus toxoid. (United States)


    A meningococcal vaccine conjugated to protein CRM 197 (Menveo) is the standard vaccine for immunisation against invasive meningococcal infections caused by serogroups A, C, W135 andY, beginning at age 2 years. Nimenrix, another vaccine against meningococcal groups A, C,W135 and Y, conjugated to tetanus toxoid, was authorised for use in the European Union, starting at age 1 year. The two tetravalent meningococcal conjugate vaccines have not been compared in head-to-head trials. Four immunogenicity studies compared the tetravalent conjugate vaccine Nimenrix with an unconjugated tetravalent meningococcal vaccine in children and adults aged 2 to 55 years. The results showed that Nimenrix was more immunogenic than the unconjugated vaccine. Two immunogenicity studies showed that Nimenrix was at least as immunogenic as monovalent (group C) meningococcal conjugate vaccines in children aged from 1 to 2 years and from 2 to 10 years. In one study, prior vaccination with an unconjugated tetravalent meningococcal vaccine had little impact on the immunogenicity of a booster dose of the conjugate vaccine Nimenrix. Concomitant administration with other vaccines does not affect the immunogenicity of Nimenrix. Nimenrix causes more frequent local and systemic adverse reactions than the unconjugated tetravalent meningococcal vaccine and monovalent group C meningococcal conjugate vaccines. In children over 2 years of age, Nimenrix has no advantages over Menveo for vaccination against meningococcal serogroups A, C, W135 andY. In contrast, between the ages of 1 and 2 years, Nimenrix is the only vaccine with established immunogenicity. In addition, it has an acceptable harm-benefit balance.

  5. Experimental design to optimize an Haemophilus influenzae type b conjugate vaccine made with hydrazide-derivatized tetanus toxoid. (United States)

    Laferriere, Craig; Ravenscroft, Neil; Wilson, Seanette; Combrink, Jill; Gordon, Lizelle; Petre, Jean


    The introduction of type b Haemophilus influenzae conjugate vaccines into routine vaccination schedules has significantly reduced the burden of this disease; however, widespread use in developing countries is constrained by vaccine costs, and there is a need for a simple and high-yielding manufacturing process. The vaccine is composed of purified capsular polysaccharide conjugated to an immunogenic carrier protein. To improve the yield and rate of the reductive amination conjugation reaction used to make this vaccine, some of the carboxyl groups of the carrier protein, tetanus toxoid, were modified to hydrazides, which are more reactive than the ε -amine of lysine. Other reaction parameters, including the ratio of the reactants, the size of the polysaccharide, the temperature and the salt concentration, were also investigated. Experimental design was used to minimize the number of experiments required to optimize all these parameters to obtain conjugate in high yield with target characteristics. It was found that increasing the reactant ratio and decreasing the size of the polysaccharide increased the polysaccharide:protein mass ratio in the product. Temperature and salt concentration did not improve this ratio. These results are consistent with a diffusion controlled rate limiting step in the conjugation reaction. Excessive modification of tetanus toxoid with hydrazide was correlated with reduced yield and lower free polysaccharide. This was attributed to a greater tendency for precipitation, possibly due to changes in the isoelectric point. Experimental design and multiple regression helped identify key parameters to control and thereby optimize this conjugation reaction.

  6. Long-term thermal stability of group C meningococcal polysaccharide-tetanus toxoid conjugate vaccine. (United States)

    Lee, Shwu-Maan; Petermann, Robert; Porte, Quallyna; Berezuk, Greg; Crowe, Brian; Shirtz, John


    The stability of vaccines during storage and handling is a prerequisite for optimal potency at the time of immunization. Meningococcal group C conjugate vaccines have been successfully incorporated in mass immunization programs, however, thus far no long-term real-time stability studies of these vaccines have been reported. Stability of de-O-acetylated group C meningococcal polysaccharide coupled to tetanus toxoid (GCMP-TT) was evaluated in real time on the basis of immunogenicity and physiochemical properties. The vaccine is formulated as a 0.5 mL suspension containing 10 mug GCMP conjugated to 10-20 mug of TT adsorbed on 0.5 mg aluminum in saline. The single dose syringes were stored under refrigeration (5 +/- 3 degrees C) and at room temperature (25 +/- 2 degrees C) for up to 42 months and at elevated temperature (40 +/- 2 degrees C) for up to 6 months. At both refrigerated and room temperatures, no time-dependent change in animal potency was detectable through 42 months. After the nine months maximum recommended storage period at room temperature, 96% of the baseline serum bactericidal antibody (SBA) titer was maintained. Time-dependent decreases in SBA level and anti-GCMP-TT IgG level were observed at 40 +/- 2 degrees C. No changes in GCMP-TT adsorption and pH occurred in all the studies. Loss of integrity increased over six months at 40 +/- 2 degrees C (p = 0.004). Free sugar content did not change over 36 months under refrigeration. GCMP-TT retained immunogenicity and physicochemical properties under refrigeration and at room temperature (25 +/- 2 degrees C) for up to 42 months.

  7. Preparation and evaluation of immunogenic conjugates of Salmonella enterica serovar Typhi O-specific polysaccharides with diphtheria toxoid. (United States)

    Ali, Aamir; An, So Jung; Cui, Changfa; Haque, Abdul; Carbis, Rodney


    Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a major health problem particularly in developing countries. The available vaccines have certain limitations regarding their efficacy, and inability to induce an immune response especially in individuals under 2 years of age. Conjugate vaccines which consist of a bacteria-specific polysaccharide chemically bound to a carrier protein overcome these problems by inducing a T-cell dependent immune response characterized by enhanced immunogenicity in all ages. In this study, O-specific polysaccharides (OSP) of S. Typhi were conjugated to diphtheria toxoid (DT) using adipic acid dihydrazide (ADH) as a linker. These conjugates (OSP-AH-DT) were then evaluated for their immunogenicity using mice as a model and showed significantly higher levels of IgG ELISA titers (P = 0.0241 and 0.0245) than lipopolysaccharides alone. Different immunization  schedules were compared and it was found that schedule-B (three injections with 4-weeks interval) induced higher immune responses than schedule-A (three injections with 2-weeks interval). We showed that diphtheria toxoid can be successfully employed as a carrier protein for conjugation with Salmonella OSP and play an important role in facilitating adequate immune response.

  8. Meningococcal quadrivalent (serogroups A, C, W135 and Y) tetanus toxoid conjugate vaccine (Nimenrix™). (United States)

    Croxtall, Jamie D; Dhillon, Sohita


    Nimenrix™ (MenACWY-TT) is a quadrivalent meningococcal conjugate vaccine, comprising the polysaccharide serogroups A, C, W135 and Y, and tetanus toxoid (TT) as carrier protein. It is the first quadrivalent vaccine (administered as a single dose) to be approved in Europe for active immunization of individuals aged ≥ 12 months against invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W135 and Y. Administration of a single dose of Nimenrix™ elicited a strong immune response against all four vaccine serogroups in healthy toddlers aged 12-23 months, children and adolescents aged 2-17 years and adults aged 18-55 years in randomized, multicentre, phase III trials. In toddlers, Nimenrix™ was noninferior to Meningitec® in terms of seroresponse rates against meningococcal serogroup C 42 days post-vaccination. In children, adolescents and adults, Nimenrix™ was noninferior to Mencevax™ in terms of vaccination response rates against all four serogroups 1 month post-vaccination. Furthermore, several phase II studies and a phase III trial showed that the immune response elicited by Nimenrix™ in all age groups persisted for 7-42 months after the primary vaccination (when evaluated by rabbit serum bactericidal activity), with the vaccine also inducing immune memory in toddlers. In addition, several randomized, multicentre, phase III, noninferiority trials showed that when coadministered with other childhood vaccines or a seasonal flu vaccine, the immunogenicity of Nimenrix™ or that of the coadministered vaccine was generally not altered. Nimenrix® was generally well tolerated in all age groups whether administered as a single vaccine or coadministered with other routine vaccines. The incidence of grade 3 local or systemic solicited adverse events during the first 4 days following vaccination and of serious adverse events over an extended follow-up period of up to 6 months was low (<4.5%). Although protective effectiveness and longer

  9. Synthesis of antifungal vaccines by conjugation of β-1,2 trimannosides with T-cell peptides and covalent anchoring of neoglycopeptide to tetanus toxoid. (United States)

    Cartmell, Jonathan; Paszkiewicz, Eugenia; Dziadek, Sebastian; Tam, Pui-Hang; Luu, Thanh; Sarkar, Susmita; Lipinski, Tomasz; Bundle, David R


    Selective strategies for the construction of novel three component glycoconjugate vaccines presenting Candida albicans cell wall glycan (β-1,2 mannoside) and polypeptide fragments on a tetanus toxoid carrier are described. The first of two conjugation strategies employed peptides bearing an N-terminal thiopropionyl residue for conjugation to a trisaccharide equipped with an acrylate linker and a C-terminal S-acetyl thioglycolyl moiety for subsequent linking of neoglycopeptide to bromoacetylated tetanus toxoid. Michael addition of acrylate trisaccharides to peptide thiol under mildly basic conditions gave a mixture of N- and C- terminal glyco-peptide thioethers. An adaptation of this strategy coordinated S-acyl protection with anticipated thioester exchange equilibria. This furnished a single chemically defined fully synthetic neoglycopeptide conjugate that could be anchored to a tetanus toxoid carrier and avoids the introduction of exogenous antigenic groups. The second strategy retained the N-terminal thiopropionyl residue but replaced the C-terminal S-acetate functionality with an azido group that allowed efficient, selective formation of neoglycopeptide thioethers and subsequent conjugation of these with propargylated tetanus toxoid, but introduced potentially antigenic triazole linkages.

  10. Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine for infants and toddlers. (United States)

    Bryant, Kristina A; Marshall, Gary S


    The highest rates of invasive meningococcal disease occur in children under 2 years of age, yet as of early 2011 no vaccine was licensed for the youngest infants. However, a novel vaccine consisting of capsular polysaccharides from Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroups C and Y conjugated to tetanus toxoid (HibMenCY-TT; MenHibrix, GlaxoSmithKline) is in the late stages of development. In clinical trials involving more than 7800 children, HibMenCY-TT was shown to be safe and immunogenic when administered at 2, 4, 6 and 12-15 months of age. Anti-polyribosylribitol phosphate antibody responses were noninferior to those elicited by licensed monovalent Hib vaccines, and most vaccinees developed bactericidal antibodies against N. meningitidis serogroups C and Y. The majority of subjects retained antibody responses as far as 3 years after vaccination. If licensed, HibMenCY-TT not only represents an incremental option for protection against invasive Hib, but also has the potential to prevent invasive meningococcal disease without increasing the number of injections.

  11. Enhanced immunogenicity of a tricomponent mannan tetanus toxoid conjugate vaccine targeted to dendritic cells via Dectin-1 by incorporating β-glucan. (United States)

    Lipinski, Tomasz; Fitieh, Amira; St Pierre, Joëlle; Ostergaard, Hanne L; Bundle, David R; Touret, Nicolas


    In a previous attempt to generate a protective vaccine against Candida albicans, a β-mannan tetanus toxoid conjugate showed poor immunogenicity in mice. To improve the specific activation toward the fungal pathogen, we aimed to target Dectin-1, a pattern-recognition receptor expressed on monocytes, macrophages, and dendritic cells. Laminarin, a β-glucan ligand of Dectin-1, was incorporated into the original β-mannan tetanus toxoid conjugate providing a tricomponent conjugate vaccine. A macrophage cell line expressing Dectin-1 was employed to show binding and activation of Dectin-1 signal transduction pathway by the β-glucan-containing vaccine. Ligand binding to Dectin-1 resulted in the following: 1) activation of Src family kinases and Syk revealed by their recruitment and phosphorylation in the vicinity of bound conjugate and 2) translocation of NF-κB to the nucleus. Treatment of immature bone marrow-derived dendritic cells (BMDCs) with tricomponent or control vaccine confirmed that the β-glucan-containing vaccine exerted its enhanced activity by virtue of dendritic cell targeting and uptake. Immature primary cells stimulated by the tricomponent vaccine, but not the β-mannan tetanus toxoid vaccine, showed activation of BMDCs. Moreover, treated BMDCs secreted increased levels of several cytokines, including TGF-β and IL-6, which are known activators of Th17 cells. Immunization of mice with the novel type of vaccine resulted in improved immune response manifested by high titers of Ab recognizing C. albicans β-mannan Ag. Vaccine containing laminarin also affected distribution of IgG subclasses, showing that vaccine targeting to Dectin-1 receptor can benefit from augmentation and immunomodulation of the immune response.

  12. Experimental vaccination of pigs with an Actinobacillus pleuropneumoniae serotype 5b capsular polysaccharide tetanus toxoid conjugate

    DEFF Research Database (Denmark)

    Andresen, Lars Ole; Jacobsen, M.J.; Nielsen, J.P.


    ) and 8 pigs were vaccinated with Ap5bCP-TT and adjuvant (group 0). Pigs vaccinated with Ap5bCP-TT developed antibody responses to the capsular polysaccharide from A. pleuropneumoniae serotype 5b (Ap5bCP). After challenge, all pigs in groups A and B had severe clinical signs of disease and were euthanized......The protective efficacy of an Actinobacillus pleuropneumoniae serotype 5b capsular polysaccharide-tetanus toroid conjugate (Ap5bCP-TT) against homologous challenge of pigs was investigated. Four pigs were non-vaccinated controls (group A), 4 pigs were injected with adjuvant without antigen (group B...... vaccinated with Ap5bCP-TT had statistically significant reduced values of the mass ratio of affected to unaffected lung tissue compared to pigs in groups A and B (p = 0.01 and p = 0.007, respectively). The results showed that Ap5bCP-TT-vaccination had considerable protective efficacy against lethality...

  13. Meningococcal groups C and Y and haemophilus B tetanus toxoid conjugate vaccine (HibMenCY-TT; MenHibrix(®)): a review. (United States)

    Perry, Caroline M


    The meningococcal groups C and Y and Haemophilus b (Hib) tetanus toxoid conjugate vaccine (HibMenCY-TT) contains Neisseria meningitidis serogroup C and Y capsular polysaccharide antigens, and Hib capsular polysaccharide [polyribosyl-ribitol-phosphate (PRP)]. The HibMenCY-TT vaccine is available in the USA for use as active immunization to prevent invasive disease caused by N. meningitidis serogroups C (MenC) and Y (MenY), and Hib in children 6 weeks-18 months of age. HibMenCY-TT is the first meningococcal vaccine available for use in the USA that can be administered to infants as young as 6 weeks of age. In a randomized, controlled, phase III clinical trial, the HibMenCY-TT vaccine, administered to infants at 2, 4, 6 and 12-15 months of age, was immunogenic against MenC and MenY, and met the prespecified criteria for immunogenicity. Anti-PRP antibodies, which have been shown to correlate with protection against Hib invasive disease, were also induced in the infants who received the HibMenCY-TT vaccine, with induced levels of this antibody noninferior to those occurring in the control group of infants who received a Hib tetanus toxoid conjugate vaccine at 2, 4, and 6 months and a single dose of Hib conjugated to N. meningitidis outer membrane protein at 12-15 months. In several randomized, controlled clinical trials, HibMenCY-TT was coadministered with vaccines that are routinely administered to infants and toddlers in the USA. These vaccines included: diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus vaccine combined; 7-valent Streptococcus pneumoniae polysaccharide conjugate vaccine; measles, mumps and rubella vaccine; and varicella vaccine. Coadministration of these vaccines did not interfere with the immunogenicity of the HibMenCY-TT vaccine. Similarly, immune responses to the coadministered vaccines were not affected by the HibMenCY-TT vaccine. The tolerability profile of the Hib

  14. Protective Effect of Vitamin D3 and Gp63 Conjugated with Tetanus Toxoid on Outcome of Cutaneous Leishmaniasis Lesions in Balb/C Mice

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    S Soudi


    Full Text Available Introduction: GP63 is a major surface protease of Leishmania promastigotes that plays an important role in its virulance. As GP63 on its own can not develop an effective protection against leishmaniasis, the goal of this study was to evaluate the protective effect of GP63 conjugated with tetanus toxoid (TT and Vitamin D3 in susceptible BALB/c mice against cutaneous leishmaniasis. Methods: This study was a basic-applied experimental study performed in Tarbiat Modarres University from September 2002 to April 2005. Cloned virulant Leishmania (L. major [MRHO / IR / 75 / ER] strain was cultured and 5109 cells were harvested. GP63 Molecule was purified and conjugated with TT and conjugated molecule was used for immunization of 8 groups of female BALB/c mice. Results: Results showed that the group of mice receiving conjugated molecule with Vitamin D3 had significant differences from other groups regarding lesion progression (P0.05. The culture of spleen cells showed that the disease did not become systemic in this group. Conclusion: Conjugation of GP63 with TT strengthens cell immunity and its use along with vitamin D3 provokes macrophages activity. This basis can be used for production of an appropriate preparation for protection against Leishmaniasis.

  15. Immunogenicity of meningococcal quadrivalent (serogroup A, C, W135 and Y) tetanus toxoid conjugate vaccine: systematic review and meta-analysis. (United States)

    Pellegrino, Paolo; Perrone, Valentina; Radice, Sonia; Capuano, Annalisa; Clementi, Emilio


    Meningococcal meningitis represents one of the leading cause of bacterial meningitis in developed countries. Among the thirteen described serogroups, only five are usually responsible of invasive infections making immunisation against multiple serogroups the best strategy to protect individuals from this disease. Herein we carried out a systematic review and meta-analysis, in accordance with the PRISMA statement, of the recently EU-licensed meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT). We included 15 randomised clinical trials, comparing MenACWY-TT and Men-PS (ten studies), MenACWY-TT and MenC-CRM197 (four studies) and MenACWY-TT and MenACWY-DT (one study). All studies included in the meta-analysis showed high immunogenicity for MenACWY-TT vaccines in all tested serogroups. Our results suggest that the MenACWY-TT vaccine is as immunogenic as the other commercial available meningococcal vaccines.

  16. Efficacy, but not antibody titer or affinity, of a heroin hapten conjugate vaccine correlates with increasing hapten densities on tetanus toxoid, but not on CRM197 carriers. (United States)

    Jalah, Rashmi; Torres, Oscar B; Mayorov, Alexander V; Li, Fuying; Antoline, Joshua F G; Jacobson, Arthur E; Rice, Kenner C; Deschamps, Jeffrey R; Beck, Zoltan; Alving, Carl R; Matyas, Gary R


    Vaccines against drugs of abuse have induced antibodies in animals that blocked the biological effects of the drug by sequestering the drug in the blood and preventing it from crossing the blood-brain barrier. Drugs of abuse are too small to induce antibodies and, therefore, require conjugation of drug hapten analogs to a carrier protein. The efficacy of these conjugate vaccines depends on several factors including hapten design, coupling strategy, hapten density, carrier protein selection, and vaccine adjuvant. Previously, we have shown that 1 (MorHap), a heroin/morphine hapten, conjugated to tetanus toxoid (TT) and mixed with liposomes containing monophosphoryl lipid A [L(MPLA)] as adjuvant, partially blocked the antinociceptive effects of heroin in mice. Herein, we extended those findings, demonstrating greatly improved vaccine induced antinociceptive effects up to 3% mean maximal potential effect (%MPE). This was obtained by evaluating the effects of vaccine efficacy of hapten 1 vaccine conjugates with varying hapten densities using two different commonly used carrier proteins, TT and cross-reactive material 197 (CRM197). Immunization of mice with these conjugates mixed with L(MPLA) induced very high anti-1 IgG peak levels of 400-1500 μg/mL that bound to both heroin and its metabolites, 6-acetylmorphine and morphine. Except for the lowest hapten density for each carrier, the antibody titers and affinity were independent of hapten density. The TT carrier based vaccines induced long-lived inhibition of heroin-induced antinociception that correlated with increasing hapten density. The best formulation contained TT with the highest hapten density of ≥30 haptens/TT molecule and induced %MPE of approximately 3% after heroin challenge. In contrast, the best formulation using CRM197 was with intermediate 1 densities (10-15 haptens/CRM197 molecule), but the %MPE was approximately 13%. In addition, the chemical synthesis of 1, the optimization of the conjugation

  17. Effects of early vaccination with a gonadotropin releasing factor analog-diphtheria toxoid conjugate on boar taint and growth performance of male pigs. (United States)

    Kantas, D; Papatsiros, V; Tassis, P; Tzika, E; Pearce, M C; Wilson, S


    The aim of this study was to evaluate safety (in terms of detecting possible adverse clinical effects attributable to vaccination), efficacy, and effects on growth performance of a gonadotropin releasing factor analog-diphtheria toxoid conjugate (commercially distributed as Improvac; Zoetis, Zaventem, Belgium) in male pigs raised in a commercial Greek farm. A total of 1,230 male pigs was enrolled in 16 weekly batches and allocated to 3 groups: barrows (castrated on the next day after birth [study Day 0]), pigs vaccinated with the above-mentioned product, and intact boars. Vaccinated pigs were injected subcutaneously with 2 mL of the anti-gonadotropin releasing factor (GnRF) vaccine at 9 to 11 wk of age (60-78 d) and 15 to 17 wk of age (102-120 d) and slaughtered at 22 to 25 wk of age (152-176 d). No clinical abnormalities or adverse events attributable to vaccination occurred. Mean BW of vaccinated pigs was 6% greater compared with barrows at slaughter (P vaccinated pigs had greater ADG than barrows from castration to slaughter (8%). In detail, a lower ADG from first to second vaccination (-12%; P vaccination to slaughter (P vaccinated pigs and intact boars was not significantly different throughout the study, except from first to second vaccination (boars greater; P = 0.0059) and second vaccination to slaughter (vaccinates greater; P = 0.0390). Feed conversion ratio of barrows was 11 and 8% greater compared with vaccinated pigs (P = 0.0005) and boars (P = 0.0062) from first to second vaccination but was 23 to 26% lower compared with vaccinated pigs (P vaccination to slaughter and 7 to 9.5% lower from the second vaccination to slaughter (P = 0.0029 and P = 0.0003 for vaccinates and intact boars, respectively). At slaughter, the belly fat androstenone concentration of all vaccinated pigs and 64% of intact boars was below 200 ng/g. Belly fat skatole concentration was below 20 ng/g in samples from all groups. In conclusion, vaccination against GnRF using the Gn

  18. Generation of polyclonal catalytic antibodies against cocaine using transition state analogs of cocaine conjugated to diphtheria toxoid. (United States)

    Basmadjian, G P; Singh, S; Sastrodjojo, B; Smith, B T; Avor, K S; Chang, F; Mills, S L; Seale, T W


    Six novel transition state analogs (TSAs) of cocaine (10-14 and 17) and one non-cocaine, p-aminophenylphosphonyl ester of cyclohexanol (19), were synthesized and characterized by 1H- and 13C-NMR and FAB-MS. (1R)-ecgonine methyl ester or cyclohexanol were subjected to phenylphosphonylation in the presence of dicyclohexyl carbodiimde (DCC) and 4-N,N-dimethyl aminopyridine (4-DMAP). TSA-IV (10), however, was synthesized from norcocaine which was protected with dibromoethane to yield 4 before acid hydrolysis, esterification and phenylphosphonylation were carried out. TSA-III (11) TSA-I (12) and (19), using various length spacer arms, were coupled with the immunogenic protein, diphtheria toxoid (DT). The TSAs coupled with DT were used to immunize mice and after appropriate boosts their sera were tested for the presence and titer of anti-TSA polyclonal antibodies using ELISA. Preliminary results show that the mice immunized with these TSAs produced high titers of polyclonal catalytic antibodies, except for (19), with the ability to hydrolyze the substrate 125I-4'-iodococaine in an in vitro assay, even in the presence of noncatalytic anti-TSA antibodies.

  19. Modulation of benzo[a]pyrene induced neurotoxicity in female mice actively immunized with a B[a]P–diphtheria toxoid conjugate

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    Schellenberger, Mario T.; Grova, Nathalie; Farinelle, Sophie; Willième, Stéphanie [Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, L-1950 Luxembourg, Grand-Duchy of Luxembourg (Luxembourg); Schroeder, Henri [University of Nancy, URAFPA, INRA UC340, F-54500 Vandoeuvre-lès-Nancy (France); Muller, Claude P., E-mail: [Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, L-1950 Luxembourg, Grand-Duchy of Luxembourg (Luxembourg)


    Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also neurotoxic for mammalian species. To develop a prophylactic immune strategy against detrimental effects of B[a]P, female Balb/c mice immunized with a B[a]P–diphtheria toxoid (B[a]P–DT) conjugate vaccine were sub-acutely exposed to 2 mg/kg B[a]P and behavioral performances were monitored in tests related to learning and memory, anxiety and motor coordination. mRNA expression of the NMDA receptor (NR1, 2A and 2B subunits) involved in the above behavioral functions was measured in 5 brain regions. B[a]P induced NMDA1 expression in three (hippocampus, amygdala and cerebellum) of five brain regions investigated, and modulated NMDA2 in two of the five brain regions (frontal cortex and cerebellum). Each one of these B[a]P-effects was reversed in mice that were immunized against this PAH, with measurable consequences on behavior such as anxiety, short term learning and memory. Thus active immunization against B[a]P with a B[a]P–DT conjugate vaccine had a protective effect and attenuated the pharmacological and neurotoxic effects even of high concentrations of B[a]P. - Highlights: • B[a]P-antibodies attenuated B[a]P induced NMDA expression in several brain regions. • B[a]P had measurable consequences on anxiety, short term learning and memory. • B[a]P immunization attenuated the pharmacological and neurotoxic effects of B[a]P. • Vaccination may also provide some protection against chemical carcinogenesis.

  20. Safety and immunogenicity of three doses of an eleven-valent diphtheria toxoid and tetanus protein – conjugated pneumococcal vaccine in Filipino infants

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    Käyhty Helena


    Full Text Available Abstract Background An 11-valent pneumococcal conjugate vaccine could provide significantly larger reduction in pneumococcal disease burden than the currently available 7-valent vaccine formulation in many countries. Methods In total, 50 infants were enrolled to this open, uncontrolled study, which evaluated the safety and immunogenicity of an aluminium adjuvanted 11-valent mixed-carrier diphtheria toxoid or tetanus protein-conjugated vaccine (11-PncTD when administered in three doses at 6, 10 and 14 weeks of age simultaneously with DTwP//PRP-T and OPV vaccines in Filipino infants. Results The rates of local reactions between the two injection sites, those associated with the 11-PncTD vaccine and those with the DTwP//PRP-T were almost of equal frequency for all three vaccine doses except for induration, which was significantly more common in the DTP//PRP-T injection site. Fever was present in 39%, 22% and 21% of infants following each of the three doses. Antibody responses were determined by an enzyme immunoassay method before the first vaccination and after the three doses. The vaccine elicited a significant anti-pneumococcal polysaccharide antibody response against all serotypes included in the vaccine, except for type 14, for which the pre-vaccination geometric mean antibody concentration (GMC was high (1.61 μg/ml. The GMCs one month after the vaccination series ranged from 1.1 micrograms/ml for type 6B to 23.4 μg/ml for type 4. Conclusion The 11-PncTD vaccine is safe, well-tolerated and immunogenic. The effectiveness of the non-adjuvanted formulation of the vaccine in preventing pneumonia is currently being evaluated in the Philippines.

  1. Efficacy and safety of vi-tetanus toxoid conjugated typhoid vaccine (PedaTyph™) in Indian children: School based cluster randomized study. (United States)

    Mitra, Monjori; Shah, Nitin; Ghosh, Apurba; Chatterjee, Suparna; Kaur, Iqbal; Bhattacharya, Nisha; Basu, Suparna


    Vi polysaccharide typhoid vaccines cannot be used in children vaccine prepared by binding Vi to tetanus toxoids (Vi-TT) induces protective levels even in children vaccination with a Vi-TT vaccine in children 6 months to 12 years of age. Overall, 1765 subjects were recruited from two registered municipal urban slums of southern Kolkata. Most of the children of the slum dwellers attended the schools in the locality which was selected with permission from the school authority. Schools were randomly divided into vaccinated (Test group) and unvaccinated group (Control group). Children and their siblings of test group received 2-doses of PedaTyph™ vaccine at 6 weeks interval. Control group received vaccines as per national guidelines. Adverse events (AEs) were examined after 30 minutes, 1 month and clinical events were observed till 12 months post-vaccination. Incidence of culture positive typhoid fever in the control group was 1.27% vis-a-vis none in vaccine group during 12 months. In subgroup evaluated for immunogenicity, an antibody titer value of 1.8 EU/ml (95% CI: 1.5 EU/ml, 2.2 EU/ml), 32 EU/ml (95% CI: 27.0 EU/ml, 39.0 EU/ml) and 14 EU/ml (95% CI: 12.0 EU/ml, 17.0 EU/ml) at baseline, 6 weeks and 12 months, respectively was observed. Sero-conversion among the sub-group was 100% after 6 weeks of post-vaccination and 83% after 12 months considering 4-fold rise from baseline. The efficacy of vaccine was 100 % (95% CI: 97.6%, 100%) in the first year of follow-up with minimal AEs post vaccination. Vi conjugate typhoid vaccine conferred 100% protection against typhoid fever in 1765 children 6 months to 12 years of age with high immunogenicity in a subgroup from the vaccine arm.

  2. Immunogenicity and safety of measles-mumps-rubella and varicella vaccines coadministered with a fourth dose of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in toddlers: a pooled analysis of randomized trials. (United States)

    Bryant, Kristina; McVernon, Jodie; Marchant, Colin; Nolan, Terry; Marshall, Gary; Richmond, Peter; Marshall, Helen; Nissen, Michael; Lambert, Stephen; Aris, Emmanuel; Mesaros, Narcisa; Miller, Jacqueline


    A pooled analysis was conducted of 1257 toddlers who received a fourth dose of Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) or Hib conjugate vaccine (Hib polysaccharide conjugated to N. meningitidis outer membrane protein) coadministered with measles-mumps-rubella (MMR) and varicella (VAR) vaccines (NCT00134719/NCT00289783). Noninferiority of immunological responses to MMR and VAR was demonstrated between groups and incidences of MMR- and VAR-specific solicited symptoms were similar, indicating that HibMenCY-TT can be coadministered with MMR and VAR.

  3. Carrier priming effect of CRM197 is related to an enhanced B and T cell activation in meningococcal serogroup A conjugate vaccination. Immunological comparison between CRM197 and diphtheria toxoid. (United States)

    Pecetta, S; Tontini, M; Faenzi, E; Cioncada, R; Proietti, D; Seubert, A; Nuti, S; Berti, F; Romano, M R


    Glycoconjugate vaccines are composed of capsular polysaccharides (CPSs) of a pathogenic bacteria covalently linked to carrier proteins. Pre-exposure to the carrier is known to influence the efficacy of the glycoconjugate, by inducing enhanced or suppressed anti-CPS response. Following our previous work on the immunogenicity of diphtheria toxin mutant CRM197 and formaldehyde-treated diphtheria toxoid (DT) as carriers for meningococcal A (MenA) conjugates in mouse model, we further investigated the role of the carrier on the immunological response to glycoconjugate vaccines. We previously showed that high dosage DT priming could result in carrier-induced epitopic suppression (CIES), an event that did not occur for CRM197 priming, and we observed that anti-DT IgGs could cross-react with DT based conjugates in vitro. Here, we confirmed the cross-reactivity of anti-carrier IgGs with DT conjugates in vivo. Furthermore, we analyzed the splenocytes of animals primed with the carrier and subsequently immunized with the MenA conjugate. Pre-exposure to the carrier protein, both CRM197 and DT, resulted in increased carrier-specific plasma and memory B cell response. However, only for CRM197 priming an enhanced carbohydrate-specific plasma cell response was observed. Analysis of circulating IgGs confirmed these observations. Memory to the CPS resulted to be non-influenced by carrier priming. Analysis of T helper response showed an enhancement effect for CRM197 priming, while DT priming resulted in constrained T cell activation. Stimulation with CRM197, which does not require formaldehyde detoxification, of splenocytes from animal immunized with DT suggested that the formaldehyde treatment used to produce DT might be the cause of limited presentation of the antigen to the T cells. We concluded that the dominant carrier-specific B cell response in case of limited T cell recruitment might explain the previously observed CIES phenomenon in case of DT priming.

  4. Antibody persistence up to 5 years after vaccination of toddlers and children between 12 months and 10 years of age with a quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine. (United States)

    Vesikari, Timo; Forsten, Aino; Bianco, Veronique; Van der Wielen, Marie; Miller, Jacqueline M


    We studied the persistence of serum bactericidal antibody using rabbit and human complement (rSBA/hSBA, cut-offs 1:8) 5 y after a single dose of meningococcal serogroups A, C, W, Y tetanus toxoid conjugate vaccine (MenACWY-TT) compared with age-appropriate control vaccines in toddlers and children (NCT00427908). Children were previously randomized (3:1) to receive either MenACWY-TT or control vaccine (MenC-CRM197 in 1-vaccine [Men-PS] in 2-vaccine and discontinued from the study. A repeated measurement statistical model assessed potential selection effects due to drop-outs. At year 5 in MenACWY-TT-vaccinated-toddlers for serogroups A, C, W, and Y respectively, percentages with rSBA titers ≥1:8 were 73.5%, 77.6%, 34.7%, and 42.9%, hSBA ≥1:8 were 35.6%, 91.7%, 82.6% and 80.0%. For MenC-CRM197 recipients, 63.6% had persisting rSBA-MenC titers ≥1:8 and 90.9% had hSBA-MenC ≥1:8 (not significantly different versus MenACWY-TT for either assay: exploratory analyses). In 2-vaccinees were 90.8%, 90.8%, 78.6%, and 78.6% and 15.4%, 100%, 0.0%, 7.7% in Men-PS-vaccinees (significantly different for serogroups A, W and Y, exploratory analyses). Serogroups A, W and Y rSBA GMTs were ≥ 26-fold higher in MenACWY-TT-vaccinees. As expected, GMTs modeled at year 5 to assess the impact of subject drop out (mainly for revaccination), appeared lower for serogroup C. No vaccine-related SAEs were reported. Antibody persistence was observed for all serogroups up to 5 y after MenACWY-TT vaccination.

  5. Safety and immunogenocity of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine in healthy Chinese children aged 6 months to 5 years old. (United States)

    Hu, Jian-li; Tao, Hong; Li, Jing-xin; Dai, Wei-ming; Song, Bin; Sun, Jin-fang; Liu, Pei; Tang, Jie; Liu, Wen-yu; Wang, Shi-yuan; Zhu, Feng-cai


    A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine (Hib-MenAC vaccine) has been developed to protect children against diseases caused by Hib, MenA, and MenC. This study investigated the safety and immunogenicity of the Hib-MenAC vaccine administered in 2-dose series to children aged 6-23 months and in a single dose to children aged 2-5 y. A randomized, positive-controlled, non-inferiority clinical trial was conducted for 1200 healthy participants in each age group. Within each age group, participants were randomly allocated to the Hib-MenAC group or the control group at a ratio of 1:1. Adverse reactions were recorded within 28 d after each dose. Blood samples were obtained to assess immunogenicity on day 0 and at 28 d after a complete vaccination course. For the investigational vaccine, the incidence of total adverse reactions in vaccinees aged 6-23 months was 46.8% and that in vaccinees aged 2-5 y was 29.8%. Most adverse reactions were mild or moderate. One non-fatal serious adverse event occurred in the Hib-MenAC group, but was unrelated to vaccination. The seroconversion rate to the 3 components reached 94.0%, and the proportion of vaccinees with rSBA titers ≥ 1:8 and PRP ≥ 0.15 g/mL reached 97.0% in both age groups. The safety and immunogenicity of the Hib-MenAC vaccine were non-inferior when compared to the licensed vaccines. It was concluded that the novel vaccine would be expected to protect children against all of the targeted diseases.

  6. Comparison of CRM197, diphtheria toxoid and tetanus toxoid as protein carriers for meningococcal glycoconjugate vaccines. (United States)

    Tontini, M; Berti, F; Romano, M R; Proietti, D; Zambonelli, C; Bottomley, M J; De Gregorio, E; Del Giudice, G; Rappuoli, R; Costantino, P; Brogioni, G; Balocchi, C; Biancucci, M; Malito, E


    Glycoconjugate vaccines are among the most effective and safest vaccines ever developed. Diphtheria toxoid (DT), tetanus toxoid (TT) and CRM197 have been mostly used as protein carriers in licensed vaccines. We evaluated the immunogenicity of serogroup A, C, W-135 and Y meningococcal oligosaccharides conjugated to CRM197, DT and TT in naïve mice. The three carriers were equally efficient in inducing an immune response against the carbohydrate moiety in immunologically naïve mice. The effect of previous exposure to different dosages of the carrier protein on the anti-carbohydrate response was studied using serogroup A meningococcal (MenA) saccharide conjugates as a model. CRM197 showed a strong propensity to positively prime the anti-carbohydrate response elicited by its conjugates or those with the antigenically related carrier DT. Conversely in any of the tested conditions TT priming did not result in enhancement of the anti-carbohydrate response elicited by the corresponding conjugates. Repeated exposure of mice to TT or to CRM197 before immunization with the respective MenA conjugates resulted in a drastic suppression of the anti-carbohydrate response in the case of TT conjugate and only in a slight reduction in the case of CRM197. The effect of carrier priming on the anti-MenA response of DT-based conjugates varied depending on their carbohydrate to protein ratio. These data may have implications for human vaccination since conjugate vaccines are widely used in individuals previously immunized with DT and TT carrier proteins.

  7. 9 CFR 113.114 - Tetanus Toxoid. (United States)


    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Tetanus Toxoid. 113.114 Section 113... Bacterial Products § 113.114 Tetanus Toxoid. Tetanus Toxoid shall be produced from a culture of Clostridium... purified and concentrated. Each serial of biological product containing tetanus toxoid fraction shall...

  8. Co-administration of a novel Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine does not interfere with the immune response to antigens contained in infant vaccines routinely used in the United States. (United States)

    Marshall, Gary S; Marchant, Colin D; Blatter, Mark; Friedland, Leonard R; Aris, Emmanuel; Miller, Jacqueline M


    An investigational combined Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (HibMenCY-TT) has been developed to protect infants from invasive disease caused by Hib and these meningococcal serogroups without adding injections to the immunization schedule. Incorporation of this novel vaccine into the US vaccination schedule will require demonstration of a lack of immunologic interference with other routine pediatric vaccines. This study assessed the immune response to 7-valent pneumococcal conjugate vaccine (PCV7) and combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine (DTaP-HepB-IPV) when separately co-administered with HibMenCY-TT as compared to a US-licensed H. influenzae type b tetanus toxoid conjugate vaccine (Hib-TT) at 2, 4, 6 (N=606) and 12-15 months of age (N=366). HibMenCY-TT was non-inferior to Hib-TT in terms of antibody responses to all Streptococcus pneumoniae serotypes contained in PCV7 and the diphtheria, tetanus, pertussis, hepatitis B and poliovirus antigens contained in DTaP-HepB-IPV one month after the third vaccine dose, and the anti-tetanus geometric mean antibody concentration (GMC) was significantly higher in the HibMenCY-TT group than in the Hib-TT group. In an exploratory analysis, no significant differences in the proportion of subjects with anti-pneumococcal antibody concentrations ≥0.2 µg/ml or anti-pneumococcal GMC were seen between the two groups after the fourth vaccine dose. A schedule of HibMenCY-TT given concomitantly with PCV7 and DTaP-HepB-IPV would be expected to protect infants against all of the targeted diseases.

  9. An asymmetric and slightly dimerized structure for the tetanus toxoid protein used in glycoconjugate vaccines. (United States)

    Abdelhameed, Ali Saber; Morris, Gordon A; Adams, Gary G; Rowe, Arthur J; Laloux, Olivier; Cerny, Louis; Bonnier, Benjamin; Duvivier, Pierre; Conrath, Karel; Lenfant, Christophe; Harding, Stephen E


    Tetanus toxoid protein has been characterized with regard oligomeric state and hydrodynamic (low-resolution) shape, important parameters with regard its use in glycoconjugate vaccines. From sedimentation velocity and sedimentation equilibrium analysis in the analytical ultracentrifuge tetanus toxoid protein is shown to be mostly monomeric in solution (~86%) with approximately 14% dimer. The relative proportions do not appear to change significantly with concentration, suggesting the two components are not in reversible equilibrium. Hydrodynamic solution conformation studies based on high precision viscometry, combined with sedimentation data show the protein to be slightly extended conformation in solution with an aspect ratio ~3. The asymmetric structure presents a greater surface area for conjugation with polysaccharide than a more globular structure, underpinning its popular choice as a conjugation protein for glycoconjugate vaccines.

  10. Potential protective immunogenicity of tetanus toxoid, diphtheria toxoid and Cross Reacting Material 197 (CRM197) when used as carrier proteins in glycoconjugates. (United States)

    Bröker, Michael


    When tetanus toxoid (TT), diphtheria toxoid (DT) or Cross Reacting Material 197 (CRM197), a non-toxic diphtheria toxin mutant protein, are used as carrier proteins in glycoconjugate vaccines, these carriers induce a protein specific antibody response as measured by in vitro assays. Here, it was evaluated whether or not glycoconjugates based on TT, DT or CRM197 can induce a protective immune response as measured by potency tests according to the European Pharmacopoeia. It could be shown, that the conjugate carriers TT and DT can induce a protective immune response against a lethal challenge by toxins in animals, while glycoconjugates based on CRM197 failed to induce a protective immune response. Opportunities for new applications of glycoconjugates are discussed.

  11. An investigational tetravalent meningococcal serogroups A, C, W-135 and Y-tetanus toxoid conjugate vaccine co-administered with Infanrix™ hexa is immunogenic, with an acceptable safety profile in 12-23-month-old children. (United States)

    Knuf, Markus; Pantazi-Chatzikonstantinou, Anna; Pfletschinger, Ulrich; Tichmann-Schumann, Irmingard; Maurer, Hartwig; Maurer, Lothar; Fischbach, Thomas; Zinke, Henrike; Pankow-Culot, Heidemarie; Papaevangelou, Vassiliki; Bianco, Veronique; Van der Wielen, Marie; Miller, Jacqueline M


    Tetravalent meningococcal serogroups ACWY conjugate vaccines will provide an advantage to those at most risk of invasive meningococcal disease; namely young children. Co-administration of ACWY-TT with DTaP-HBV-IPV/Hib was assessed in a randomized trial in 793 children aged 12-23 months. Pre-specified criteria for non-inferiority of immunogenicity following co-administration versus separate ACWY-TT and DTaP-HBV-IPV/Hib administration were reached. One month post-vaccination, ≥ 97.3% of ACWY-TT vaccinees had rSBA titres ≥ 1:8 (all serogroups). Seroprotection/seropositivity rates against DTaP-HBV-IPV/Hib antigens were ≥ 98.2%. The safety profile of co-administration was similar to that of DTaP-HBV-IPV/Hib alone. ACWY-TT and DTaP-HBV-IPV/Hib co-administration during the second year would facilitate introduction of ACWY-TT into routine toddler vaccination schedules.

  12. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP). (United States)

    Broder, Karen R; Cortese, Margaret M; Iskander, John K; Kretsinger, Katrina; Slade, Barbara A; Brown, Kristin H; Mijalski, Christina M; Tiwari, Tejpratap; Weston, Emily J; Cohn, Amanda C; Srivastava, Pamela U; Moran, John S; Schwartz, Benjamin; Murphy, Trudy V


    During spring 2005, two tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) products formulated for use in adolescents (and, for one product, use in adults) were licensed in the United States (BOOSTRIX, GlaxoSmithKline Biologicals, Rixensart, Belgium [licensed May 3, 2005, for use in persons aged 10-18 years], and ADACEL, sanofi pasteur, Toronto, Ontario, Canada [licensed June 10, 2005, for use in persons aged 11-64 years]). Prelicensure studies demonstrated safety and efficacy against tetanus, diphtheria, and pertussis when Tdap was administered as a single booster dose to adolescents. To reduce pertussis morbidity in adolescents and maintain the standard of care for tetanus and diphtheria protection, the Advisory Committee on Immunization Practices (ACIP) recommends that: 1) adolescents aged 11-18 years should receive a single dose of Tdap instead of tetanus and diphtheria toxoids vaccine (Td) for booster immunization against tetanus, diphtheria, and pertussis if they have completed the recommended childhood diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP)/ diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) vaccination series (five doses of pediatric DTP/DTaP before the seventh birthday; if the fourth dose was administered on or after the fourth birthday, the fifth dose is not needed) and have not received Td or Tdap. The preferred age for Tdap vaccination is 11-12 years; 2) adolescents aged 11-18 years who received Td, but not Tdap, are encouraged to receive a single dose of Tdap to provide protection against pertussis if they have completed the recommended childhood DTP/DTaP vaccination series. An interval of at least 5 years between Td and Tdap is encouraged to reduce the risk for local and systemic reactions after Tdap vaccination. However, an interval less than 5 years between Td and Tdap can be used; and 3) vaccine providers should administer Tdap and tetravalent meningococcal conjugate

  13. Detection of anti-tetanus toxoid antibody on modified polyacrylonitrile fibers. (United States)

    Jain, Swati; Chattopadhyay, Sruti; Jackeray, Richa; Zainul Abid, C K V; Kumar, Manoj; Singh, Harpal


    Accurate determination of concentration of immunoglobulin (IgG) to tetanus toxoid is important in order to evaluate the immunogenicity of tetanus toxoid vaccines, immune competence in individual patients and to measure the prevalence of immunity in populations. Surface modified polyacrylonitrile (PAN) fibers were evaluated as a matrix to develop highly sensitive method for the detection of anti-tetanus antibody in a sandwich ELISA format. In the proposed method tetanus toxoid immobilized on modified PAN fibers was used to detect anti-tetanus antibody (raised in horse hence represented as horse anti-tetanus toxoid or HAT-Ab) with horse raddish peroxidase enzyme conjugated with Rabbit anti-Horse IgG (RAH-HRP) as the label within 2.5h. A sigmoidal pattern for the detection of different concentration of antibody ranging from 1.0 to 0.0001 IU mL(-1) was validated. The immunoassay recorded a very high sensitivity as concentration as low as 0.0005 IU mL(-1) of HAT-Ab was detected. The intra- and inter-assay precision for 3 parallel measurements of 0.01 and for 0.001 IU mL(-1) of antibody varied from 5.4% to 11% and 5.7% to 20% respectively. PAN fibers were also used to qualitatively access the presence of different level of anti-tetanus antibody spiked in human blood. Seroepidemiological studies to measure the immunity against tetanus were conducted with twenty-five human beings belonging to various age groups using modified PAN-ELISA. The sensitivity, specificity and the reproducibility of the developed immunoassay indicate the potential application of modified PAN fibers in the field of immunodiagnostics.

  14. 9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid. (United States)


    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Staphylococcus Aureus Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus... Staphylococcus aureus which has been inactivated and is nontoxic. Each serial of biological product...

  15. ACYW135群脑膜炎球菌多糖结合破伤风毒素疫苗免疫学效果的Meta分析%The Meta-analysis of immunogenicity of meningococcal ACYW135 polysaccharide tetanus toxoid conjugate vaccine

    Institute of Scientific and Technical Information of China (English)

    胡昱; 李倩; 张兵; 陈雅萍


    目的 评价ACYW135群脑膜炎球菌多糖结合破伤风毒素疫苗(MPCV-ACYW135-TT)的免疫学效果.方法 检索National Center for Biotechnology Information (NCBI)、Cochrane协作网图书馆、中国生物医学文献数据库、中国期刊全文数据库和万方全文数据库,将有关评价MPCV-ACYW135免疫学效果的随机对照试验(RCT)的研究纳入分析.以接种疫苗1个月后产生的血清杀菌活性(SBA)抗体阳转率(PRR)和几何平均滴度(GMT)作为结局指标,合并不同研究中试验组与对照组间的PRR和GMT的率差(RD)或标准化均数差(SMD).使用RevMan5.1软件进行Meta分析.结果 共纳入13篇文献:有9篇比较了MPCV-ACYW135-TT和ACYW135群脑膜炎球菌多糖疫苗(MPV-ACYW135)之间免疫学效果差异,4篇比较了MPCV-ACYW135-TT和C群脑膜炎球菌多糖结合白喉毒素变异体197疫苗(MPCV-C-CMR197)之间免疫学效果差异.相比于MPV-A-CYW135;受试者在接种MPCV-ACYW135-TT后产生的针对A、C、Y和W135这4个血清型抗体PRR的RD在0.03~0.15之间;产生的针对A、Y和W135这3个血清型抗体GMT的SMD在0.33~1.22之间.1~2岁组幼儿在接种MPCV-ACYW135-TT后产生的针对C群抗体GMT与接种MPCV-C-CMR197差异无统计学意义(H>0.05).结论 MPCV-ACYW135-TT与其他已上市应用的脑膜炎球菌疫苗有相似的免疫效果.%Objective To evaluate the immunogenicity of meningococcal ACYW135 polysaccharide tetanus toxoid conjugate vaccine (MPCV-ACYW135-TT).Methods Searching random control trials (RCT) in National Center for Biotechnology Information (NC BI),Cochrane Library (CL),China Biology Medicine disc (C BMd),China National Knowledge Infrastructure (CNKI) and Wanfang Database for comparing immunogenicity of MPCV-ACYW135-TT.The positive response rate (PRR) and geometric mean titer (GMT) of serum bactericidal activity (SBA) antibody with an interval of one month after vaccination were used as our endpoints.We pooled risk difference (RD) or standardized

  16. A clinical trial examining the effect of increased total CRM(197) carrier protein dose on the antibody response to Haemophilus influenzae type b CRM(197) conjugate vaccine. (United States)

    Usonis, Vytautas; Bakasenas, Vytautas; Lockhart, Stephen; Baker, Sherryl; Gruber, William; Laudat, France


    CRM(197) is a carrier protein in certain conjugate vaccines. When multiple conjugate vaccines with the same carrier protein are administered simultaneously, reduced response to vaccines and/or antigens related to the carrier protein may occur. This study examined responses of infants who, in addition to diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine (DTaP) received either diphtheria CRM(197)-based Haemophilus influenzae type b conjugate vaccine (HbOC) or HbOC and a diphtheria CRM(197)-based combination 9-valent pneumococcal conjugate vaccine/meningococcal group C conjugate vaccine. Administration of conjugate vaccines with CRM(197) carrier protein load >50 microg did not reduce response to CRM(197) conjugate vaccines or immunogenicity to immunologically cross-reactive diphtheria toxoid.

  17. Solution conformation and flexibility of capsular polysaccharides from Neisseria meningitidis and glycoconjugates with the tetanus toxoid protein (United States)

    Abdelhameed, Ali Saber; Morris, Gordon A.; Almutairi, Fahad; Adams, Gary G.; Duvivier, Pierre; Conrath, Karel; Harding, Stephen E.


    The structural integrity of meningococcal native, micro-fluidized and activated capsular polysaccharides and their glycoconjugates – in the form most relevant to their potential use as vaccines (dilute solution) - have been investigated with respect to their homogeneity, conformation and flexibility. Sedimentation velocity analysis showed that the polysaccharide size distributions were generally bimodal with some evidence for higher molar mass forms at higher concentration. Weight average molar masses Mw where lower for activated polysaccharides. Conjugation with tetanus toxoid protein however greatly increased the molar mass and polydispersity of the final conjugates. Glycoconjugates had an approximately unimodal log-normal but broad and large molar mass profiles, confirmed by sedimentation equilibrium “SEDFIT MSTAR” analysis. Conformation analysis using HYDFIT (which globally combines sedimentation and viscosity data), “Conformation Zoning” and Wales-van Holde approaches showed a high degree of flexibility – at least as great as the unconjugated polysaccharides, and very different from the tetanus toxoid (TT) protein used for the conjugation. As with the recently published finding for Hib-TT complexes, it is the carbohydrate component that dictates the solution behaviour of these glycoconjugates, although the lower intrinsic viscosities suggest some degree of compaction of the carbohydrate chains around the protein.

  18. Carrier priming with CRM 197 or diphtheria toxoid has a different impact on the immunogenicity of the respective glycoconjugates: biophysical and immunochemical interpretation. (United States)

    Pecetta, S; Lo Surdo, P; Tontini, M; Proietti, D; Zambonelli, C; Bottomley, M J; Biagini, M; Berti, F; Costantino, P; Romano, M R


    Glycoconjugate vaccines play an enormous role in preventing infectious diseases. The main carrier proteins used in commercial conjugate vaccines are the non-toxic mutant of diphtheria toxin (CRM197), diphtheria toxoid (DT) and tetanus toxoid (TT). Modern childhood routine vaccination schedules include the administration of several vaccines simultaneously or in close sequence, increasing the concern that the repeated exposure to conjugates based on these carrier proteins might interfere with the anti-polysaccharide response. Extending previous observations we show here that priming mice with CRM197 or DT does not suppress the response to the carbohydrate moiety of CRM197 meningococcal serogroup A (MenA) conjugates, while priming with DT can suppress the response to DT-MenA conjugates. To explain these findings we made use of biophysical and immunochemical techniques applied mainly to MenA conjugates. Differential scanning calorimetry and circular dichroism data revealed that the CRM197 structure was altered by the chemical conjugation, while DT and the formaldehyde-treated form of CRM197 were less impacted, depending on the degree of glycosylation. Investigating the binding and avidity properties of IgGs induced in mice by non-conjugated carriers, we found that CRM197 induced low levels of anti-carrier antibodies, with decreased avidity for its MenA conjugates and poor binding to DT and respective MenA conjugates. In contrast, DT induced high antibody titers able to bind with comparable avidity both the protein and its conjugates but showing very low avidity for CRM197 and related conjugates. The low intrinsic immunogenicity of CRM197 as compared to DT, the structural modifications induced by glycoconjugation and detoxification processes, resulting in conformational changes in CRM197 and DT epitopes with consequent alteration of the antibody recognition and avidity, might explain the different behavior of CRM197 and DT in a carrier priming context.

  19. Protection of monkeys against the lethal effects of male funnel-web spider (Atrax robustus) venom by immunization with a toxoid. (United States)

    Sheumack, D D; Phillips, C A; Mylecharane, E J; Spence, I; Claassens, R; Brown, M R; Comis, A; Howden, M E


    A stable toxoid was prepared from robustoxin (the lethal polypeptide neurotoxin in the venom of the male funnel-web spider, Atrax robustus) by polymerization with glutaraldehyde. This material was non-toxic in new-born mice. Administration of the toxoid to three Macaca fascicularis monkeys (50-80 micrograms/kg s.c. at 14-day intervals for 8-12 weeks) produced no toxic effects; anti-robustoxin antibodies were detected in serum samples by immunodiffusion tests within 13-27 days. In vivo evidence of successful protection with the toxoid was obtained by challenging the monkeys with male A. robustus venom (50 micrograms/kg i.v.) under anaesthesia with pentobarbitone (one monkey), or with ketamine, halothane and nitrous oxide, 1-26 weeks after the last injection of the toxoid. Only minor respiratory, cardiovascular and skeletal motor disturbances were produced, and all monkeys recovered fully and uneventfully. Challenge with the same dose of venom in non-immunized or robustoxin N-terminal decapeptide ovalbumin conjugate-treated monkeys resulted in typical lethal neurotoxic effects, culminating in severe hypotension or death from circulatory and respiratory failure within 280 min.

  20. A glycoconjugate of Haemophilus influenzae Type b capsular polysaccharide with tetanus toxoid protein: hydrodynamic properties mainly influenced by the carbohydrate. (United States)

    Abdelhameed, Ali Saber; Adams, Gary G; Morris, Gordon A; Almutairi, Fahad M; Duvivier, Pierre; Conrath, Karel; Harding, Stephen E


    Three important physical properties which may affect the performance of glycoconjugate vaccines against serious disease are molar mass (molecular weight), heterogeneity (polydispersity), and conformational flexibility in solution. The dilute solution behaviour of native and activated capsular polyribosylribitol (PRP) polysaccharides extracted from Haemophilus influenzae type b (Hib), and the corresponding glycoconjugate made by conjugating this with the tetanus toxoid (TT) protein have been characterized and compared using a combination of sedimentation equilibrium and sedimentation velocity in the analytical ultracentrifuge with viscometry. The weight average molar mass of the activated material was considerably reduced (Mw ~ 0.24 × 10(6) g.mol(-1)) compared to the native (Mw ~ 1.2 × 10(6) g.mol(-1)). Conjugation with the TT protein yielded large polydisperse structures (of Mw ~ 7.4 × 10(6) g.mol(-1)), but which retained the high degree of flexibility of the native and activated polysaccharide, with frictional ratio, intrinsic viscosity, sedimentation conformation zoning behaviour and persistence length all commensurate with highly flexible coil behaviour and unlike the previously characterised tetanus toxoid protein (slightly extended and hydrodynamically compact structure with an aspect ratio of ~3). This non-protein like behaviour clearly indicates that it is the carbohydrate component which mainly influences the physical behaviour of the glycoconjugate in solution.

  1. Tetanus toxoid purification: chromatographic procedures as an alternative to ammonium-sulphate precipitation. (United States)

    Stojićević, Ivana; Dimitrijević, Ljiljana; Dovezenski, Nebojša; Živković, Irena; Petrušić, Vladimir; Marinković, Emilija; Inić-Kanada, Aleksandra; Stojanović, Marijana


    Given an existing demand to establish a process of tetanus vaccine production in a way that allows its complete validation and standardization, this paper focuses on tetanus toxoid purification step. More precisely, we were looking at a possibility to replace the widely used ammonium-sulphate precipitation by a chromatographic method. Based on the tetanus toxin's biochemical characteristics, we have decided to examine the possibility of tetanus toxoid purification by hydrophobic chromatography, and by chromatographic techniques based on interaction with immobilized metal ions, i.e. chelating chromatography and immobilized metal affinity chromatography. We used samples obtained from differently fragmented crude tetanus toxins by formaldehyde treatment (assigned as TTd-A and TTd-B) as starting material for tetanus toxoid purification. Obtained results imply that purification of tetanus toxoid by hydrophobic chromatography represents a good alternative to ammonium-sulphate precipitation. Tetanus toxoid preparations obtained by hydrophobic chromatography were similar to those obtained by ammonium-sulphate precipitation in respect to yield, purity and immunogenicity. In addition, their immunogenicity was similar to standard tetanus toxoid preparation (NIBSC, Potters Bar, UK). Furthermore, the characteristics of crude tetanus toxin preparations had the lowest impact on the final purification product when hydrophobic chromatography was the applied method of tetanus toxoid purification. On the other hand, purifications of tetanus toxoid by chelating chromatography or immobilized metal affinity chromatography generally resulted in a very low yield due to not satisfactory tetanus toxoid binding to the column, and immunogenicity of the obtained tetanus toxoid-containing preparations was poor.

  2. Physicochemical and immunochemical assays for monitoring consistent production of tetanus toxoid. (United States)

    Metz, Bernard; Tilstra, Wichard; van der Put, Robert; Spruit, Nanda; van den Ijssel, Jan; Robert, Jolanda; Hendriksen, Coenraad; Kersten, Gideon


    The detoxification of tetanus toxin by formaldehyde is a crucial step in the production of tetanus toxoid. The inactivation results in chemically modified proteins and it determines largely the ultimate efficacy and safety of the vaccine. Currently, the quality of tetanus toxoid lots is evaluated in potency and safety tests performed in animals. As a possible alternative, this article describes a panel of in vitro methods, which provides detailed information about the quality of tetanus toxoid. Ten experimental lots of tetanus toxoid were prepared using increasing concentrations of formaldehyde and glycine to obtain tetanus toxoids having differences in antigenicity, immunogenicity, residual toxicity and protein structure. The structural properties of each individual toxoid were determined using immunochemical and physicochemical methods, including biosensor analysis, ELISA, circular dichroism, TNBS assay, differential scanning calorimetry, fluorescence and SDS-PAGE. The quality of a tetanus toxoid lot can be assessed by these set of analytical techniques. Based on antigenicity, immunogenicity and residual toxicity data, criteria are formulated that tetanus toxoids lot have to meet in order to have a high quality. The in vitro methods are a valuable selection of techniques for monitoring consistency of production of tetanus toxoid, especially for the detoxification process of tetanus toxin.

  3. Comparison of five commercial anti-tetanus toxoid immunoglobulin G enzyme-linked immunosorbent assays. (United States)

    Perry, A L; Hayes, A J; Cox, H A; Alcock, F; Parker, A R


    Five commercially available enzyme-linked immunosorbent assays for the measurement of anti-tetanus toxoid immunoglobulin G (IgG) antibodies were evaluated for performance. The data suggest that there are manufacturer-dependent differences in sensitivity and accuracy for the determination of tetanus toxoid IgG antibodies that could result in different diagnostic interpretations.

  4. Comparison of gel filtration and ammonium sulphate precipitation in the purification of diphtheria toxin and toxoid. (United States)

    Møyner, K; Christiansen, G


    Crude diphtheria toxin and toxoid were subjected to purification by gel filtration and stepwise ammonium sulphate precipitation. The various fractions obtained by the purification procedures were studied by immunological methods. A high molecular weight fraction of glycoprotein nature was present in all of the crude preparations studied. The fraction was antigenically non-identical with the real toxin or toxoid and did not have its origin in the culture medium. It showed a long flocculation time when tested against equine diphtheria toxoid antiserum. The fraction could be removed from the crude preparations by gel filtration or by precipitation with 21% (w/v) ammonium sulphate. When comparing toxoids purified by each of these methods, the method of gel filtration resulted in a somewhat higher degree of purity, suggesting that this method would be more suitable than the AS precipitation method for the purification of diphtheria toxoid.

  5. Potential protective immunogenicity of tetanus toxoid, diphtheria toxoid and Cross Reacting Material 197 (CRM197) when used as carrier proteins in glycoconjugates


    Bröker, Michael


    When tetanus toxoid (TT), diphtheria toxoid (DT) or Cross Reacting Material 197 (CRM197), a non-toxic diphtheria toxin mutant protein, are used as carrier proteins in glycoconjugate vaccines, these carriers induce a protein specific antibody response as measured by in vitro assays. Here, it was evaluated whether or not glycoconjugates based on TT, DT or CRM197 can induce a protective immune response as measured by potency tests according to the European Pharmacopoeia. It could be shown, that ...

  6. Development of Vi conjugate - a new generation of typhoid vaccine. (United States)

    Szu, Shousun Chen


    Typhoid fever remains to be a serious disease burden worldwide with an estimated annual incidence about 20 million. The licensed vaccines showed moderate protections and have multiple deficiencies. Most important of all, none of the licensed typhoid vaccines demonstrated protection for children under 5 years old. These limitations impeded successful implementation of typhoid vaccination programs. To improve immunogenicity Vi was conjugated to rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. Vi-rEPA showed higher and longer lasting anti-Vi IgG in adults and children than Vi alone in high endemic areas. In school-age children and adults, the immunity persisted more than 8 years. In a double-blind, placebo-controlled and randomized efficacy trial in 2- to 5-year-old children, Vi-rEPA conferred 89% protective efficacy against typhoid fever and the protection lasted at least 4 years. When given concomitantly with infant routine vaccines, Vi-rEPA was safe, immunogenic and showed no interference with the routine vaccines. Vi conjugate vaccine was also attempted and successfully demonstrated by several other laboratories and manufactures. Using either rEPA or different carrier proteins, such as diphtheria or tetanus toxoid, recombinant diphtheria toxin (CRM197), the Vi conjugates synthesized was significantly more immunogenic than Vi alone. Recently, two Vi-tetanus toxoid conjugates were licensed in India for all ages, starts as young as 3 month old. This new generation of typhoid vaccine opens up a new era for typhoid prevention and elimination.

  7. Immune responses of Asian elephants (Elephas maximus) to commercial tetanus toxoid vaccine. (United States)

    Lindsay, William A; Wiedner, Ellen; Isaza, Ramiro; Townsend, Hugh G G; Boleslawski, Maria; Lunn, D P


    Although captive elephants are commonly vaccinated annually against tetanus using commercially available tetanus toxoid vaccines marketed for use in horses and livestock, no data exists to prove that tetanus toxoid vaccination produces measurable antibody titers in elephants. An ELISA test was created to measure antibody responses to tetanus toxoid vaccinations in 22 Asian elephants ranging in age from 24 to 56 years (mean age 39 years) over a 7-month period. All animals had been previously vaccinated with tetanus toxoid vaccine, with the last booster administered 4 years before the start of the study. The great majority of elephants had titers prior to booster vaccination, and following revaccination all elephants demonstrated anamnestic increases in titers, indicating that this species does respond to tetanus vaccination. Surprisingly older animals mounted a significantly higher response to revaccination than did younger animals.

  8. Induction of potential protective immunity against enterotoxemia in calves by single or multiple recombinant Clostridium perfringens toxoids. (United States)

    Jiang, Zhigang; De, Yanyan; Chang, Jitao; Wang, Fang; Yu, Li


    Cattle enterotoxemia caused by Clostridium perfringens toxins is a noncontagious, sporadic, and fatal disease characterized by sudden death. Strategies for controlling and preventing cattle enterotoxemia are based on systematic vaccination of herds with toxoids. Because the process of producing conventional clostridial vaccines is dangerous, expensive, and time-consuming, the prospect of recombinant toxoid vaccines against diseases caused by C. perfringens toxins is promising. In this study, nontoxic recombinant toxoids derived from α-, β- and ε-toxins of C. perfringens, namely, rCPA247-370 , rCPB and rEtxHP, respectively, were expressed in Escherichia coli. High levels of specific IgG antibodies and neutralizing antibodies against the toxins were detected in sera from calves vaccinated with either a single recombinant toxoid or a mixed cocktail of all three recombinant toxoids, indicating the potential of these recombinant toxoids to provide calves with protective immunity against enterotoxemia caused by C. perfringens.

  9. Quantitative estimation of diphtheria and tetanus toxoids. 6. Use of different antibody titration methods for evaluation of immunogenicity in animals during potency assay of diphtheria toxoid. (United States)

    Lyng, J; Heron, I


    Two diphtheria toxoid preparations were compared in potency assays in guinea-pigs using different methods for evaluation of the responses to vaccination. The methods used were the direct skin challenge (Schick test) and ELISA and VERO cell titration of antibodies. The different evaluation methods resulted in the same relative potencies between the toxoids. It was observed that when first-vaccination sera were compared with a second-vaccination serum, the relative antibody concentration depended on whether ELISA or VERO cell titration was used.

  10. Stabilization of tetanus toxoid formulation containing aluminium hydroxide adjuvant against agitation. (United States)

    Solanki, Vipul A; Jain, Nishant K; Roy, Ipsita


    The aggregation of tetanus toxoid leads to reduced bioavailability of the vaccine and failure of immunization programmes in many parts of the globe. One of the main reasons for denaturation and aggregation of tetanus toxoid formulations is agitation of the protein during transport. We have identified that agitation leads to collapse of the gel matrix of aluminium hydroxide which is used as an adjuvant in these preparations. This results in desorption of the toxoid from the matrix, which then loses its antigenicity due to agitation-induced denaturation of the protein. We show that incorporation of some compatible osmolytes like sorbitol, glucose and arginine, but not trehalose, is able to protect the adjuvant matrix from degradation, and retain the integrity of the vaccine preparation in terms of its antigenicity.

  11. Stabilization of tetanus toxoid formulation containing aluminium hydroxide adjuvant against freeze-thawing. (United States)

    Solanki, Vipul A; Jain, Nishant K; Roy, Ipsita


    Exposure to subzero temperature leads to loss of vaccine potency. This can happen due to degradation of adjuvant surface and/or inactivation of the antigen. When adsorbed on aluminium hydroxide and subjected to freeze-thawing, tetanus toxoid was desorbed from the gel matrix and the preparation was found to lose its antigenicity. Analyses showed that the gel particles were denatured after freezing. When freeze-thawing was carried out in the presence of glucose, sorbitol and arginine, the degradation of gel particles was inhibited. A higher fraction of the protein could be retained on the gel. However, the antigenicity of these preparations was quite low. In the presence of trehalose, the protein could be partially retained on aluminium hydroxide. Being a cryoprotectant, trehalose was also able to inhibit the freezing-induced denaturation of tetanus toxoid, which resulted in retention of antigenicity of the adjuvanted toxoid.

  12. Protection against avian necrotic enteritis after immunisation with NetB genetic or formaldehyde toxoids. (United States)

    Fernandes da Costa, Sérgio P; Mot, Dorien; Bokori-Brown, Monika; Savva, Christos G; Basak, Ajit K; Van Immerseel, Filip; Titball, Richard W


    NetB (necrotic enteritis toxin B) is a recently identified β-pore-forming toxin produced by Clostridium perfringens. This toxin has been shown to play a major role in avian necrotic enteritis. In recent years, a dramatic increase in necrotic enteritis has been observed, especially in countries where the use of antimicrobial growth promoters in animal feedstuffs has been banned. The aim of this work was to determine whether immunisation with a NetB toxoid would provide protection against necrotic enteritis. The immunisation of poultry with a formaldehyde NetB toxoid or with a NetB genetic toxoid (W262A) resulted in the induction of antibody responses against NetB and provided partial protection against disease.

  13. Specific detection of tetanus toxoid using an aptamer-based matrix. (United States)

    Modh, Harshvardhan B; Bhadra, Ankan K; Patel, Kinjal A; Chaudhary, Rajeev K; Jain, Nishant K; Roy, Ipsita


    Batch-to-batch variation of therapeutic proteins produced by biological means requires rigorous monitoring at all stages of the production process. A large number of animals are employed for risk assessment of biologicals, which has low ethical and economic acceptability. Research is now focussed on the validation of in vitro and ex vivo tests to replace live challenges. Among in vitro methods, enzyme-linked immunosorbent assay (ELISA) is considered to be the gold standard for estimation of integrity of tetanus toxoid. ELISA utilizes antibodies for detection, which, because of their biological origin and limited modifiability, may have low stability and result in irreproducibility. We have developed a method using highly specific and selective RNA aptamers for detection of tetanus toxoid. Using displacement assay, we first identified aptamers which bind to different aptatopes on the surface of the toxoid. Pairs of these aptamers were employed as capture-detection ligands in a sandwich-ALISA (aptamer-linked immobilized sorbent assay) format. The binding efficiency was confirmed by the fluorescence intensity in each microtire plate well. Using aptamers alone, detection of tetanus toxoid was possible with the same level of sensitivity as antibody. Aptamers were also used in the capture ALISA format. Adjuvanted tetanus toxoid was subjected to accelerated stress testing, including thermal, mechanical and freeze-thawing stress conditions. The loss in antigenicity of the preparation determined by ALISA in each case was found to be similar to that determined by conventional ELISA. Thus, it is possible to replace antibodies with aptamers to develop a more robust detection tool for tetanus toxoid.

  14. Tetanus toxoid IgE may be useful in predicting allergy during childhood. (United States)

    Ciprandi, G; De Amici, M; Quaglini, S; Labò, E; Castellazzi, A M; Miraglia Del Giudice, M; Marseglia, A; Bianchi, L; Moratti, R; Marseglia, G L


    Hypersensitivity reactions after immunization with tetanus toxoid are occasionally observed in atopic and non-atopic individuals. High IgE levels in infancy may predict subsequent allergy. The aims of this study were: i) to evaluate the role of specific IgE to tetanus toxoid in children in response to tetanus immunization and the possible factors associated with specific IgE levels, and ii) to investigate the correlation between specific IgE levels to tetanus toxoid and the late development of allergy (up to 12 years). Initially, 278 healthy infants (152 males and 126 females, aged 12 months) living in an urban city were screened for serum total IgE and specific IgE to tetanus toxoid, after having obtained informed consent from parents. After 12 years, 151 children could be evaluated. Total IgE summed with tetanus specific IgE were significantly associated with allergy at 12 years. In conclusion, this study demonstrates that serum total IgE and tetanus specific IgE may be predictive of subsequent allergy onset.

  15. 9 CFR 113.110 - Clostridium Botulinum Type C Bacterin-Toxoid. (United States)


    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Clostridium Botulinum Type C Bacterin-Toxoid. 113.110 Section 113.110 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Inactivated...

  16. CD4 T-helper cell cytokine phenotypes and antibody response following tetanus toxoid booster immunization (United States)

    Routine methods for enumerating antigen-specific T-helper cells may not identify low-frequency phenotypes such as Th2 cells. We compared methods of evaluating such responses to identify tetanus toxoid- (TT) specific Th1, Th2, Th17 and IL10+ cells. Eight healthy subjects were given a TT booster vacci...

  17. Update on the use of meningococcal serogroup C CRM₁₉₇-conjugate vaccine (Meningitec) against meningitis. (United States)

    Badahdah, Al-Mamoon; Rashid, Harunor; Khatami, Ameneh


    Meningitec is a CRM197-conjugated meningococcal serogroup C (MenC) vaccine, first licensed in 1999. It has been used as a primary and booster vaccine in infants, toddlers, older children and adults, and has been shown to be immunogenic and well-tolerated in all age groups, including premature infants. Vaccine effectiveness has been demonstrated using combined data on all three licensed MenC conjugate vaccines. Evidence from clinical trials, however, suggests that the different MenC conjugate vaccines behave differently with respect to the induction and persistence of bactericidal antibody and generation of immune memory. It appears that Meningitec has a less favorable immunologic profile compared particularly to tetanus toxoid (TT) MenC conjugate vaccines. Data from comparative trials have raised interesting questions on priming of the immune system by conjugate vaccines, particularly in infants. The results from these and other studies are reviewed here with specific focus on Meningitec.

  18. Quantitation of antibody-secreting cells in the blood after vaccination with Haemophilus influenzae type b conjugate vaccine

    DEFF Research Database (Denmark)

    Barington, T; Heilmann, C; Andersen, V


    -specific antibody-secreting cells (AbSC) of the isotypes IgM, IgG, and IgA. The appearance of AbSC in the blood after vaccination of adults with diphtheria toxoid-conjugated Hib polysaccharide was investigated. AbSC were detected from post-vaccination day 5 to day 14. IgA was the predominant isotype among......The human B-lymphocyte response to protein-conjugated polysaccharide antigens has not previously been studied at the cellular level. In order to do so, we developed and evaluated haemolytic plaque-forming cell assays detecting Haemophilus influenzae type b (Hib) capsular polysaccharide...

  19. Stabilization of tetanus and diphtheria toxoids against moisture-induced aggregation.


    Schwendeman, S P; Costantino, H R; Gupta, R.K.; Siber, G R; Klibanov, A M; Langer, R.


    The progress toward single-dose vaccines has been limited by the poor solid-state stability of vaccine antigens within controlled-release polymers, such as poly(lactide-co-glycolide). For example, herein we report that lyophilized tetanus toxoid aggregates during incubation at 37 degrees C and elevated humidity--i.e., conditions relevant to its release from such systems. The mechanism and extent of this aggregation are dependent on the moisture level in the solid protein, with maximum aggrega...

  20. Improved protection against cholera in adult rabbits with a combined flagellar-toxoid vaccine.


    Resnick, I. G.; Ford, C W; Shackleford, G M; Berry, L J


    Ligated ileal loops of adult rabbits were used to evaluate the prophylactic potential against cholera of a combined vaccine consisting of toxin-free crude flagella (CF) and glutaraldehyde-derived cholera toxoid (TV). The resulting fluid accumulation ratios were compared with those in rabbits immunized with saline (controls) and with CF and TV alone. Data for single vaccines confirmed the superior protection effect of CF over TV. In rabbits vaccinated with both CF and TV, maximal fluid accumul...

  1. A nonadjuvanted transcutaneous tetanus patch is effective in boosting anti-tetanus toxoid immune responses. (United States)

    Seid, Robert C; Reinisch, Christoph; Schlegl, Robert; Moehlen, Michael; Meinke, Andreas; Lundberg, Urban


    Dry tetanus toxoid (TTx) patches were formulated without any adjuvant, with excipients to impart antigen stabilization and to enhance skin delivery. The booster effects of the TTx patches were assessed using a guinea pig model. The study revealed significant rises in TTx IgG titers induced by the TTx patches after a low-dose subcutaneous (s.c.) prime with TTx adsorbed to aluminum hydroxide. The TTx patch can therefore be considered an effective alternative to a subcutaneous booster.

  2. Preparation and testing of a Haemophilus influenzae Type b/Hepatitis B surface antigen conjugate vaccine. (United States)

    An, So Jung; Woo, Joo Sung; Chae, Myung Hwa; Kothari, Sudeep; Carbis, Rodney


    The majority of conjugate vaccines focus on inducing an antibody response to the polysaccharide antigen and the carrier protein is present primarily to induce a T-cell dependent response. In this study conjugates consisting of poly(ribosylribitolphosphate) (PRP) purified from Haemophilus influenzae Type b bound to Hepatitis B virus surface antigen (HBsAg) virus like particles were prepared with the aim of inducing an antibody response to not only the PRP but also the HBsAg. A conjugate consisting of PRP bound to HBsAg via an adipic acid dihydrazide (ADH) spacer induced strong IgG antibodies to both the PRP and HBsAg. When conjugation was performed without the ADH spacer the induction of an anti-PRP response was equivalent to that seen by conjugate with the ADH spacer, however, a negligible anti-HBsAg response was induced. For comparison, PRP was conjugated to diphtheria toxoid (DT) and Vi polysaccharide purified from Salmonella Typhi conjugated to HBsAg both using an ADH spacer. The PRPAH-DT conjugate induced strong anti-PRP and anti-DT responses, the Vi-AHHBsAg conjugate induced a good anti-HBsAg response but not as strong as that induced by the PRPAH-HBsAg conjugate. This study demonstrated that in mice it was possible to induce robust antibody responses to both polysaccharide and carrier protein provided the conjugate has certain physico-chemical properties. A PRPAH-HBsAg conjugate with the capacity to induce anti-PRP and anti-HBsAg responses could be incorporated into a multivalent pediatric vaccine and simplify formulation of such a vaccine.

  3. Comparative Immunogenicity of the Tetanus Toxoid and Recombinant Tetanus Vaccines in Mice, Rats, and Cynomolgus Monkeys. (United States)

    Yu, Rui; Fang, Ting; Liu, Shuling; Song, Xiaohong; Yu, Changming; Li, Jianmin; Fu, Ling; Hou, Lihua; Xu, Junjie; Chen, Wei


    Tetanus is caused by the tetanus neurotoxin (TeNT) and is one of the most dreaded diseases especially in the developing countries. The current vaccine against tetanus is based on an inactivated tetanus toxin, which is effective but has many drawbacks. In our previous study, we developed a recombinant tetanus vaccine based on protein TeNT-Hc, with clear advantages over the toxoid vaccine in terms of production, characterization, and homogeneity. In this study, the titers, growth extinction, and persistence of specific antibodies induced by the two types of vaccine in mice, rats, and cynomolgus monkeys were compared. The booster vaccination efficacy of the two types of vaccines at different time points and protection mechanism in animals were also compared. The recombinant tetanus vaccine induced persistent and better antibody titers and strengthened the immunity compared with the commercially available toxoid vaccine in animals. Our results provide a theoretical basis for the development of a safe and effective recombinant tetanus vaccine to enhance the immunity of adolescents and adults as a substitute for the current toxoid vaccine.

  4. Effect of Vaccination with Carrier Protein on Response to Meningococcal C Conjugate Vaccines and Value of Different Immunoassays as Predictors of Protection


    Burrage, Moya; Robinson, Andrew; Borrow, Ray; Andrews, Nick; Southern, Joanna; Findlow, Jamie; Martin, Sarah; Thornton, Carol; Goldblatt, David; Corbel, Michael; Sesardic, Dorothea; Cartwight, Keith; Richmond, Peter; Miller, Elizabeth


    In order to plan for the wide-scale introduction of meningococcal C conjugate (MCC) vaccine for United Kingdom children up to 18 years old, phase II trials were undertaken to investigate whether there was any interaction between MCC vaccines conjugated to tetanus toxoid (TT) or a derivative of diphtheria toxin (CRM197) and diphtheria-tetanus vaccines given for boosting at school entry or leaving. Children (n = 1,766) received a diphtheria-tetanus booster either 1 month before, 1 month after, ...

  5. Immunogenicity of MenACWY-CRM in Korean Military Recruits: Influence of Tetanus-Diphtheria Toxoid Vaccination on the Vaccine Response to MenACWY-CRM. (United States)

    Kim, Han Wool; Park, In Ho; You, Sooseong; Yu, Hee Tae; Oh, In Soo; Sung, Pil Soo; Shin, Eui Cheol; Kim, Kyung Hyo


    The quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) has been introduced for military recruits in Korea since 2012. This study was performed to evaluate the immunogenicity of MenACWY-CRM in Korean military recruits. In addition, the influence of tetanus-diphtheria toxoids (Td) vaccination on the vaccine response to MenACWY-CRM was analyzed. A total of 75 military recruits were enrolled. Among them, 18 received a dose of MenACWY-CRM only (group 1), and 57 received Td three days before MenACWY-CRM immunization (group 2). The immunogenicity of MenACWY-CRM was compared between the two groups. The serum bactericidal activity with baby rabbit complement was measured before and three weeks after immunization against serogroups A, C, W-135, and Y. The geometric mean titers (GMTs) against four serogroups were significantly increased in both groups after immunization. Compared to group 2, group 1 exhibited significantly higher vaccine responses in several aspects: post-immune GMTs against serogroup A and C, seroresponse rates against serogroup A, and a fold increases of titers against serogroup A, C, and Y. MenACWY-CRM was immunogenic against all vaccine-serogroups in Korean military recruits. Vaccine response to MenACWY-CRM was influenced by Td administered three days earlier.

  6. ELISA detection of specific functional antibodies in human serum to Escherichia coli, tetanus toxoid, and diphtheria-tetanus toxoids: normal values for IgG, IgA, and IgM. (United States)

    Moen, R C; Oemichen, S L; Kiggens, A J; Hong, R


    An inexpensive, easily performed enzyme-linked immunosorbent assay (ELISA) was developed to measure specific IgG, IgA, and IgM antibodies to the common antigens Escherichia coli, diphtheria-tetanus toxoid, and tetanus toxoid. Normal values were established. Classical antibody deficiency disease states were confirmed and delineated by these assays. Additionally, several instances were discovered when functional antibody levels were abnormal when the serum immunoglobulin levels were normal. The use of ELISA assays for antibodies to common antigens provides a useful technique to measure and monitor isotype responses of the humoral immune system.

  7. 绵羊破伤风的诊断与防治%Diagnosis and Treatment on Tetanus Toxoid in Sheep

    Institute of Scientific and Technical Information of China (English)

    夏俊; 袁燕; 李新玉; 白春莲; 万利


    Diagnosis and treatment on Tetanus Toxoid in Sheep,author introduced that disease development,clinical symptoms and pathology alteration,diagnose and distinguish diagnose,treatment,preventive measures of Tetanus Toxoid in Sheep.In order to offering reference for culturist and veterinarian's preventive measures to Tetanus Toxoid in Sheep.%通过对一起绵羊破伤风疫情的诊治,笔者从该病的发病情况、临床症状及病理变化、临床诊断与实验室诊断、治疗、预防、防控措施等方面对绵羊破伤风疫病进行了介绍,旨在为养殖户及基层兽医进行绵羊破伤风疫病防治工作时提供借鉴。

  8. Comparative quantitation for the protein content of diphtheria and tetanus toxoids by DC protein assay and Kjeldahl method. (United States)

    Doshi, J B; Ravetkar, S D; Ghole, V S; Rehani, K


    DPT, a combination vaccine against diphtheria, tetanus and pertussis is available since many years and still continued in the national immunisation schedule of many countries. Although highly potent, reactions to DPT vaccine are well known, mainly attributed to the factors like Pertussis component, aluminum adjuvant and lower purity of tetanus and diphtheria toxoids. The latter most important aspect has become a matter of concern, specially for the preparation of next generation combination vaccines with more number of antigens in combination with DPT. Purity of toxoid is expressed as Lf (Limes flocculation) per mg of protein nitrogen. The Kjeldahl method (KM) of protein nitrogen estimation suggested by WHO and British Pharmacopoeia is time consuming and less specific. Need has been felt to explore an alternative method which is quick and more specific for toxoid protein determination. DC (detergent compatible) protein assay, an improved Lowry's method, has been found to be much more advantageous than Kjeldahl method.

  9. Collaborative study for the calibration of a replacement International Standard for Tetanus Toxoid Adsorbed. (United States)

    Tierney, Rob; Stickings, Paul; Hockley, Jason; Rigsby, Peter; Iwaki, Masaaki; Sesardic, Dorothea


    We present the results of a collaborative study for the establishment of a replacement International Standard (IS) for Tetanus Toxoid Adsorbed. Two candidate preparations were included in the study, one of which was established as the 4th IS for Tetanus Toxoid Adsorbed at the WHO Expert Committee on Biological Standardization meeting in October 2010. This preparation was found to have a unitage of 490 IU/ampoule, based on calibration in guinea pig challenge assays. Results from mouse challenge assays suggest that the relative performance of two candidate preparations may differ significantly between guinea pigs and mice. The authors note that the number of laboratories that performed guinea pig challenge assays, which are used to calibrate and assign IU, is much lower than in previous collaborative studies and this may have implications for calibration of replacement standards in the future. The issue of assigning separate units to the IS for guinea pig and mouse assays is discussed. The study also assessed performance of the replacement standard in serological assays which are used as alternative procedures to challenge assays for tetanus potency testing. Results suggest that the replacement standard is suitable for use as the reference vaccine in serological assays.

  10. Real time and accelerated stability studies of Tetanus toxoid manufactured in public sector facilities of Pakistan. (United States)

    Parveen, Ghazala; Hussain, Shahzad; Malik, Farnaz; Begum, Anwar; Mahmood, Sidra; Raza, Naeem


    Tetanus is an acute illness represented by comprehensive increased inflexibility and spastic spasms of skeletal muscles. The poor quality tetanus toxoid vaccine can raise the prevalence of neonatal tetanus. WHO has taken numerous steps to assist national regulatory authorities and vaccine manufacturers to ensure its quality and efficacy. It has formulated international principles for stability evaluation of each vaccine, which are available in the form of recommendations and guidelines. The aim of present study was to ensure the stability of tetanus vaccines produced by National Institute of Health, Islamabad, Pakistan by employing standardized methods to ensure constancy of tetanus toxoid at elevated temperature, if during storage/transportation cold chain may not be maintained in hot weather. A total of three batches filled during full-scale production were tested. All Stability studies determination were performed on final products stored at 2-8°C and elevated temperatures in conformance with the ICH Guideline of Stability Testing of Biological Products. These studies gave comparison between real time shelf-life stability and accelerated stability studies. The findings indicate long﷓term thermo stability and prove that this tetanus vaccine can remain efficient under setting of routine use when suggested measures for storage and handling are followed in true spirit.

  11. Diphtheria toxoid-containing microparticulate powder formulations for pulmonary vaccination : Preparation, characterization and evaluation in guinea pigs

    NARCIS (Netherlands)

    Amidi, Maryam; Pellikaan, Hubert C.; Hirschberg, Hoang; de Boerd, Anne H.; Crommelin, Daan J. A.; Hennink, Wim E.; Kersten, Gideon; Jiskoot, Wim


    this study, the potential of N-Trimethyl chitosan (TMC, degree of quaternization 50%) and dextran microparticles for pulmonary delivery of diphtheria toxoid (DT) was investigated. The antigen-containing microparticles were prepared by drying of an aqueous solution of polymer and DT through a supercr

  12. Revisiting conjugate schedules. (United States)

    MacAleese, Kenneth R; Ghezzi, Patrick M; Rapp, John T


    The effects of conjugate reinforcement on the responding of 13 college students were examined in three experiments. Conjugate reinforcement was provided via key presses that changed the clarity of pictures displayed on a computer monitor in a manner proportional to the rate of responding. Experiment 1, which included seven parameters of clarity change per response, revealed that responding decreased as the percentage clarity per response increased for all five participants. These results indicate that each participant's responding was sensitive to intensity change, which is a parameter of conjugate reinforcement schedules. Experiment 2 showed that responding increased during conjugate reinforcement phases and decreased during extinction phases for all four participants. Experiment 3 also showed that responding increased during conjugate reinforcement and further showed that responding decreased during a conjugate negative punishment condition for another four participants. Directions for future research with conjugate schedules are briefly discussed.

  13. Post-exposure vaccination with tetanus toxoid alone, does not protect against tetanus: an illustrative case

    Directory of Open Access Journals (Sweden)

    Sunitha B


    Full Text Available Tetanus is a life threatening infectious disease caused by the anaerobic Gram-positive bacillus Clostridium tetani which enters the body through an open wound. A 60-years-old male patient who was referred to our institute with a history of a rusted iron with complaints of nail prick injury and difficulty in opening the mouth. This individual previously not receive tetanus immunoglobulin. Prior to coming to our institute, the rusted iron nail was extracted and he had received tetanus toxoid. After he was admitted in the tetanus ward at our institute, he developed spasms. He was treated with intravenous diazepam and tetanus immunoglobulins. Wound exploration revealed a retained residual foreign body that was a part of his rubber foot wear in the wound. He died on the sixth day of admission. The present case highlights the need for administering appropriate active and passive immunization for tetanus along with meticulous wound care.

  14. Short-term booster effect of diphtheria toxoid in initially long-term protected individuals. (United States)

    Danilova, Elena; Shiryayev, Alexey; Skogen, Vegard; Kristoffersen, Einar Klaeboe; Sjursen, Haakon


    The main objective of this study was to investigate the booster antibody response in individuals with initially high levels of diphtheria antitoxin. Sixty individuals eligible for the routine booster by the age of 18 years each received a single dose of 5 Lf of diphtheria toxoid in diphtheria-tetanus vaccine. A double antigen ELISA was used for the assessment of the antibody levels. Chaotropic disruption in paired ELISA was used to test antibody avidity. The ratio between initial and maximum antibody concentrations after 1 month was >10 times higher and after 6 months still four times higher in those with initial antibody levels antibody levels >/=1 IU/ml a two-fold decrease was observed after 6 months compared to the initial levels. Thus, vaccination of individuals with initial long-term protection against diphtheria (antibody levels >/=1 IU/ml) is unnecessary and should be avoided.

  15. Towards Rational Design of a Toxoid Vaccine against the Heat-Stable Toxin of Escherichia coli (United States)

    Taxt, Arne M.; Diaz, Yuleima; Aasland, Rein; Clements, John D.; Nataro, James P.; Sommerfelt, Halvor


    Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrheal disease and death in children <5 years old. ETEC strains that express the heat-stable toxin (ST), with or without the heat-labile toxin, are among the four most important diarrhea-causing pathogens. This makes ST an attractive target for an ETEC vaccine. An ST vaccine should be nontoxic and elicit an immune response that neutralizes native ST without cross-reacting with the human endogenous guanylate cyclase C receptor ligands. To identify variants of ST with no or low toxicity, we screened a library of all 361 possible single-amino-acid mutant forms of ST by using the T84 cell assay. Moreover, we identified mutant variants with intact epitopes by screening for the ability to bind neutralizing anti-ST antibodies. ST mutant forms with no or low toxicity and intact epitopes are termed toxoid candidates, and the top 30 candidates all had mutations of residues A14, N12, and L9. The identification of nontoxic variants of L9 strongly suggests that it is a novel receptor-interacting residue, in addition to the previously identified N12, P13, and A14 residues. The screens also allowed us to map the epitopes of three neutralizing monoclonal antibodies, one of which cross-reacts with the human ligand uroguanylin. The common dominant epitope residue for all non-cross-reacting antibodies was Y19. Our results suggest that it should be possible to rationally design ST toxoids that elicit neutralizing immune responses against ST with minimal risk of immunological cross-reactivity. PMID:26883587

  16. Salmonella typhi O:9,12 polysaccharide-protein conjugates: characterization and immunoreactivity with pooled and individual normal human sera, sera from patients with paratyphoid A and B and typhoid fever, and animal sera. (United States)

    Aron, L; Di Fabio, J; Cabello, F C


    Polysaccharide of O:9,12 specificity purified from Salmonella typhi was conjugated to tetanus toxoid or bovine serum albumin in order to obtain defined antigenic material that would contain O chain free of other S. typhi antigens and that would be suitable for characterizing host humoral response to only S. typhi O-chain antigens. These artificial conjugates were strongly reactive in immunodots with 18 pooled and 3 individual serum samples from patients with typhoid fever and with rabbit anti-Salmonella O antiserum (group D, factors 1, 9, and 12). They reacted weakly with one serum sample from one human with paratyphoid A. These results suggest that the periodate oxidation and the reductive amination used in the conjugation conserved the immunogenicity of the O chain and allowed its absorption to nitrocellulose. They also suggest that the bovine serum albumin conjugate could be used in the diagnosis of S. typhi infections as normal sera may react with the protein molecule of the tetanus toxoid conjugate.

  17. Vi capsular polysaccharide-protein conjugates for prevention of typhoid fever. Preparation, characterization, and immunogenicity in laboratory animals. (United States)

    Szu, S C; Stone, A L; Robbins, J D; Schneerson, R; Robbins, J B


    The Vi has proven to be a protective antigen in two double masked, controlled clinical trials in areas with high rates of typhoid fever (approximately 1% per annum). In both studies the protective efficacy of the Vi was approximately 70%. Approximately 75% of subjects in these areas responded with a fourfold or greater rise of serum Vi antibodies. In contrast, the Vi elicited a fourfold or greater rise in 95-100% of young adults in France and the United States. Methods were devised, therefore, to synthesize Vi-protein conjugates in order to both enhance the antibody response and confer T-dependent properties to the Vi (and theoretically increase its protective action in populations at high risk for typhoid fever). We settled on a method that used the heterobifunctional crosslinking reagent, N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP), to bind thiol derivatives of the Vi to proteins. This synthetic scheme was reproducible, provided high yields of Vi-protein conjugates, and was applicable to several medically relevant proteins such as diphtheria and tetanus toxoids. The resultant conjugates were more immunogenic in mice and juvenile Rhesus monkeys than the Vi alone. In contrast to the T-independent properties of the Vi, conjugates of this polysaccharide with several medically relevant proteins induced booster responses in mice and in juvenile Rhesus monkeys. Clinical studies with Vi-protein conjugates are planned. This scheme is also applicable to synthesize protein conjugates with other polysaccharides that have carboxyl functions.

  18. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine in adults aged 65 years and older - Advisory Committee on Immunization Practices (ACIP), 2012. (United States)


    Since 2005, the Advisory Committee on Immunization Practices (ACIP) has recommended a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine booster dose for all adolescents aged 11 through 18 years (preferred at 11 through 12 years) and for those adults aged 19 through 64 years who have not yet received a dose. In October 2010, despite the lack of an approved Tdap vaccine for adults aged 65 years and older, ACIP recommended that unvaccinated adults aged 65 years and older be vaccinated with Tdap if in close contact with an infant, and that other adults aged 65 years and older may receive Tdap. In July 2011, the Food and Drug Administration (FDA) approved expanding the age indication for Boostrix (GlaxoSmithKline Biologicals, Rixensart, Belgium) to aged 65 years and older. In February 2012, ACIP recommended Tdap for all adults aged 65 years and older. This recommendation supersedes previous Tdap recommendations regarding adults aged 65 years and older.

  19. Technical and diagnostic performance of five commercial anti-diphtheria toxoid IgG enzyme-linked immunosorbent assay kits. (United States)

    Faruq, A; Dadson, L; Cox, H; Alcock, F; Parker, A R


    The technical and diagnostic performances of five commercially available enzyme-linked immunosorbent assays for the measurement of anti-diphtheria toxoid IgG antibodies were evaluated. There was good agreement between the relative sensitivities of the five assays, but the relative specificity of one of the assays differed from that of the other four assays. Three of the five assays possessed recoveries of the international reference material NIBSC 00/496 within the range of 90% to 110% at antibody levels >0.1 IU/ml. The data suggest that there are manufacture-dependent differences in relative sensitivity, specificity, and accuracy for the determination of anti-diphtheria toxoid IgG antibodies that could result in different diagnostic interpretations.

  20. Impaired cellular immune response to tetanus toxoid but not to cytomegalovirus in effectively HAART-treated HIV-infected children. (United States)

    Alsina, Laia; Noguera-Julian, Antoni; Fortuny, Clàudia


    Despite of highly active antiretroviral therapy, the response to vaccines in HIV-infected children is poor and short-lived, probably due to a defect in cellular immune responses. We compared the cellular immune response (assessed in terms of IFN-γ production) to tetanus toxoid and to cytomegalovirus in a series of 13 HIV-perinatally-infected children and adolescents with optimal immunovirological response to first line antiretroviral therapy, implemented during chronic infection. A stronger cellular response to cytomegalovirus (11 out of 13 patients) was observed, as compared to tetanus toxoid (1 out of 13; p=0.003). These results suggest that the repeated exposition to CMV, as opposed to the past exposition to TT, is able to maintain an effective antigen-specific immune response in stable HIV-infected pediatric patients and strengthen current recommendations on immunization practices in these children.

  1. [Pneumococcal vaccination: conjugated vaccine induces herd immunity and reduces antibiotic resistance]. (United States)

    Pletz, M W; Maus, U; Hohlfeld, J M; Lode, H; Welte, T


    Pneumococcal infections (pneumonia, otitis media, sinusitis, meningitis) are common and usually involve toddlers and the elderly. Currently, two pneumococcal vaccines are in clinical use. The older vaccine consists of pure capsular polysaccharides from 23 pneumococcal serotypes and induces only a limited B-cell response because polysaccharides are poor antigens that stimulate mainly B-cells. In 2000, a vaccination program with a novel 7-valent pneumococcal conjugate vaccine was launched in the U.S. The conjugation of capsular polysaccharides with a highly immunogenic diphtheria toxoid protein induces both a T cell and B cell response that results in specific humoral and mucosal immunity. Since children are the main reservoir of pneumococci, the 7-valent conjugate vaccine seems to eradicate the respective pneumococcal serotypes within the population, as demonstrated by recent US data. Pronounced herd immunity resulted in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as in a reduction of antibiotic resistance rates. However, recent data suggest a replacement of vaccine-serotypes by non-vaccine serotypes, which conquer the ecological niche created by the vaccine. In order to encounter this problem a 13-valent conjugated vaccine is currently under development.

  2. Divalent toxoids loaded stable chitosan-glucomannan nanoassemblies for efficient systemic, mucosal and cellular immunostimulatory response following oral administration. (United States)

    Harde, Harshad; Siddhapura, Krupa; Agrawal, Ashish Kumar; Jain, Sanyog


    The present study reports dual tetanus and diphtheria toxoids loaded stable chitosan-glucomannan nanoassemblies (sCh-GM-NAs) formulated using tandem ionic gelation technique for oral mucosal immunization. The stable, lyophilized sCh-GM-NAs exhibited ~152 nm particle size and ~85% EE of both the toxoids. The lyophilized sCh-GM-NAs displayed excellent stability in biomimetic media and preserved chemical, conformation and biological stability of encapsulated toxoids. The higher intracellular APCs uptake of sCh-GM-NAs was concentration and time dependent which may be attributed to the receptor mediated endocytosis via mannose and glucose receptor. The higher Caco-2 uptake of sCh-GM-NAs was further confirmed by ex vivo intestinal uptake studies. The in vivo evaluation revealed that sCh-GM-NAs posed significantly (p<0.001) higher humoral, mucosal and cellular immune response than other counterparts by eliciting complete protective levels of anti-TT and anti-DT (~0.1 IU/mL) antibodies. Importantly, commercial 'Dual antigen' vaccine administered through oral or intramuscular route was unable to elicit all type of immune response. Conclusively, sCh-GM-NAs could be considered as promising vaccine adjuvant for oral mucosal immunization.

  3. Chitosan-HPMC-blended microspheres as a vaccine carrier for the delivery of tetanus toxoid. (United States)

    Arthanari, Saravanakumar; Mani, Ganesh; Peng, Mei Mei; Jang, Hyun Tae


    The purpose of this research was to develop a suitable and alternate adjuvant for the tetanus toxoid (TT) vaccine that induces long term immunity after a single-dose immunization. In our study, the preformulation studies were carried out by using different ratios (7/3, 8/2, and 9/1) of chitosan-hydroxypropyl methylcellulose (HPMC)-blended empty microspheres. Moreover, TT was stabilized with heparin (at heparin concentrations of 1%, 2%, 3%, and 4% w/v) and encapsulated in ideal chitosan - HPMC (CHBMS) microspheres, by the water-in-oil-in-water (W/O/W) multiple emulsion method. The vaccine entrapment and the in vitro release efficiency of the CHBMS was evaluated for a period of 90 days. The release of antigens from the microspheres was determined by ELISA. Antigen integrity was investigated by SDS-PAGE. From the optimization studies, it was found that a chitosan/HPMC ratio of 8/2 produced a good yield, with microspheres that were spherical, regular and uniformly-sized. In the CHBMS, a heparin concentration of 3% w/v resulted in well-sustained antigen delivery for a period of 90 days. It was found that the characteristics of initial release could be observed in 2 days, followed by a constant release, and an almost 100% complete release in 90 days. From the in vitro release characteristics, the ideal batch of CHBMS (3% w/v heparin) was evaluated for in vivo studies by the antibody induction method. The antibody levels were measured for different combinations for the period of 9 months, and finally, with a second booster dose after 1 year. In conclusion, it was observed that CHBMS (combination-1) resulted in the antibody level of 4.5 IU/mL of guinea pig serum, and the level was 3.5 IU/mL for the Central Research Institute's alum-adsorbed tetanus toxoid (CRITT) (combination 2), after 1 year, with a second booster dose. This novel approach of using CHBMS may have potential advantages for single-step immunization with vaccines.

  4. Segmented conjugated polymers

    Indian Academy of Sciences (India)

    G Padmanaban; S Ramakrishnan


    Segmented conjugated polymers, wherein the conjugation is randomly truncated by varying lengths of non-conjugated segments, form an interesting class of polymers as they not only represent systems of varying stiffness, but also ones where the backbone can be construed as being made up of chromophores of varying excitation energies. The latter feature, especially when the chromophores are fluorescent, like in MEHPPV, makes these systems particularly interesting from the photophysics point of view. Segmented MEHPPV- samples, where x represents the mole fraction of conjugated segments, were prepared by a novel approach that utilizes a suitable precursor wherein selective elimination of one of the two eliminatable groups is affected; the uneliminated units serve as conjugation truncations. Control of the composition x of the precursor therefore permits one to prepare segmented MEHPPV- samples with varying levels of conjugation (elimination). Using fluorescence spectroscopy, we have seen that even in single isolated polymer chains, energy migration from the shorter (higher energy) chromophores to longer (lower energy) ones occurs – the extent of which depends on the level of conjugation. Further, by varying the solvent composition, it is seen that the extent of energy transfer and the formation of poorly emissive inter-chromophore excitons are greatly enhanced with increasing amounts of non-solvent. A typical S-shaped curve represents the variation of emission yields as a function of composition suggestive of a cooperative collapse of the polymer coil, reminiscent of conformational transitions seen in biological macromolecules.

  5. Hoffmeister Series Ions Protect Diphtheria Toxoid from Structural Damages at Solvent/Water Interface

    Directory of Open Access Journals (Sweden)

    Pedro S. de Araujo


    Full Text Available During the W1/O phase (in the W1/O/W2 process of protein microencapsulation within poly-lactide-co-glycolide (PLGA, hydrophobic interfaces are expanded where interfacial adsorption occurs followed by protein unfolding and aggregation. Spectroscopic and immunological techniques were used to ascertain the effects of the Hoffmeister series ions on Diphtheria toxoid (Dtxd stability during the W1/O phase. A correlation was established between salts used in aqueous solutions and the changes in Dtxd solubility and conformation. The Dtxd α-helical content was quite stable thus leading to the conclusion that encapsulation was followed by protein aggregation, with minor exposition of hydrophobic residues and a small change at the S-S dihedral angle. Dtxd aggregation is 95% avoided by the chaotropic SCN-. This was used to prepare a stable Dtxd and immunologically recognized/PLGA formulation in the presence of 30 mM SNC-. The recovery increased by 10.42% or 23.2% when microencapsulation was within the -COOMe or -COOH (12kDa PLGA, respectively. In conclusion, the aim of this work was achieved, which was to obtain the maximum of Dtxd stability after contact with CH2Cl2 to begin its PLGA microencapsulation within ideal conditions. This was a technological breakthrough because a simple solution like salt addition avoided heterologous proteins usage.

  6. Diphtheria toxoid loaded poly-(epsilon-caprolactone) nanoparticles as mucosal vaccine delivery systems. (United States)

    Singh, Jasvinder; Pandit, Sreenivas; Bramwell, Vincent W; Alpar, H Oya


    Poly-(epsilon-caprolactone) (PCL), a poly(lactide-co-glycolide) (PLGA)-PCL blend and co-polymer nanoparticles encapsulating diphtheria toxoid (DT) were investigated for their potential as a mucosal vaccine delivery system. The nanoparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method, demonstrated release profiles which were dependent on the properties of the polymers. An in vitro experiment using Caco-2 cells showed significantly higher uptake of PCL nanoparticles in comparison to polymeric PLGA, the PLGA-PCL blend and co-polymer nanoparticles. The highest uptake mediated by the most hydrophobic nanoparticles using Caco-2 cells was mirrored in the in vivo studies following nasal administration. PCL nanoparticles induced DT serum specific IgG antibody responses significantly higher than PLGA. A significant positive correlation between hydrophobicity of the nanoparticles and the immune response was observed following intramuscular administration. The positive correlation between hydrophobicity of the nanoparticles and serum DT specific IgG antibody response was also observed after intranasal administration of the nanoparticles. The cytokine assays showed that the serum IgG antibody response induced is different according to the route of administration, indicated by the differential levels of IL-6 and IFN-gamma. The nanoparticles eliciting the highest IgG antibody response did not necessarily elicit the highest levels of the cytokines IL-6 and IFN-gamma.

  7. Optimization of tetanus toxoid ammonium sulfate precipitation process using response surface methodology. (United States)

    Brgles, Marija; Prebeg, Pero; Kurtović, Tihana; Ranić, Jelena; Marchetti-Deschmann, Martina; Allmaier, Günter; Halassy, Beata


    Tetanus toxoid (TTd) is a highly immunogenic, detoxified form of tetanus toxin, a causative agent of tetanus disease, produced by Clostridium tetani. Since tetanus disease cannot be eradicated but is easily prevented by vaccination, the need for the tetanus vaccine is permanent. The aim of this work was to investigate the possibility of optimizing TTd purification, i.e., ammonium sulfate precipitation process. The influence of the percentage of ammonium sulfate, starting amount of TTd, buffer type, pH, temperature, and starting purity of TTd on the purification process were investigated using optimal design for response surface models. Responses measured for evaluation of the ammonium sulfate precipitation process were TTd amount (Lf/mL) and total protein content. These two parameters were used to calculate purity (Lf/mgPN) and the yield of the process. Results indicate that citrate buffer, lower temperature, and lower starting amount of TTd result in higher purities of precipitates. Gel electrophoresis combined with matrix-assisted laser desorption ionization-mass spectrometric analysis of precipitates revealed that there are no inter-protein cross-links and that all contaminating proteins have pIs similar to TTd, so this is most probably the reason for the limited success of purification by precipitation.

  8. Seroprevalence of tetanus toxoid antibody and booster vaccination efficacy in Japanese travelers. (United States)

    Mizuno, Yasutaka; Yamamoto, Akihiko; Komiya, Takako; Takeshita, Nozomi; Takahashi, Motohide


    Tetanus can be prevented by vaccination, which is especially important for overseas travelers. However, despite booster vaccination every 10 years being recommended, most Japanese adults do not receive it in the absence of physical injury or overseas travel. We aimed to investigate the level of protective immunity against tetanus among Japanese travelers, which may provide valuable information for formulating booster vaccination recommendations. 113 Japanese travelers given tetanus toxoid were recruited. The collected samples included paired samples prior to and 3-5 weeks after receiving the booster vaccination. Travelers who did not return and those lacking sample collection at the second visit were excluded. Finally, 96 paired blood samples were collected. History of immunization against tetanus, including DPT and DT vaccines, was determined from interviews or immunization records. The pre-vaccination geometric mean titer for the 96 participants was 1.07 IU/mL; 76% had a protective antitoxin level (>0.1 IU/mL), and 50% had a long-term protective antitoxin level (>1.0 IU/mL). Most participants 50 years of age had protective immunity. Among the 23 participants without protective antitoxin levels (50 years of age. Although the tetanus antitoxin level decreases with age, booster vaccination helped to achieve an adequate protective antitoxin levels in Japanese travelers tetanus especially in those >50 years old need to obtain protective immunity against tetanus according to a basic immunization schedule to prevent tetanus in travelers and residents of Japan.

  9. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. (United States)

    Mitchell, Duane A; Batich, Kristen A; Gunn, Michael D; Huang, Min-Nung; Sanchez-Perez, Luis; Nair, Smita K; Congdon, Kendra L; Reap, Elizabeth A; Archer, Gary E; Desjardins, Annick; Friedman, Allan H; Friedman, Henry S; Herndon, James E; Coan, April; McLendon, Roger E; Reardon, David A; Vredenburgh, James J; Bigner, Darell D; Sampson, John H


    After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vaccines have shown limited promise in the treatment of patients with advanced cancers including glioblastoma, the factors dictating DC vaccine efficacy remain poorly understood. Here we show that pre-conditioning the vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumour-antigen-specific DCs. To assess the effect of vaccine site pre-conditioning in humans, we randomized patients with glioblastoma to pre-conditioning with either mature DCs or Td unilaterally before bilateral vaccination with DCs pulsed with Cytomegalovirus phosphoprotein 65 (pp65) RNA. We and other laboratories have shown that pp65 is expressed in more than 90% of glioblastoma specimens but not in surrounding normal brain, providing an unparalleled opportunity to subvert this viral protein as a tumour-specific target. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumour growth in a manner dependent on the chemokine CCL3. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen may represent a viable strategy to improve anti-tumour immunotherapy.

  10. Qualidade conjugal: mapeando conceitos

    Directory of Open Access Journals (Sweden)

    Clarisse Mosmann


    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.

  11. Polymers for Protein Conjugation

    Directory of Open Access Journals (Sweden)

    Gianfranco Pasut


    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.

  12. Embryotoxicity and teratogenicity studies of poly (DL-lactide-co-glycolide) microspheres incorporated tetanus toxoid in Wistar rats. (United States)

    Chandrasekaran, R; Giri, D K; Chaudhury, M R


    Tetanus Toxoid loaded biodegradable microspheres (MTT) (poly (DL-Lactide-co-Glycolide) were administered intramuscularly to pregnant Wistar rats from Days 6 to 15 of gestation, at 1, 5 and 10-times the human equivalent dose of TT. Developmental defects in relation to soft tissues and skeleton, weight and sex of live pups and early fetal deaths from treated and control rats were analysed. The findings in treatment groups were comparable to those in the controls. These observations show that MTT was safe for pregnant rats and developing pups.

  13. Maternal tetanus toxoid vaccination and neonatal mortality in rural north India.

    Directory of Open Access Journals (Sweden)

    Abhishek Singh

    Full Text Available OBJECTIVES: Preventable neonatal mortality due to tetanus infection remains common. We aimed to examine antenatal vaccination impact in a context of continuing high neonatal mortality in rural northern India. METHODS AND FINDINGS: Using the third round of the Indian National Family Health Survey (NFHS 2005-06, mortality of most recent singleton births was analysed in discrete-time logistic model with maternal tetanus vaccination, together with antenatal care utilisation and supplementation with iron and folic acid. 59% of mothers reported receiving antenatal care, 48% reported receiving iron and folic acid supplementation and 68% reported receiving two or more doses of tetanus toxoid (TT vaccination. The odds of all-cause neonatal death were reduced following one or more antenatal dose of TT with odds ratios (OR of 0.46 (95% CI 0.26 to 0.78 after one dose and 0.45 (95% CI 0.31 to 0.66 after two or more doses. Reported utilisation of antenatal care and iron-folic acid supplementation did not influence neonatal mortality. In the statistical model, 16% (95% CI 5% to 27% of neonatal deaths could be attributed to a lack of at least two doses of TT vaccination during pregnancy, representing an estimated 78,632 neonatal deaths in absolute terms. CONCLUSIONS: Substantial gains in newborn survival could be achieved in rural North India through increased coverage of antenatal TT vaccination. The apparent substantial protective effect of a single antenatal dose of TT requires further study. It may reflect greater population vaccination coverage and indicates that health programming should prioritise universal antenatal coverage with at least one dose.

  14. CD4 T-helper cell cytokine phenotypes and antibody response following tetanus toxoid booster immunization. (United States)

    Livingston, Kimberly A; Jiang, Xiaowen; Stephensen, Charles B


    Routine methods for enumerating antigen-specific T-helper cells may not identify low-frequency phenotypes such as Th2 cells. We compared methods of evaluating such responses to identify tetanus toxoid- (TT) specific Th1, Th2, Th17 and IL10(+) cells. Eight healthy subjects were given a TT booster vaccination. Blood was drawn before, 3, 7, 14, and 28days after vaccination and peripheral blood mononuclear cells (PBMC) were cultured for 7days with TT, negative control (diluent), and a positive control (Staphylococcus enterotoxin B [SEB]). Activation markers (CD25 and CD69) were measured after 44h (n=8), cytokines in supernatant after 3 and 7days, and intracellular cytokine staining (ICS) of proliferated cells (identified by dye dilution) after 7days (n=6). Vaccination increased TT-specific expression of CD25 and CD69 on CD3(+)CD4(+) lymphocytes, and TT-specific proliferation at 7, 14 and 28days post vaccination. Vaccination induced TT-specific Th1 (IFN-γ, TNF-α, and IL-2) Th2 (IL-13, IL-5, and IL-4), Th17 (IL-17A) and IL-10(+) cells as measured by ICS. TT-specific Th1 cells were the most abundant (12-15% of all TT-specific CD4(+) T-cells) while IL10(+) (1.8%) Th17 (1.1%) and Th2 cells (0.2-0.6%) were less abundant. TT-specific cytokine concentrations in PBMC supernatants followed the same pattern where a TT-specific IL-9 response was also seen. In conclusion, TT booster vaccination induced a broad T-helper cell response. This method of evaluating cytokine phenotypes may be useful in examining the impact of nutrition and environmental conditions on the plasticity of T-helper cell memory responses.

  15. Tetanus toxoid vaccine: elimination of neonatal tetanus in selected states of India. (United States)

    Verma, Ramesh; Khanna, Pardeep


    Tetanus is caused by a neurotoxin produced by Clostridium tetani (C. tetani), a spore-forming bacterium. Infection begins when tetanus spores are introduced into damaged tissue. Tetanus is characterized by muscle rigidity and painful muscle spasms caused by tetanus toxin's blockade of inhibitory neurons that normally oppose and modulate the action of excitatory motor neurons. Maternal and neonatal tetanus (MNT) are caused by unhygienic methods of delivery, abortion, or umbilical-cord care. Maternal and neonatal tetanus are both forms of generalized tetanus and have similar clinical courses. About 90% of neonates with tetanus develop symptoms in the first 3-14 d of life, mostly on days 6-8, distinguishing neonatal tetanus from other causes of neonatal mortality which typically occur during the first two days of life. Overall case fatality rates for patients admitted to the hospital with neonatal tetanus in developing countries are 8-50%, while the fatality rate can be as high as 100% without hospital care. Tetanus toxoid (TT) vaccination of pregnant women to prevent neonatal tetanus was included in WHO's Expanded Program on Immunization (EPI) a few years after its inception in 1974. In 2000, WHO, UNICEF, and UNFPA formed a partnership to relaunch efforts toward this goal, adding the elimination of maternal tetanus as a program objective, and setting a new target date of 2005. By February 2007, 40 countries had implemented tetanus vaccination campaigns in high-risk areas, targeting more than 94 million women, and protecting more than 70 million subjects with at least two doses of TT. In 2011, 653 NT cases were reported in India compared with 9313 in 1990. As of February 2012, 25 countries and 15 States and Union Territories of India, all of Ethiopia except Somaliland, and almost 29 of 34 provinces in Indonesia have been validated to have eliminated MNT.

  16. Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products

    Energy Technology Data Exchange (ETDEWEB)

    May, J.C. E-mail:; Rey, L. E-mail:; Lee, C.-J.; Arciniega, Juan


    Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine.

  17. Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products (United States)

    May, J. C.; Rey, L.; Lee, Chi-Jen; Arciniega, Juan


    Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine.

  18. Transcutaneous vaccination using a hydrogel patch induces effective immune responses to tetanus and diphtheria toxoid in hairless rat. (United States)

    Matsuo, Kazuhiko; Ishii, Yumiko; Quan, Ying-Shu; Kamiyama, Fumio; Mukai, Yohei; Yoshioka, Yasuo; Okada, Naoki; Nakagawa, Shinsaku


    Transcutaneous immunization (TCI) targeting the Langerhans cells (LCs) of the epidermal layer is a promising needle-free, easy-to-use, and non-invasive vaccination method. We developed a hydrogel patch formulation to promote the penetration of antigenic proteins into the stratum corneum. Here, we investigated the characteristics of the immune responses induced by this vaccination method and the vaccine efficacy of TCI using a hydrogel patch containing tetanus and diphtheria toxoids. Our TCI system induced toxoid-specific IgG production in an antigen dose-, patch area-, and application period-dependent manner. Moreover, IgG subclass analysis indicated that our TCI predominantly elicited a Th2-type immune response rather than a Th1-type immune response. Importantly, our TCI system induced antigen-specific immune memory based on the booster effect and showed potent efficacy, comparable to that of subcutaneous immunization in toxin-challenge experiments. On the basis of these results, we are now performing translational research to apply TCI for tetanus and diphtheria.

  19. An in vitro immune response model to determine tetanus toxoid antigen (vaccine) specific immunogenicity: Selection of sensitive assay criteria. (United States)

    Piersma, Sytse J; Leenaars, Marlies P P A M; Guzylack-Piriou, Laurence; Summerfield, Artur; Hendriksen, Coenraad F M; McCullough, Ken C


    Many vaccines employed in childhood vaccination programmes are produced by conventional techniques, resulting in complex biological mixtures for which batch-related quality control requires in vivo potency testing. Monitoring consistency via in vitro tests during the vaccine production has the capacity to replace certain of the in vivo methods. In this respect, determining vaccine antigen immunogenicity through functional immunological tests has high potential. Advances in immunology have made it possible to analyse this biological activity by in vitro means. The present study established such an in vitro test system for tetanus toxoid (TT). This measured vaccine immunogenicity through an antigen-specific secondary (recall) response in vitro, using a porcine model growing in value for its closeness to human immune response characteristics. Discrimination between the specific recall TT antigen and diphtheria toxoid (DT) was possible using both peripheral blood mononuclear cell cultures and monocyte-derived dendritic cells in co-culture with autologous specific lymphocytes. TT-specific activation was detected with highest discrimination capacity using proliferation assays, as well as IFN-gamma and TT-specific antibody ELISPOTS (measuring secreting T and B lymphocytes, respectively). These in vitro systems show a high potential for replacing animal experimentation to evaluate the immunogenicity of complex vaccines.

  20. Long-term effects of tetanus toxoid inoculation on the demography and life expectancy of the Cayo Santiago rhesus macaques. (United States)

    Kessler, Matthew J; Hernández Pacheco, Raisa; Rawlins, Richard G; Ruiz-Lambrides, Angelina; Delgado, Diana L; Sabat, Alberto M


    Tetanus was a major cause of mortality in the free-ranging population of rhesus monkeys on Cayo Santiago prior to 1985 when the entire colony was given its first dose of tetanus toxoid. The immediate reduction in mortality that followed tetanus toxoid inoculation (TTI) has been documented, but the long-term demographic effects of eliminating tetanus infections have not. This study uses the Cayo Santiago demographic database to construct comparative life tables 12 years before, and 12 years after, TTI. Life tables and matrix projection models are used to test for differences in: (i) survival among all individuals as well as among social groups, (ii) long-term fitness of the population, (iii) age distribution, (iv) reproductive value, and (v) life expectancy. A retrospective life table response experiment (LTRE) was performed to determine which life cycle transition contributed most to observed changes in long-term fitness of the population post-TTI. Elimination of clinical tetanus infections through mass inoculation improved the health and well-being of the monkeys. It also profoundly affected the population by increasing survivorship and long-term fitness, decreasing the differences in survival rates among social groups, shifting the population's age distribution towards older individuals, and increasing reproductive value and life expectancy. These findings are significant because they demonstrate the long-term effects of eradicating a major cause of mortality at a single point in time on survival, reproduction, and overall demography of a naturalistic population of primates.

  1. Conjugation in "Escherichia coli" (United States)

    Phornphisutthimas, Somkiat; Thamchaipenet, Arinthip; Panijpan, Bhinyo


    Bacterial conjugation is a genetic transfer that involves cell-to-cell between donor and recipient cells. With the current method used to teach students in genetic courses at the undergraduate level, the transconjugants are identified using bacterial physiology and/or antibiotic resistance. Using physiology, however, is difficult for both…

  2. DNA-cell conjugates (United States)

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


    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.

  3. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert


    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....

  4. Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines.

    NARCIS (Netherlands)

    Theeten, H.; Rumke, H.C.; Hoppener, F.J.; Vilatimo, R.; Narejos, S.; Damme, P. van; Hoet, B.


    OBJECTIVE: To evaluate immunogenicity and reactogenicity of primary vaccination with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) or dTpa-inactivated poliovirus (dTpa-IPV) vaccine compared to diphtheria-tetanus-toxoid vaccines (Td) in adults > or = 40 years of age without

  5. Acute necrotizing encephalopathy secondary to diphtheria, tetanus toxoid and whole-cell pertussis vaccination: diffusion-weighted imaging and proton MR spectroscopy findings

    Energy Technology Data Exchange (ETDEWEB)

    Aydin, Hale; Ozgul, Esra; Agildere, Ahmet Muhtesem [Baskent University Hospital, Department of Radiology, Ankara (Turkey)


    We present a previously healthy 6-month-old boy who was admitted to our hospital with lethargy, hypotonia and focal clonic seizures 6 days following diptheria, tetanus toxoid and whole-cell pertussis vaccination. A diagnosis of acute necrotising encephalopathy was made with the aid of MRI, including diffusion-weighted imaging and proton MR spectroscopy. (orig.)

  6. Prevalencia de anticuerpos IgG al toxoide tetánico en trabajadores sanitarios

    Directory of Open Access Journals (Sweden)

    B. Pérez Bermúdez


    Full Text Available Introducción: En el año 2009 el Ministerio de Sanidad y Consumo de España publica una nueva guía para la vacunación de la Difteria y Tétanos. Existen discrepancias con los tiempos de inoculación de las dosis de recuerdo con otros países y sociedades médicas. Material y métodos: Estudio descriptivo. Las variables analizadas fueron: IgG-Toxoide Tetánico, tiempo última dosis de vacunación, dosis totales, edad, sexo, hospital, habito tabáquico e índice de masa corporal. Se construyó un modelo de Regresión Logística. Con el fin de determinar los puntos de corte más sensibles y específicos para las variables temporales (tiempo desde la última dosis y edad se calcularon las curvas R.O.C Resultados: Las variables, edad O,R= 17,56 (1,840 - 167,760, dosis de vacuna inoculadas al trabajador, O,R= 0,064 (0,006 - 0,908 y tiempo de la última dosis de vacunación, O,R= 1,03 (1,017 - 1,047, son las variables significativas en el análisis multivariante. Los puntos de cortes, para la edad son 54 años (Sensibilidad S= 0,72, Especificidad SP=0,77 y 15 años tras la última dosis años (S= 0,88, SP=0,86, por encima de este corte la probabilidad de no tener anticuerpos al Tétanos es alta. Conclusiones: Ante un trabajador que refiere o documenta que hace más de 15 años de la ultima dosis deberíamos plantearnos la revacunación, si además este trabajador refiere no tener más de 5 dosis inoculadas y tiene más de 54 años la revacunación sería muy recomendable.

  7. Bacillus anthracis Capsular Conjugates Elicit Chimpanzee Polyclonal Antibodies That Protect Mice from Pulmonary Anthrax. (United States)

    Chen, Zhaochun; Schneerson, Rachel; Lovchik, Julie A; Dai, Zhongdong; Kubler-Kielb, Joanna; Agulto, Liane; Leppla, Stephen H; Purcell, Robert H


    The immunogenicity of Bacillus anthracis capsule (poly-γ-D-glutamic acid [PGA]) conjugated to recombinant B. anthracis protective antigen (rPA) or to tetanus toxoid (TT) was evaluated in two anthrax-naive juvenile chimpanzees. In a previous study of these conjugates, highly protective monoclonal antibodies (MAbs) against PGA were generated. This study examines the polyclonal antibody response of the same animals. Preimmune antibodies to PGA with titers of >10(3) were detected in the chimpanzees. The maximal titer of anti-PGA was induced within 1 to 2 weeks following the 1st immunization, with no booster effects following the 2nd and 3rd immunizations. Thus, the anti-PGA response in the chimpanzees resembled a secondary immune response. Screening of sera from nine unimmunized chimpanzees and six humans revealed antibodies to PGA in all samples, with an average titer of 10(3). An anti-PA response was also observed following immunization with PGA-rPA conjugate, similar to that seen following immunization with rPA alone. However, in contrast to anti-PGA, preimmune anti-PA antibody titers and those following the 1st immunization were ≤300, with the antibodies peaking above 10(4) following the 2nd immunization. The polyclonal anti-PGA shared the MAb 11D epitope and, similar to the MAbs, exerted opsonophagocytic killing of B. anthracis. Most important, the PGA-TT-induced antibodies protected mice from a lethal challenge with virulent B. anthracis spores. Our data support the use of PGA conjugates, especially PGA-rPA targeting both toxin and capsule, as expanded-spectrum anthrax vaccines.

  8. Theory of Digitized Conjugate Surface and Solution to Conjugate Surface

    Institute of Scientific and Technical Information of China (English)

    Xiao Lai-yuan; Liao Dao-xun; Yi Chuan-yun


    In order to meet the needs of designing and processing digitized surfaces, the method to spreading digitized surface has been proposed. The key technique is to solve the problem of digitized conjugate surface. In the paper, the digitized conjugate surface was theoretically investigated, and the solution of conjugate surface based on digitized surface was also studied. The digitized conjugate surface theory was then proposed, and applied to build the model of solving conjugate surface based on digitized surface. A corresponding algorithm was developed. This paper applies the software Conjugater-1.0 that is developed by ourselves to compute the digitized conjugate surfaces of the drum-tooth surface. This study provides theoretical and technical bases for analyzing engagement of digitized surface, simulation and numerical processing technique.

  9. Collaborative study for the validation of serological methods for potency testing of diphtheria toxoid vaccines-part 1. (United States)

    Winsnes, R; Sesardic, D; Daas, A; Behr-Gross, M-E


    A collaborative study on the evaluation of an alternative functional assay, the Vero cell method, to the Ph. Eur. in vivo challenge procedures for potency determination of diphtheria toxoid in 6 different combined vaccines was initiated in January 2001. The study was an extension of a previous study for the validation of serological methods for potency testing of tetanus toxoid vaccines for human use. To allow interim evaluation of test results and to monitor study progress, the project was divided into three consecutive phases. The results of Phase I and II studies are presented in this report. Pre-validation (Phase I) study, performed in two laboratories, indicated that comparable diphtheria potency estimates were obtained in the Ph. Eur. direct intradermal challenge assay in guinea pigs, in Vero cell assay and in indirect ELISA for five vaccines of different potencies (range of estimates: ca. 20-200 IU/ml). The correlation coefficients between the challenge assay and the Vero cell assay corresponded to those between the challenge assay and ELISA, confirming that the antibodies play an important role in protection and that predominantly protective/neutralising antibodies are present in guinea pigs, at the time point investigated. It was observed, for Vero cell assays, that about 16-35 (9-28 in Phase II study) fold lower titre of individual serum samples were obtained when using equine, rather than guinea pig reference serum. The study also provided preliminary information that sera from the same guinea pigs may be used for potency determination of both diphtheria and tetanus toxoid components of vaccines. In Phase II, another five laboratories analysed a subset of the vaccines included in Phase I study plus an additional vaccine. Four laboratories performed the lethal challenge assay and one laboratory carried out the intradermal challenge assay. All laboratories also performed the Vero cell assay and both ELISA for diphtheria antitoxin and ELISA for tetanus

  10. The use of toxoid for the prevention of tetanus neonatorum. Final report of a double-blind controlled field trial. (United States)

    Newell, K W; Dueñas Lehmann, A; LeBlanc, D R; Garces Osorio, N


    With a view to determining the effectiveness of a method for the control of tetanus neonatorum which would be independent of medical examination or care, a double-blind field trial covering 1618 women was conducted between 1961 and 1966 in a rural area of Colombia with an estimated existing tetanus neonatorum death rate of 11.6 per 100 births. The study group was given 1-3 injections of 1 ml of an aluminium-phosphate-adsorbed tetanus toxoid more than 6 weeks apart, and the control group a similar number of injections of an influenza-virus vaccine.There was no statistically significant difference between those in the two groups given one injection. Those in the control group given 2 or 3 injections had a tetanus neonatorum death rate of 7.8 deaths per 100 births, and the corresponding subjects in the study group had none. This difference is unlikely to have occurred by chance.

  11. Evidence of increased carriage of Corynebacterium spp. in healthy individuals with low antibody titres against diphtheria toxoid. (United States)

    Bergamini, M; Fabrizi, P; Pagani, S; Grilli, A; Severini, R; Contini, C


    This study evaluated whether a correlation exists between carriage of corynebacteria and the lack of immunity to diphtheria toxoid. Samples of both nasal and pharyngeal secretions were taken from 500 apparently healthy subjects of both sexes and of all ages and inoculated onto Tinsdale's medium. A serum sample was also taken for ELISA test to determine the titre of diphtheria toxin antibodies. None of the subjects carried Corynebacterium diphtheriae. Ninety-three strains of Corynebacterium spp. were isolated from 93 subjects and 86 of these were classified to species or group level by biochemical tests. C. xerosis was the most common (25.8%) followed by C. pseudodiphthericum (16.1%), C. jeikeium and C. striatum (both 10.8%), and C. urealyticum (9.7%). Three other species accounted for approximately 20% of strains and seven were unclassified as biochemically atypical corynebacteria. Non-protective antibodies to diphtheria toxin were found in 80 of the 93 subjects and a strong statistical association was demonstrated between carriage of corynebacteria and non-protective levels of anti-toxin antibodies. The remaining 13 subjects had protective levels of antitoxin antibodies. In contrast, only 45 of the 407 non-colonized subjects had non-protective antitoxin titres. The prevalence of carriage increased with age among males as did the percentage of non-protected subjects. The prevalence of female carriers of corynebacteria was significantly lower. Serum samples from 12 subjects with different antibody titres to diphtheria toxoid reacted to varying degrees with whole-cell lysates of a number of species of corynebacteria. The results suggest that a causal relationship may exist between nasopharyngeal carriage of corynebacteria and a low anti-diphtheria toxin immune response.

  12. Moderate PEGylation of the carrier protein improves the polysaccharide-specific immunogenicity of meningococcal group A polysaccharide conjugate vaccine. (United States)

    Zhang, Tingting; Yu, Weili; Wang, Yanfei; Hu, Tao


    Neisseria meningitidis can cause severe and fulminant diseases such as meningitis. Meningococcal capsular polysaccharide (PS) is a key virulence determinant that is not able to induce immunological memory. Conjugation of PS to a carrier protein can significantly increase the immunogenicity of PS and induce immunological memory. Due to the classically described carrier-induced epitopic suppression (CIES) mechanisms, a strong immune response against the carrier protein could suppress the immune response to PS after coadministration of free carrier protein with the conjugate vaccine. However, it was not clear whether suppressing or enhancing the protein-specific immunogenicity could improve the PS-specific immunogenicity of the conjugate vaccine. Thus, moderate PEGylation, extensive PEGylation and oligomerization were used to regulate the immunogenicity of tetanus toxoid (TT) in the conjugate vaccine (PS-TT). Moderate PEGylation led to a 2.7-fold increase in the PS-specific IgG titers elicited by PS-TT. In contrast, extensive PEGylation and oligomerization of TT led to 1.4-fold and 1.6-fold decrease in the PS-specific IgG titers elicited by PS-TT, respectively. The PS-specific immunogenicity of PS-TT can be increased by moderate PEGylation through mild suppression of the TT-specific immunogenicity. The PS-specific immunogenicity of PS-TT was decreased through significant suppression or enhancement of the TT-specific immunogenicity. Thus, our study contributes to understand the CIES mechanisms and improve the PS-specific immunogenicity of a meningococcal PS conjugate vaccine.

  13. Preparation and testing of a Vi conjugate vaccine using pneumococcal surface protein A (PspA) from Streptococcus pneumoniae as the carrier protein. (United States)

    Kothari, Neha; Genschmer, Kristopher R; Kothari, Sudeep; Kim, Jeong Ah; Briles, David E; Rhee, Dong Kwon; Carbis, Rodney


    In the current study pneumococcal surface protein A (PspA) was conjugated to Vi capsular polysaccharide from Salmonella Typhi to make available a vaccine against typhoid fever that has the potential to also provide broad protection from Streptococcus pneumoniae. High yielding production processes were developed for the purification of PspAs from families 1 and 2. The purified PspAs were conjugated to Vi with high recovery of both Vi and PspA. The processes developed especially for PspA family 2 could readily be adapted for large scale production under cGMP conditions. Previously we have shown that conjugation of diphtheria toxoid (DT) to Vi polysaccharide improves the immune response to Vi but can also enhance the response to DT. In this study it was shown that conjugation of PspA to Vi enhanced the anti-PspA response and that PspA was a suitable carrier protein as demonstrated by the characteristics of a T-cell dependent response to the Vi. We propose that a bivalent vaccine consisting of PspA from families 1 and 2 bound to Vi polysaccharide would protect against typhoid fever and has the potential to also protect against pneumococcal disease and should be considered for use in developing countries.

  14. Effect of vaccination with carrier protein on response to meningococcal C conjugate vaccines and value of different immunoassays as predictors of protection. (United States)

    Burrage, Moya; Robinson, Andrew; Borrow, Ray; Andrews, Nick; Southern, Joanna; Findlow, Jamie; Martin, Sarah; Thornton, Carol; Goldblatt, David; Corbel, Michael; Sesardic, Dorothea; Cartwight, Keith; Richmond, Peter; Miller, Elizabeth


    In order to plan for the wide-scale introduction of meningococcal C conjugate (MCC) vaccine for United Kingdom children up to 18 years old, phase II trials were undertaken to investigate whether there was any interaction between MCC vaccines conjugated to tetanus toxoid (TT) or a derivative of diphtheria toxin (CRM(197)) and diphtheria-tetanus vaccines given for boosting at school entry or leaving. Children (n = 1,766) received a diphtheria-tetanus booster either 1 month before, 1 month after, or concurrently with one of three MCC vaccines conjugated to CRM(197) or TT. All of the MCC vaccines induced high antibody responses to the serogroup C polysaccharide that were indicative of protection. The immune response to the MCC-TT vaccine was reduced as a result of prior immunization with a tetanus-containing vaccine, but antibody levels were still well above the lower threshold for protection. Prior or simultaneous administration of a diphtheria-containing vaccine did not affect the response to MCC-CRM(197) vaccines. The immune responses to the carrier proteins were similar to those induced by a comparable dose of diphtheria or tetanus vaccine. The results also demonstrate that, for these conjugate vaccines in these age groups, both standard enzyme-linked immunosorbent assays and those that measure high-avidity antibodies to meningococcal C polysaccharide correlated equally well with assays that measure serum bactericidal antibodies, the established serological correlate of protection for MCC vaccines.

  15. A Bordetella pertussis proteoliposome induces protection in mice without affecting the immunogenicity of diphtheria and tetanus toxoids in a trivalent formulation. (United States)

    Castillo, Sonsire Fernández; Chovel, Mario Landys; Hernández, Niurka Gutiérrez; González, Lorena Corcho; Blanco, Amaya; Hernández, Daily Serrano; Medina, Mildrey Fariñas; Tito, Maydelis Álvarez; Quiñoy, José Luis Pérez


    In this study, a formulation of Bordetella pertussis proteoliposome (PLBp), diphtheria, and tetanus toxoids and alum (DT-PLBp) was evaluated as a trivalent vaccine candidate in BALB/c mice. Vaccine-induced protection was estimated using the intranasal challenge for pertussis and enzyme-linked immunosorbent assay fvto assess serological responses for diphtheria or tetanus. Both, diphtheria-tetanus-whole cell pertussis (DTP) and diphtheria-tetanus vaccines (DT) were used as controls. Animals immunized with DT-PLBp, PLBp alone, and DTP showed total reduction of CFU in lungs 7 days after intranasal challenge. Likewise, formulations DT-PLBp, DTP, and DT elicited antibody levels ≥2 IU/mL against tetanus and diphtheria, considered protective when neutralization tests are used. Overall, results showed that combination of PLBp with tetanus and diphtheria toxoids did not affect the immunogenicity of each antigen alone.

  16. A Bordetella pertussis proteoliposome induces protection in mice without affecting the immunogenicity of diphtheria and tetanus toxoids in a trivalent formulation (United States)


    In this study, a formulation of Bordetella pertussis proteoliposome (PLBp), diphtheria, and tetanus toxoids and alum (DT-PLBp) was evaluated as a trivalent vaccine candidate in BALB/c mice. Vaccine-induced protection was estimated using the intranasal challenge for pertussis and enzyme-linked immunosorbent assay fvto assess serological responses for diphtheria or tetanus. Both, diphtheria-tetanus-whole cell pertussis (DTP) and diphtheria-tetanus vaccines (DT) were used as controls. Animals immunized with DT-PLBp, PLBp alone, and DTP showed total reduction of CFU in lungs 7 days after intranasal challenge. Likewise, formulations DT-PLBp, DTP, and DT elicited antibody levels ≥2 IU/mL against tetanus and diphtheria, considered protective when neutralization tests are used. Overall, results showed that combination of PLBp with tetanus and diphtheria toxoids did not affect the immunogenicity of each antigen alone. PMID:27489808

  17. Modification of T-cell antigenic properties of tetanus toxoid by SDS-PAGE separation. Implications for T-cell blotting

    DEFF Research Database (Denmark)

    Christensen, C B; Theander, T G


    Using Tetanus Toxoid (TT) as a model antigen the T-cell Blotting method was evaluated. Peripheral blood mononuclear cell (PBMC) cultures were stimulated by blotted nitrocellulose-bound TT or soluble TT. SDS-Poly-Acrylamide-Gel-Electrophoresis separated TT only induced proliferation in 20% of the ......Using Tetanus Toxoid (TT) as a model antigen the T-cell Blotting method was evaluated. Peripheral blood mononuclear cell (PBMC) cultures were stimulated by blotted nitrocellulose-bound TT or soluble TT. SDS-Poly-Acrylamide-Gel-Electrophoresis separated TT only induced proliferation in 20...... that SDS-PAGE alters the ability of TT to induce T-cell proliferation, possibly due to unpolymerized acrylamide binding to proteins during SDS-PAGE. The use of SDS-PAGE T-cell blotting in the screening for T-cell antigens must therefore be reconsidered. We suggest the use of SDS-Agarose Gel Electrophoresis...

  18. Scaling up interventions to eliminate neonatal tetanus: factors associated with the coverage of tetanus toxoid and clean deliveries among women in Vientiane, Lao PDR. (United States)

    Masuno, Kanako; Xaysomphoo, Duangpachan; Phengsavanh, Alongkone; Douangmala, Somthana; Kuroiwa, Chushi


    The Lao People's Democratic Republic (PDR) is one of seven countries that have not eliminated maternal and neonatal tetanus in more than 50% of districts. We conducted a community-based household survey to assess the achievements of strategies towards maternal and neonatal tetanus elimination in the capital province. The coverage of tetanus toxoid (TT) was 79.7% by the protection-at-birth (PAB) method. The percentages of deliveries attended by skilled personnel and of deliveries at a health facility were 68.4% and 63.7%, respectively. The progress towards eliminating neonatal tetanus in Lao PDR is not sufficient despite the study sites being placed in the capital province. The lack of continuum of care for mothers and newborns is the major obstacle to scale up the tetanus toxoid coverage and PAB as well as clean deliveries.

  19. Organometallic B12-DNA conjugate

    DEFF Research Database (Denmark)

    Hunger, Miriam; Mutti, Elena; Rieder, Alexander


    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...

  20. Technical and Diagnostic Performance of Five Commercial Anti-Diphtheria Toxoid IgG Enzyme-Linked Immunosorbent Assay Kits ▿


    Faruq, A.; Dadson, L.; H Cox; Alcock, F.; Parker, A R


    The technical and diagnostic performances of five commercially available enzyme-linked immunosorbent assays for the measurement of anti-diphtheria toxoid IgG antibodies were evaluated. There was good agreement between the relative sensitivities of the five assays, but the relative specificity of one of the assays differed from that of the other four assays. Three of the five assays possessed recoveries of the international reference material NIBSC 00/496 within the range of 90% to 110% at ant...

  1. Hierarchically deflated conjugate residual

    CERN Document Server

    Yamaguchi, Azusa


    We present a progress report on a new class of multigrid solver algorithm suitable for the solution of 5d chiral fermions such as Domain Wall fermions and the Continued Fraction overlap. Unlike HDCG \\cite{Boyle:2014rwa}, the algorithm works directly on a nearest neighbour fine operator. The fine operator used is Hermitian indefinite, for example $\\Gamma_5 D_{dwf}$, and convergence is achieved with an indefinite matrix solver such as outer iteration based on conjugate residual. As a result coarse space representations of the operator remain nearest neighbour, giving an 8 point stencil rather than the 81 point stencil used in HDCG. It is hoped this may make it viable to recalculate the matrix elements of the little Dirac operator in an HMC evolution.

  2. Dihydroazulene-buckminsterfullerene conjugates

    DEFF Research Database (Denmark)

    Santella, Marco; Mazzanti, Virginia; Jevric, Martyn;


    The dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch has recently attracted interest as a molecular switch for molecular electronics. In this field, Buckminsterfullerene, C(60), has been shown to be a useful anchoring group for adhering a molecular wire to an electrode. Here we have...... combined the two units with the overall aim to elucidate how C(60) influences the DHA-VHF switching events. Efficient synthetic protocols for making covalently linked DHA-C(60) conjugates were developed, using Prato, Sonogashira, Hay, and Cadiot-Chodkiewicz reactions. These syntheses provide as well...... of DHA to its corresponding VHF. Thus, C(60) was found to significantly quench this conversion when situated closely to the DHA unit....

  3. Generalized conjugate gradient squared

    Energy Technology Data Exchange (ETDEWEB)

    Fokkema, D.R.; Sleijpen, G.L.G. [Utrecht Univ. (Netherlands)


    In order to solve non-symmetric linear systems of equations, the Conjugate Gradient Squared (CGS) is a well-known and widely used iterative method. In practice the method converges fast, often twice as fast as the Bi-Conjugate Gradient method. This is what you may expect, since CGS uses the square of the BiCG polynomial. However, CGS may suffer from its erratic convergence behavior. The method may diverge or the approximate solution may be inaccurate. BiCGSTAB uses the BiCG polynomial and a product of linear factors in an attempt to smoothen the convergence. In many cases, this has proven to be very effective. Unfortunately, the convergence of BiCGSTAB may stall when a linear factor (nearly) degenerates. BiCGstab({ell}) is designed to overcome this degeneration of linear factors. It generalizes BiCGSTAB and uses both the BiCG polynomial and a product of higher order factors. Still, CGS may converge faster than BiCGSTAB or BiCGstab({ell}). So instead of using a product of linear or higher order factors, it may be worthwhile to look for other polynomials. Since the BiCG polynomial is based on a three term recursion, a natural choice would be a polynomial based on another three term recursion. Possibly, a suitable choice of recursion coefficients would result in method that converges faster or as fast as CGS, but less erratic. It turns out that an algorithm for such a method can easily be formulated. One particular choice for the recursion coefficients leads to CGS. Therefore one could call this algorithm generalized CGS. Another choice for the recursion coefficients leads to BiCGSTAB. It is therefore possible to mix linear factors and some polynomial based on a three term recursion. This way one may get the best of both worlds. The authors will report on their findings.

  4. Toxicity and immunogenicity of Enterotoxigenic Escherichia coli heat-labile and heat-stable toxoid fusion 3xSTa(A14Q)-LT(S63K/R192G/L211A) in a murine model. (United States)

    Zhang, Chengxian; Knudsen, David E; Liu, Mei; Robertson, Donald C; Zhang, Weiping


    Diarrhea is the second leading cause of death to young children. Enterotoxigenic Escherichia coli (ETEC) are the most common bacteria causing diarrhea. Adhesins and enterotoxins are the virulence determinants in ETEC diarrhea. Adhesins mediate bacterial attachment and colonization, and enterotoxins including heat-labile (LT) and heat-stable type Ib toxin (STa) disrupt fluid homeostasis in host cells that leads to fluid hyper-secretion and diarrhea. Thus, adhesins and enterotoxins have been primarily targeted in ETEC vaccine development. A recent study reported toxoid fusions with STa toxoid (STa(P13F)) fused at the N- or C-terminus, or inside the A subunit of LT(R192G) elicited neutralizing antitoxin antibodies, and suggested application of toxoid fusions in ETEC vaccine development (Liu et al., Infect. Immun. 79:4002-4009, 2011). In this study, we generated a different STa toxoid (STa(A14Q)) and a triple-mutant LT toxoid (LT(S63K/R192G/L211A), tmLT), constructed a toxoid fusion (3xSTa(A14Q)-tmLT) that carried 3 copies of STa(A14Q) for further facilitation of anti-STa immunogenicity, and assessed antigen safety and immunogenicity in a murine model to explore its potential for ETEC vaccine development. Mice immunized with this fusion antigen showed no adverse effects, and developed antitoxin antibodies particularly through the IP route. Anti-LT antibodies were detected and were shown neutralizing against CT in vitro. Anti-STa antibodies were also detected in the immunized mice, and serum from the IP immunized mice neutralized STa toxin in vitro. Data from this study indicated that toxoid fusion 3xSTa(A14Q)-tmLT is safe and can induce neutralizing antitoxin antibodies, and provided helpful information for vaccine development against ETEC diarrhea.

  5. Toxicity and immunogenicity of Enterotoxigenic Escherichia coli heat-labile and heat-stable toxoid fusion 3xSTa(A14Q-LT(S63K/R192G/L211A in a murine model.

    Directory of Open Access Journals (Sweden)

    Chengxian Zhang

    Full Text Available Diarrhea is the second leading cause of death to young children. Enterotoxigenic Escherichia coli (ETEC are the most common bacteria causing diarrhea. Adhesins and enterotoxins are the virulence determinants in ETEC diarrhea. Adhesins mediate bacterial attachment and colonization, and enterotoxins including heat-labile (LT and heat-stable type Ib toxin (STa disrupt fluid homeostasis in host cells that leads to fluid hyper-secretion and diarrhea. Thus, adhesins and enterotoxins have been primarily targeted in ETEC vaccine development. A recent study reported toxoid fusions with STa toxoid (STa(P13F fused at the N- or C-terminus, or inside the A subunit of LT(R192G elicited neutralizing antitoxin antibodies, and suggested application of toxoid fusions in ETEC vaccine development (Liu et al., Infect. Immun. 79:4002-4009, 2011. In this study, we generated a different STa toxoid (STa(A14Q and a triple-mutant LT toxoid (LT(S63K/R192G/L211A, tmLT, constructed a toxoid fusion (3xSTa(A14Q-tmLT that carried 3 copies of STa(A14Q for further facilitation of anti-STa immunogenicity, and assessed antigen safety and immunogenicity in a murine model to explore its potential for ETEC vaccine development. Mice immunized with this fusion antigen showed no adverse effects, and developed antitoxin antibodies particularly through the IP route. Anti-LT antibodies were detected and were shown neutralizing against CT in vitro. Anti-STa antibodies were also detected in the immunized mice, and serum from the IP immunized mice neutralized STa toxin in vitro. Data from this study indicated that toxoid fusion 3xSTa(A14Q-tmLT is safe and can induce neutralizing antitoxin antibodies, and provided helpful information for vaccine development against ETEC diarrhea.

  6. Infectious bovine keratoconjunctivitis: enhancement of Moraxella bovis pili immunogenicity with diphtheria-tetanus toxoids and pertussis vaccine. (United States)

    Pugh, G W; Kopecky, K E; McDonald, T J


    A study was conducted to determine whether diphtheria-tetanus-toxoids and pertussis vaccine (DPT) would enhance the immunogenicity of homologous Moraxella bovis pili fractions. Thirty-six calves were divided into 4 groups (I, II, III, and IV) of 9 calves each. Calves in group I were not vaccinated and served as controls. Calves in group II were vaccinated with pili fractions only. Calves in group III were vaccinated with DPT only. Calves in group IV were vaccinated with DPT and pili. Vaccination consisted of 2 inoculations, 21 days apart. Fourteen days after the last vaccinal inoculation was done, the eyes of all calves were exposed to a hemolytic homologous strain of M bovis. The percentage of eyes with disease was significantly less in calves given DPT and pili (P less than 0.001) and calves given pili only (P less than 0.05) than in calves given DPT only or nonvaccinated calves. The lesions were less severe in calves vaccinated with pili only than in calves not vaccinated with pili. Serologic results also showed a positive relationship between the development of serum antibodies against pili and immunity. The results indicate that DPT enhanced the immune response and if used as an adjuvant, might be useful in the development of a vaccine against infectious bovine keratoconjunctivitis.

  7. Tetanus toxoid-loaded layer-by-layer nanoassemblies for efficient systemic, mucosal, and cellular immunostimulatory response following oral administration. (United States)

    Harde, Harshad; Agrawal, Ashish Kumar; Jain, Sanyog


    The present study reports the tetanus toxoid (TT)-loaded layer-by-layer nanoassemblies (layersomes) with enhanced protection, permeation, and presentation for comprehensive oral immunization. The stable and lyophilized TT-loaded layersomes were prepared by a thin-film hydration method followed by alternate layer-by-layer coating of an electrolyte. The developed system was assessed for in vitro stability of antigen and formulation, cellular uptake, ex vivo intestinal uptake, and immunostimulatory response using a suitable experimental protocol. Layersomes improved the stability in simulated biological media as well as protected the integrity/conformation and native 3D structure of TT as confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism (CD), and fluorescence spectroscopy, respectively. The cell culture studies demonstrated a 3.8-fold higher permeation of layersomes in Caco-2 cells and an 8.5-fold higher uptake by antigen-presenting cells (RAW 264.7). The TT-loaded layersomes elicited a complete immunostimulatory profile consisting of higher systemic (serum IgG titer), mucosal (sIgA titer), and cellular (interleukin-2 (IL-2) and interferon-γ (IFN-γ) levels) immune response after peroral administration in mice. The modified TT inhibition assay further confirmed the elicitation of complete protective levels of anti-TT antibody (>0.1 IU/mL) by layersomes. In conclusion, the proposed strategy is expected to contribute significantly in the field of stable liposome technology for mass immunization through the oral route.

  8. Effect of Spirulina (Arthrospira) supplementation on the immune response to tetanus toxoid vaccination in a mouse model. (United States)

    Chu, Wan-Loy; Quynh, Le Van; Radhakrishnan, Ammu Kutty


    The aim of this study was to investigate whether Spirulina (Arthrospira) supplementation could enhance the immune response to tetanus toxoid (TT) vaccine in a mouse model. Vaccination of TT was performed on day 7 and 21 in mice fed daily with Spirulina (50 and 150 mg/kg body weight). Both Spirulina supplementation and TT vaccination did not significantly affect body weight gain of the mice. Supplementation of Spirulina significantly enhanced IgG level (p = .01) after the first but not after the second TT vaccination. The anti-TT IgG levels of the groups that received low dose and high dose of Spirulina were not significantly different. Spirulina supplementation did not show significant effects on in vitro splenocyte proliferation and cytokine (IFN-γ and IL-4) production induced by Con A and TT. This study showed that Spirulina supplementation could enhance primary immune response in terms of antibody production, but not secondary immune response following TT vaccination in a mouse model.

  9. Impairment of the humoral and CD4(+) T cell responses in HTLV-1-infected individuals immunized with tetanus toxoid. (United States)

    Souza, Anselmo; Santos, Silvane; Carvalho, Lucas P; Grassi, Maria Fernanda R; Carvalho, Edgar M


    T cells from HTLV-1-infected individuals have a decreased ability to proliferate after stimulation with recall antigens. This abnormality may be due to the production of regulatory cytokine or a dysfunctional antigen presentation. The aims of this study were to evaluate the antibody production and cytokine expression by lymphocytes before and after immunization with tetanus toxoid (TT) and to evaluate the immune response of monocytes after stimulation with TT and frequency of dendritic cells (DC) subsets. HTLV-1 carriers (HC) and uninfected controls (UC) with negative serology for TT were immunized with TT, and the antibody titers were determined by ELISA as well as the cell activation markers expression by monocytes. The frequencies of DC subsets were determined by flow cytometry. Following immunization, the IgG anti-TT titers and the frequency of CD4(+) T cells expressing IFN-γ, TNF-α and IL-10 in response to TT were lower in the HC than in the UC. Additionally, monocytes from HC did not exhibit increased HLA-DR expression after stimulation with TT, and presented low numbers of DC subsets, therefore, it's necessary to perform functional studies with antigen-presenting cells. Collectively, our finding suggests that HC present an impairment of the humoral and CD4(+) T cell immune responses after vaccination.

  10. Aptamer-Drug Conjugates. (United States)

    Zhu, Guizhi; Niu, Gang; Chen, Xiaoyuan


    Western medicine often aims to specifically treat diseased tissues or organs. However, the majority of current therapeutics failed to do so owing to their limited selectivity and the consequent "off-target" side effects. Targeted therapy aims to enhance the selectivity of therapeutic effects and reduce adverse side effects. One approach toward this goal is to utilize disease-specific ligands to guide the delivery of less-specific therapeutics, such that the therapeutic effects can be guided specifically to diseased tissues or organs. Among these ligands, aptamers, also known as chemical antibodies, have emerged over the past decades as a novel class of targeting ligands that are capable of specific binding to disease biomarkers. Compared with other types of targeting ligands, aptamers have an array of unique advantageous features, which make them promising for developing aptamer-drug conjugates (ApDCs) for targeted therapy. In this Review, we will discuss ApDCs for targeted drug delivery in chemotherapy, gene therapy, immunotherapy, photodynamic therapy, and photothermal therapy, primarily of cancer.

  11. Sequential measurements of conjugate observables

    Energy Technology Data Exchange (ETDEWEB)

    Carmeli, Claudio [Dipartimento di Fisica, Universita di Genova, Via Dodecaneso 33, 16146 Genova (Italy); Heinosaari, Teiko [Department of Physics and Astronomy, Turku Centre for Quantum Physics, University of Turku, 20014 Turku (Finland); Toigo, Alessandro, E-mail:, E-mail:, E-mail: [Dipartimento di Matematica ' Francesco Brioschi' , Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)


    We present a unified treatment of sequential measurements of two conjugate observables. Our approach is to derive a mathematical structure theorem for all the relevant covariant instruments. As a consequence of this result, we show that every Weyl-Heisenberg covariant observable can be implemented as a sequential measurement of two conjugate observables. This method is applicable both in finite- and infinite-dimensional Hilbert spaces, therefore covering sequential spin component measurements as well as position-momentum sequential measurements.

  12. Safety and preliminary immunogenicity of Cuban pneumococcal conjugate vaccine candidate in healthy children: a randomized phase I clinical trial. (United States)

    Dotres, Carlos P; Puga, Rinaldo; Ricardo, Yariset; Broño, Carmen R; Paredes, Beatriz; Echemendía, Vladimir; Rosell, Sandra; González, Nadezhda; García-Rivera, Dagmar; Valdés, Yury; Goldblatt, David; Vérez-Bencomo, Vicente


    A new heptavalent conjugate vaccine (PCV7-TT) is under development in Cuba. PCV7-TT contains 2 μg of serotypes 1, 5, 14, 18C, 19F, 23F and 4 μg of 6B, each one conjugated to tetanus toxoid (TT). This vaccine was designed with the serotypes that cause most invasive pneumococcal diseases (IPD) worldwide. In the present study, we investigated the safety and explored the immunogenicity of PCV7-TT during a controlled, randomized and double blind clinical trial phase I in 4-5-year-old children. PCV7-TT was well tolerated and as safe as Synflorix used as control vaccine. Following a single-dose vaccination, all individual serotypes included in PCV7-TT induced statistically significant increase of IgG GMC and OPA GMT. These are the first clinical results of PCV7-TT in children and they pave the way toward next clinical trials in children and infants. This clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173.

  13. Persistence of serogroup C antibody responses following quadrivalent meningococcal conjugate vaccination in United States military personnel. (United States)

    Patel, Manisha; Romero-Steiner, Sandra; Broderick, Michael P; Thomas, Cynthia G; Plikaytis, Brian D; Schmidt, Daniel S; Johnson, Scott E; Milton, Andrea S; Carlone, George M; Clark, Thomas A; Messonnier, Nancy E; Cohn, Amanda C; Faix, Dennis J


    Serogroup C meningococcal (MenC) disease accounts for one-third of all meningococcal cases and causes meningococcal outbreaks in the U.S. Quadrivalent meningococcal vaccine conjugated to diphtheria toxoid (MenACYWD) was recommended in 2005 for adolescents and high risk groups such as military recruits. We evaluated anti-MenC antibody persistence in U.S. military personnel vaccinated with either MenACYWD or meningococcal polysaccharide vaccine (MPSV4). Twelve hundred subjects vaccinated with MenACYWD from 2006 to 2008 or MPSV4 from 2002 to 2004 were randomly selected from the Defense Medical Surveillance System. Baseline serologic responses to MenC were assessed in all subjects; 100 subjects per vaccine group were tested during one of the following six post-vaccination time-points: 5-7, 11-13, 17-19, 23-25, 29-31, or 35-37 months. Anti-MenC geometric mean titers (GMT) were measured by rabbit complement serum bactericidal assay (rSBA) and geometric mean concentrations (GMC) by enzyme-linked immunosorbent assay (ELISA). Continuous variables were compared using the Wilcoxon rank sum test and the proportion of subjects with an rSBA titer ≥ 8 by chi-square. Pre-vaccination rSBA GMT was antibody.

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

    Energy Technology Data Exchange (ETDEWEB)



    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.

  15. Development and Preliminary Application of ELISA Method for Diphtheria Toxoid%白喉类毒素ELISA检测方法的建立及初步应用

    Institute of Scientific and Technical Information of China (English)

    刘朝阳; 景辉; 陈艳红; 张斌; 马相虎; 朱金华


    目的 建立白喉类毒素双抗体夹心ELISA检测方法,并进行验证及初步应用.方法 以马抗白喉类毒素血清作为包被抗体,HRP标记的白喉絮状反应抗毒素作为酶标抗体,建立白喉类毒素双抗体夹心ELISA检测方法,并对该方法进行重复性、特异性验证、最佳线性范围和检测限确定及初步应用.结果 经验证,该方法重复性好,特异性强,白喉类毒素含量在0.9765~125.0000ng/ml之间时线性关系良好,检测限为7.812 ng/ml,该方法检测了3批白喉类毒素原液,与动物实验结果基本相符.结论 已建立了白喉类毒素双抗体夹心ELISA检测方法,可用于检测白喉类毒素的含量和抗原性.%Objective To develop, verify and preliminarily apply a double antibody sandwich ELISA method for diphtheria toxoid. Methods A double antibody sandwich ELISA method was developed using horse antiserum against diphtheria toxoid as coating antibody and HRP-labeled diphtheria flocculation antitoxin as enzyme labeled antibody, then verified for reproducibility and specificity, determined for optimal linear range and detection limit, and applied preliminarily. Results The developed method showed high reproducibility and specificity, of which the optimal linear range and detection limit were 0. 976 5 ~ 125. 000 0 ng/ml and 7. 812 ng/ml respectively. Three batches of bulk diphtheria toxoid were detected by the developed method, and the results were basically consistent with thoes by animal test. Conclusion A double antibody sandwich ELISA method was developed, which might be used for determination of content and antigenicity of diphtheria toxoid.

  16. Nitrogen-gas bubbling during the cultivation of Clostridium tetani produces a higher yield of tetanus toxin for the preparation of its toxoid. (United States)

    De Luca, M M; Abeiro, H D; Bernagozzi, J A; Basualdo, J A


    We investigated the effect of exposing cultures of Clostridium tetani to nitrogen (N2) gas on the recovery of tetanus toxin to be processed for the preparation of its toxoid. N2 was bubbled through nine 10-liter cultures during the growth of the bacteria, while nine parallel control incubations were maintained without bubbling. We found that treatment of the C. tetani anaerobes with an inert gas in this manner during cultivation produced a highly significant increase in the yield of tetanus toxin from them in comparison with the standard procedure.

  17. Men with low vitamin A stores respond adequately to primary yellow fever and secondary tetanus toxoid vaccination. (United States)

    Ahmad, Shaikh M; Haskell, Marjorie J; Raqib, Rubhana; Stephensen, Charles B


    Current recommendations for vitamin A intake and liver stores (0.07 micromol/g) are based on maintaining normal vision. Higher levels may be required for maintaining normal immune function. The objective of this study was to assess the relationship between total body vitamin A stores in adult men and measures of adaptive immune function. We conducted an 8-wk residential study among 36 healthy Bangladeshi men with low vitamin A stores. Subjects received a standard diet and were randomized in a double-blind fashion to receive vitamin A (240 mg) or placebo during wk 2 and 3. Subjects received Yellow Fever Virus (YFV) and tetanus toxoid (TT) vaccines during wk 5. Vitamin A stores were estimated by isotopic dilution during wk 8. Vaccine-specific lymphocyte proliferation, cytokine production, and serum antibody responses were evaluated before and after vaccination. Vitamin A supplementation increased YFV- and TT-specific lymphocyte proliferation and YFV-specific interleukin (IL)-5, IL-10, and tumor necrosis factor-alpha production but inhibited development of a TT-specific IL-10 response. Both groups developed protective antibody responses to both vaccines. Some responses correlated positively with vitamin A stores. These findings indicate that the currently recommended vitamin A intake is sufficient to sustain a protective response to YFV and TT vaccination. However, YFV-specific lymphocyte proliferation, some cytokine responses, and neutralizing antibody were positively associated with liver vitamin A stores > 0.084 micromol/g. Such increases may enhance vaccine protection but raise the question of whether immune-mediated chronic diseases may by exacerbated by high-level dietary vitamin A.

  18. Measurement of antibodies to pneumococcal, meningococcal and haemophilus polysaccharides, and tetanus and diphtheria toxoids using a 19-plexed assay. (United States)

    Whitelegg, Alison M E; Birtwistle, Jane; Richter, Alex; Campbell, John P; Turner, James E; Ahmed, Tarana M; Giles, Lynda J; Fellows, Mark; Plant, Tim; Ferraro, Alastair J; Cobbold, Mark; Drayson, Mark T; MacLennan, Calman A


    The measurement of antibody responses to vaccination is useful in the assessment of immune status in suspected immune deficiency. Previous reliance on enzyme-linked immunoabsorbent assays (ELISA) has been cumbersome, time-consuming and expensive. The availability of flow cytometry systems has led to the development of multiplexed assays enabling simultaneous measurement of antibodies to several antigens. We optimized a flow cytometric bead-based assay to measure IgG and IgM concentrations in serum to 19 antigens contained in groups of bacterial subunit vaccines: pneumococcal vaccines, meningococcal vaccines, Haemophilus influenzae b (Hib), and tetanus and diphtheria toxoid vaccines. 89-SF was employed as the standard serum. The assay was used to determine specific antibody levels in serum from 193 healthy adult donors. IgG and pneumococcal IgM antibody concentrations were measurable across 3 log10 ranges encompassing the threshold protective IgG antibody levels for each antigen. There was little interference between antibody measurements by the 19-plexed assay compared with monoplexed assays, and a lack of cross-reactive IgG antibody, but evidence for cross-reacting IgM antibody for 3/19 pneumococcal antigens. 90th centile values for 15/19 IgG concentrations and 12/12 IgM concentrations of the 193 adult sera were within these ranges and percentages of sera containing protective IgG antibody levels varied from 4% to 95% depending on antigen. This multiplexed assay can simultaneously measure antibody levels to 19 bacterial vaccine antigens. It is suitable for use in standard clinical practice to assess the in vivo immune response to test vaccinations and measure absolute antibody levels to these antigens.

  19. Evaluation of TLR agonists as potential mucosal adjuvants for HIV gp140 and tetanus toxoid in mice.

    Directory of Open Access Journals (Sweden)

    Viviana Buffa

    Full Text Available In the present study we investigate the impact of a range of TLR ligands and chitosan as potential adjuvants for different routes of mucosal immunisation (sublingual (SL, intranasal (IN, intravaginal (IVag and a parenteral route (subcutaneous (SC in the murine model. We assess their ability to enhance antibody responses to HIV-1 CN54gp140 (gp140 and Tetanus toxoid (TT in systemic and vaginal compartments. A number of trends were observed by route of administration. For non-adjuvanted antigen, SC>SL>IN immunisation with respect to systemic IgG responses, where endpoint titres were greater for TT than for gp140. In general, co-administration with adjuvants increased specific IgG responses where IN = SC>SL, while in the vaginal compartment IN>SL>SC for specific IgA. In contrast, for systemic and mucosal IgA responses to antigen alone SL>IN = SC. A number of adjuvants increased specific systemic IgA responses where in general IN>SL>SC immunisation, while for mucosal responses IN = SL>SC. In contrast, direct intravaginal immunisation failed to induce any detectable systemic or mucosal responses to gp140 even in the presence of adjuvant. However, significant systemic IgG responses to TT were induced by intravaginal immunisation with or without adjuvant, and detectable mucosal responses IgG and IgA were observed when TT was administered with FSL-1 or Poly I∶C. Interestingly some TLRs displayed differential activity dependent upon the route of administration. MPLA (TLR4 suppressed systemic responses to SL immunisation while enhancing responses to IN or SC immunisation. CpG B enhanced SL and IN responses, while having little or no impact on SC immunisation. These data demonstrate important route, antigen and adjuvant effects that need to be considered in the design of mucosal vaccine strategies.

  20. Neonatal immune response of Brazilian beef cattle to vaccination with Clostridium botulinum toxoids types C and D by indirect ELISA

    Directory of Open Access Journals (Sweden)

    VCM Curci


    Full Text Available Types C and D strains of Clostridium botulinum are commonly related to avian and mammalian botulism. Although there are numerous vaccine recommendations, little research has been conducted to indicate the real effectiveness of vaccine timing or the ideal immunization protocol for young beef calves. Four commercially available vaccines, two bivalent (Clostridium botulinum types C and D; vaccines 1 and 2 and two polyvalent (all Clostridium spp. including Clostridium botulinum types C and D; vaccines 3 and 4, that are currently used in Brazilian herds, were tested in order to verify the maternal immune response. One hundred cows, divided into four vaccinated groups and one unvaccinated group, were given a two-dose subcutaneous immunization, at day zero, followed by a second dose given at 42 days post-vaccination, which corresponded to 40 days before birth. Serum samples (n = 75 were collected only from healthy neonatal calves at 0, 7, 45 and 90 days post-calving (DPC and subjected to indirect ELISA using the purified C and D holotoxins as capture antigens. The serological profile showed that all vaccines were able to induce a satisfactory neonatal immune response to both holotoxins at 7 DPC. However, at 45 and 90 DPC, a significant reduction (p < 0.05 was observed in the antibody level against C and D holotoxins in all tested vaccines. Neonatal immunization in calves is compromised by significant levels of maternal antibodies so that the necessity of planning a calf vaccination program involves assessment of disease risks at the production site. Finally, our findings represent the first demonstration of maternal immunity transferred to neonatal beef calves, including immunity levels after vaccination against Clostridium botulinum toxoids C and D.

  1. Persistence Mechanisms of Conjugative Plasmids

    DEFF Research Database (Denmark)

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


    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 successful propagation and long-term continued existence of these extra-chromosomal elements is extensive. Apart from the accessory genetic elements that may provide plasmid-harboring cells a selective advantage, special focus is placed on the mechanisms conjugative plasmids employ to ensure their stable...... maintenance in the host cell. These importantly include the ability to self-mobilize in a process termed conjugative transfer, which may occur across species barriers. Other plasmid stabilizing mechanisms include the multimer resolution system, active partitioning, and post-segregational-killing of plasmid...

  2. Conjugate Gradient with Subspace Optimization

    CERN Document Server

    Karimi, Sahar


    In this paper we present a variant of the conjugate gradient (CG) algorithm in which we invoke a subspace minimization subproblem on each iteration. We call this algorithm CGSO for "conjugate gradient with subspace optimization". It is related to earlier work by Nemirovsky and Yudin. We apply the algorithm to solve unconstrained strictly convex problems. As with other CG algorithms, the update step on each iteration is a linear combination of the last gradient and last update. Unlike some other conjugate gradient methods, our algorithm attains a theoretical complexity bound of $O(\\sqrt{L/l} \\log(1/\\epsilon))$, where the ratio $L/l$ characterizes the strong convexity of the objective function. In practice, CGSO competes with other CG-type algorithms by incorporating some second order information in each iteration.

  3. Effect of currently approved carriers and adjuvants on the pre-clinical efficacy of a conjugate vaccine against oxycodone in mice and rats.

    Directory of Open Access Journals (Sweden)

    Marco Pravetoni

    Full Text Available Vaccination against the highly abused prescription opioid oxycodone has shown pre-clinical efficacy for blocking oxycodone effects. The current study further evaluated a candidate vaccine composed of oxycodone derivatized at the C6 position (6OXY conjugated to the native keyhole limpet hemocyanin (nKLH carrier protein. To provide an oxycodone vaccine formulation suitable for human studies, we studied the effect of alternative carriers and adjuvants on the generation of oxycodone-specific serum antibody and B cell responses, and the effect of immunization on oxycodone distribution and oxycodone-induced antinociception in mice and rats. 6OXY conjugated to tetanus toxoid (TT or a GMP grade KLH dimer (dKLH was as effective as 6OXY conjugated to the nKLH decamer in mice and rats, while the 6OXY hapten conjugated to a TT-derived peptide was not effective in preventing oxycodone-induced antinociception in mice. Immunization with 6OXY-TT s.c. absorbed on alum adjuvant provided similar protection to 6OXY-TT administered i.p. with Freund's adjuvant in rats. The toll-like receptor 4 (TLR4 agonist monophosphoryl lipid A (MPLA adjuvant, alone or in combination with alum, offered no advantage over alum alone for generating oxycodone-specific serum antibodies or 6OXY-specific antibody secreting B cells in mice vaccinated with 6OXY-nKLH or 6OXY-TT. The immunogenicity of oxycodone vaccines may be modulated by TLR4 signaling since responses to 6OXY-nKLH in alum were decreased in TLR4-deficient mice. These data suggest that TT, nKLH and dKLH carriers provide consistent 6OXY conjugate vaccine immunogenicity across species, strains and via different routes of administration, while adjuvant formulations may need to be tailored to individual immunogens or patient populations.

  4. Antibody Persistence in Young Children 5 Years after Vaccination with a Combined Haemophilus influenzae Type b-Neisseria meningitidis Serogroup C Conjugate Vaccine Coadministered with Diphtheria-Tetanus-Acellular Pertussis-Based and Pneumococcal Conjugate Vaccines. (United States)

    Tejedor, Juan Carlos; Brzostek, Jerzy; Konior, Ryszard; Grunert, Detlef; Kolhe, Devayani; Baine, Yaela; Van Der Wielen, Marie


    We evaluated antibody persistence in children up to 5 years after administration of a combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine coadministered with a pneumococcal conjugate vaccine. This is the follow-up study of a randomized trial ( registration no. NCT00334334/00463437) in which healthy children were vaccinated (primary vaccinations at 2, 4, and 6 months of age and booster vaccination at 11 to 18 months of age) with Hib-MenC-TT or a control MenC conjugate vaccine, coadministered with diphtheria-tetanus-acellular pertussis (DTPa)-based combination vaccines (DTPa/Hib for control groups) and a pneumococcal conjugate vaccine (10-valent pneumococcal nontypeable H. influenzae protein D conjugate vaccine [PHiD-CV] or 7-valent cross-reacting material 197 [CRM197] conjugate vaccine [7vCRM]). MenC antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (i.e., rabbit SBA [rSBA]), and antibodies against Hib polyribosylribitol phosphate (PRP) were measured with an enzyme-linked immunosorbent assay. Antibody persistence up to 5 years after booster vaccination is reported for 530 children ∼6 years of age. The percentages of children with seroprotective rSBA-MenC titers were between 24.2% and 40.1% in all groups approximately 5 years after booster vaccination. More than 98.5% of children in each group retained seroprotective anti-PRP concentrations. No vaccine-related serious adverse events and no events related to a lack of vaccine efficacy were reported. Approximately 5 years after booster vaccination, the majority of children retained seroprotective anti-PRP antibody concentrations. The percentage of children retaining seroprotective rSBA-MenC titers was low (≤40%), suggesting that a significant proportion of children may be unprotected against MenC disease. (This study has been registered at under

  5. On contravariant product conjugate connections

    Directory of Open Access Journals (Sweden)

    A. M. Blaga


    Full Text Available Invariance properties for the covariant and contravariant connections on a Riemannian manifold with respect to an almost product structure are stated. Restricting to a distribution of the contravariant connections is also discussed. The particular case of the conjugate connection is investigated and properties of the extended structural and virtual tensors for the contravariant connections are given.

  6. Actinomycete integrative and conjugative elements

    NARCIS (Netherlands)

    Poele, Evelien M. te; Bolhuis, Henk; Dijkhuizen, Lubbert


    This paper reviews current knowledge on actinomycete integrative and conjugative elements (AICEs). The best characterised AICEs, pSAM2 of Streptomyces ambofaciens (10.9 kb), SLP1 (17.3 kb) of Streptomyces coelicolor and pMEA300 of Amycolatopsis methanolica (13.3 kb), are present as integrative eleme

  7. IgG and IgG subclass specific antibody responses to diphtheria and tetanus toxoids in newborns and infants given DTP immunization. (United States)

    Dengrove, J; Lee, E J; Heiner, D C; St Geme, J W; Leake, R; Baraff, L J; Ward, J I


    To evaluate immune responses to diphtheria and tetanus toxoids in infants we used enzyme-linked immunosorbent assays to detect total IgG and specific IgG-1, IgG-2, IgG-3, and IgG-4 antibody. One group of infants received a newborn dose and subsequently received the usual three doses of DTP. A second group of infants received only the routine dosage at 2, 4, and 6 months of age. In sera acquired at birth, 6, and 9 months of age, there were no statistically significant differences between the two vaccine groups in IgG antibody responses to diphtheria or tetanus, or in IgG subclass tetanus-specific antibody responses. In individual children, tetanus-specific subclass responses were similar in pattern to that for total IgG tetanus antibody, i.e. each IgG subclass response appeared to be regulated by similar mechanisms in that child, but the regulation differed between children. In contrast to a prior study of pertussis immunity, maternally acquired antibody did not significantly affect immune responses to diphtheria or tetanus toxoid by 9 months of age. There was no discernible tolerance due to early tetanus or diphtheria immunization or to high levels of maternally acquired antibody.

  8. Non-invasive, epicutaneous immunisation with toxoid in deformable vesicles protects mice against tetanus, chiefly owing to a Th2 response. (United States)

    Chopra, Amla; Cevc, Gregor


    A non-invasive, intra/transcutaneous immunisation of mice with a suitable combination of tetanus toxoid, ultradeformable vesicle (Transfersome®) carrier, and monophosphoryl lipid A adjuvant targets immuno-competent cells in a body and can protect 100% of the tested mice against an otherwise lethal (50×LD50) parenteral tetanus toxin challenge. The late immune response to the epicutaneously applied tetanus toxoid in such vesicles consists chiefly of circulating IgG1 and IgG2b antibody isotypes, indicative of a specific Th2 cellular response bias. Immunisations by subcutaneous injections moreover protect 100% of mice against a similar, otherwise lethal, dose of tetanus toxin. However, the immune response to transcutaneous and invasive immunisation differs. The latter elicits mainly IgG1 and IgG2b as well as IgG2a antibody isotypes, indicative of a mixed Th1/Th2 response. The cytokine response of the intra/transcutaneously and subcutaneously immunised mice reflects the difference in the organ-specific manner. IFN-γ concentration is appreciably increased in the draining lymph nodes and IL-10 in spleen. Since tetanus is a neutral antigen, both the Th1-specific IFN-γ and the Th-2 specific-IL-10 are observable.

  9. Adsorption of Toll-Like Receptor 4 Agonist to Alum-Based Tetanus Toxoid Vaccine Dampens Pro-T Helper 2 Activities and Enhances Antibody Responses. (United States)

    Bortolatto, Juliana; Mirotti, Luciana; Rodriguez, Dunia; Gomes, Eliane; Russo, Momtchilo


    Aluminum salts gels (alum) are TLR-independent adjuvants and have been used to boost antibody responses in alum-based vaccines such as diphtheria, pertussis, and tetanus toxoid (DPT) triple vaccine. However, the pro-Th2 activity of alum-based vaccine formulations has not been fully appreciated. Here we found that alum-based tetanus toxoid (TT) vaccine was biased toward a Th-2 profile as shown by TT-induced airway eosinophilic inflammation, type 2 cytokine production, and high levels of IgE anaphylactic antibodies. The adsorption into alum of prototypic TLR4 agonists such as lipopolysaccharides (LPS) derived from Escherichia coli consistently dampened TT-induced Th2 activities without inducing IFNγ or Th1-like responses in the lung. Conversely, adsorption of monophosphoryl lipid A (MPLA) extracted from Salmonella minnesota, which is a TIR-domain-containing adapter-inducing interferon-β- (TRIF-) biased TLR4 agonist, was less effective in decreasing Th-2 responses. Importantly, in a situation with antigenic competition (OVA plus TT), TT-specific IgG1 or IgG2a was decreased compared with TT sensitization. Notably, LPS increased the production of IgG1 and IgG2a TT-specific antibodies. In conclusion, the addition of LPS induces a more robust IgG1 and IgG2a TT-specific antibody production and concomitantly decreases Th2-cellular and humoral responses, indicating a potential use of alum/TLR-based vaccines.

  10. Bacteriophytochromes control conjugation in Agrobacterium fabrum. (United States)

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


    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.

  11. Glutathione conjugation as a bioactivation reaction

    NARCIS (Netherlands)

    Bladeren, P.J. van


    In general, glutathione conjugation is regarded as a detoxication reaction. However, depending on the properties of the substrate, bioactivation is also possible. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate

  12. Double phase conjugation in tungsten bronze crystals. (United States)

    Sharp, E J; Clark Iii, W W; Miller, M J; Wood, G L; Monson, B; Salamo, G J; Neurgaonkar, R R


    In this paper we report a new method for double phase conjugation particularly suited to the tungsten bronze crystal strontium barium niobate. It has also been observed to produce conjugate waves in BaTiO(3) and BSKNN. This new arrangement is called the bridge conjugator because the two beams enter opposing [100] crystal faces and fan together to form a bridge without reflection off a crystal face. Our measurements indicate that the bridge conjugator is competitive with previously reported double phase conjugate mirrors in reflectivity, response time, ease of alignment, and fidelity.

  13. Conjugative plasmids of Neisseria gonorrhoeae.

    Directory of Open Access Journals (Sweden)

    Emilia Pachulec

    Full Text Available Many clinical isolates of the human pathogen Neisseria gonorrhoeae contain conjugative plasmids. The host range of these plasmids is limited to Neisseria species, but presence of a tetracycline (tetM determinant inserted in several of these plasmids is an important cause of the rapid spread of tetracycline resistance. Previously plasmids with different backbones (Dutch and American type backbones and with and without different tetM determinants (Dutch and American type tetM determinants have been identified. Within the isolates tested, all plasmids with American or Dutch type tetM determinants contained a Dutch type plasmid backbone. This demonstrated that tetM determinants should not be used to differentiate between conjugal plasmid backbones. The nucleotide sequences of conjugative plasmids with Dutch type plasmid backbones either not containing the tetM determinant (pEP5233 or containing Dutch (pEP5289 or American (pEP5050 type tetM determinants were determined. Analysis of the backbone sequences showed that they belong to a novel IncP1 subfamily divergent from the IncP1alpha, beta, gamma, delta and epsilon subfamilies. The tetM determinants were inserted in a genetic load region found in all these plasmids. Insertion was accompanied by the insertion of a gene with an unknown function, and rearrangement of a toxin/antitoxin gene cluster. The genetic load region contains two toxin/antitoxins of the Zeta/Epsilon toxin/antitoxin family previously only found in Gram positive organisms and the virulence associated protein D of the VapD/VapX toxin/antitoxin family. Remarkably, presence of VapX of pJD1, a small cryptic neisserial plasmid, in the acceptor strain strongly increased the conjugation efficiency, suggesting that it functions as an antitoxin for the conjugative plasmid. The presence of the toxin and antitoxin on different plasmids might explain why the host range of this IncP1 plasmid is limited to Neisseria species. The isolated plasmids

  14. Fiber bundle phase conjugate mirror (United States)

    Ward, Benjamin G.


    An improved method and apparatus for passively conjugating the phases of a distorted wavefronts resulting from optical phase mismatch between elements of a fiber laser array are disclosed. A method for passively conjugating a distorted wavefront comprises the steps of: multiplexing a plurality of probe fibers and a bundle pump fiber in a fiber bundle array; passing the multiplexed output from the fiber bundle array through a collimating lens and into one portion of a non-linear medium; passing the output from a pump collection fiber through a focusing lens and into another portion of the non-linear medium so that the output from the pump collection fiber mixes with the multiplexed output from the fiber bundle; adjusting one or more degrees of freedom of one or more of the fiber bundle array, the collimating lens, the focusing lens, the non-linear medium, or the pump collection fiber to produce a standing wave in the non-linear medium.

  15. Conjugated Polymers for Energy Production

    DEFF Research Database (Denmark)

    Livi, Francesco

    arylation (DAr) and direct arylation polymerization (DArP) have been applied to the preparation of PPDTBT, making this polymer readily available in only 4 synthetic steps and thus easily transferable to a large scale-production setup. DArP avoids organometallic species and therefore is an appealing......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...... for scalable PSCs fully printed under ambient conditions [Adv. Energy Mater. 2015, 5, 1402186]. PPDTBT resulted to be the conjugated polymer with the best photovoltaic performance within the 104 synthesized macromolecules. Therefore, further studies have been done on such material. The impact of side chain...

  16. Conjugated polyelectrolytes fundamentals and applications

    CERN Document Server

    Liu, Bin


    This is the first monograph to specifically focus on fundamentals and applications of polyelectrolytes, a class of molecules that gained substantial interest due to their unique combination of properties. Combining both features of organic semiconductors and polyelectrolytes, they offer a broad field for fundamental research as well as applications to analytical chemistry, optical imaging, and opto-electronic devices. The initial chapters introduce readers to the synthesis, optical and electrical properties of various conjugated polyelectrolytes. This is followed by chapters on the applica

  17. Licensure of a Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus Vaccine and Guidance for Use as a Booster Dose. (United States)

    Liang, Jennifer; Wallace, Greg; Mootrey, Gina


    On March 24, 2015, the Food and Drug Administration licensed an additional combined diphtheria and tetanus toxoids and acellular pertussis adsorbed (DTaP) and inactivated poliovirus (IPV) vaccine (DTaP-IPV) (Quadracel, Sanofi Pasteur Inc.). Quadracel is the second DTaP-IPV vaccine to be licensed for use among children aged 4 through 6 years in the United States (1). Quadracel is approved for administration as a fifth dose in the DTaP series and as a fourth or fifth dose in the IPV series in children aged 4 through 6 years who have received 4 doses of DTaP-IPV-Hib (Pentacel, Sanofi Pasteur) and/or DTaP (Daptacel, Sanofi Pasteur) vaccine (2,3). This report summarizes the indications for Quadracel vaccine and provides guidance from the Advisory Committee on Immunization Practices (ACIP) for its use.

  18. Reactogenicidad e inmunogenicidad de una nueva vacuna de toxoide tetánico y diftérico con concentración reducida en adolescentes cubanos

    Directory of Open Access Journals (Sweden)

    Rolando Felipe Ochoa.


    Full Text Available Se realizó un estudio aleatorizado, controlado y a doble ciegas en 225 adolescentes cubanos entre 13 y 16 años de edad, con el objetivo de evaluar la reactogenicidad y la inmunogenicidad de una nueva vacuna de toxoide tetánico y toxoide diftérico con concentración reducida, producida en el Instituto Finlay, con respecto a su similar comercial IMOVAX dT adult de Aventis Pasteur. Se tomaron muestras de suero antes y 21 días después de la vacunación. La reactogenicidad de ambas vacunas fue similar. Los síntomas y signos, tanto locales como generales fueron moderados y aparecieron principalmente durante las primeras 72 h después de la vacunación. Todos los voluntarios vacunados alcanzaron niveles protectores (³0,1 UI/mL de antitoxina contra el tétanos y la difteria. El 99,25% de los inmunizados con la vacuna experimental y el 98,36% de los voluntarios del grupo control presentaron niveles de antitoxina tetánica correspondientes a una protección de larga duración (³1,0 UI/mL; para la antitoxina diftérica se alcanzaron estos niveles en el 81,20% y 80,33% de los voluntarios en cada grupo. Los títulos medios geométricos de antitoxina tetánica (21,73 UI/mL y antitoxina diftérica (2,55 UI/mL inducidos por la nueva vacuna fueron superiores (p<0,05 a los del grupo control: 15,55 UI/mL y 1,84 UI/Ml respectivamente(p<0.05.

  19. Modelling conjugation with stochastic differential equations. (United States)

    Philipsen, K R; Christiansen, L E; Hasman, H; Madsen, H


    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 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 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 to the model without plate conjugation. The modelling approach described in this article can be applied generally when modelling dynamical systems.

  20. Modelling conjugation with stochastic differential equations

    DEFF Research Database (Denmark)

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


    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...

  1. Cysteine S-conjugate β-lyases


    Arthur J. L. Cooper; Krasnikov, Boris F.; Pinto, John T.; Bruschi, Sam A.


    Cysteine S-conjugate β-lyases are pyridoxal 5′-phosphate (PLP)-containing enzymes that catalyze the conversion of cysteine S-conjugates [RSCH2CH(NH3+)CO2−] and selenium Se-conjugates [RSeCH2CH(NH3+)CO2−] that contain a leaving group in the β position to pyruvate, ammonium and a sulfur-containing fragment (RSH) or selenium-containing fragment (RSeH), respectively. At least ten PLP enzymes catalyze β-elimination reactions with such cysteine S-conjugates. All are enzymes involved in amino acid m...

  2. The Tcp conjugation system of Clostridium perfringens. (United States)

    Wisniewski, Jessica A; Rood, Julian I


    The Gram-positive pathogen Clostridium perfringens possesses a family of large conjugative plasmids that is typified by the tetracycline resistance plasmid pCW3. Since these plasmids may carry antibiotic resistance genes or genes encoding extracellular or sporulation-associated toxins, the conjugative transfer of these plasmids appears to be important for the epidemiology of C. perfringens-mediated diseases. Sequence analysis of members of this plasmid family identified a highly conserved 35kb region that encodes proteins with various functions, including plasmid replication and partitioning. The tcp conjugation locus also was identified in this region, initially based on low-level amino acid sequence identity to conjugation proteins from the integrative conjugative element Tn916. Genetic studies confirmed that the tcp locus is required for conjugative transfer and combined with biochemical and structural analyses have led to the development of a functional model of the Tcp conjugation apparatus. This review summarises our current understanding of the Tcp conjugation system, which is now one of the best-characterized conjugation systems in Gram-positive bacteria.

  3. Test of charge conjugation invariance. (United States)

    Nefkens, B M K; Prakhov, S; Gårdestig, A; Allgower, C E; Bekrenev, V; Briscoe, W J; Clajus, M; Comfort, J R; Craig, K; Grosnick, D; Isenhower, D; Knecht, N; Koetke, D; Koulbardis, A; Kozlenko, N; Kruglov, S; Lolos, G; Lopatin, I; Manley, D M; Manweiler, R; Marusić, A; McDonald, S; Olmsted, J; Papandreou, Z; Peaslee, D; Phaisangittisakul, N; Price, J W; Ramirez, A F; Sadler, M; Shafi, A; Spinka, H; Stanislaus, T D S; Starostin, A; Staudenmaier, H M; Supek, I; Tippens, W B


    We report on the first determination of upper limits on the branching ratio (BR) of eta decay to pi0pi0gamma and to pi0pi0pi0gamma. Both decay modes are strictly forbidden by charge conjugation (C) invariance. Using the Crystal Ball multiphoton detector, we obtained BR(eta-->pi0pi0gamma)pi0pi0pi0gamma)<6 x 10(-5) at the 90% confidence level, in support of C invariance of isovector electromagnetic interactions.

  4. Waveguide mutually pumped phase conjugators


    James, S. W.; Youden, K.E.; Jeffrey, P. M.; EASON, R. W.; Chandler, P.J.; Zhang, L.; Townsend, P.D.


    The operation of the Bridge Mutually Pumped Phase Conjugator is reported in a planar waveguide structure in photorefractive BaTiO3. The waveguide was fabricated by the technique of ion implantation. using 1.5 MeV H+ at a dose of 10^16 ions/cm^2. An order of magnitude decrease in response time is observed in the waveguide as compared to typical values obtained in bulk crystals, probably resulting from a combination of the optical confinement within the waveguide, and possibly modification of t...

  5. Suplementación con selenio en vaquillas: Efecto sobre la respuesta inmune a las vacunas Brucella abortus cepa RB51 y toxoide tetánico Selenium suplementation in heifers: Effect on the immune response to Brucella abortus strain RB51 and tetanus toxoid vaccines

    Directory of Open Access Journals (Sweden)

    V Leyán


    Full Text Available El trabajo tiene por objetivo evaluar el efecto de una suplementación con selenio (Se sobre la respuesta inmune a las vacunas Toxoide tetánico y Brucella abortus cepa RB51 en vaquillas con un adecuado balance metabólico de selenio (GSH-Px >130 U/g Hb. Para ello se empelaron 32 vaquillas Friesian de 18 a 24 meses de edad, asignadas al azar a dos grupos de 16 animales; uno suplementado (Se-S el día 0 con una dosis de selenato de bario (1 mg Se/kg, s.c., permaneciendo el otro como control no suplementado (No-S. Todas las vaquillas fueron mantenidas durante 9 meses (abril a enero a pastoreo sobre una pradera naturalizada con un contenido de Se de 0,04 ppm/MS. Los animales fueron inmunizados con vacuna RB51 el día 60 y posteriormente con Toxoide tetánico los días 120 y 150. Muestras de sangre fueron obtenidas previo a la suplementación y cada 15 días hasta el término del experimento. El balance metabólico de selenio fue evaluado mediante la actividad sanguínea de Glutatión peroxidasa (GSH-Px. La respuesta inmune humoral se evaluó determinando los anticuerpos séricos específicos para ambos antígenos mediante ELISA y la respuesta inmune celular mediante pruebas de intradermorreacción a antígenos de Brucella abortus. La administración de Se aumentó (P 0,05 en ambos grupos experimentales, mientras que la respuesta celular a la vacuna RB51 fue menor (P The effect of selenium (Se supplementation on the immune response to tetanus toxoid and Brucella abortus strain RB51 vaccines was studied in heifers with a normal Se status (GSH-Px activity > 130 U/g Hb. Frisian heifers (n-32, 18 to 24 months old were randomly allocated into two groups of 16 animals each. Animals from one group were supplemented (Se-S with one dose of barium selenate (1 mg/Se/kg. s.c. on day 0; animals from the other group remained as a control without supplementation (No-S. The heifers grazed during 9 months (April to January a pasture that contained 0.04 ppm/DM of Se

  6. Photoluminescence of Conjugated Star Polymers (United States)

    Ferguson, J. B.; Prigodin, N. V.; Epstein, A. J.; Wang, F.


    Higher dimensionality "star" polymers provide new properties beyond those found in their linear analogs. They have been used to improving electronic properties for nonlinear optics through exciton transfer and molecular antenna structures for example (M. Kawa, J. M. J. Frechet, Chem. Mater. 10, 286 (1998).). We report on photoluminescence properties of star polymers with a hyperbranched core (both hyperbranched phenlyene and hyperbranched triphenylamine) and polyhexylthiophene arms. The arm is a conjugated oligomer of polythiophene that has been investigated extensively for metallic like conductivity when doped as well as utilized in field effect transistors in its undoped form (A. Tsumara, H. Koezuka, T. Ando, Appl. Phys. Lett. 49, 1210 (1986).). The cores are respectively, a nonconjugated polymer in the case of hyperbranched phenlyene and a conjugated polymer in the case of hyperbranched triphenylamine. The photoluminesce spectrum (λ_max at 575 nm) is identical for both star polymers with the two electronically different hyperbranched cores and for linear polythiophene alone. We conclude the wave functions of the core and arms do not strongly interact to form states different from their individual states and excitons formed on the hyperbranched cores migrate to the lower bandgap polythiophene before recombining.

  7. Subgap Absorption in Conjugated Polymers (United States)

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


    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 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.

  8. Immune interference on conjugate vaccines by carrier proteins or co-administrated vaccines%载体蛋白及多种疫苗同时接种对结合疫苗的免疫干扰

    Institute of Scientific and Technical Information of China (English)



    多种多糖-蛋白结合疫苗被开发成功,用于预防b型流感嗜血杆菌、脑膜炎球菌和肺炎链球菌感染,为婴幼儿健康提供了保障.常用的载体蛋白是破伤风类毒素、白喉类毒素和白喉类毒素突变体CRM197.在临床研究中观察到,相同载体或不同载体结合疫苗同时接种,或者与DTP/HBV/IPV等疫苗同时接种时,会干扰对某些抗原的免疫应答,其中可能有多种机制在起作用.随着更多的结合疫苗有望进入婴幼儿期基础免疫程序和无细胞百日咳疫苗(aP)逐渐代替全细胞百日咳疫苗(wP),如何选择合适的或者新的载体蛋白和佐剂、谨慎设计临床研究方案和接种程序等问题日益受到关注.%Polysaccharide-protein conjugate vaccines are developed successfully to prevent Haemophilus influenzae type b,Neisseria meningitidis and Streptococus pnuemoniae infections,especially for infants.The most commonly used carrier proteins are tetanus toxoid,diphtheria toxoid,and diphtheria toxin variant CRM197.In clinical trials,immune interference has been observed when conjugate vaccines with the same or different carrier proteins were co-administrated,or the conjugate vaccines were immunized concurrently with DTP/HBV/IPV.Several mechanisms may work together.As more conjugate vaccines are expected to be included into the childhood primary immunization schedule,and whole cell pertussis vaccine (wP) is replaced by acellular pertussis vaccine (aP) gradually,the problemns,including how to choose suitable carrier proteins and adjuvants,carefully designing the clinical trial and immunization schedule,attract more people's attention.

  9. 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...

  10. Kinetic models of conjugated metabolic cycles (United States)

    Ershov, Yu. A.


    A general method is developed for the quantitative kinetic analysis of conjugated metabolic cycles in the human organism. This method is used as a basis for constructing a kinetic graph and model of the conjugated citric acid and ureapoiesis cycles. The results from a kinetic analysis of the model for these cycles are given.


    Institute of Scientific and Technical Information of China (English)

    Ernst Hairer


    For the numerical treatment of Hamiltonian differential equations, symplectic integra-tors are the most suitable choice, and methods that are conjugate to a symplectic integrator share the same good long-time behavior. This note characterizes linear multistep methods whose underlying one-step method is conjugate to a symplectic integrator. The bounded-hess of parasitic solution components is not addressed.

  12. LEDs based on conjugated PPV block copolymers

    NARCIS (Netherlands)

    Brouwer, H.J.; Hilberer, A.; Krasnikov, V.V.; Werts, M.; Wildeman, J.; Hadziioannou, G.


    A way to control the bandgap in semi-conducting polymers is by preparing polymers with a partially conjugated backbone. In our laboratory, three conjugated copolymers containing PPV trimers as light emitting chromophores have been synthesized, which emit in the blue, green and orange wavelength regi


    DEFF Research Database (Denmark)


    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...


    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

  15. The Conjugate Acid-Base Chart. (United States)

    Treptow, Richard S.


    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)

  16. Energetic Tuning in Spirocyclic Conjugated Polymers

    Directory of Open Access Journals (Sweden)

    Hugo Bronstein


    Full Text Available Precise control of the energy levels in a conjugated polymer is the key to allowing their exploitation in optoelectronic devices. The introduction of spirocycles into conjugated polymers has traditionally been used to enhance their solid state microstructure. Here we present a highly novel method of energetic tuning through the use of electronically active spirocyclic systems. By modifying the size and oxidation state of a heteroatom in an orthogonal spirocycle we demonstrate energetic fine tuning in both the absorption and emission of a conjugated polymer. Furthermore, the synthesis of highly novel triplet-decker spirocyclic conjugated polymers is presented. This new method of energetic manipulation in a conjugated polymer paves the way for future application targeted synthesis of polymers with electronically active spirocycles.

  17. Peptide-LNA oligonucleotide conjugates

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte


    properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper......Although peptide-oligonucleotide conjugates (POCs) are well-known for nucleic acids delivery and therapy, reports on internal attachment of peptides to oligonucleotides are limited in number. To develop a convenient route for preparation of internally labeled POCs with improved biomedical......(i)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. DNA/RNA target binding affinity and selectivity of the resulting POCs were improved in comparison to LNA/DNA mixmers and unmodified DNA controls. This clearly demonstrates that internal attachment of peptides to oligonucleotides can significantly...

  18. Photoconductive properties of conjugated polymers

    CERN Document Server

    Halls, J J M


    The research described in my dissertation has involved the fabrication and characterisation of photovoltaic cells based on conjugated polymers, including the widely studied polymer poly(p-phenylenevinylene). These materials have semiconducting properties which arise from the delocalisation of electrons along the pi-electron systems of the polymer chains. Research into these materials is motivated both by their novel electronic properties, and also their potential for use in a wide range of applications including light-emitting diodes (LEDs), thin-film transistors, and photovoltaic cells (solar cells and light detectors). Light absorbed in a photovoltaic cell generates opposite charges which are collected at two different electrodes, giving rise to an electric current

  19. Test of Charge Conjugation Invariance (United States)

    Nefkens, B. M.; Prakhov, S.; Gårdestig, A.; Allgower, C. E.; Bekrenev, V.; Briscoe, W. J.; Clajus, M.; Comfort, J. R.; Craig, K.; Grosnick, D.; Isenhower, D.; Knecht, N.; Koetke, D.; Koulbardis, A.; Kozlenko, N.; Kruglov, S.; Lolos, G.; Lopatin, I.; Manley, D. M.; Manweiler, R.; Marušić, A.; McDonald, S.; Olmsted, J.; Papandreou, Z.; Peaslee, D.; Phaisangittisakul, N.; Price, J. W.; Ramirez, A. F.; Sadler, M.; Shafi, A.; Spinka, H.; Stanislaus, T. D.; Starostin, A.; Staudenmaier, H. M.; Supek, I.; Tippens, W. B.


    We report on the first determination of upper limits on the branching ratio (BR) of η decay to π0π0γ and to π0π0π0γ. Both decay modes are strictly forbidden by charge conjugation (C) invariance. Using the Crystal Ball multiphoton detector, we obtained BR(η→π0π0γ)<5×10-4 at the 90% confidence level, in support of C invariance of isoscalar electromagnetic interactions of the light quarks. We have also measured BR(η→π0π0π0γ)<6×10-5 at the 90% confidence level, in support of C invariance of isovector electromagnetic interactions.

  20. ACYW135群脑膜炎球菌多糖结合疫苗的研制%Development of groups ACYW135 meningococcal polysaccharide conjugate vaccine

    Institute of Scientific and Technical Information of China (English)

    张明华; 任涛; 曹欣; 唐秀丽; 韩菲; 王婷婷; 胡鹏; 张美香; 郝倩


    Objective To prepare a safe and effective quadrivalent meningococcal polysaccharide conjugate vaccine.Methods Groups A,C,Y and W135 meningococcal polysaccharide were activated by cyanogen bromide,respectively.With 1,6-adipic acid dihydrazide as linking agent,monovalent meningococcal polysaccharide conjugate vaccines were prepared by carbodiimide-mediated coupling of meningococcal polysaccharide with carrier protein diphtheria toxoid (DT),then groups ACYW135 meningococcal polysaccharide-DT conjugate vaccine (ACYW135-DT) was prepared by mixing each monovalent meningococcal polysaccharide conjugate vaccine in a certain proportion.Mice were immunized with ACYW135-DT,and antibodies to each polysaccharide were detected by indirect ELISA.The statistical analysis of the results were made by t test.Results Each index of the prepared ACYW135-DT achieved quality control standard.ACYW135-DT had a good safety and immunogenicity.The levels of IgG antibodies to group A (t =24.487,P<0.01),group C (t =17.056,P <0.01),group Y (t =26.213,P <0.01) and group W135 (t =17.392,P <0.01) polysaccharides in mice immunized with ACYW135-DT were significantly higher than those in mice immunized quadrivalent meningococcal polysaccharide vaccine.Conclusion ACYW135-DT is successfully prepared with this technology.%目的 制备安全有效的四价脑膜炎球菌多糖结合疫苗.方法 用溴化氰分别将A、C、Y、W135群脑膜炎球菌多糖活化,以己二酸二酰肼作为连接剂,碳化二亚胺作为偶联剂,先制备单价A、C、Y、W135群脑膜炎球菌多糖-白喉类毒素(diphtheria toxoid,DT)结合疫苗,再配比制成ACYW135群脑膜炎球菌多糖结合疫苗(groups ACYW135 meningococcal polysaccharide-DT conjugate vaccine,ACYW135-DT).以ACYW135-DT免疫小鼠,用间接ELISA检测小鼠血清抗各多糖抗体,采用t检验对检测结果进行统计学分析.结果 制备的ACYW135-DT的各项指标均达到质控标准,而且ACYW 135-DT具有良好

  1. Conjugated amplifying polymers for optical sensing applications. (United States)

    Rochat, Sébastien; Swager, Timothy M


    Thanks to their unique optical and electrochemical properties, conjugated polymers have attracted considerable attention over the last two decades and resulted in numerous technological innovations. In particular, their implementation in sensing schemes and devices was widely investigated and produced a multitude of sensory systems and transduction mechanisms. Conjugated polymers possess numerous attractive features that make them particularly suitable for a broad variety of sensing tasks. They display sensory signal amplification (compared to their small-molecule counterparts) and their structures can easily be tailored to adjust solubility, absorption/emission wavelengths, energy offsets for excited state electron transfer, and/or for use in solution or in the solid state. This versatility has made conjugated polymers a fluorescence sensory platform of choice in the recent years. In this review, we highlight a variety of conjugated polymer-based sensory mechanisms together with selected examples from the recent literature.

  2. Design and Application of Antimicrobial Peptide Conjugates

    Directory of Open Access Journals (Sweden)

    Andre Reinhardt


    Full Text Available Antimicrobial peptides (AMPs are an interesting class of antibiotics characterized by their unique antibiotic activity and lower propensity for developing resistance compared to common antibiotics. They belong to the class of membrane-active peptides and usually act selectively against bacteria, fungi and protozoans. AMPs, but also peptide conjugates containing AMPs, have come more and more into the focus of research during the last few years. Within this article, recent work on AMP conjugates is reviewed. Different aspects will be highlighted as a combination of AMPs with antibiotics or organometallic compounds aiming to increase antibacterial activity or target selectivity, conjugation with photosensitizers for improving photodynamic therapy (PDT or the attachment to particles, to name only a few. Owing to the enormous resonance of antimicrobial conjugates in the literature so far, this research topic seems to be very attractive to different scientific fields, like medicine, biology, biochemistry or chemistry.

  3. Natural autoantibodies, IgG antibodies to tetanus toxoid and CD5+ B cells in patients with Mediterranean visceral leishmaniasis. The Leishmania Study Group. (United States)

    Louzir, H; Belal-Kacemi, L; Sassi, A; Laouini, D; Ben Ismail, R; Dellagi, K


    Natural autoantibodies (NaAb) and IgG antibodies to tetanus toxoid (TT) were analysed in the sera of 38 children with active visceral leishmaniasis (VL) previously vaccinated with TT and in 30 healthy controls matched for sex and age. Patients exhibited high levels of NaAb to a panel of self antigens (tubulin, myosin, myoglobin, actin) contrasting to a low level of IgG to TT. Analysis of the circulating B cells in 26 untreated patients showed a low percentage of CD5+ per total B cells (3-66%, mean 36.6%) compared with 14 normal controls (17.8-66.6%, mean 52.7%) (P < 0.001). Evaluation of these parameters after antimonial therapy showed a significant decrease of the level of the NaAb (P < 0.0005), and a spontaneous increase of the level of the IgG to TT without any vaccine boosting (P < 0.01). In contrast, there was a significant increase in CD5+ B cells (P < 0.0005). This result suggests that CD5+ B cells may be sequestrated in parasitized lymphoid organs and may be released after remission. These findings show that the polyclonal B cell activation that occurs during active VL involves mainly B cells bearing NaAb and are in favour of a functional dichotomy of B cells.

  4. Transcutaneous immunization with cross-reacting material CRM(197) of diphtheria toxin boosts functional antibody levels in mice primed parenterally with adsorbed diphtheria toxoid vaccine. (United States)

    Stickings, Paul; Peyre, Marisa; Coombes, Laura; Muller, Sylviane; Rappuoli, Rino; Del Giudice, Giuseppe; Partidos, Charalambos D; Sesardic, Dorothea


    Transcutaneous immunization (TCI) capitalizes on the accessibility and immunocompetence of the skin, elicits protective immunity, simplifies vaccine delivery, and may be particularly advantageous when frequent boosting is required. In this study we examined the potential of TCI to boost preexisting immune responses to diphtheria in mice. The cross-reacting material (CRM(197)) of diphtheria toxin was used as the boosting antigen and was administered alone or together with either one of two commonly used mucosal adjuvants, cholera toxin (CT) and a partially detoxified mutant of heat-labile enterotoxin of Escherichia coli (LTR72). We report that TCI with CRM(197) significantly boosted preexisting immune responses elicited after parenteral priming with aluminum hydroxide-adsorbed diphtheria toxoid (DTxd) vaccine. In the presence of LTR72 as an adjuvant, toxin-neutralizing antibody titers were significantly higher than those elicited by CRM(197) alone and were comparable to the functional antibody levels induced after parenteral booster immunization with the adsorbed DTxd vaccine. Time course study showed that high levels of toxin-neutralizing antibodies persisted for at least 14 weeks after the transcutaneous boost. In addition, TCI resulted in a vigorous antigen-specific proliferative response in all groups of mice boosted with the CRM(197) protein. These findings highlight the promising prospect of using booster administrations of CRM(197) via the transcutaneous route to establish good herd immunity against diphtheria.

  5. The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced Amyloid β Binding Antibodies on Cynomolgus Monkeys and Guinea Pigs

    Directory of Open Access Journals (Sweden)

    Akira Yano


    Full Text Available The reduction of brain amyloid beta (Aβ peptides by anti-Aβ antibodies is one of the possible therapies for Alzheimer’s disease. We previously reported that the Aβ peptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT induced anti-Aβ antibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβ antibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ40, and Aβ42 compared to Aβ fibrils. The levels of serum anti-Aβ antibodies and plasma Aβ peptides increased in both animals and decreased the brain Aβ40 level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβ antibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβ peptides and their toxic effects via clearance of Aβ peptides by generated antibodies.


    Directory of Open Access Journals (Sweden)

    Sawitri Sawitri


    Full Text Available Latar belakang: Salah satu strategi untuk mencapai eliminasi tetanus neonatorum adalah mengembangkan intensifikasi imunisasi tetanus toxoid (TT pada wanita usia subur khususnya para calon pengantin.  Tujuan: Mengetahui gambaran persepsi petugas kesehatan dan petugas KUA terhadap pelaksanaan program imunisasi TT bagi calon pengantin. Metode: Merupakan penelitian kualitatif dengan pendekatan fenomenologi, yang dilakukan di 3 Kecamatan di Tangerang Selatan tahun 2011, yaitu Kecamatan Ciputat, Pamulang dan Serpong Utara. Informan terdiri dari 6 informan kunci (3 petugas puskesmas dan 3 petugas KUA dan 4 informan pendukung (calon pengantin. Pengumpulan data dilakukan dengan wawancara mendalam dan observasi. Hasil: Persepsi petugas puskesmas dan petugas KUA tentang manfaat imunisasi TT sudah baik, tetapi proses sosialisasi program belum efektif. Hambatan pelaksanaan program yang berasal dari calon pengantin diantaranya karena kurangnya pengetahuan, takut disuntik, dan persepsi yang salah tentang imunisasi TT yang dianggap sebagai kontrasepsi. Hambatan dari petugas yaitu masih kurangnya petugas, beban kerja terlalu banyak, dan terbatasnya petugas yang paham tentang program tersebut.  Kesimpulan: Pelaksanaan program imunisasi TT belum optimal dikarenakan terdapat beberapa hambatan dari petugas puskesmas, petugas KUA maupun dari calon pengantin.   Kata kunci: Imunisasi tetanus, calon pengantin, kesehatan reproduksi

  7. Autoantibody response and pregnancy-related pathology induced by combined LPS and tetanus toxoid hyperimmunization in BALB/c and C57BL/6 mice. (United States)

    Petrušić, Vladimir; Todorović, Nevena; Živković, Irena; Dimitrijević, Rajna; Muhandes, Lina; Rajnpreht, Irena; Dimitrijević, Ljiljana


    Recent data concerning antiphospholipid syndrome (APS) induction have shown that β2-glycoprotein I (β2GPI) binds lipopolysaccharide (LPS), which results in conformational changes, exposition of a cryptic epitope and possible pathological anti-β2GPI antibody production. In order to investigate the effects of LPS on the induction of APS-related pathology, we performed hyperimmunization of BALB/c and C57BL/6 mice with LPS, alone or in combination with tetanus toxoid (TTd), a protein structurally similar to β2GPI. We report that, although high affinity pathological anti-β2GPI antibodies were produced in all groups of animals, the reproductive pathology was recorded only in mice that received both LPS and TTd, implying on the important roles of both infections and molecular mimicry in APS pathogenesis. Moreover, APS-related reproductive pathology was more pronounced in BALB/c (lowered fertility and fecundity) than C57BL/6 mice (lowered fecundity), which correlated well with the disruption in natural antibody network observed in BALB/c mouse strain.

  8. Enhanced mucosal immune responses against tetanus toxoid using novel delivery system comprised of chitosan-functionalized gold nanoparticles and botanical adjuvant: characterization, immunogenicity, and stability assessment. (United States)

    Barhate, Ganesh; Gautam, Manish; Gairola, Sunil; Jadhav, Suresh; Pokharkar, Varsha


    Approaches based on combined use of delivery systems and adjuvants are being favored to maximize efficient mucosal delivery of antigens. Here, we describe a novel delivery system comprised of chitosan-functionalized gold nanoparticles (CsAuNPs) and saponin-containing botanical adjuvant; Asparagus racemosus extract (ARE) for oral delivery of tetanus toxoid (TT). A significant increase in TT-specific IgG (34.53-fold) and IgA (43.75-fold) was observed when TT-CsAuNPs were formulated with ARE (TT-ARE-CsAuNPs). The local IgA immune responses for TT also showed a significant increase (106.5-fold in intestine washes and 99.74-fold in feces) with ARE-based formulations as compared with plain TT group. No effect of ARE was observed on size, charge, and loading properties of CsAuNPs. Additionally, no effect of ARE and CsAuNPs was observed on antigenicity and secondary structure of TT as determined by fluorescence, circular dichroism, and Fourier transform infrared spectroscopy. The stability studies demonstrated excellent stability profile of formulation at recommended storage conditions. The study establishes the possible role of immunomodulatory adjuvants in particulate delivery systems for mucosal delivery of vaccines.

  9. Production of tag-free recombinant fusion protein encompassing promiscuous T cell epitope of tetanus toxoid and dog zona pellucida glycoprotein-3 for contraceptive vaccine development. (United States)

    Gupta, Neha; Shrestha, Abhinav; Panda, Amulya Kumar; Gupta, Satish Kumar


    Affinity tags can interfere in various physicochemical properties and immunogenicity of the recombinant proteins. In the present study, tag-free recombinant fusion protein encompassing promiscuous T cell epitope of tetanus toxoid [TT; amino acid (aa) residues 830-844] followed by dilysine linker and dog zona pellucida glycoprotein-3 (ZP3; aa residues 23-348) (TT-KK-ZP3) was expressed in Escherichia coli. The recombinant protein, expressed as inclusion bodies (IBs), was purified by isolation of IBs, processed to remove host cell proteins, followed by solubilization and refolding. A specific 39 kDa protein including ZP3 was identified by SDS-PAGE. CD spectra showed the presence of α-helices and β-sheets, and fluorescent spectroscopy revealed emission maxima of 265 A.U. at 339 nm for refolded protein and showed red shift in the presence of 6 M guanidine hydrochloride. Immunization of inbred FvB/J female mice with purified recombinant TT-KK-ZP3 (25 μg/animal) led to generation of high antibody titers against the recombinant protein. The antibodies reacted specifically with ZP matrix surrounding mouse oocytes. Immunized mice showed significant reduction in fertility as compared to the control group. The studies described herein provide a simple method to produce and purify tag-free recombinant protein for the development of a contraceptive vaccine.

  10. Subnormal and waning immunity to tetanus toxoid in previously vaccinated HIV-infected children and response to booster doses of the vaccine. (United States)

    Choudhury, Shahana A; Matin, Fazle


    Little is known regarding waning immunity to tetanus toxoid (TT) in HIV-infected children and the need for booster doses before the recommended interval of 5-10 years. Anti-tetanus antibodies were assessed by ELISA in 24 HIV-infected and 24 control children. A protective level (>0.1 IU/ml) of TT antibodies was observed in 62% of HIV-infected children and in 100% of controls. HIV-infected children with five doses had a significantly (p=0.01) lower prevalence of protective immunity compared to controls. Follow-up anti-TT antibody levels in nine HIV-infected children declined from 1.27 to 0.26 IU/ml, but levels did not decline in the seven controls; five of the seven (71%) children with a non-protective level of antibodies responded with a level>0.16 IU/ml following one booster dose of the vaccine. HIV-infected children may need TT boosters before the recommended 5-10 years.

  11. Determinants of utilization of sufficient tetanus toxoid immunization during pregnancy: evidence from the Kenya Demographic and Health Survey, 2008-2009. (United States)

    Haile, Zelalem T; Chertok, Ilana R Azulay; Teweldeberhan, Asli K


    Although the effectiveness of tetanus toxoid (TT) immunization during pregnancy in preventing maternal and neonatal tetanus is well established, in many developing countries, TT immunization programs are underutilized. The objective of this study was to examine factors associated with sufficient TT immunization among postpartum women in Kenya. Population based secondary data analysis was conducted using de-identified data from the 2008-2009 Kenyan Demographic and Health Survey (KDHS) for 1,370 female participants who had a live birth during or within 12 months of the cross-sectional survey. Chi-square test and independent sample t test were conducted to assess bivariate associations and a multivariable logistic regression analysis was conducted to examine associations before and after adjustment for demographic, socioeconomic, cultural, and access to care factors. The main factors contributing to having been sufficiently immunized against tetanus were lower birth order, higher household wealth index, women's employment, making joint health-related decisions with a partner, and higher number of antenatal care visits. Implications for health care providers and other professionals involved in development of strategies and interventions aimed at improving immunization rates are discussed.

  12. Adjuvant dependence of APS pathology-related low-affinity antibodies during secondary immune response to tetanus toxoid in BALB/c mice. (United States)

    Zivković, Irena; Petrušić, Vladimir; Dimitrijević, Rajna; Stojanović, Marijana; Dimitrijević, Ljiljana


    One of the established animal models for autoimmune disease antiphospholipid syndrome (APS) is TTd hyperimmunization of mice. Tetanus toxoid (TTd) and plasma protein β2GPI share structural homology so that immunization with TTd induces appearance of cross-reactive antibodies. In this paper, we have investigated the presence and dynamic of fluctuation of specific (anti-TTd) and auto (anti-β2GPI) antibodies induced in BALB/c mice during secondary immune response after TTd immunization with alhydrogel or glycerol as adjuvants. In addition, we followed the induced reproductive pathology as a sign of autoimmune outcome. We show undoubtedly adjuvant dependance of (1) level of induced anti-TTd IgG antibodies, (2) changes in levels of low-affinity anti-β2GPI IgG antibodies, and (3) change in fecundity and fertility during secondary immune response. These findings once more indicate the importance of chosen adjuvants used for successful immunization and eventual autoantibody outcome, this time associated with the processes involving low affinity, natural antibodies.

  13. Immunogenicity of porcine P[6], P[7]-specific △VP8* rotavirus subunit vaccines with a tetanus toxoid universal T cell epitope. (United States)

    Wen, Xiaobo; Wei, Xiaoman; Ran, Xuhua; Ni, Hongbo; Cao, Si; Zhang, Yao


    Currently, commercial porcine rotavirus vaccines remain varied limitations. The objective of this study is to develop an alternative porcine rotavirus subunit vaccine candidate by parenteral administration, which enables to elicit robust immune responses against most prevalence porcine rotavirus strains. The bacterially-expressed porcine rotavirus P[6]- or P[7]-specific truncated VP8* (aa 64-223) recombinant protein with or without a universal tetanus toxoid CD4(+) T cell epitope P2 was generated. All the recombinant subunit proteins △VP8*s or P2-△VP8*s were of high solubility and high yields. The immunogenicity of each purified △VP8* and P2-△VP8* was evaluated in mice (10 μg/dose) or guinea pigs (20 μg/dose) immunized IM with 600 μg aluminum hydroxide three times at 2-week interval. The introduction of P2T cell epitope to P[7]-△VP8* elicited significantly higher IgG titer in mice than its absence. Comparatively, P2 epitope slightly enhanced the immunogenicity of P[6]-△VP8*. P2-P[7]△VP8* elicited high titer of neutralizing antibody against heterotypic P[7]-specific rotaviruses with varied G type combination. Our data indicated that two subunit vaccines could be plausible bivalent rotavirus vaccine candidate to provide antigenic coverage of porcine rotavirus strains of global or regional importance.

  14. Synthesis and evaluation of a conjugate vaccine composed of Staphylococcus aureus poly-N-acetyl-glucosamine and clumping factor A.

    Directory of Open Access Journals (Sweden)

    Tomás Maira-Litrán

    Full Text Available The increasing frequency, severity and antimicrobial resistance of Staphylococcus aureus infections has made the development of immunotherapies against this pathogen more urgent than ever. Previous immunization attempts using monovalent antigens resulted in at best partial levels of protection against S. aureus infection. We therefore reasoned that synthesizing a bivalent conjugate vaccine composed of two widely expressed antigens of S. aureus would result in additive/synergetic activities by antibodies to each vaccine component and/or in increased strain coverage. For this we used reductive amination, to covalently link the S. aureus antigens clumping factor A (ClfA and deacetylated poly-N-β-(1-6-acetyl-glucosamine (dPNAG. Mice immunized with 1, 5 or 10 µg of the dPNAG-ClfA conjugate responded in a dose-dependent manner with IgG to dPNAG and ClfA, whereas mice immunized with a mixture of ClfA and dPNAG developed significantly lower antibody titers to ClfA and no antibodies to PNAG. The dPNAG-ClfA vaccine was also highly immunogenic in rabbits, rhesus monkeys and a goat. Moreover, affinity-purified, antibodies to ClfA from dPNAG-ClfA immune serum blocked the binding of three S. aureus strains to immobilized fibrinogen. In an opsonophagocytic assay (OPKA goat antibodies to dPNAG-ClfA vaccine, in the presence of complement and polymorphonuclear cells, killed S. aureus Newman and, to a lower extent, S. aureus Newman ΔclfA. A PNAG-negative isogenic mutant was not killed. Moreover, PNAG antigen fully inhibited the killing of S. aureus Newman by antisera to dPNAG-ClfA vaccine. Finally, mice passively vaccinated with goat antisera to dPNAG-ClfA or dPNAG-diphtheria toxoid conjugate had comparable levels of reductions of bacteria in the blood 2 h after infection with three different S. aureus strains as compared to mice given normal goat serum. In conclusion, ClfA is an immunogenic carrier protein that elicited anti-adhesive antibodies that fail to

  15. Hybrid electronics and electrochemistry with conjugated polymers. (United States)

    Inganäs, Olle


    In this critical review, we discuss the history and development of polymer devices wherein manipulation of the electronic conductivity by electrochemical redox processes in a conjugated polymer is used to form new functions. The devices employed are an electrochemical transistor, an electrolyte-gated field-effect transistor and light-emitting electrochemical cells, all of which combine doping/undoping of a conjugated polymer with modification of electronic transport (130 references).

  16. Metal-leachate-induced conjugate protein instability. (United States)

    Li, Ning; Osborne, Brandi; Singh, Satish K; Wang, Wei


    During the scale-up of an ultrafiltration/diafiltration (UF/DF) step for a protein-based conjugate vaccine, significant precipitation was observed at room temperature. It was found that a specific type of metal hosebarb fitting used in the UF/DF system, when placed in the conjugate solution, caused the precipitation. Inductively Coupled Plasma Mass Spectrometry analysis showed significant amounts of Ni(II), Zn(II), and Cu(II) present in the conjugate solution. A kinetic study showed that the concentration of these metal ions gradually increased with increasing incubation time with a corresponding decrease in conjugate concentration. Direct spiking of trace amounts of NiCl₂, ZnCl₂, and CuCl₂ into the conjugate solution also caused precipitation, and spiking studies showed that the metal ions caused precipitation of the conjugate but not of the carrier protein, antigen, or carrier protein + linker. The precipitation was found to be significantly dependent on buffer species but not solution pH and led to an irreversible loss of tertiary structure even after dissolution in and removal of guanidine hydrochloride. The precipitation is likely the result of formation of transition-metal complexes with histidine residues on the antigen peptide, which may involve both intraconjugate and interconjugate antigens. Such complexation may lead to formation of multimers that may exceed the solubility limit.

  17. Conjugated microporous polymers: design, synthesis and application. (United States)

    Xu, Yanhong; Jin, Shangbin; Xu, Hong; Nagai, Atsushi; Jiang, Donglin


    Conjugated microporous polymers (CMPs) are a class of organic porous polymers that combine π-conjugated skeletons with permanent nanopores, in sharp contrast to other porous materials that are not π-conjugated and with conventional conjugated polymers that are nonporous. As an emerging material platform, CMPs offer a high flexibility for the molecular design of conjugated skeletons and nanopores. Various chemical reactions, building blocks and synthetic methods have been developed and a broad variety of CMPs with different structures and specific properties have been synthesized, driving the rapid growth of the field. CMPs are unique in that they allow the complementary utilization of π-conjugated skeletons and nanopores for functional exploration; they have shown great potential for challenging energy and environmental issues, as exemplified by their excellent performance in gas adsorption, heterogeneous catalysis, light emitting, light harvesting and electrical energy storage. This review describes the molecular design principles of CMPs, advancements in synthetic and structural studies and the frontiers of functional exploration and potential applications.

  18. Heavy-chain isotype patterns of human antibody-secreting cells induced by Haemophilus influenzae type b conjugate vaccines in relation to age and preimmunity

    DEFF Research Database (Denmark)

    Barington, T; Juul, Lars; Gyhrs, A;


    The influence of preexisting immunity on the heavy-chain isotypes of circulating antibody-secreting cells (AbSC) induced by vaccination with Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP) coupled to tetanus toxoid (TT) or diphtheria toxoid (DT) and by vaccination with TT or DT...

  19. The immunogenicity and safety of an investigational meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (ACWY-TT) compared with a licensed meningococcal tetravalent polysaccharide vaccine


    Dbaibo, Ghassan; Macalalad, Noel; Reyes, Mari Rose Aplasca-De Los; Dimaano, Efren; Bianco, Véronique; Baine, Yaela; Miller, Jacqueline


    Immunogenicity and safety of ACWY-TT compared with licensed ACWY polysaccharide vaccine (MenPS) in healthy adults, and lot-to-lot consistency of three ACWY-TT lots were evaluated in a phase 3, open, controlled study. Adults aged 18–55 y were randomized to receive ACWY-TT (one of three lots) or MenPS. Serum bactericidal antibodies (rSBA) were measured pre- and 1 mo post-vaccination. Adverse events (AEs) were assessed 4 d (solicited symptoms) and 31 d (unsolicited symptoms) post-vaccination. Se...

  20. Geometric and Meshing Properties of Conjugate Curves for Gear Transmission

    Directory of Open Access Journals (Sweden)

    Dong Liang


    Full Text Available Conjugate curves have been put forward previously by authors for gear transmission. Compared with traditional conjugate surfaces, the conjugate curves have more flexibility and diversity in aspects of gear design and generation. To further extend its application in power transmission, the geometric and meshing properties of conjugate curves are discussed in this paper. Firstly, general principle descriptions of conjugate curves for arbitrary axial position are introduced. Secondly, geometric analysis of conjugate curves is carried out based on differential geometry including tangent and normal in arbitrary contact direction, characteristic point, and curvature relationships. Then, meshing properties of conjugate curves are further revealed. According to a given plane or spatial curve, the uniqueness of conjugated curve under different contact angle conditions is discussed. Meshing commonality of conjugate curves is also demonstrated in terms of a class of spiral curves contacting in the given direction for various gear axes. Finally, a conclusive summary of this study is given.

  1. Activation of human T cells by major histocompatability complex class II expressing neutrophils: proliferation in the presence of superantigen, but not tetanus toxoid. (United States)

    Fanger, N A; Liu, C; Guyre, P M; Wardwell, K; O'Neil, J; Guo, T L; Christian, T P; Mudzinski, S P; Gosselin, E J


    The primary function of polymorphonuclear neutrophils (PMN) in the immune response appears to be acute phagocytic clearance of foreign pathogens and release of inflammatory mediators. Consistent with their assumed lack of major histocompatibility complex (MHC) class II expression, PMN have not been considered to play a role in antigen presentation and T-cell activation. However, recent reports have shown that human PMN can express MHC class II molecules both in vitro and in vivo after stimulation with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interferon-gamma (IFN-gamma). Thus, under appropriate conditions, PMN could play a significant role in immune regulation, including T-cell activation. In this report, we demonstrate that human class II-expressing PMN can serve as accessory cells in superantigen (SAg)-mediated T-cell activation. This accessory activity for SAg presentation was present only after induction of MHC class II expression, and was especially pronounced following culture of PMN with GM-CSF plus IFN-gamma, which acted synergistically to induce MHC class II molecules on PMN. Moreover, the level of MHC class II expression and the magnitude of SAg-induced T-cell responses were found to be highly correlated and distinctly donor dependent, with PMN from some donors repeatedly showing fivefold higher responses than PMN from other donors. On the other hand, culture of PMN with GM-CSF plus IFN-gamma under conditions that resulted in optimal MHC class II expression did not enable them to function as antigen-presenting cells for either intact tetanus toxoid (TT) or for a TT peptide. These results delineate a new pathway for T-cell activation by SAg that may play an important role in the severity of SAg-induced inflammatory responses. They also identify a donor-specific polymorphism for induction of PMN MHC class II expression which may be of significance for therapies involving GM-CSF and IFN-gamma.

  2. The fully synthetic MAG-Tn3 therapeutic vaccine containing the tetanus toxoid-derived TT830-844 universal epitope provides anti-tumor immunity. (United States)

    Laubreton, Daphné; Bay, Sylvie; Sedlik, Christine; Artaud, Cécile; Ganneau, Christelle; Dériaud, Edith; Viel, Sophie; Puaux, Anne-Laure; Amigorena, Sebastian; Gérard, Catherine; Lo-Man, Richard; Leclerc, Claude


    Malignant transformations are often associated with aberrant glycosylation processes that lead to the expression of new carbohydrate antigens at the surface of tumor cells. Of these carbohydrate antigens, the Tn antigen is particularly highly expressed in many carcinomas, especially in breast carcinoma. We designed MAG-Tn3, a fully synthetic vaccine based on three consecutive Tn moieties that are O-linked to a CD4+ T cell epitope, to induce anti-Tn antibody responses that could be helpful for therapeutic vaccination against cancer. To ensure broad coverage within the human population, the tetanus toxoid-derived peptide TT830-844 was selected as a T-helper epitope because it can bind to various HLA-DRB molecules. We showed that the MAG-Tn3 vaccine, which was formulated with the GSK proprietary immunostimulant AS15 and designed for human cancer therapy, is able to induce an anti-Tn antibody response in mice of various H-2 haplotypes, and this response correlates with the ability to induce a specific T cell response against the TT830-844 peptide. The universality of the TT830-844 peptide was extended to new H-2 and HLA-DRB molecules that were capable of binding this T cell epitope. Finally, the MAG-Tn3 vaccine was able to induce anti-Tn antibody responses in cynomolgus monkeys, which targeted Tn-expressing tumor cells and mediated tumor cell death both in vitro and in vivo. Thus, MAG-Tn3 is a highly promising anticancer vaccine that is currently under evaluation in a phase I clinical trial.

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

    DEFF Research Database (Denmark)

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


    -conjugation patterns, but identical lengths, i.e. an anthracene (linear conjugation), an anthraquinone (cross-conjugation), and a dihydroanthracene (broken conjugation) derivative. To benchmark reliable trends, conductance experiments on these series have been performed by various techniques. Here, we compare data...... characterized by beta = 0.37 +/- 0.03 angstrom(-1) (CP-AFM). Remarkably, for the second series, we do not only find that the linearly conjugated anthracene-containing wire is the most conductive, but also that the cross-conjugated anthraquinone-containing wire is less conductive than the broken...

  4. CO-releasing molecule (CORM) conjugate systems. (United States)

    Kautz, Anna Christin; Kunz, Peter C; Janiak, Christoph


    The development of CORMs (CO-releasing molecules) as a prodrug for CO administration in living organisms has attracted significant attention. CORMs offer the promising possibility of a safe and controllable release of CO in low amounts triggered by light, ligands, enzymes, etc. For the targeting of specific tissues or diseases and to prevent possible side effects from metals and other residues after CO release, these CORMs are attached to biocompatible systems, like peptides, polymers, nanoparticles, dendrimers, protein cages, non-wovens, tablets, and metal-organic frameworks. We discuss in this review the known CORM carrier conjugates, in short CORM conjugates, with covalently-bound or incorporated CORMs for medicinal and therapeutic applications. Most conjugates are nontoxic, show increasing half-lives of CO release, and make use of the EPR-effect, but still show problems because of a continuous background of CO release and the absence of an on/off-switch for the CO release.

  5. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

    Directory of Open Access Journals (Sweden)

    Jacqueline M. Miller


    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.

  6. Tight-binding treatment of conjugated polymers

    DEFF Research Database (Denmark)

    Lynge, Thomas Bastholm

    This PhD thesis concerns conjugated polymers which constitute a constantly growing research area. Today, among other things, conjugated polymers play a role in plastic based solar cells, photodetectors and light emitting diodes, and even today such plastic-based components constitute an alternative...... of tomorrow. This thesis specifically treats the three conjugated polymers trans-polyacetylene (tPA), poly(para-phenylene) (PPP) and poly(para-phe\\-nylene vinylene) (PPV). The present results, which are derived within the tight-binding model, are divided into two parts. In one part, analytic results...... are derived for the optical properties of the polymers expressed in terms of the optical susceptibility both in the presence and in the absence of a static electric field. In the other part, the cumputationally efficient Density Functional-based Tight-Binding (DFTB) model is applied to the description...

  7. Theoretical study of conjugated porphyrin polymers

    DEFF Research Database (Denmark)

    Pedersen, T.G.; Lynge, T.B.; Kristensen, P.K.


    The optical gap of conjugated triply linked porphyrin chains is exceptionally low (similar to 0.5 eV). Hence, such chains are candidates for organic infrared detectors and solar cells harvesting the infrared part of the solar spectrum. However, a low exciton binding energy is required for these a......The optical gap of conjugated triply linked porphyrin chains is exceptionally low (similar to 0.5 eV). Hence, such chains are candidates for organic infrared detectors and solar cells harvesting the infrared part of the solar spectrum. However, a low exciton binding energy is required...... for these applications. From a theoretical analysis of excitons in long metalloporphyrin chains, we demonstrate that the binding energy is much lower than in usual conjugated polymers. Our calculated absorption spectra are in good agreement with measurements. (c) 2004 Elsevier B.V. All rights reserved....

  8. Conjugate gradient algorithms using multiple recursions

    Energy Technology Data Exchange (ETDEWEB)

    Barth, T.; Manteuffel, T.


    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.

  9. Phase conjugation of high energy lasers.

    Energy Technology Data Exchange (ETDEWEB)

    Bliss, David E; Valley, Michael T.; Atherton, Briggs W.; Bigman, Verle Howard; Boye, Lydia Ann; Broyles, Robin Scott; Kimmel, Mark W.; Law, Ryan J.; Yoder, James R.


    In this report we explore claims that phase conjugation of high energy lasers by stimulated Brillouin scattering (SBS) can compensate optical aberrations associated with severely distorted laser amplifier media and aberrations induced by the atmosphere. The SBS media tested was a gas cell pressurized up to 300 psi with SF6 or Xe or both. The laser was a 10 Hz, 3J, Q-switched Nd:YAG with 25 ns wide pulses. Atmospheric aberrations were created with space heaters, helium jets and phase plates designed with a Kolmogorov turbulence spectrum characterized by a Fried parameter, ro , ranging from 0.6 6.0 mm. Phase conjugate tests in the laboratory were conducted without amplification. For the strongest aberrations, D/ro ~ 20, created by combining the space heaters with the phase plate, the Strehl ratio was degraded by a factor of ~50. Phase conjugation in SF6 restored the peak focusable intensity to about 30% of the original laser. Phase conjugate tests at the outdoor laser range were conducted with laser amplifiers providing gain in combination with the SBS cell. A large 600,000 BTU kerosene space heater was used to create turbulence along the beam path. An atmospheric structure factor of Cn2 = 5x10-13 m2/3 caused the illumination beam to expand to a diameter 250mm and overfill the receiver. The phase conjugate amplified return could successfully be targeted back onto glints 5mm in diameter. Use of a lenslet arrays to lower the peak focusable intensity in the SBS cell failed to produce a useful phase conjugate beam; The Strehl ratio was degraded with multiple random lobes instead of a single focus. I will review literature results which show how multiple beams can be coherently combined by SBS when a confocal reflecting geometry is used to focus the laser in the SBS cell.

  10. Conjugate metamaterials and the perfect lens

    CERN Document Server

    Xu, Yadong; Xu, Lin; Chen, Huanyang


    In this letter, we show how transformation optics makes it possible to design what we call conjugate metamaterials. We show that these materials can also serve as substrates for making a subwavelength-resolution lens. The so-called "perfect lens", which is a lens that could focus all components of light (including propagating and evanescent waves), can be regarded as a limiting case, in which the respective conjugate metamaterials approach the characteristics of left-handed metamaterials, which have a negative refractive index.

  11. Conjugated Polymers as Actuators: Modes of Actuation

    DEFF Research Database (Denmark)

    Skaarup, Steen

    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...

  12. Conjugated polymers as actuators: modes of actuation

    DEFF Research Database (Denmark)

    Skaarup, Steen


    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...

  13. Dynamics of Photogenerated Polarons in Conjugated Polymers (United States)

    An, Z.; Wu, C. Q.; Sun, X.


    Within a tight-binding electron-phonon interacting model, we investigate the dynamics of photoexcitations to address the generation mechanism of charged polarons in conjugated polymers by using a nonadiabatic evolution method. Besides the neutral polaron exciton which is well known, we identify a novel product of lattice dynamic relaxation from the photoexcited states in a few hundreds of femtoseconds, which is a mixed state composed of both charged polarons and neutral excitons. Our results show that the charged polarons are generated directly with a yield of about 25%, which is independent of the excitation energies, in good agreement with results from experiments. Effects of the conjugation length are also discussed.

  14. [Conjugate vaccines against bacterial infections: typhoid fever]. (United States)

    Paniagua, J; García, J A; López, C R; González, C R; Isibasi, A; Kumate, J


    Capsular polysaccharides have been studied as possible vaccines against infectious diseases. However, they are capable to induce only short-run protection because of their T-independent properties and they would not be protective against infection in high-risk populations. The alternative to face this problem is to develop methods to join covalently the polysaccharide and proteins to both increase the immunogenicity of and to confer the property of T-dependence to this antigen. In order to obtain a conjugate vaccine against typhoid fever, in our laboratory we have tried to synthesize a conjugate immunogen between the Vi antigen and porins from Salmonella typhi.

  15. Synthesis of cyanopyridine based conjugated polymer

    Directory of Open Access Journals (Sweden)

    B. Hemavathi


    Full Text Available This data file contains the detailed synthetic procedure for the synthesis of two new cyanopyridine based conjugated polymer P1 and P2 along with the synthesis of its monomers. The synthesised polymers can be used for electroluminescence and photovoltaic (PV application. The physical data of the polymers are provided in this data file along with the morphological data of the polymer thin films. The data provided here are in association with the research article entitled ‘Cyanopyridine based conjugated polymer-synthesis and characterisation’ (Hemavathi et al., 2015 [3].

  16. Conjugate Gradient Methods with Armijo-type Line Searches

    Institute of Scientific and Technical Information of China (English)

    Yu-Hong DAI


    Two Armijo-type line searches are proposed in this paper for nonlinear conjugate gradient methods.Under these line searches, global convergence results are established for several famous conjugate gradient method.

  17. Meningococcal conjugate vaccines: optimizing global impact

    Directory of Open Access Journals (Sweden)

    Terranella A


    Full Text Available Andrew Terranella1,2, Amanda Cohn2, Thomas Clark2 1Epidemic Intelligence Service, Division of Applied Sciences, Scientific Education and Professional Development Program Office, 2Meningitis and Vaccine Preventable Diseases Branch, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA Abstract: Meningococcal conjugate vaccines have several advantages over polysaccharide vaccines, including the ability to induce greater antibody persistence, avidity, immunologic memory, and herd immunity. Since 1999, meningococcal conjugate vaccine programs have been established across the globe. Many of these vaccination programs have resulted in significant decline in meningococcal disease in several countries. Recent introduction of serogroup A conjugate vaccine in Africa offers the potential to eliminate meningococcal disease as a public health problem in Africa. However, the duration of immune response and the development of widespread herd immunity in the population remain important questions for meningococcal vaccine programs. Because of the unique epidemiology of meningococcal disease around the world, the optimal vaccination strategy for long-term disease prevention will vary by country. Keywords: conjugate vaccine, meningitis, meningococcal vaccine, meningococcal disease

  18. Theory of periodic conjugate heat transfer

    CERN Document Server

    Zudin, Yuri B


    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.

  19. Conjugation-uniqueness of exact Borel subalgebras

    Institute of Scientific and Technical Information of China (English)



    It is proved that the exact Borel subalgebras of a basic quasi-hereditary algebra are conjugate to each other. Moreover, the inner automorphism group of a basic quasi-hereditary algebra acts transitively on the set of its exact Borel subalgebras.

  20. Predicting the optical gap of conjugated systems (United States)

    Botelho, Andre Leitao

    The adapted Su-Schrieffer-Heeger model is developed in this work as a tool for in silico prediction of the optical gap of pi-conjugated systems for photovoltaic applications. Full transferability of the model ensures reliable predictive power - excellent agreement with 180 independent experimental data points covering virtually all existing conjugated system types with an accuracy exceeding the time-dependent density functional theory, one of the most accurate first-principles methods. Insights on the structure-property relation of conjugated systems obtained from the model lead to guiding rules for optical gap design: 1) fusing aromatic rings parallel to the conjugated path does not significantly lower the optical gap, 2) fusing rings perpendicularly lowers the optical gap of the monomer, but has a reduced benefit from polymerization, and 3) copolymers take advantage of the lower optical gap of perpendicular fused rings and benefit from further optical gap reduction through added parallel fused rings as electronic communicators. A copolymer of parallel and perpendicular benzodithiophenes, differing only in sulfur atom locations, is proposed as a candidate to achieve the optimal 1.2 eV donor optical gap for organic photovoltaics. For small-molecule organic photovoltaics, substituting the end pairs of carbon atoms on pentacene with sulfur atoms is predicted to lower the optical gap from 1.8 eV to 1.1 eV. Furthermore, the model offers an improvement of orders of magnitude in the computational efficiency over commonly used first-principles tools.

  1. Photorefractive phase-conjugation digital holographic microscopy (United States)

    Chang, Chi-Ching; Chan, Huang-Tian; Shiu, Min-Tzung; Chew, Yang-Kun


    In this work, we propose an innovative method for digital holographic microscopy named as photorefractive phaseconjugation digital holographic microscopy (PPCDHM) technique based on the phase conjugation dynamic holographic process in photorefractive BaTiO3 crystal and the retrieval of phase and amplitude of the object wave were performed by a reflection-type digital holographic method. Both amplitude and phase reconstruction benefit from the prior amplification by self-pumped conjugation (SPPC) as they have an increased SNR. The interest of the PPCDHM is great, because its hologram is created by interfered the amplified phase-conjugate wave field generated from a photorefractive phase conjugator (PPC) correcting the phase aberration of the imaging system and the reference wave onto the digital CCD camera. Therefore, a precise three-dimensional description of the object with high SNR can be obtained digitally with only one hologram acquisition. The method requires the acquisition of a single hologram from which the phase distribution can be obtained simultaneously with distribution of intensity at the surface of the object.

  2. Vibrational Spectroscopy of Microhydrated Conjugate Base Anions

    NARCIS (Netherlands)

    Asmis, K. R.; Neumark, D. M.


    Conjugate-base anions are ubiquitous in aqueous solution. Understanding the hydration of these anions at the molecular level represents a long-standing goal in chemistry. A molecular-level perspective on ion hydration is also important for understanding the surface speciation and reactivity of aeros

  3. Continuous flow synthesis of conjugated polymers. (United States)

    Seyler, Helga; Jones, David J; Holmes, Andrew B; Wong, Wallace W H


    A selection of conjugated polymers, widely studied in organic electronics, was synthesised using continuous flow methodology. As a result of superior heat transfer and reagent control, excellent polymer molecular mass distributions were achieved in significantly reduced reaction times compared to conventional batch reactions.

  4. Compositions for directed alignment of conjugated polymers (United States)

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


    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).

  5. Some aspects of geomagnetically conjugate phenomena

    Energy Technology Data Exchange (ETDEWEB)

    Rycroft, M.J.


    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.

  6. Bacillus thuringiensis Conjugation in Simulated Microgravity (United States)

    Beuls, Elise; van Houdt, Rob; Leys, Natalie; Dijkstra, Camelia; Larkin, Oliver; Mahillon, Jacques


    Spaceflight experiments have suggested a possible effect of microgravity on the plasmid transfer among strains of the Gram-positive Bacillus thuringiensis, as opposed to no effect recorded for Gram-negative conjugation. To investigate these potential effects in a more affordable experimental setup, three ground-based microgravity simulators were tested: the Rotating Wall Vessel (RWV), the Random Positioning Machine (RPM), and a superconducting magnet. The bacterial conjugative system consisted in biparental matings between two B. thuringiensis strains, where the transfer frequencies of the conjugative plasmid pAW63 and its ability to mobilize the nonconjugative plasmid pUB110 were assessed. Specifically, potential plasmid transfers in a 0-g position (simulated microgravity) were compared to those obtained under 1-g (normal gravity) condition in each device. Statistical analyses revealed no significant difference in the conjugative and mobilizable transfer frequencies between the three different simulated microgravitational conditions and our standard laboratory condition. These important ground-based observations emphasize the fact that, though no stimulation of plasmid transfer was observed, no inhibition was observed either. In the case of Gram-positive bacteria, this ability to exchange plasmids in weightlessness, as occurs under Earth's conditions, should be seen as particularly relevant in the scope of spread of antibiotic resistances and bacterial virulence.

  7. Conjugate problems in convective heat transfer

    CERN Document Server

    Dorfman, Abram S


    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.

  8. Antibody-drug conjugates: Intellectual property considerations. (United States)

    Storz, Ulrich


    Antibody-drug conjugates are highly complex entities that combine an antibody, a linker and a toxin. This complexity makes them demanding both technically and from a regulatory point of view, and difficult to deal with in their patent aspects. This article discusses different issues of patent protection and freedom to operate with regard to this promising new class of drugs.

  9. Women experiencing the intergenerationality of conjugal violence

    Directory of Open Access Journals (Sweden)

    Gilvânia Patrícia do Nascimento Paixão


    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.

  10. Conjugal Succession and the American Kinship System. (United States)

    Furstenberg, Frank F., Jr.

    Although not the preferred type of family formation, conjugal succession is now an accepted, if not expected, alternative to continuous marriage in the United States. This new trend appears to be related to a shift in the meaning of matrimony. Previously, marriage was part of a cultural pattern of transitions and as such was closely timed to…

  11. Conjugate Problems in Convective Heat Transfer: Review

    Directory of Open Access Journals (Sweden)

    Abram Dorfman


    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.

  12. Transparency in Bragg scattering and phase conjugation. (United States)

    Longhi, S


    Reflectionless transmission of light waves with unitary transmittance is shown to occur in a certain class of gain-grating structures and phase-conjugation mirrors in the unstable (above-threshold) regime. Such structures are synthesized by means of the Darboux method developed in the context of supersymmetric relativistic quantum mechanics. Transparency is associated to superluminal pulse transmission.

  13. 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...

  14. Synthesis of Indomethacin Conjugates with D-Glucosamine

    Institute of Scientific and Technical Information of China (English)

    Yi Chun ZHANG; Ying Xia LI; Hua Shi GUAN


    Two series of indomethacin conjugates with D-glucosamine were prepared with the objectives of reducing ulcerogenic potency, increasing the bioavailability of indomethacin and exerting the coordinative effects on osteoarthritis. The structures of the conjugates were identified by 1H NMR and 13C NMR. The ester conjugates inhibited edema as potent as indomethacin.

  15. Cross-Conjugated n-Dopable Aromatic Polyketone

    NARCIS (Netherlands)

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


    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 r

  16. Resolution of Digitized Conjugate Tooth-Face Surface Based on the Theory of Digitized Conjugate Surfaces

    Institute of Scientific and Technical Information of China (English)

    XIAO Lai-yuan; LIAO Dao-xun; YI Chuan-yun


    According to the principle of meshing engagement and the theory of the digitized conjugate surface, this paper applies the software Conjugater-l. 0 that is developed by ourselves to compute, respectivcly, the digitized conjugate curved surfaces of the straight-tooth surface and drum-tooth surface,which will establish the theoretical and technical foundation for digitized engaging analysis, simulation, and digitized manufacturing technology of the diversified gears.

  17. Inclusion of a universal tetanus toxoid CD4(+) T cell epitope P2 significantly enhanced the immunogenicity of recombinant rotavirus ΔVP8* subunit parenteral vaccines. (United States)

    Wen, Xiaobo; Wen, Ke; Cao, Dianjun; Li, Guohua; Jones, Ronald W; Li, Jianping; Szu, Shousun; Hoshino, Yasutaka; Yuan, Lijuan


    Currently available live oral rotavirus vaccines, Rotarix(®) and RotaTeq(®), are highly efficacious in developed countries. However, the immunogenicity and efficacy of such vaccines in some developing countries are low. We reported previously that bacterially-expressed rotavirus ΔVP8* subunit vaccine candidates with P[8], P[4] or P[6] specificity elicited high-titer virus neutralizing antibodies in animals immunized intramuscularly. Of note was the finding that antibodies induced with the P[8]ΔVP8* vaccine neutralized both homotypic P[8] and heterotypic P[4] rotavirus strains to high titer. To further improve its vaccine potential, a tetanus toxoid universal CD4(+) T cell epitope P2 was introduced into P[8] or P[6]ΔVP8* construct. The resulting recombinant fusion proteins expressed in Escherichia coli were of high solubility and were produced with high yield. Two doses (10 or 20 μg/dose) of the P2-P[8]ΔVP8* vaccine or P2-P[6]ΔVP8* vaccine with aluminum phosphate adjuvant elicited significantly higher geometric mean homologous neutralizing antibody titers than the vaccines without P2 in intramuscularly immunized guinea pigs. Interestingly, high levels of neutralizing antibody responses induced in guinea pigs with 3 doses of the P2-P[8]ΔVP8* vaccine persisted for at least 6 months. Furthermore, in the gnotobiotic piglet challenge study, three intramuscular doses (50 μg/dose) of the P2-P[8]ΔVP8* vaccine with aluminum phosphate adjuvant significantly delayed the onset of diarrhea and significantly reduced the duration of diarrhea and the cumulative diarrhea score after oral challenge with virulent human rotavirus Wa (G1P[8]) strain. The P2-P[8]ΔVP8* vaccine induced serum virus neutralizing antibody and VP4-specific IgG antibody production prechallenge, and primed the pigs for higher antibody and intestinal and systemic virus-specific IFN-γ producing CD4(+) T cell responses postchallenge. These two subunit vaccines could be used at a minimum singly or

  18. Inmunogenicidad de conjugados de polisacárido de Neisseria meningitidis serogrupo C unido al toxoide tetánico por diferentes brazos espaciadores

    Directory of Open Access Journals (Sweden)

    Osmir Cabrera


    Full Text Available El desarrollo de las vacunas conjugadas compuestas por polisacáridos unidos covalentemente a proteínas contra Haemophilus influenzae type b, han demostrado ser eficaces en infantes, lo que condujo al desarrollo activo de las vacunas conjugadas contra otros microorganismos por varios grupos de investigaci ón. La influencia en la respuesta inmune de la estructura de los brazos espaciadores utilizados en conjugados de polisacárido de N. meningitidis serogrupo C (PMGC-toxoide tetánico (TT fue evaluado en ratones Balb/c. Se determin ó la generación de anticuerpos IgG anti-PMGC e IgG anti-TT en los sueros de los animales inoculados por medio de un ELISA indirecto. También se evaluaron las subclases de anticuerpos IgG1 e IgG2a anti PMGC. El 1,6-diaminohexano (AH, el 1,8-diaminooctano (AO, el ácido 6-aminohexanoico (AA y la dihidrazida del ácido adípico (ADH, fueron utilizados como brazos espaciadores con diferentes estructuras químicas, unidos al PMGC y al TT por medio de la reacción con carbodiimida. El suero de todos los ratones que fueron inoculados con los conjugados presentaron elevados títulos de IgG anti-PMGC y los valores más elevados se encontraron en los sueros de animales inoculados con el conjugado en los que se utilizó al ADH como brazo espaciador. En los grupos de animales inmunizados con los conjugados que utilizaron al AO y al ADH se detectaron títulos de IgG2a superiores a los detectados para el PMGC no conjugado; se observaron los títulos de IgG2a más elevados en los sueros de ratones inmunizados con conjugados con ADH. Las concentraciones de anticuerpos IgG anti-TT observados en los sueros de los ratones inmunizados con los conjugados fueron más elevados que los determinados en el suero de animales inmunizados con el TT. Se concluyó que la respuesta inmune obtenida en los ratones después de ser inoculados con los conjugados varía en dependencia del brazo del espaciador utilizado, siendo más elevada cuando se


    Institute of Scientific and Technical Information of China (English)

    DUAN Zhenyun; CHEN Houjun; LIU Jian


    Bertrand surface is presented by abstracting and subliming the common characteristic of the usual surfaces including rotational surfaces, developable surfaces, normal circular-arc surfaces,etc. Basic characteristic of Bertrand surface is that normals along generator are coplanar. Bertrand conjugate principle is studied and its basic characteristic is that the instantaneous contact line between a pair of Bertrand conjugate surfaces is generator. Bertrand conjugate can be divided into three kinds of typical conjugation forms in terms of the generators that are general plane curve, circular-arc and straight line. Basic conjugate condition is given respectively, and structure condition, which reflects transmission forms and directrix characteristic of this kind of conjugation, is researched. As typical engineering application of Bertrand conjugate surface principle, transmission technology of loxodromic-type normal circular-arc bevel gear is studied.

  20. Highly sensitive biosensors based on water-soluble conjugated polymers

    Institute of Scientific and Technical Information of China (English)

    XU Hui; WU Haiping; FAN Chunhai; LI Wenxin; ZHANG Zhizhou; HE Lin


    Conjugated, conductive polymers are a kind of important organic macromolecules, which has found applications in a variety of areas. The application of conjugated polymers in developing fluorescent biosensors represents the merge of polymer sciences and biological sciences. Conjugated polymers are very good light harvesters as well as fluorescent polymers, and they are also "molecular wires". Through elaborate designs, these important features, i.e. efficient light harvesting and electron/energy transfer, can be used as signal amplification in fluorescent biosensors. This might significantly improve the sensitivity of conjugated polymer-based biosensors. In this article, we reviewed the application of conjugated polymers, via either electron transfer or energy transfer, to detections of gene targets, antibodies or enzymes. We also reviewed recent efforts in conjugated polymer-based solid-state sensor designs as well as chip-based multiple target detection. Possible directions in this conjugated polymer-based biosensor area are also discussed.

  1. Conjugation of fluorescent proteins with DNA oligonucleotides. (United States)

    Lapiene, Vidmantas; Kukolka, Florian; Kiko, Kathrin; Arndt, Andreas; Niemeyer, Christof M


    This work describes the synthesis of covalent ssDNA conjugates of six fluorescent proteins, ECFP, EGFP, E(2)GFP, mDsRed, Dronpa, and mCherry, which were cloned with an accessible C-terminal cystein residue to enable site-selective coupling using a heterobispecific cross-linker. The resulting conjugates revealed similar fluorescence emission intensity to the unconjugated proteins, and the functionality of the tethered oligonucleotide was proven by specific Watson-Crick base pairing to cDNA-modified gold nanoparticles. Fluorescence spectroscopy analysis indicated that the fluorescence of the FP is quenched by the gold particle, and the extent of quenching varied with the intrinsic spectroscopic properties of FP as well as with the configuration of surface attachment. Since this study demonstrates that biological fluorophores can be selectively incorporated into and optically coupled with nanoparticle-based devices, applications in DNA-based nanofabrication can be foreseen.

  2. Health benefits of conjugated linoleic acid (CLA). (United States)

    Koba, Kazunori; Yanagita, Teruyoshi


    Conjugated linoleic acid (CLA) is a group of positional and geometric (cis or trans) isomers of linoleic acid with a conjugated double bond. The most representative CLA isomers are 9c,11t-18:2 and 10t,12c-18:2. CLA has been shown to exert various potent physiological functions such as anticarcinogenic, antiobese, antidiabetic and antihypertensive properties. This means CLA can be effective to prevent lifestyle diseases or metabolic syndromes. Also, reports suggest that physiological effects of CLA are different between the isomers, for example the 10t,12c isomer is anticarcinogenic, antiobese and antidiabetic, whereas the 9c,11t isomer is mainly anticarcinogenic. We describe here the physiological properties of CLA including the possible mechanism and the possibility to benefit human health.

  3. Discrete modelling of bacterial conjugation dynamics

    CERN Document Server

    Goni-Moreno, Angel


    In bacterial populations, cells are able to cooperate in order to yield complex collective functionalities. Interest in population-level cellular behaviour is increasing, due to both our expanding knowledge of the underlying biological principles, and the growing range of possible applications for engineered microbial consortia. Researchers in the field of synthetic biology - the application of engineering principles to living systems - have, for example, recently shown how useful decision-making circuits may be distributed across a bacterial population. The ability of cells to interact through small signalling molecules (a mechanism known as it quorum sensing) is the basis for the majority of existing engineered systems. However, horizontal gene transfer (or conjugation) offers the possibility of cells exchanging messages (using DNA) that are much more information-rich. The potential of engineering this conjugation mechanism to suit specific goals will guide future developments in this area. Motivated by a l...

  4. Conjugated Linoleic Acid: good or bad nutrient

    Directory of Open Access Journals (Sweden)

    Gonçalves Daniela C


    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.

  5. Conjugated Polymer Actuators: Prospects and Limitations

    DEFF Research Database (Denmark)

    Skaarup, Steen


    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......-5 V), . Taking status after about 15 years of research efforts, most of these predictions have come true, the main exception being the much lower speeds actually realized in actuators....

  6. Solventless processing of conjugated polymers - a review


    Brandão, Lúcia; Viana, Júlio; Bucknall, David G.; Bernardo, Gabriel


    The molecular mobility of polymers in their solid or molten states allows their processing without the need for toxic, “non-friendly” solvents. In this work, the main features of solvent-free processing methods applied to conjugated polymers are reviewed taking into consideration that these materials are largely used in a broad range of (opto-)electronic applications, including organic field-effect transistors, polymer light-emitting diodes and polymer photovoltaic devices. This review addres...

  7. Applications of Conjugated Polymers to DNA Sensing

    Institute of Scientific and Technical Information of China (English)

    Jadranka; Travas-Sejdic; Christian; Soeller


    1 Results Detection of biomolecules relies on a highly specific recognition event between an analyte biomolecule and a probe that is often closely connected or integrated within a sensor transducer element to provide a suitable signal. More widespread application of gene detection on a routine basis demands the development of a new generation of gene sensors that are fast, reliable and cost-effective.Conjugated polymers (CPs) have been shown to be a versatile substrate for DNA sensor construction, where...

  8. Cancer Chemopreventive Ability of Conjugated Linolenic Acids

    Directory of Open Access Journals (Sweden)

    Kazuo Miyashita


    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.

  9. Peptide conjugation: before or after nanoparticle formation? (United States)

    Valetti, Sabrina; Mura, Simona; Noiray, Magali; Arpicco, Silvia; Dosio, Franco; Vergnaud, Juliette; Desmaële, Didier; Stella, Barbara; Couvreur, Patrick


    We report herein a detailed study concerning the impact of different bioconjugation and nanoformulation strategies on the in vitro targeting ability of peptide-decorated squalenoyl gemcitabine (SQdFdC) nanoparticles (NPs). NPs have been functionalized with the CKAAKN peptide, previously identified as an efficient homing device within the pancreatic pathological microenvironment. Two approaches have been followed: (i) either the CKAAKN peptide was directly conjugated at the surface of preformed SQdFdC nanoparticles (conjugation after NP formation) or (ii) it was first reacted with a maleimide squalenoyl derivative before the resulting bioconjugate was co-nanoprecipitated with SQdFdC to form the peptide-decorated NPs (conjugation before NP formation). NPs were characterized with respect to mean diameter, zeta potential, and stability over time. Then, their specific interaction with the sFRP-4 protein was evaluated by surface plasmon resonance. Although both synthetic strategies allowed us to formulate NPs able to interact with the corresponding receptor, enhanced target binding and better specific avidity were observed with CKAAKN-NPs functionalized before NP formation. These NPs displayed the highest cell uptake and cytotoxicity in an in vitro model of human MIA Paca-2 pancreatic cancer cells.

  10. Conjugation, characterization and toxicity of lipophosphoglycan-polyacrylic acid conjugate for vaccination against leishmaniasis. (United States)

    Topuzogullari, Murat; Cakir Koc, Rabia; Dincer Isoglu, Sevil; Bagirova, Melahat; Akdeste, Zeynep; Elcicek, Serhat; Oztel, Olga N; Yesilkir Baydar, Serap; Canim Ates, Sezen; Allahverdiyev, Adil M


    Research on the conjugates of synthetic polyelectrolytes with antigenic molecules, such as proteins, peptides, or carbohydrates, is an attractive area due to their highly immunogenic character in comparison to classical adjuvants. For example, polyacrylic acid (PAA) is a weak polyelectrolyte and has been used in several biomedical applications such as immunological studies, drug delivery, and enzyme immobilization. However, to our knowledge, there are no studies that document immune-stimulant properties of PAA in Leishmania infection. Therefore, we aimed to develop a potential vaccine candidate against leishmaniasis by covalently conjugating PAA with an immunologically vital molecule of lipophosphoglycan (LPG) found in Leishmania parasites. In the study, LPG and PAA were conjugated by a multi-step procedure, and final products were analyzed with GPC and MALDI-TOF MS techniques. In cytotoxicity experiments, LPG-PAA conjugates did not indicate toxic effects on L929 and J774 murine macrophage cells. We assume that LPG-PAA conjugate can be a potential vaccine candidate, and will be immunologically characterized in further studies to prove its potential.

  11. Nanostructured conjugated polymers for photovoltaic devices (United States)

    Xi, Dongjuan

    This dissertation focuses on making new systems of interdigitated bilayer structures for organic solar cells from two aspects: (i) fabricating vertically aligned semiconductor nanorod arrays by low-temperature solution process; (ii) applying the resulting nanorods arrays in solar cell devices with pre-formed or in-situ electropolymerized conjugated polymers. Two low-temperature solution methods are investigated to fabricate vertically aligned semiconductor nanorod arrays. The first method is using porous templates to prepare vertically aligned conjugated polymer nanorods arrays. In-situ anodized nanoporous alumina film is specifically designed to suspend on substrates to improve the wettability of organic solution to the alumina film, and to generate a big foot anchoring the polymer nanorods. With this specific design, vertically aligned polymer nanotube arrays with high density, 3x1010/cm2, is achieved and the nanotubes can stand vertically at the aspect ratio of 5. The second method is low-temperature direct growth of high quality semiconductor nanorod arrays without any templates by electrochemical deposition. Vertically aligned cadmium sulfide nanorod arrays are achieved by studying the growth mechanism of cadmium sulfide nanocrystal deposition and fine tuning the solution composition of the electrolyte. Chlorine doping, as a function of chlorine ion concentration in the electrolyte, modifies crystal lattice, and therefore the build-in stress, which dominates the morphology of the deposited nanocrystals as nanorods or thin films. Scanning electron microscopy, x-ray diffraction and transmission electron microscopy are applied to study the microstructures of the nanorods. Optical, electrical and field emission properties of the cadmium sulfide nanorod arrays are also studied in detail to pursue further applications of the nanorod arrays as nano-lasers and cold field emitters. Organic solar cells based on template-processed polythiophene nanotube arrays will be

  12. Antibody Conjugates: From Heterogeneous Populations to Defined Reagents

    Directory of Open Access Journals (Sweden)

    Patrick Dennler


    Full Text Available Monoclonal antibodies (mAbs and their derivatives are currently the fastest growing class of therapeutics. Even if naked antibodies have proven their value as successful biopharmaceuticals, they suffer from some limitations. To overcome suboptimal therapeutic efficacy, immunoglobulins are conjugated with toxic payloads to form antibody drug conjugates (ADCs and with chelating systems bearing therapeutic radioisotopes to form radioimmunoconjugates (RICs. Besides their therapeutic applications, antibody conjugates are also extensively used for many in vitro assays. A broad variety of methods to functionalize antibodies with various payloads are currently available. The decision as to which conjugation method to use strongly depends on the final purpose of the antibody conjugate. Classical conjugation via amino acid residues is still the most common method to produce antibody conjugates and is suitable for most in vitro applications. In recent years, however, it has become evident that antibody conjugates, which are generated via site-specific conjugation techniques, possess distinct advantages with regard to in vivo properties. Here, we give a comprehensive overview on existing and emerging strategies for the production of covalent and non-covalent antibody conjugates.

  13. Co-conjugation vis-à-vis individual conjugation of α-amylase and glucoamylase for hydrolysis of starch. (United States)

    Jadhav, Swati B; Singhal, Rekha S


    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.

  14. Design and characterization of a chimeric multiepitope construct containing CfaB, heat-stable toxoid, CssA, CssB, and heat-labile toxin subunit B of enterotoxigenic Escherichia coli: a bioinformatic approach. (United States)

    Zeinalzadeh, Narges; Salmanian, Ali Hatef; Ahangari, Ghasem; Sadeghi, Mahdi; Amani, Jafar; Bathaie, S Zahra; Jafari, Mahyat


    Enterotoxigenic Escherichia coli (ETEC) strains are the most common cause of bacterial diarrhea in children in developing countries and travelers to these areas. Enterotoxins and colonization factors (CFs) are two key virulence factors in ETEC pathogenesis, and the heterogeneity of the CFs is the bottleneck in reaching an effective vaccine. In this study, a candidate subunit vaccine, which is composed of CfaB, CssA and CssB, structural subunits of colonization factor antigen I and CS6 CFs, labile toxin subunit B, and the binding subunit of heat-labile and heat-stable toxoid, was designed to provide broad-spectrum protection against ETEC. The different features of chimeric gene, its mRNA stability, and chimeric protein properties were analyzed by using bioinformatic tools. The optimized chimeric gene was chemically synthesized and expressed successfully in a prokaryotic host. The purified protein was used for assessment of bioinformatic data by experimental methods.

  15. Evaluation of tetanus toxoid immunization of childbearing age women in Inner Mongolia Autonomous Region%内蒙古自治区育龄期妇女接种破伤风类毒素免疫效果评价

    Institute of Scientific and Technical Information of China (English)

    闫绍宏; 魏永刚; 武贵森; 夏伟; 金仁杰; 陈永生; 白吉日根


    目的 评价内蒙古自治区农村、牧区育龄期妇女开展破伤风类毒素(TT)接种的效果.方法 在开展破伤风类毒素接种的突泉县和未开展接种的扎赉特旗分别采用东西南北中5个方位抽取10个乡级单位,用间接血凝方法检测487名18~35岁育龄期妇女破伤风抗毒素(TAT)抗体水平.结果 开展TT接种的突泉县育龄期妇女达到破伤风保护水平43.1%(>0.01 IU/ml),TAT几何平均滴度为0.034 IU/ml;而未开展TT接种的扎赉特旗育龄期妇女破伤风保护率为8.33%,TAT几何平均滴度为0.005 5 IU/ml.结论 育龄期妇女TT接种是消除新生儿破伤风的策略之一,做好新生儿破伤风高危地区育龄期妇女TT接种,消除新生儿破伤风效果显著,应加强对18~35岁低年龄组育龄期妇女的TT接种.%OBJECTIVE To evaluate the effect of tetanus toxoid immunization of childbearing age women in rural and pasturing areas of Inner Mongolia Autonomous Region.METHODS 10 counties were collected from the east,west,north,south and middle directions in Tuquan County which developed the tetanus toxoid immunization as well as the Zalaiteqi which did not develop the immunization respectively.From these 10 counties,487 childbearing age women were aged 18-35 collected randomly and their antibody level of serum tetanus antitoxin (TAT) were detected by indirect blood coagulation and general situation investigation on.RESULTS In Tuquan County,the protection rate reached 43.1% (> 0.01 IU/ml) and the TAT geometry average titer was 0.034 IU/ml.In Zalaiteqi,the protection rate was 8.33% and the TAT geometry average titer was 0.005 5 IU/ml.CONCLUSION The tetanus toxoid immunization of childbearing age women is one of the strategies to eliminate the neonatal tetanus,so we should strengthen the tetanus toxoid immunization of childbearing age women from 18 to 35 years old.

  16. Luminescence of a conjugated polymer containing europium (III) chelate

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Hao; Xie, Fang, E-mail:


    A europium (III) chelate has been incorporated in a conjugated polymer, poly-[2,2′-bipyridine-5,5′-diyl-(2,5-dihexyl-1,4-phenylene)]. From the absorbance and emission spectra measurement and using the Judd–Ofelt theory, an efficient energy transfer between the conjugated polymer and the europium (III) chelate has been confirmed. The luminescence lifetime of Eu{sup 3+} ion in the conjugated polymer is 0.352 ms and the emission cross section of this material is 3.11×10{sup −21} cm{sup 2}. -- Highlights: • A europium chelate has been incorporated in a conjugated polymer. • Energy transfer in the conjugated polymer containing europium chelate is efficient. • The conjugated polymer containing europium chelate is a promising optical material.

  17. Synthesis, characterization and biological activity of Rhein-cyclodextrin conjugate (United States)

    Liu, Manshuo; Lv, Pin; Liao, Rongqiang; Zhao, Yulin; Yang, Bo


    Cyclodextrin conjugate complexation is a useful method to enhance the solubility and absorption of poorly soluble drugs. A series of new Rhein-β-cyclodextrin conjugates (Rh-CD conjugates) have been synthesized and examined. Rhein is covalently linked with the β-CD by amido linkage in a 1:1 molar ratio. The conjugates were characterized by 1H NMR, 13C NMR, HRMS, powder X-ray diffraction (powder XRD) as well as thermogravimetric analysis (TGA). The results reveal that incorporation of β-CD could improve the aqueous solubility of Rhein and the cytotoxicity against hepatocellular carcinoma (HepG2) cell line as well as antibacterial activity against three organisms. The improved biological activity and the satisfactory water solubility of the conjugates will be potentially useful for developing novel drug-cyclodextrin conjugates, such as herbal medicine.

  18. Conjugates of abscisic acid, brassinosteroids, ethylene, gibberellins, and jasmonates. (United States)

    Piotrowska, Alicja; Bajguz, Andrzej


    Phytohormones, including auxins, abscisic acid, brassinosteroids, cytokinins, ethylene, gibberellins, and jasmonates, are involved in all aspects of plant growth, and developmental processes as well as environmental responses. However, our understanding of hormonal homeostasis is far from complete. Phytohormone conjugation is considered as a part of the mechanism to control cellular levels of these compounds. Active phytohormones are changed into multiple forms by acylation, esterification or glycosylation, for example. It seems that conjugated compounds could serve as pool of inactive phytohormones that can be converted to active forms by de-conjugation reactions. Some conjugates are thought to be temporary storage forms, from which free active hormones can be released after hydrolysis. It is also believed that conjugation serves functions, such as irreversible inactivation, transport, compartmentalization, and protection against degradation. The nature of abscisic acid, brassinosteroid, ethylene, gibberellin, and jasmonate conjugates is discussed.

  19. Evolution of conjugation and type IV secretion systems. (United States)

    Guglielmini, Julien; de la Cruz, Fernando; Rocha, Eduardo P C


    Genetic exchange by conjugation is responsible for the spread of resistance, virulence, and social traits among prokaryotes. Recent works unraveled the functioning of the underlying type IV secretion systems (T4SS) and its distribution and recruitment for other biological processes (exaptation), notably pathogenesis. We analyzed the phylogeny of key conjugation proteins to infer the evolutionary history of conjugation and T4SS. We show that single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) conjugation, while both based on a key AAA(+) ATPase, diverged before the last common ancestor of bacteria. The two key ATPases of ssDNA conjugation are monophyletic, having diverged at an early stage from dsDNA translocases. Our data suggest that ssDNA conjugation arose first in diderm bacteria, possibly Proteobacteria, and then spread to other bacterial phyla, including bacterial monoderms and Archaea. Identifiable T4SS fall within the eight monophyletic groups, determined by both taxonomy and structure of the cell envelope. Transfer to monoderms might have occurred only once, but followed diverse adaptive paths. Remarkably, some Firmicutes developed a new conjugation system based on an atypical relaxase and an ATPase derived from a dsDNA translocase. The observed evolutionary rates and patterns of presence/absence of specific T4SS proteins show that conjugation systems are often and independently exapted for other functions. This work brings a natural basis for the classification of all kinds of conjugative systems, thus tackling a problem that is growing as fast as genomic databases. Our analysis provides the first global picture of the evolution of conjugation and shows how a self-transferrable complex multiprotein system has adapted to different taxa and often been recruited by the host. As conjugation systems became specific to certain clades and cell envelopes, they may have biased the rate and direction of gene transfer by conjugation within prokaryotes.

  20. A Hybrid of DL and WYL Nonlinear Conjugate Gradient Methods

    Directory of Open Access Journals (Sweden)

    Shengwei Yao


    Full Text Available The conjugate gradient method is an efficient method for solving large-scale nonlinear optimization problems. In this paper, we propose a nonlinear conjugate gradient method which can be considered as a hybrid of DL and WYL conjugate gradient methods. The given method possesses the sufficient descent condition under the Wolfe-Powell line search and is globally convergent for general functions. Our numerical results show that the proposed method is very robust and efficient for the test problems.

  1. Synthesis and characterization of HPMA copolymer-5-FU conjugates

    Institute of Scientific and Technical Information of China (English)

    Fang Yuan; Fu Chen; Qing Yu Xiang; Xuan Qin; Zhi Rong Zhang; Yuan Huang


    N-(2-Hydroxypropyl)methacrylamide copolymer-5-fluorouracil (PHPMA-FU)conjugates were synthesized by a novel and simplified synthetic mute,and characterized by UV,FTIR and HPLC analyses.The conjugated content of 5-fluorouracil (5-FU)was 3.41 ± 0.07 wt%.The stabilities of PHPMA-FU conjugates under different conditions were studied.The results showed that HPMA copolymer was a potential carrier for tumor-targeting delivery of 5-FU.

  2. Design, synthesis, characterization and study of novel conjugated polymers

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wu [Iowa State Univ., Ames, IA (United States)


    After introducing the subject of conjugated polymers, the thesis has three sections each containing a literature survey, results and discussion, conclusions, and experimental methods on the following: synthesis, characterization of electroluminescent polymers containing conjugated aryl, olefinic, thiophene and acetylenic units and their studies for use in light-emitting diodes; synthesis, characterization and study of conjugated polymers containing silole unit in the main chain; and synthesis, characterization and study of silicon-bridged and butadiene-linked polythiophenes.

  3. Polymer decorated gold nanoparticles in nanomedicine conjugates. (United States)

    Capek, Ignác


    Noble metal, especially gold nanoparticles and their conjugates with biopolymers have immense potential for disease diagnosis and therapy on account of their surface plasmon resonance (SPR) enhanced light scattering and absorption. Conjugation of noble metal nanoparticles to ligands specifically targeted to biomarkers on diseased cells allows molecular-specific imaging and detection of disease. The development of smart gold nanoparticles (AuNPs) that can deliver therapeutics at a sustained rate directly to cancer cells may provide better efficacy and lower toxicity for treating cancer tumors. We highlight some of the promising classes of targeting systems that are under development for the delivery of gold nanoparticles. Nanoparticles designed for biomedical applications are often coated with polymers containing reactive functional groups to conjugate targeting ligands, cell receptors or drugs. Using targeted nanoparticles to deliver chemotherapeutic agents in cancer therapy offers many advantages to improve drug/gene delivery and to overcome many problems associated with conventional radiotherapy and chemotherapy. The targeted nanoparticles were found to be effective in killing cancer cells which were studied using various anticancer assays. Cell morphological analysis shows the changes occurred in cancer cells during the treatment with AuNPs. The results determine the influence of particle size and concentration of AuNPs on their absorption, accumulation, and cytotoxicity in model normal and cancer cells. As the mean particle diameter of the AuNPs decreased, their rate of absorption by the intestinal epithelium cells increased. These results provide important insights into the relationship between the dimensions of AuNPs and their gastrointestinal uptake and potential cytotoxicity. Furthermore gold nanoparticles efficiently convert the absorbed light into localized heat, which can be exploited for the selective laser photothermal therapy of cancer. We also review

  4. Multicellular computing using conjugation for wiring. (United States)

    Goñi-Moreno, Angel; Amos, Martyn; de la Cruz, Fernando


    Recent efforts in synthetic biology have focussed on the implementation of logical functions within living cells. One aim is to facilitate both internal "re-programming" and external control of cells, with potential applications in a wide range of domains. However, fundamental limitations on the degree to which single cells may be re-engineered have led to a growth of interest in multicellular systems, in which a "computation" is distributed over a number of different cell types, in a manner analogous to modern computer networks. Within this model, individual cell type perform specific sub-tasks, the results of which are then communicated to other cell types for further processing. The manner in which outputs are communicated is therefore of great significance to the overall success of such a scheme. Previous experiments in distributed cellular computation have used global communication schemes, such as quorum sensing (QS), to implement the "wiring" between cell types. While useful, this method lacks specificity, and limits the amount of information that may be transferred at any one time. We propose an alternative scheme, based on specific cell-cell conjugation. This mechanism allows for the direct transfer of genetic information between bacteria, via circular DNA strands known as plasmids. We design a multi-cellular population that is able to compute, in a distributed fashion, a Boolean XOR function. Through this, we describe a general scheme for distributed logic that works by mixing different strains in a single population; this constitutes an important advantage of our novel approach. Importantly, the amount of genetic information exchanged through conjugation is significantly higher than the amount possible through QS-based communication. We provide full computational modelling and simulation results, using deterministic, stochastic and spatially-explicit methods. These simulations explore the behaviour of one possible conjugation-wired cellular computing

  5. Sources and Bioactive Properties of Conjugated Dietary Fatty Acids. (United States)

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


    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.

  6. 2-Deoxystreptamine Conjugates by Truncation–Derivatization of Neomycin

    Directory of Open Access Journals (Sweden)

    Floris L. van Delft


    Full Text Available A small library of truncated neomycin-conjugates is prepared by consecutive removal of 2,6-diaminoglucose rings, oxidation-reductive amination of ribose, oxidation-conjugation of aminopyridine/aminoquinoline and finally dimerization. The dimeric conjugates were evaluated for antibacterial activity with a unique hemocyanin-based biosensor. Based on the outcome of these results, a second-generation set of monomeric conjugates was prepared and found to display significant antibacterial activity, in particular with respect to kanamycin-resistant E. coli.

  7. A class of globally convergent conjugate gradient methods

    Institute of Scientific and Technical Information of China (English)

    DAI; Yuhong(戴彧虹); YUAN; Yaxiang(袁亚湘)


    Conjugate gradient methods are very important ones for solving nonlinear optimization problems,especially for large scale problems. However, unlike quasi-Newton methods, conjugate gradient methods wereusually analyzed individually. In this paper, we propose a class of conjugate gradient methods, which can beregarded as some kind of convex combination of the Fletcher-Reeves method and the method proposed byDai et al. To analyze this class of methods, we introduce some unified tools that concern a general methodwith the scalarβk having the form of φk/φk-1. Consequently, the class of conjugate gradient methods canuniformly be analyzed.

  8. Inorganic Nanoparticles Conjugated with Biofunctional Molecules

    Institute of Scientific and Technical Information of China (English)



    1 Results We have attempted to conjugate inorganic nanoparticles with biofunctional molecules.Recently we were quite successful in demonstrating that a two-dimensional inorganic compound like layered double hydroxide (LDH),and natural and synthetic clays can be used as gene or drug delivery carriers1-4.To the best of our knowledge,such inorganic vectors are completely new and different from conventionally developed ones such as viruses and cationic liposomes,those which are limited in certain cases of ap...

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

    KAUST Repository

    Lima, Igo T.


    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.

  10. Evaluation of Haemophilus influenzae Type B Conjugate Vaccine (Meningococcal Protein Conjugate in Canadian Infants

    Directory of Open Access Journals (Sweden)

    David W Scheifele


    Full Text Available Objective: To assess adverse effects and immune responses with a three-dose series of Haemophilus influenzae type b meningococcal protein conjugate (PedvaxHIB or Hib.OMP vaccine, including any immunological response alterations from concurrent administration with routine vaccines for infants.

  11. 78 FR 18999 - Prospective Grant of Start-Up Exclusive License: Photosensitizing Antibody-Fluorophore Conjugates... (United States)


    ...: Photosensitizing Antibody-Fluorophore Conjugates for Photoimmunotherapy AGENCY: National Institutes of Health...-01), and entitled ``Photosensitizing Antibody- Fluorophore Conjugates,'' to Aspyrian Therapeutics.... The field of use may be limited to ``use of photosensitizing antibody-fluorophore conjugate by...

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

    NARCIS (Netherlands)

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


    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 albumin-hepar

  13. Opto-electronic properties of charged conjugated molecules

    NARCIS (Netherlands)

    Fratiloiu, S.


    The aim of this thesis is to provide fundamental insight into the nature and opto-electronic properties of charge carriers on conjugated oligomers and polymers. Electronic structure, optical absorption properties and distribution of charge carriers along the chains of different conjugated materials

  14. Targeting cancer cells with folic acid-iminoboronate fluorescent conjugates. (United States)

    Cal, Pedro M S D; Frade, Raquel F M; Chudasama, Vijay; Cordeiro, Carlos; Caddick, Stephen; Gois, Pedro M P


    Herein we present the synthesis of fluorescent 2-acetylbenzeneboronic acids that undergo B-N promoted conjugation with lysozyme and N-(2-aminoethyl) folic acid (EDA-FA), generating conjugates that are selectively recognized and internalized by cancer cells that over-express folic acid receptors.


    Institute of Scientific and Technical Information of China (English)

    Shujun LIAN; Changyu WANG; Lixia CAO


    In this paper, a new region of βκ with respect to βPRPκ is given. With two Armijo-type line searches, the authors investigate the global convergence properties of the dependent PRP conjugate gradient methods, which extend the global convergence results of PRP conjugate gradient method proved by Grippo and Lucidi (1997) and Dai and Yuan (2002).

  16. Comparative study of the three different fluorophore antibody conjugation strategies. (United States)

    Shrestha, Dilip; Bagosi, Adrienn; Szöllősi, János; Jenei, Attila


    The progression in bioconjugational chemistry has significantly contributed to the evolution and success of protein biology. Mainly, antibody chemistry has been a subject of intensive study owing to the expansion of research areas warranted by using various derivatives of conjugated antibodies. Three reactive moieties (amine, sulfhydryl and carbohydrate) in the antibodies are chiefly favored for the conjugational purpose. This feature is known for decades, nevertheless, amine based conjugation is still the most preferred strategy despite the appreciation the other two methods receive in conserving the antigen binding affinity (ABA). No single report has been published, according to our knowledge, where these three conjugation strategies were applied to the same fluorophore antibody systems. In this study, we evaluated conjugation yield, time demand and cost efficiency of these conjugation procedures. Our results showed that amine based conjugations was by far the best technique due to its simplicity, rapidity, ease of operation, higher conjugate yield, cheaper cost and potential for larger fluorophore/protein labeling ratio without having much effect in ABA. Furthermore, sulfhydryl labeling clearly excelled in terms of reduced non-specific binding and mild effect in ABA but was usually complicated by an asymmetric antibody reduction due to mercaptoethylamine while carbohydrate oxidation based strategy performed the worst during our experiment.

  17. Prostaglandin phospholipid conjugates with unusual biophysical and cytotoxic properties

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob; Adolph, Sidsel K.; Andresen, Thomas Lars;


    The synthesis of two secretory phospholipase A(2) IIA sensitive 15-deoxy-Delta(12,14)-prostaglandin J(2) phospholipid conjugates is described and their biophysical and biological properties are reported. The conjugates spontaneously form particles in the liposome size region upon dispersion in an...


    Institute of Scientific and Technical Information of China (English)

    DAI Yuhong


    Conjugate gradient methods are very important methods for unconstrained optimization, especially for large scale problems. In this paper, we propose a new conjugate gradient method, in which the technique of nonmonotone line search is used. Under mild assumptions, we prove the global convergence of the method. Some numerical results are also presented.

  19. Responsive Guest Encapsulation of Dynamic Conjugated Microporous Polymers. (United States)

    Xu, Lai; Li, Youyong


    The host-guest complexes of conjugated microporous polymers encapsulating C60 and dye molecules have been investigated systematically. The orientation of guest molecules inside the cavities, have different terms: inside the open cavities of the polymer, or inside the cavities formed by packing different polymers. The host backbone shows responsive dynamic behavior in order to accommodate the size and shape of incoming guest molecule or guest aggregates. Simulations show that the host-guest binding of conjugated polymers is stronger than that of non-conjugated polymers. This detailed study could provide a clear picture for the host-guest interaction for dynamic conjugated microporous polymers. The mechanism obtained could guide designing new conjugated microporous polymers.

  20. Genetic Drift Suppresses Bacterial Conjugation in Spatially Structured Populations (United States)

    Freese, Peter D.; Korolev, Kirill S.; Jiménez, José I.; Chen, Irene A.


    Conjugation is the primary mechanism of horizontal gene transfer that spreads antibiotic resistance among bacteria. Although conjugation normally occurs in surface-associated growth (e.g., biofilms), it has been traditionally studied in well-mixed liquid cultures lacking spatial structure, which is known to affect many evolutionary and ecological processes. Here we visualize spatial patterns of gene transfer mediated by F plasmid conjugation in a colony of Escherichia coli growing on solid agar, and we develop a quantitative understanding by spatial extension of traditional mass-action models. We found that spatial structure suppresses conjugation in surface-associated growth because strong genetic drift leads to spatial isolation of donor and recipient cells, restricting conjugation to rare boundaries between donor and recipient strains. These results suggest that ecological strategies, such as enforcement of spatial structure and enhancement of genetic drift, could complement molecular strategies in slowing the spread of antibiotic resistance genes.

  1. In vitro biological properties of flavonoid conjugates found in vivo. (United States)

    Williamson, G; Barron, D; Shimoi, K; Terao, J


    For some flavonoids such as quercetin, isoflavones and catechins, the pathways of absorption and metabolism are now reasonably well characterised and understood. By definition, for biological activity of flavonoids to be manifest, the target tissue, which includes the blood and vascular system, must respond to the form(s) of flavonoid that it encounters. Bioavailability studies have shown that the circulating form of most flavonoids is as conjugates, with a few notable exceptions. There have been several recent papers on the in vitro biological properties of conjugates that have been found in vivo. This paper reviews the properties of these conjugates. Most of the information currently available is on quercetin glucuronides, but also on isoflavone and catechin conjugates. In addition to the biological properties of the conjugates, the partition coefficients and methods of synthesis are also presented.

  2. The Vi conjugate typhoid vaccine is safe, elicits protective levels of IgG anti-Vi, and is compatible with routine infant vaccines. (United States)

    Thiem, Vu Dinh; Lin, Feng-Ying C; Canh, Do Gia; Son, Nguyen Hong; Anh, Dang Duc; Mao, Nguyen Duc; Chu, Chiayung; Hunt, Steven W; Robbins, John B; Schneerson, Rachel; Szu, Shousun C


    Typhoid fever remains a serious problem in developing countries. Current vaccines are licensed for individuals who are 5 years old or older. A conjugate of the capsular polysaccharide (CP) of Salmonella enterica serovar Typhi (Vi) bound to recombinant exoprotein A of Pseudomonas aeruginosa (Vi-rEPA) enhanced Vi immunogenicity and protected 2- to 5-year-olds in Vietnam. In this study, Vi-rEPA was evaluated for use in infants. A total of 301 full-term Vietnamese infants received Expanded Program on Immunization (EPI) vaccines alone or with Vi-rEPA or Haemophilus influenzae type b-tetanus toxoid conjugate (Hib-TT) at 2, 4, and 6 months and Vi-rEPA or Hib-TT alone at 12 months. Infants were visited 6, 24, and 48 h after each injection to monitor adverse reactions. Maternal, cord, and infant sera were assayed for IgG anti-Vi and for IgG antibodies to Hib CP and the diphtheria, tetanus, and pertussis toxins at 7, 12, and 13 months. No vaccine-related serious adverse reactions occurred. In the Vi-rEPA group, the IgG anti-Vi geometric mean (GM) increased from the cord level of 0.66 to 17.4 enzyme-linked immunosorbent assay units (EU) at 7 months, declined to 4.76 EU at 12 months, and increased to 50.1 EU 1 month after the 4th dose (95% of infants had levels of ≥ 3.5 EU, the estimated protective level). Controls had no increase of the IgG anti-Vi GM. Infants with cord anti-Vi levels of <3.5 EU responded with significantly higher IgG anti-Vi levels than those with levels of ≥ 3.5 EU. Anti-diphtheria, -tetanus, and -pertussis toxin levels were similar in all groups. Vi-rEPA was safe, induced protective anti-Vi levels, and was compatible with EPI vaccines, and it can be used in infants. High cord IgG anti-Vi levels partially suppressed infant responses to Vi-rEPA.

  3. 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


    . 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......-green emission and the zinc-porphyrin linked homopolymers emit near-infrared/infrared light. This was demonstrated to be due to electroluminescence pumping of the zinc-porphyrin moieties that were covalently linked to homopolymer material. When only one zinc-porphyrin dye was incorporated into the backbone...

  4. Conjugated polymers with pyrrole as the conjugated bridge: synthesis, characterization, and two-photon absorption properties. (United States)

    Li, Qianqian; Zhong, Cheng; Huang, Jing; Huang, Zhenli; Pei, Zhiguo; Liu, Jun; Qin, Jingui; Li, Zhen


    The synthesis, one- and two-photon absorption (2PA) and emission properties of two novel pyrrole-based conjugated polymers (P1 and P2) are reported. They emitted strong yellow-green and orange fluorescence with fluorescent quantum yields (Φ) of 46 and 33%, respectively. Their maximal 2PA cross sections (δ) measured by the two-photon-induced fluorescence method using femtosecond laser pulses in THF were 2392 and 1938 GM per repeating unit, respectively, indicating that the 2PA chromophores consisting of the triphenylamine with nonplanar structure as the donor and electron-rich pyrrole as the conjugated bridge could be the effective repeating units to enhance the δ values.

  5. Identification of excited states in conjugated polymers

    CERN Document Server

    Hartwell, L J


    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 instrument was developed and optimised for each different sample. Lock-i...

  6. Conjugated Linoleic Acid (CLA-An Overview

    Directory of Open Access Journals (Sweden)

    D J Crumb


    Full Text Available Summary: Conjugated linoleic acid (CLA is a group of octadecadienoic acids that are naturally present in the highest concentrations in foods originating in ruminant animals, and dairy products such as milk. Especially large numbers of CLA polymers have been detected in beef, lamb and milk fat. Results from many in vitro and animal studies, though conflicting, have suggested that CLA supplementation may have beneficial effect on obesity, weight management, cancer, diabetes and atherosclerosis. This article provides a brief overview on the functionality, safety and toxicity of CLA as described in literature. .   Industrial Relevance: CLA is a functional food and dietary supplement ingredient with potential benefits against a number of metabolic chronic diseases. However, the mechanism of action and its toxicological effects are not very well understood. These factors may play an important role in the effectiveness as CLA as a viable functional dietary bioactive compound.

  7. Spiropyran main-chain conjugated polymers. (United States)

    Sommer, Michael; Komber, Hartmut


    The first main-chain conjugated copolymers based on alternating spiropyran (SP) and 9,9-dioctylfluorene (F8) units synthesized via Suzuki polycondensation (SPC) are presented. The reaction conditions of SPC are optimized to obtain materials of type P(para-SP-F8) with appreciably high molecular weights up to M(w) ≈ 100 kg mol(-1). (13)C NMR is used to identify the random orientation of the non-symmetric SP unit in P(p-SP-F8). Ultrasound-induced isomerization of P(p-SP-F8) to the corresponding merocyanine form P(p-MC-F8) yields a deep-red solution. This isomerization reaction is followed by (1)H NMR in solution using sonication, whereby the color increasingly changes to deep red. The possibility to incorporate multiple SP units into main-chain polymers significantly broadens existing SP-based polymeric architectures.

  8. Nonlinear optical response in doped conjugated polymers

    CERN Document Server

    Harigaya, K


    Exciton effects on conjugated polymers are investigated in soliton lattice states. We use the Su-Schrieffer-Heeger model with long-range Coulomb interactions. The Hartree-Fock (HF) approximation and the single-excitation configuration- interaction (single-CI) method are used to obtain optical absorption spectra. The third-harmonic generation (THG) at off-resonant frequencies is calculated as functions of the soliton concentration and the chain length of the polymer. The magnitude of the THG at the 10 percent doping increases by the factor about 10^2 from that of the neutral system. This is owing to the accumulation of the oscillator strengths at the lowest exciton with increasing the soliton concentration. The increase by the order two is common for several choices of Coulomb interaction strengths.

  9. Monotone operators and "bigger conjugate" functions

    CERN Document Server

    Bauschke, Heinz H; Wang, Xianfu; Yao, Liangjin


    We study a question posed by Stephen Simons in his 2008 monograph involving "bigger conjugate" (BC) functions and the partial infimal convolution. As Simons demonstrated in his monograph, these function have been crucial to the understanding and advancement of the state-of-the-art of harder problems in monotone operator theory, especially the sum problem. In this paper, we provide some tools for further analysis of BC--functions which allow us to answer Simons' problem in the negative. We are also able to refute a similar but much harder conjecture which would have generalized a classical result of Br\\'ezis, Crandall and Pazy. Our work also reinforces the importance of understanding unbounded skew linear relations to construct monotone operators with unexpected properties.

  10. Coexistence of Self-pumped Phase Conjugation and Mutual-pumped Phase Conjugation in Ce∶BaTiO3

    Institute of Scientific and Technical Information of China (English)

    SHE Weilong; Lee Wing-Kee


    Self-pumped phase conjugation(SPPC) and mutual-pumped phase conjugation (MPPC) have been found to coexist in Ce∶BaTiO3 by using two coherent beams of 514.5nm wavelength from an argon ion laser. Both phase conjugations are of the stimulated backscattering and four-wave mixing type. For 7/6 incident power ratio and 26 mW total incident power,he shortest phase conjugate mirror formation time is 10s . Phase conjugate reflectivity of one the beams can reach 70%,hich is ~20% higher than the SPPC reflectivity using only one beam. When the total incident power is increased to 40 mW and the incident power ratio remains constant,a maximum phase conjugatate reflectivity of as much as 88% is obtained.

  11. Establishment and preliminary application of an ELISA method for determination of tetanus toxoid%检测破伤风类毒素的酶联免疫吸附法的建立及应用

    Institute of Scientific and Technical Information of China (English)

    王玲; 王珣; 韩俊杰; 张建玲; 杨云凯; 张娜; 佟芳; 潘殊男; 张霖阳


    Objective To establish an ELISA method for quantitative determination of tetanus toxoid (TT ) for DTaP .Methods Rabbits were immunized with purified TT to prepare high‐titer serum antibodies against TT .Polyclonal anti‐TT antibodies were purified by octanoic acid‐ammonium sulfate precipitation method and labeled with horseradish peroxidase to establish a double antibody sandwich ELISA method .Results The ELISA method had good specificity for TT and no cross reactivities with filamentous hemagglutinin ,pertussis toxin or diphtheria toxoid .The best linearity of the ELISA method was within the range of 0 .5‐16 .0 Lf /L TT (R 2 > 0 .99) .The coefficient of variation and recover rates of intra‐ and inter‐assay were 4 .7% ‐9 .8% and 92 .7% ‐109 .0% ,respectively ,when 14 .0 ,12 .0 ,6 .0 ,3 .0 and 1 .5 Lf /L TT standards were detected ,and the precision and accuracy both met requirements of quality control . The detection limit of the ELISA method was 1 .5 Lf /L TT . Conclusion The established ELISA method can be applied to detecting TT during purification of tetanus vaccine and lays foundation for quality control of TT .%目的:建立定量检测白喉‐破伤风‐无细胞百日咳疫苗生产过程中破伤风类毒素(tetanus toxoid ,TT )的方法。方法 TT 免疫家兔以制备高效价血清抗 TT 抗体。辛酸‐硫酸铵沉淀法纯化抗TT 多克隆抗体并进行辣根过氧化物酶标记,建立双抗体夹心 ELISA 法。结果建立的 ELISA 法与丝状血凝素、百日咳毒素及白喉类毒素无交叉反应,特异性较好。该 ELISA 法在0.5~16.0 Lf /L TT 检测区间有最佳线性,决定系数>0.99。实验内和实验间检测14.0、12.0、6.0、3.0和1.5 Lf/L TT ,变异系数为4.7%~9.8%,回收率为92.7%~109.0%,精密度和准确度均符合常规质控要求。该法的定量下限为1.5 Lf/L TT 。结论建立的 ELISA 法可有效检测破

  12. Synthesis and antimicrobial activity of gold nanoparticle conjugates with cefotaxime (United States)

    Titanova, Elena O.; Burygin, Gennady L.


    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.

  13. Nanostructured conjugated polymers in chemical sensors: synthesis, properties and applications. (United States)

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


    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.

  14. IRDye78 Conjugates for Near-Infrared Fluorescence Imaging

    Directory of Open Access Journals (Sweden)

    Atif Zaheer


    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.


    Energy Technology Data Exchange (ETDEWEB)

    Schanze, Kirk S [University of Florida


    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.

  16. Conjugation vs hyperconjugation in molecular structure of acrolein (United States)

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


    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.

  17. Conjugated organometallic materials containing tungsten centers (United States)

    Jones, Marya

    Our group is interested in the optical and electronic properties of organometallic analogues of conjugated organic compounds. Specifically, in this thesis we will discuss the properties of complexes in which W≡C moieties replace C≡C fragments within the framework of oligo(phenyleneethynylenes) and a C4-polyyne. A family of derivatives of the type Ph(C≡CC6H4 )m(L)4W≡C(C6H 4C≡C)nPh (m = 0, 1; n = 0, 1, 2) have been prepared and characterized by X-ray crystallography, electronic-absorption spectroscopy, and electrochemistry. This substitution has allowed us to directly compare the electronic and optical properties of these organometallic complexes with those of their organic analogues. We found that while these systems exhibit redox and spectroscopic properties similar to those of their organic counterparts they also exhibit new characteristics that are due to the incorporation of the metal center. The design of these compounds has also allowed us to address how the position of the metal within the backbone affects the electronic and optical properties of these compounds. We found that the position of the metal is important in controlling the electronic structure of the material, thus suggesting that the properties of these compounds can be further tuned by changing the position of the metal within the conjugated carbon chain. In addition, we have appended sulfur and isocyanide functionalities to oligo(phenyleneethynylene) analogues. A family of compounds of the type Cl(dppe) 2W(≡CC6H4-4-(C≡CC6H 4)m-4'-R) (m = l, 2; R = N≡C, SCH2CH 2Si(CH3)3) have been prepared and characterized by electronic-absorption spectroscopy and electrochemistry. Differences between the sulfur and isocyanide functionalities are examined, along with the effects of extending conjugation along the arylidyne chain. Evidence that the sulfur-containing arylidyne complexes form self-assembled monolayers on Au and Pt electrodes is presented. In addition, the electron-transfer rates for

  18. Vibrational spectroscopy of microhydrated conjugate base anions. (United States)

    Asmis, Knut R; Neumark, Daniel M


    Conjugate-base anions are ubiquitous in aqueous solution. Understanding the hydration of these anions at the molecular level represents a long-standing goal in chemistry. A molecular-level perspective on ion hydration is also important for understanding the surface speciation and reactivity of aerosols, which are a central component of atmospheric and oceanic chemical cycles. In this Account, as a means of studying conjugate-base anions in water, we describe infrared multiple-photon dissociation spectroscopy on clusters in which the sulfate, nitrate, bicarbonate, and suberate anions are hydrated by a known number of water molecules. This spectral technique, used over the range of 550-1800 cm(-1), serves as a structural probe of these clusters. The experiments follow how the solvent network around the conjugate-base anion evolves, one water molecule at a time. We make structural assignments by comparing the experimental infrared spectra to those obtained from electronic structure calculations. Our results show how changes in anion structure, symmetry, and charge state have a profound effect on the structure of the solvent network. Conversely, they indicate how hydration can markedly affect the structure of the anion core in a microhydrated cluster. Some key results include the following. The first few water molecules bind to the anion terminal oxo groups in a bridging fashion, forming two anion-water hydrogen bonds. Each oxo group can form up to three hydrogen bonds; one structural result, for example, is the highly symmetric, fully coordinated SO(4)(2-)(H(2)O)(6) cluster, which only contains bridging water molecules. Adding more water molecules results in the formation of a solvent network comprising water-water hydrogen bonding in addition to hydrogen bonding to the anion. For the nitrate, bicarbonate, and suberate anions, fewer bridging sites are available, namely, three, two, and one (per carboxylate group), respectively. As a result, an earlier onset of water

  19. Biomedical Applications of DNA-Conjugated Gold Nanoparticles. (United States)

    Wang, Chun-Chi; Wu, Shou-Mei; Li, Hung-Wen; Chang, Huan-Tsung


    Gold nanoparticles (AuNPs) are useful for diagnostic and biomedical applications, mainly because of their ease in preparation and conjugation, biocompatibility, and size-dependent optical properties. However, bare AuNPs do not possess specificity for targets. AuNPs conjugated with DNA aptamers offer specificity for various analytes, such as proteins and small molecules/ions. Although DNA aptamers themselves have therapeutic and target-recognizing properties, they are susceptible to degradation in vivo. When DNA aptamers are conjugated to AuNPs, their stability and cell uptake efficiency both increase, making aptamer-AuNPs suitable for biomedical applications. Additionally, drugs can be efficiently conjugated with DNA aptamer-AuNPs to further enhance their therapeutic efficiency. This review focuses on the applications of DNA aptamer-based AuNPs in several biomedical areas, including anticoagulation, anticancer, antibacterial, and antiviral applications.

  20. Optimised deconjugation of androgenic steroid conjugates in bovine urine

    DEFF Research Database (Denmark)

    Pedersen, Mikael; Frandsen, Henrik Lauritz; Andersen, Jens Hinge


    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 and glucuronid......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...... 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...... in ethyl acetate were used for deconjugation and the extract was purified by solid-phase extraction. The final extract was evaporated to dryness, re-dissolved and analysed by LC-MS/MS....

  1. Band-structure engineering in conjugated 2D polymers. (United States)

    Gutzler, Rico


    Conjugated polymers find widespread application in (opto)electronic devices, sensing, and as catalysts. Their common one-dimensional structure can be extended into the second dimension to create conjugated planar sheets of covalently linked molecules. Extending π-conjugation into the second dimension unlocks a new class of semiconductive polymers which as a consequence of their unique electronic properties can find usability in numerous applications. In this article the theoretical band structures of a set of conjugated 2D polymers are compared and information on the important characteristics band gap and valence/conduction band dispersion is extracted. The great variance in these characteristics within the investigated set suggests 2D polymers as exciting materials in which band-structure engineering can be used to tailor sheet-like organic materials with desired electronic properties.

  2. Conjugate heat transfer with the entropic lattice Boltzmann method. (United States)

    Pareschi, G; Frapolli, N; Chikatamarla, S S; Karlin, I V


    A conjugate heat-transfer model is presented based on the two-population entropic lattice Boltzmann method. The present approach relies on the extension of Grad's boundary conditions to the two-population model for thermal flows, as well as on the appropriate exact conjugate heat-transfer condition imposed at the fluid-solid interface. The simplicity and efficiency of the lattice Boltzmann method (LBM), and in particular of the entropic multirelaxation LBM, are retained in the present approach, thus enabling simulations of turbulent high Reynolds number flows and complex wall boundaries. The model is validated by means of two-dimensional parametric studies of various setups, including pure solid conduction, conjugate heat transfer with a backward-facing step flow, and conjugate heat transfer with the flow past a circular heated cylinder. Further validations are performed in three dimensions for the case of a turbulent flow around a heated mounted cube.

  3. Conjugated Polymers/DNA Hybrid Materials for Protein Inactivation. (United States)

    Zhao, Likun; Zhang, Jiangyan; Xu, Huiming; Geng, Hao; Cheng, Yongqiang


    Chromophore-assisted light inactivation (CALI) is a powerful tool for analyzing protein functions due to the high degree of spatial and temporal resolution. In this work, we demonstrate a CALI approach based on conjugated polymers (CPs)/DNA hybrid material for protein inactivation. The target protein is conjugated with single-stranded DNA in advance. Single-stranded DNA can form CPs/DNA hybrid material with cationic CPs via electrostatic and hydrophobic interactions. Through the formation of CPs/DNA hybrid material, the target protein that is conjugated with DNA is brought into close proximity to CPs. Under irradiation, CPs harvest light and generate reactive oxygen species (ROS), resulting in the inactivation of the adjacent target protein. This approach can efficiently inactivate any target protein which is conjugated with DNA and has good specificity and universality, providing a new strategy for studies of protein function and adjustment of protein activity.

  4. Preparation of Conjugated Linoleic Acid and Identification of Its Isomers

    Institute of Scientific and Technical Information of China (English)

    郭诤; 张根旺; 孙彦


    Conjugated linoleic acid(CLA)is a kind of fatty acid with physiological activities and potential appli-cation prospect ,A synthesis method of conjugated linoleic acid and a purification technology were studied .CLA was prepared and purified by urea-complexation and conjugation using safflower oil as raw material,The purity of CLA and total recovery of the product was more than 95% and 48%,respectively,The main isomers produced in alkali-catalyzed conjugation were identified by gas chromatography (GC)linked to mass spectrometry(MS) and Fourier transform infrared spectroscopy(FTIR),The total amount of the two main isomers (9cis,11trans-and 10trans,12cis-CLA) determined by GC was more than 90% of the product.

  5. New Conjugates of Quinoxaline as Potent Antitubercular and Antibacterial Agents

    Directory of Open Access Journals (Sweden)

    Ramalingam Peraman


    Full Text Available Considering quinoxaline as a privileged structure for the design of potent intercalating agents, some new sugar conjugates of quinoxaline were synthesized and characterized by IR, 1HNMR, 13C NMR, and mass spectral data. In vitro testing for antitubercular and antimicrobial activities was performed against Mycobacterium tuberculosis H37Rv and some pathogenic bacteria. Results revealed that conjugate containing ribose moiety demonstrated the most promising activity against Mycobacteria and bacteria with minimum inhibitory concentrations (MIC of 0.65 and 2.07 μM, respectively. Other conjugates from xylose, glucose, and mannose were moderately active whilst disaccharides conjugates were found to be less active. In silico docking analysis of prototype compound revealed that ATP site of DNA gyrase B subunit could be a possible site for inhibitory action of these synthesized compounds.

  6. New Conjugates of Quinoxaline as Potent Antitubercular and Antibacterial Agents. (United States)

    Peraman, Ramalingam; Kuppusamy, Rajendran; Killi, Sunil Kumar; Reddy, Y Padmanabha


    Considering quinoxaline as a privileged structure for the design of potent intercalating agents, some new sugar conjugates of quinoxaline were synthesized and characterized by IR, (1)HNMR, (13)C NMR, and mass spectral data. In vitro testing for antitubercular and antimicrobial activities was performed against Mycobacterium tuberculosis H 37 Rv and some pathogenic bacteria. Results revealed that conjugate containing ribose moiety demonstrated the most promising activity against Mycobacteria and bacteria with minimum inhibitory concentrations (MIC) of 0.65 and 2.07 μM, respectively. Other conjugates from xylose, glucose, and mannose were moderately active whilst disaccharides conjugates were found to be less active. In silico docking analysis of prototype compound revealed that ATP site of DNA gyrase B subunit could be a possible site for inhibitory action of these synthesized compounds.

  7. "Angle" Operator Conjugate to Photon's Intrinsic Angular Momentum

    Institute of Scientific and Technical Information of China (English)



    We find the correct "angle" operator conjugate to the intrinsic angular momentum of the photon by introducing a suitable representation which involves both left-handed and right-handed polarization photon operators.

  8. BSA-boronic acid conjugate as lectin mimetics. (United States)

    Narla, Satya Nandana; Pinnamaneni, Poornima; Nie, Huan; Li, Yu; Sun, Xue-Long


    We report bovine serum albumin (BSA)-boronic acid (BA) conjugates as lectin mimetics and their glyco-capturing capacity. The BSA-BA conjugates were synthesized by amidation of carboxylic acid groups in BSA with aminophenyl boronic acid in the presence of EDC, and were characterized by Alizarin Red S (ARS) assay and SDS-PAGE gel. The BSA-BA conjugates were immobilized onto maleimide-functionalized silica beads and their sugar capturing capacity and specificity were confirmed by ARS displacement assay. Further, surface plasmon resonance (SPR) analysis of the glyco-capturing activity of the BSA-BA conjugates was conducted by immobilizing BSA-BA onto SPR gold chip. Overall, we demonstrated a BSA-BA-based lectin mimetics for glyco-capturing applications. These lectin mimetics are expected to provide an important tool for glycomics and biosensor research and applications.

  9. Fullerene-biomolecule conjugates and their biomedicinal applications. (United States)

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


    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.

  10. Matrix summability of the conjugate deries of derived Fourier series

    Directory of Open Access Journals (Sweden)

    Shyam Lal


    Full Text Available In this paper, a new theorem on matrix summability of the conjugate series of a derived Fourier series is proved, which improves and generalizes all the previous known results in this line of work.

  11. Phase conjugation of gap solitons: A numerical study

    Indian Academy of Sciences (India)

    V S C Manga Rao; S Dutta Gupta


    We study the effect of a nearby phase-conjugate mirror (PCM) on the gap soliton of a Kerr non-linear periodic structure. We show that phase conjugation of the gap soliton (in the sense of replication of the amplitude profile in the reverse direction) is possible under the condition of PCM reflectivity approaching unity. This is in contrast with the results for linear structures, where the wave profiles can be conjugated for arbitrary values of the PCM reflectivity. The sensitivity of the conjugation of the gap solitons to PCM reflectivity is ascribed to the fine balance of non-linearity with dispersion, necessary for their existence.

  12. A Restarted Conjugate Gradient Method for Ill-posed Problems

    Institute of Scientific and Technical Information of China (English)

    Yan-fei Wang


    This paper presents a restarted conjugate gradient iterative algorithm for solving ill-posed problems.The damped Morozov's discrepancy principle is used as a stopping rule. Numerical experiments are given to illustrate the efficiency of the method.

  13. Partial Hermitian Conjugate Separability Criteria for Pure Quantum States

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xin; WU Hua; LI Yan-Song; LONG Gui-Lu


    We propose a criterion for the separability of quantum pure states using the concept of a partial Hermitian conjugate.It is equivalent to the usual positive partial transposition criteria,with a simple physical interpretation.

  14. Charge Transport in Conjugated Block Copolymers (United States)

    Smith, Brandon; Le, Thinh; Lee, Youngmin; Gomez, Enrique

    Interest in conjugated block copolymers for high performance organic photovoltaic applications has increased considerably in recent years. Polymer/fullerene mixtures for conventional bulk heterojunction devices, such as P3HT:PCBM, are severely limited in control over interfaces and domain length scales. In contrast, microphase separated block copolymers self-assemble to form lamellar morphologies with alternating electron donor and acceptor domains, thereby maximizing electronic coupling and local order at interfaces. Efficiencies as high as 3% have been reported in solar cells for one block copolymer, P3HT-PFTBT, but the details concerning charge transport within copolymers have not been explored. To fill this gap, we probed the transport characteristics with thin-film transistors. Excellent charge mobility values for electron transport have been observed on aluminum source and drain contacts in a bottom gate, bottom contact transistor configuration. Evidence of high mobility in ordered PFTBT phases has also been obtained following thermal annealing. The insights gleaned from our investigation serve as useful guideposts, revealing the significance of the interplay between charge mobility, interfacial order, and optimal domain size in organic block copolymer semiconductors.

  15. Microfluidic Fabrication of Conjugated Polymer Sensor Fibers

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  16. DNA Interaction Studies of Selected Polyamine Conjugates (United States)

    Szumilak, Marta; Merecz, Anna; Strek, Malgorzata; Stanczak, Andrzej; Inglot, Tadeusz W.; Karwowski, Boleslaw T.


    The interaction of polyamine conjugates with DNA double helix has been studied. Binding properties were examined by ethidium bromide (EtBr) displacement and DNA unwinding/topoisomerase I/II (Topo I/II) activity assays, as well as dsDNA thermal stability studies and circular dichroism spectroscopy. Genotoxicity of the compounds was estimated by a comet assay. It has been shown that only compound 2a can interact with dsDNA via an intercalative binding mode as it displaced EtBr from the dsDNA-dye complex, with Kapp = 4.26 × 106 M−1; caused an increase in melting temperature; changed the circular dichroism spectrum of dsDNA; converted relaxed plasmid DNA into a supercoiled molecule in the presence of Topo I and reduced the amount of short oligonucleotide fragments in the comet tail. Furthermore, preliminary theoretical study has shown that interaction of the discussed compounds with dsDNA depends on molecule linker length and charge distribution over terminal aromatic chromophores. PMID:27657041

  17. Stellar photometry with Multi Conjugate Adaptive Optics

    CERN Document Server

    Fiorentino, Giuliana; McConnachie, Alan; Stetson, Peter B; Bono, Giuseppe; Turri, Paolo; Andersen, David; Veran, Jean-Pierre; Diolaiti, Emiliano; Schreiber, Laura; Ciliegi, Paolo; Bellazzini, Michele; Tolstoy, Eline; Monelli, Matteo; Iannicola, Giacinto; Ferraro, Ivan; Testa, Vincenzo


    We overview the current status of photometric analyses of images collected with Multi Conjugate Adaptive Optics (MCAO) at 8-10m class telescopes that operated, or are operating, on sky. Particular attention will be payed to resolved stellar population studies. Stars in crowded stellar systems, such as globular clusters or in nearby galaxies, are ideal test particles to test AO performance. We will focus the discussion on photometric precision and accuracy reached nowadays. We briefly describe our project on stellar photometry and astrometry of Galactic globular clusters using images taken with GeMS at the Gemini South telescope. We also present the photometry performed with DAOPHOT suite of programs into the crowded regions of these globulars reaching very faint limiting magnitudes Ks ~21.5 mag on moderately large fields of view (~1.5 arcmin squared). We highlight the need for new algorithms to improve the modeling of the complex variation of the Point Spread Function across the ?eld of view. Finally, we outl...

  18. Lactancia materna y respuesta humoral contra vacunas de toxoide tetánico y diftérico en niños de 2 años

    Directory of Open Access Journals (Sweden)

    Deyanira La Rosa


    Full Text Available Teniendo en cuenta que el impacto de la lactancia materna sobre la respuesta a la vacunación es controversial, se evaluó la influencia de la lactancia materna sobre la respuesta humoral a las vacunas con toxoide tetánico y diftérico en niños de 2 años de edad que culminaron la etapa básica de inmunización del esquema de vacunación infantil. Se seleccionaron 44 niños que se diferenciaron en dos grupos de estudios, de acuerdo con el tiempo que fueron amamantados. Para la determinación de las concentraciones de antitoxina diftérica y tetánica se utilizaron ensayos inmunoenzimáticos en fase sólida (ELISA. Al aplicar el test de Student en los resultados obtenidos se constató que recibir la lactancia materna exclusiva por 6 meses o más determinó un incremento en las concentraciones de antitoxina diftérica, mientras que no se evidenciaron diferencias en cuanto a las concentraciones de antitoxina tetánica detectadas entre los niños lactados de manera exclusiva por 6 meses o más, con aquellos lactados por períodos inferiores.

  19. Solid State NMR and Fluorescence Studies of Conjugated Polymer Nanocomposties

    Institute of Scientific and Technical Information of China (English)

    Chao Jun JING; Liu Sheng CHEN; Yi SHI; Xi Gao JIN


    13C spin-lattice relaxation times (T1) of a conjugated polymer MEH-PPV in polymer/layered silicate nanocomposites together with the steady state fluorescence emission and transient fluorescence decay measurements have been investigated. The T1 values of the conjugated carbons decrease dramatically according to the reduction of polymer concentration in the nano composites, while the fluorescence life times (τ) show a linear prolonging tendency. The results are explained from the point of view of molecular dynamics.

  20. Synthesis of arylpyrazole linked benzimidazole conjugates as potential microtubule disruptors. (United States)

    Kamal, Ahmed; Shaik, Anver Basha; Polepalli, Sowjanya; Kumar, G Bharath; Reddy, Vangala Santhosh; Mahesh, Rasala; Garimella, Srujana; Jain, Nishant


    In an attempt to develop potent and selective anticancer agents, a series of twenty arylpyrazole linked benzimidazole conjugates (10a-t) were designed and synthesized as microtubule destabilizing agents. The joining of arylpyrazole to the benzimidazole moiety resulted in a four ring (A, B, C and D) molecular scaffold that comprises of polar heterocyclic rings in the middle associated with rotatable single bonds and substituted aryl rings placed in the opposite directions. These conjugates were evaluated for their ability to inhibit the growth of sixty cancer cell line panel of the NCI. Among these some conjugates like 10a, 10b, 10d, 10e, 10p and 10r exhibited significant growth inhibitory activity against most of the cell lines ranging from 0.3 to 13μM. Interestingly, the conjugate 10b with methoxy group on D-ring expressed appreciable cytotoxic potential. A549 cells treated with some of the potent conjugates like 10a, 10b and 10d arrested cells at G2/M phase apart from activating cyclin-B1 protein levels and disrupting microtubule network. Moreover, these conjugates effectively inhibited tubulin polymerization with IC50 values of 1.3-3.8μM. Whereas, the caspase assay revealed that they activate the casepase-3 leading to apoptosis. Particularly 10b having methoxy substituent induced activity almost 3 folds higher than CA-4. Furthermore, a competitive colchicine binding assay and molecular modeling analysis suggests that these conjugates bind to the tubulin successfully at the colchicine binding site. These investigations reveal that such conjugates having pyrazole and benzimidazole moieties have the potential in the development of newer chemotherapeutic agents.


    Institute of Scientific and Technical Information of China (English)

    Yu-hong Dai; Ya-xiang Yuan


    The conjugate gradient method for unconstrained optimization problems varies with a scalar. In this note, a general condition concerning the scalar is given, which ensures the global convergence of the method in the case of strong Wolfe line searches. It is also discussed how to use the result to obtain the convergence of the famous Fletcher-Reeves, and Polak-Ribiere-Polyak conjugate gradient methods. That the condition cannot be relaxed in some sense is mentioned.

  2. Various methods of gold nanoparticles (GNPs conjugation to antibodies

    Directory of Open Access Journals (Sweden)

    Mir Hadi Jazayeri


    These applications require an increasingly complex level of surface decoration in order to achieve efficacy, and limit off-target toxicity. This review will discuss the chemical and physical approaches commonly utilized in relation to surface decoration and the powerful system used to indicate success of the conjugation. Finally, we review the range of recent studies about covalent and noncovalent modes for conjugation of antibodies to the particle surface that aim to advance gold nanoparticle treatments and diagnostics toward the clinic.

  3. Synthesis of Conjugated Polymers for Light Emitting and Photovoltalc Applications

    Institute of Scientific and Technical Information of China (English)


    1 Results The initial report of polymeric light-emitting diodes (PLEDs) based on poly(p-phenylenevinylene) gave birth to an intense research effort in conjugated polymers, primarily focused on the development of optoelectronic and electrochemical devices. Significant developments in modern synthetic chemistry, especially the chemistry of carbon-carbon bond formation have allowed the synthesis of various well-defined conjugated polymers and oligomers with optimized physical properties.Meanwhile, these re...

  4. O:2-CRM(197) conjugates against Salmonella Paratyphi A. (United States)

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


    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.

  5. Selective esterification of non-conjugated carboxylic acids in the presence of conjugated or aromatic carboxylic acids over active carbon supported methanesulfonic acid

    Institute of Scientific and Technical Information of China (English)

    FENG ZeWang; ZHAO XinQi; BI Hua


    Non-conjugated carboxylic acids are selectively esterified in good yields in the presence of conjugated or aromatic carboxylic acids by stirring over active carbon supported methanesulfonic acid in dichloromethane at room temperature.

  6. Degree of approximation of conjugate of Lip $ \\alpha$ class function by $ {K^\\lambda}$-summability means of conjugate series of a Fourier series

    Directory of Open Access Journals (Sweden)

    Shyam Lal


    Full Text Available In this paper the degree of approximation of conjugate of a function belonging to Lip $ \\alpha$ class by $ K^\\lambda$-summability means of conjugate series of its Fourier series has been determined.

  7. Selective esterification of non-conjugated carboxylic acids in the presence of conjugated or aromatic carboxylic acids over active carbon supported methanesulfonic acid

    Institute of Scientific and Technical Information of China (English)


    Non-conjugated carboxylic acids are selectively esterified in good yields in the presence of conjugated or aromatic carboxylic acids by stirring over active carbon supported methanesulfonic acid in di-chloromethane at room temperature.

  8. Dosing Schedules for Pneumococcal Conjugate Vaccine (United States)


    Since second generation pneumococcal conjugate vaccines (PCVs) targeting 10 and 13 serotypes became available in 2010, the number of national policy makers considering these vaccines has steadily increased. An important consideration for a national immunization program is the timing and number of doses—the schedule—that will best prevent disease in the population. Data on disease epidemiology and the efficacy or effectiveness of PCV schedules are typically considered when choosing a schedule. Practical concerns, such as the existing vaccine schedule, and vaccine program performance are also important. In low-income countries, pneumococcal disease and deaths typically peak well before the end of the first year of life, making a schedule that provides PCV doses early in life (eg, a 6-, 10- and 14-week schedule) potentially the best option. In other settings, a schedule including a booster dose may address disease that peaks in the second year of life or may be seen to enhance a schedule already in place. A large and growing body of evidence from immunogenicity studies, as well as clinical trials and observational studies of carriage, pneumonia and invasive disease, has been systematically reviewed; these data indicate that schedules of 3 or 4 doses all work well, and that the differences between these regimens are subtle, especially in a mature program in which coverage is high and indirect (herd) effects help enhance protection provided directly by a vaccine schedule. The recent World Health Organization policy statement on PCVs endorsed a schedule of 3 primary doses without a booster or, as a new alternative, 2 primary doses with a booster dose. While 1 schedule may be preferred in a particular setting based on local epidemiology or practical considerations, achieving high coverage with 3 doses is likely more important than the specific timing of doses. PMID:24336059

  9. Phenylnaphthalenes: sublimation equilibrium, conjugation, and aromatic interactions. (United States)

    Lima, Carlos F R A C; Rocha, Marisa A A; Schröder, Bernd; Gomes, Lígia R; Low, John N; Santos, Luís M N B F


    In this work, the interplay between structure and energetics in some representative phenylnaphthalenes is discussed from an experimental and theoretical perspective. For the compounds studied, the standard molar enthalpies, entropies and Gibbs energies of sublimation, at T = 298.15 K, were determined by the measurement of the vapor pressures as a function of T, using a Knudsen/quartz crystal effusion apparatus. The standard molar enthalpies of formation in the crystalline state were determined by static bomb combustion calorimetry. From these results, the standard molar enthalpies of formation in the gaseous phase were derived and, altogether with computational chemistry at the B3LYP/6-311++G(d,p) and MP2/cc-pVDZ levels of theory, used to deduce the relative molecular stabilities in various phenylnaphthalenes. X-ray crystallographic structures were obtained for some selected compounds in order to provide structural insights, and relate them to energetics. The thermodynamic quantities for sublimation suggest that molecular symmetry and torsional freedom are major factors affecting entropic differentiation in these molecules, and that cohesive forces are significantly influenced by molecular surface area. The global results obtained support the lack of significant conjugation between aromatic moieties in the α position of naphthalene but indicate the existence of significant electron delocalization when the aromatic groups are in the β position. Evidence for the existence of a quasi T-shaped intramolecular aromatic interaction between the two outer phenyl rings in 1,8-di([1,1'-biphenyl]-4-yl)naphthalene was found, and the enthalpy of this interaction quantified on pure experimental grounds as -(11.9 ± 4.8) kJ·mol(-1), in excellent agreement with the literature CCSD(T) theoretical results for the benzene dimer.

  10. Antibody conjugate radioimmunotherapy of superficial bladder cancer

    Directory of Open Access Journals (Sweden)

    Alan Perkins


    Full Text Available 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 C595 (IgG3 which reacts with the MUC1 glycoprotein antigen that is aberrantly expressed in a high proportion of bladder tumours. Radioimmunoconjugates of the C595 antibody have been produced with high radiolabelling efficiency and immunoreactivity using Tc-99m 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.A administração de anticorpos conjugados para o tratamento do câncer está agora provando ser de valor clínico. Nós estamos atualmente realizando um programa de estudos clínicos usando o anticorpo monoclonal C595 (IgG3 que reage com a glicoproteína MUC1 que está aberrantemente expressa numa alta proporção de tumores de bexiga. Tem sido produzidos radioimunoconjugados do anticorpo C595, com alta eficiência de radiomarcação e a imunoreatividade, usando-se o Tc-99m e In-111, para o diagnóstico por imagem e estagiamento de doenças. Tem sido produzidos, também, radionuclídeos citotóxicos (Cu-67 e Re-188 para o tratamento de cânceres superficiais de bexiga. A fase terapêutica I/II já se iniciou, envolvendo a administração intravesical do anticorpo diretamente na bexiga.

  11. Recent advances in conjugated polymers for light emitting devices. (United States)

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


    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.

  12. Recent Advances in Conjugated Polymers for Light Emitting Devices

    Directory of Open Access Journals (Sweden)

    Mohan Raja


    Full Text Available 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.

  13. Optical study of pi-conjugated polymers and pi-conjugated polymers/fullerene blends (United States)

    Drori, Tomer

    In this research, we studied the optical properties of a variety of pi-conjugated polymers and pi-conjugated polymers/fullerene blends, using various continuous wave optical spectroscopies. We found an illumination-induced metastable polaron-supporting phase in films of a soluble derivative of poly-p-phenylene vinylene (MEH-PPV). Pristine, MEH-PPV polymer films in the dark do not show long-lived photogenerated polarons. Prolonged UV illumination, however, is found to induce a reversible, metastable phase characterized by its ability to support abundant long-lived photogenerated polarons. We also discovered a photobleaching band in our photomodulation measurement around 0.9eV that scales with and thus is related to the observed polaron band. In the dark, the illumination-induced metastable phase reverts back to the phase of the original MEH-PPV within about 30 min at room temperature. We also applied our experimental techniques in polymer/fullerene blends for studying the photophysics of bulk heterostructures with below-gap excitation. In contrast to the traditional view, we found that below-gap excitation, which is incapable of generating intrachain excitons, nevertheless efficiently generates polarons on the polymer chains and fullerene molecules. Using frequency dependence photomodulation, we distinguished between the two mechanisms of photoinduced charge transfer using above-gap and below-gap excitations, and found a distinguishable long polaron lifetime when photogenerated with below-gap excitation. The polaron action spectrum extends deep inside the gap as a result of a charge-transfer complex state formed between the polymer chain and fullerene molecule. Using the electroabsorption technique, we were able to detect the optical transition of the charge transfer complex state that lies below the gap of the polymer and the fullerene. With appropriate design engineering the long-lived polarons might be harvested in solar cell devices. Another system studied was

  14. 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: [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China)


    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.

  15. Relaxation Oscillation with Picosecond Spikes in a Conjugated Polymer Laser

    Directory of Open Access Journals (Sweden)

    Wafa Musa Mujamammi


    Full Text Available Optically pumped conjugated polymer lasers are good competitors for dye lasers, often complementing and occasionally replacing them. This new type of laser material has broad bandwidths and high optical gains comparable to conventional laser dyes. Since the Stokes’ shift is unusually large, the conjugated polymer has a potential for high power laser action, facilitated by high concentration. This paper reports the results of a new conjugated polymer, the poly[(9,9-dioctyl-2,7-divinylenefluorenylene-alt-co-{2-methoxy-5-(2-ethylhexyloxy-1,4-phenylene}](PFO-co-MEH-PPV material, working in the green region. Also discussed are the spectral and temporal features of the amplified spontaneous emissions (ASE from the conjugated polymer PFO-co-MEH-PPV in a few solvents. When pumped by the third harmonic of the Nd:YAG laser of 10 ns pulse width, the time-resolved spectra of the ASE show relaxation oscillations and spikes of 600 ps pulses. To the best of our knowledge, this is the first report on relaxation oscillations in conjugated-polymer lasers.

  16. Social behavior and decision making in bacterial conjugation. (United States)

    Koraimann, Günther; Wagner, Maria A


    Bacteria frequently acquire novel genes by horizontal gene transfer (HGT). 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.

  17. Controlling molecular ordering in solution-state conjugated polymers. (United States)

    Zhu, J; Han, Y; Kumar, R; He, Y; Hong, K; Bonnesen, P V; Sumpter, B G; Smith, S C; Smith, G S; Ivanov, I N; Do, C


    Rationally encoding molecular interactions that can control the assembly structure and functional expression in a solution of conjugated polymers hold great potential for enabling optimal organic optoelectronic and sensory materials. In this work, we show that thermally-controlled and surfactant-guided assembly of water-soluble conjugated polymers in aqueous solution is a simple and effective strategy to generate optoelectronic materials with the desired molecular ordering. We have studied a conjugated polymer consisting of a hydrophobic thiophene backbone and hydrophilic, thermo-responsive ethylene oxide side groups, which shows a step-wise, multi-dimensional assembly in water. By incorporating the polymer into phase-segregated domains of an amphiphilic surfactant in solution, we demonstrate that both chain conformation and degree of molecular ordering of the conjugated polymer can be tuned in hexagonal, micellar and lamellar phases of the surfactant solution. The controlled molecular ordering in conjugated polymer assembly is demonstrated as a key factor determining the electronic interaction and optical function.

  18. Tocilizumab - Alendronate Conjugate for Treatment of Rheumatoid Arthritis. (United States)

    Lee, Hwiwon; Bhang, Suk Ho; Lee, Jeong Ho; Kim, Hyemin; Hahn, Sei Kwang


    An autoimmune disease of rheumatoid arthritis (RA) causes severe inflammation on the synovial membrane, which results in the destruction of articular cartilage and bone. Here, Tocilizumab (TCZ) - Alendronate (ALD) conjugate is synthesized for the early intervention of RA. A humanized monoclonal antibody of TCZ shows an immunosuppressive effect, targeting interleukin-6 (IL-6) receptor in the RA pathogenesis. ALD is an anti-inflammatory bisphosphonate drug which can bind to the exposed bone surface. ALD is conjugated selectively to N-glycan on Fc region of TCZ using a chemical linker of 3-(2-pyridyldithio) propionyl hydrazide (PDPH) - poly(ethylene glycol) - N-hydroxysuccinimide (PDPH-PEG-NHS). The successful synthesis of TCZ-ALD conjugate is corroborated by 1H NMR, the purpald assay, mass spectrometry (MS), and high performance liquid chromatography (HPLC). In vitro binding affinity and cell viability tests confirmed the biological activity of TCZ-ALD conjugate. Furthermore, in vivo efficacy of TCZ-ALD conjugate is confirmed by micro computed tomography (CT), histological, and western blot analyses for the treatment of RA.

  19. The Preparation and Characterization of Conjugated Linolenic Acid

    Institute of Scientific and Technical Information of China (English)

    Cao Ying; Yang Lin; Chen Zhen-Yu


    Conjugated Linolenic Acid (CLN) has recently been shown to have a more strong cytotoxic effect on various human tumor cell lines than CLA. In CLN, all the three double bonds are conjugated, whereas they are methylene-interrupted in LN. Some seed oil, such as tung oil and pomegranate seed oil, principally consist of CLN, accounting for 76.5% and 75.5%, respectively.CLN can be characterized using the combination of gas chromatography (GC), highperformance liquid chromatography (HPLC) and UV /VIS spectrophotomea-ic analysis. GC can separate the CLN from other fatty acids and HPLC can separate the individual CLN isomers.The conjugated triene formation has a maximum absorbency at 268 nm and the conjugated diene formation has an absorbency at 235 nm in UV spectrum.CLN was prepared from linseed oil by isomerization reaction in our present study. By treating at was isomerized and the product was purified by recrystallizing in the methanol. The GC and UV /VIS spectrophotometric analysis were used to characterize the obtained products. It was found that the a-LN in the linseed oil was converted to the corresponding conjugated diene acids and CLN. The GC analysis also showed that there formed about 20% CLN when reacting for 10h with 40% KOH/ethylene glycol.

  20. Polymer-cysteamine conjugates: new mucoadhesive excipients for drug delivery? (United States)

    Kast, Constantia E; Bernkop-Schnürch, Andreas


    In the present study, the features of two new thiolated polymers--the so-called thiomers--were investigated. Mediated by a carbodiimide cysteamine was covalently attached to sodium carboxymethylcellulose (Na-CMC) and neutralised polycarbophil (Na-PCP). Depending on the weight-ratio polymer to cysteamine during the coupling reaction, the resulting CMC-cysteamine conjugate and PCP-cysteamine conjugate showed in maximum 43 +/- 15 and 138 +/- 22 micromole thiol groups per g polymer (mean +/- S.D.; n=3), respectively, which were used for further characterisation. Tensile studies carried out with the CMC-cysteamine conjugate on freshly excised porcine intestinal mucosa displayed no significantly (Paqueous solutions the disintegration time of tablets based on the CMC- and PCP-cysteamine conjugates was prolonged 1.5 and 3.2-fold, respectively, in comparison to tablets containing the corresponding unmodified polymers. According to these results, especially the PCP-cysteamine conjugate represents a promising new pharmaceutical excipient for various drug delivery systems.

  1. Polysaccharide-specific memory B cells generated by conjugate vaccines in humans conform to the CD27+IgG+ isotype-switched memory B Cell phenotype and require contact-dependent signals from bystander T cells activated by bacterial proteins to differentiate into plasma cells. (United States)

    Clarke, Edward T; Williams, Neil A; Findlow, Jamie; Borrow, Ray; Heyderman, Robert S; Finn, Adam


    The polysaccharides (PS) surrounding encapsulated bacteria are generally unable to activate T cells and hence do not induce B cell memory (BMEM). PS conjugate vaccines recruit CD4(+) T cells via a carrier protein, such as tetanus toxoid (TT), resulting in the induction of PS-specific BMEM. However, the requirement for T cells in the subsequent activation of the BMEM at the time of bacterial encounter is poorly understood, despite having critical implications for protection. We demonstrate that the PS-specific BMEM induced in humans by a meningococcal serogroup C PS (Men C)-TT conjugate vaccine conform to the isotype-switched (IgG(+)CD27(+)) rather than the IgM memory (IgM(+)CD27(+)) phenotype. Both Men C and TT-specific BMEM require CD4(+) T cells to differentiate into plasma cells. However, noncognate bystander T cells provide such signals to PS-specific BMEM with comparable effect to the cognate T cells available to TT-specific BMEM. The interaction between the two populations is contact-dependent and is mediated in part through CD40. Meningococci drive the differentiation of the Men C-specific BMEM through the activation of bystander T cells by bacterial proteins, although these signals are enhanced by T cell-independent innate signals. An effect of the TT-specific T cells activated by the vaccine on unrelated BMEM in vivo is also demonstrated. These data highlight that any protection conferred by PS-specific BMEM at the time of bacterial encounter will depend on the effectiveness with which bacterial proteins are able to activate bystander T cells. Priming for T cell memory against bacterial proteins through their inclusion in vaccine preparations must continue to be pursued.

  2. Thin Films Formed from Conjugated Polymers with Ionic, Water-Soluble Backbones. (United States)

    Voortman, Thomas P; Chiechi, Ryan C


    This paper compares the morphologies of films of conjugated polymers in which the backbone (main chain) and pendant groups are varied between ionic/hydrophilic and aliphatic/hydrophobic. We observe that conjugated polymers in which the pendant groups and backbone are matched, either ionic-ionic or hydrophobic-hydrophobic, form smooth, structured, homogeneous films from water (ionic) or tetrahydrofuran (hydrophobic). Mismatched conjugated polymers, by contrast, form inhomogeneous films with rough topologies. The polymers with ionic backbone chains are conjugated polyions (conjugated polymers with closed-shell charges in the backbone), which are semiconducting materials with tunable bad-gaps, not unlike uncharged conjugated polymers.

  3. Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen and a toxoid fusion of heat-stable toxin (STa and heat-labile toxin (LT of enterotoxigenic Escherichia coli (ETEC retain broad anti-CFA and antitoxin antigenicity.

    Directory of Open Access Journals (Sweden)

    Xiaosai Ruan

    Full Text Available Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs and two distinct enterotoxins [heat-labile toxin (LT and heat-stable toxin type Ib (STa or hSTa]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2:243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3, CFA/IV (CS4, CS5, CS6] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5:1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in

  4. Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen) and a toxoid fusion of heat-stable toxin (STa) and heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC) retain broad anti-CFA and antitoxin antigenicity. (United States)

    Ruan, Xiaosai; Sack, David A; Zhang, Weiping


    Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent

  5. Chemically optimized antimyosin Fab conjugates with chelating polymers: importance of the nature of the protein-polymer single site covalent bond for biodistribution and infarction localization. (United States)

    Trubetskoy, V S; Narula, J; Khaw, B A; Torchilin, V P


    Murine antimyosin Fab fragment was conjugated with 111In-labeled N-terminal-modified DTPA-polylysine using three bifunctional reagents: N-hydroxysuccinimide esters of 3-(2-pyridyldithio)propionic acid (SPDP conjugate), 4-(maleimidomethyl)cyclohexanecarboxylic acid (SMCC conjugate) and bromoacetic acid (BrAc conjugate) for potential localization of experimental myocardial infarction. Using various antibody preparations and a rabbit acute myocardial infarction model the following parameters were observed: (1) an in vitro antigen binding activity of SPDP conjugate = SMCC conjugate > BrAc conjugate, (2) a blood clearance rate of SPDP conjugate > BrAc conjugate > SMCC conjugate, (3) a liver and splenic accumulation of SPDP conjugate > BrAc conjugate > SMCC conjugate, and (4) the infarcted tissue activity showed an accumulation of SMCC conjugate > SPDP conjugate > BrAc conjugate. This study exemplifies the importance of rational chemical design of antimyosin Fab-chelating polymer conjugate for improved target tissue localization in vivo.

  6. Conjugates of a Photoactivated Rhodamine with Biopolymers for Cell Staining (United States)

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


    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


    Institute of Scientific and Technical Information of China (English)

    I.D. Coope; C.J. Price


    A derivative-free frame-based conjugate gradients algorithm is presented. Convergence is shown for C1 functions, and this is verified in numerical trials. The algorithm is tested on a variety of low dimensional problems, some of which are ill-conditioned, and is also tested on problems of high dimension. Numerical results show that the algorithm is effective on both classes of problems. The results are compared with those from a discrete quasiNewton method, showing that the conjugate gradients algorithm is competitive. The algorithm exhibits the conjugate gradients speed-up on problems for which the Hessian at the solution has repeated or clustered eigenvalues. The algorithm is easily parallelizable.

  8. Streamline upwind finite element method for conjugate heat transfer problems

    Institute of Scientific and Technical Information of China (English)

    Niphon Wansophark; Atipong Malatip; Pramote Dechaumphai; Yunming Chen


    This paper presents a combined finite element method for solving conjugate heat transfer problems where heat conduction in a solid is coupled with heat convection in viscous fluid flow. The streamline upwind finite element method is used for the analysis of thermal viscous flow in the fluid region, whereas the analysis of heat conduction in solid region is performed by the Galerkin method. The method uses the three-node triangular element with equal-order interpolation functions for all the variables of the velocity components,the pressure and the temperature. The main advantage of the proposed method is to consistently couple heat transfer along the fluid-solid interface. Three test cases, i.e. conjugate Couette flow problem in parallel plate channel, counter-flow in heat exchanger, and conjugate natural convection in a square cavity with a conducting wall, are selected to evaluate the efficiency of the present method.

  9. Principles of conjugating quantum dots to proteins via carbodiimide chemistry. (United States)

    Song, Fayi; Chan, Warren C W


    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.

  10. Repercussions of imprisonment for conjugal violence: discourses of men 1 (United States)

    de Sousa, Anderson Reis; Pereira, Álvaro; Paixão, Gilvânia Patrícia do Nascimento; Pereira, Nadirlene Gomes; Campos, Luana Moura; Couto, Telmara Menezes


    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. PMID:27982312

  11. Synthesis and Spectral Studies of CdTe–Dendrimer Conjugates

    Directory of Open Access Journals (Sweden)

    Ghosh Srabanti


    Full Text Available Abstract In order to couple high cellular uptake and target specificity of dendrimer molecule with excellent optical properties of semiconductor nanoparticles, the interaction of cysteine-capped CdTe quantum dots with dendrimer was investigated through spectroscopic techniques. NH2-terminated dendrimer molecule quenched the photoluminescence of CdTe quantum dots. The binding constants and binding capacity were calculated, and the nature of binding was found to be noncovalent. Significant decrease in luminescence intensity of CdTe quantum dots owing to noncovalent binding with dendrimer limits further utilization of these nanoassemblies. Hence, an attempt is made, for the first time, to synthesize stable, highly luminescent, covalently linked CdTe–Dendrimer conjugate in aqueous medium using glutaric dialdehyde (G linker. Conjugate has been characterized through Fourier transform infrared spectroscopy and transmission electron microscopy. In this strategy, photoluminescence quantum efficiency of CdTe quantum dots with narrow emission bandwidths remained unaffected after formation of the conjugate.

  12. Synthesis and Spectral Studies of CdTe-Dendrimer Conjugates (United States)

    Ghosh, Srabanti; Saha, Abhijit


    In order to couple high cellular uptake and target specificity of dendrimer molecule with excellent optical properties of semiconductor nanoparticles, the interaction of cysteine-capped CdTe quantum dots with dendrimer was investigated through spectroscopic techniques. NH2-terminated dendrimer molecule quenched the photoluminescence of CdTe quantum dots. The binding constants and binding capacity were calculated, and the nature of binding was found to be noncovalent. Significant decrease in luminescence intensity of CdTe quantum dots owing to noncovalent binding with dendrimer limits further utilization of these nanoassemblies. Hence, an attempt is made, for the first time, to synthesize stable, highly luminescent, covalently linked CdTe-Dendrimer conjugate in aqueous medium using glutaric dialdehyde (G) linker. Conjugate has been characterized through Fourier transform infrared spectroscopy and transmission electron microscopy. In this strategy, photoluminescence quantum efficiency of CdTe quantum dots with narrow emission bandwidths remained unaffected after formation of the conjugate.

  13. Nano-assembly of nanodiamonds by conjugation to actin filaments. (United States)

    Bradac, Carlo; Say, Jana M; Rastogi, Ishan D; Cordina, Nicole M; Volz, Thomas; Brown, Louise J


    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.

  14. Conjugates of a photoactivated rhodamine with biopolymers for cell staining. (United States)

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


    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.

  15. 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.

  16. Preparation of conjugated polymer suspensions by using ultrasonic atomizer

    Energy Technology Data Exchange (ETDEWEB)

    Tada, Kazuya, E-mail:; Onoda, Mitsuyoshi


    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.

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

    Directory of Open Access Journals (Sweden)

    Sergei Yu. Zaitsev


    Full Text Available 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.

  18. New Approaches to Conjugated Polymer Electrodes for Organic Energy Storage (United States)

    Lutkenhaus, Jodie


    Conjugated polymers have been explored as electrodes in batteries and pseudocapacitors for over 30 years. Yet, their widespread implementation has been hindered for several reasons such as oxidative stability, low capacity, and rate limitations associated with ionic mobility relative to current state-of-the-art. On the other hand, conjugated polymers have much to offer because of their good electronic conductivity, high Coulombic efficiency, and theoretical capacities comparable to those of metal oxides. Our lab's current goal is to overcome the aforementioned challenges, so that conjugated polymeric electrodes can be suitable used in energy storage for applications such as mechanically flexible energy storage and structural power system. This talk will present several approaches towards synthesis and processing of polyaniline that achieve oxidatively stable, high capacity, ionically mobile electrodes. These approaches include template polymerization, synthesis of nanofibers, and layer-by-layer assembly.

  19. 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.

  20. Recent advances in the construction of antibody-drug conjugates (United States)

    Chudasama, Vijay; Maruani, Antoine; Caddick, Stephen


    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.

  1. Conjugated bilirubin in neonates with glucose-6-phosphate dehydrogenase deficiency. (United States)

    Kaplan, M; Rubaltelli, F F; Hammerman, C; Vilei, M T; Leiter, C; Abramov, A; Muraca, M


    We used a system capable of measuring conjugated bilirubin and its monoconjugated and diconjugated fractions in serum to assess bilirubin conjugation in 29 glucose-6-phosphate dehydrogenase (G6PD)-deficient, term, male newborn infants and 35 control subjects; all had serum bilirubin levels > or = 256 mumol/L (15 mg/dI). The median value for diconjugated bilirubin was lower in the G6PD-deficient neonates than in control subjects (0.06 (range 0.00 to 1.84) vs 0.21 (range 0.00 to 1.02) mumol/L, p = 0.006). Diglucuronide was undetectable in 11 (38.9%) of the G6PD-deficient infants versus 3 (8.6%) of the control subjects (p = 0.015). These findings imply a partial defect of bilirubin conjugation not previously demonstrated in G6PD-deficient newborn infants.

  2. Microscopic and spectroscopic analysis of chitosan-DNA conjugates. (United States)

    Agudelo, D; Kreplak, L; Tajmir-Riahi, H A


    Conjugations of DNA with chitosans 15 kD (ch-15), 100 kD (ch-100) and 200 kD (ch-200) were investigated in aqueous solution at pH 5.5-6.5. Multiple spectroscopic methods and atomic force microscopy (AFM) were used to locate the chitosan binding sites and the effect of polymer conjugation on DNA compaction and particle formation. Structural analysis showed that chitosan-DNA conjugation is mainly via electrostatic interactions through polymer cationic charged NH2 and negatively charged backbone phosphate groups. As polymer size increases major DNA compaction and particle formation occurs. At high chitosan concentration major DNA structural changes observed indicating a partial B to A-DNA conformational transition.

  3. The extended regulatory networks of SXT/R391 integrative and conjugative elements and IncA/C conjugative plasmids. (United States)

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


    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.

  4. Push-pull macrocycles: donor-acceptor compounds with paired linearly conjugated or cross-conjugated pathways. (United States)

    Leu, Wade C W; Fritz, Amanda E; Digianantonio, Katherine M; Hartley, C Scott


    Two-dimensional π-systems are of current interest in the design of functional organic molecules, exhibiting unique behavior for applications in organic electronics, single-molecule devices, and sensing. Here we describe the synthesis and characterization of "push-pull macrocycles": electron-rich and electron-poor moieties linked by a pair of (matched) conjugated bridges. We have developed a two-component macrocyclization strategy that allows these structures to be synthesized with efficiencies comparable to acyclic donor-bridge-acceptor systems. Compounds with both cross-conjugated (m-phenylene) and linearly conjugated (2,5-thiophene) bridges have been prepared. As expected, the compounds undergo excitation to locally excited states followed by fluorescence from charge-transfer states. The m-phenylene-based systems exhibit slower charge-recombination rates presumably due to reduced electronic coupling through the cross-conjugated bridges. Interestingly, pairing the linearly conjugated 2,5-thiophene bridges also slows charge recombination. DFT calculations of frontier molecular orbitals show that the direct HOMO-LUMO transition is polarized orthogonal to the axis of charge transfer for these symmetrical macrocyclic architectures, reducing the electronic coupling. We believe the push-pull macrocycle design may be useful in engineering functional frontier molecular orbital symmetries.

  5. 白喉类毒素酶联免疫检测法的建立及初步应用%Establishment and preliminary application of a quantitative ELISA in detection of diphtheria toxoid

    Institute of Scientific and Technical Information of China (English)

    张霖阳; 杨冰; 王珣; 张娜; 赵俊; 王玲


    目的:建立测定吸附无细胞百白破联合疫苗中白喉类毒素酶联免疫检测( ELISA)方法,并进行验证及初步应用。方法以高效价兔抗DT多克隆抗体和相应酶标抗体建立双抗体夹心ELISA法,确定线性范围同时验证该方法的重复性和特异性等确定检测限度,并初步应用。结果 DT含量在0~0.0160 Lf/mL范围内反应曲线线性关系良好(r >0.99)。该方法与破伤风类毒素(Tetanus toxoid,TT)、百日咳毒素(Pertussis toxin,PT)、百日咳丝状血凝素( Filamantous hemagglutinin,FHA)与黏着素( Pertactin,Prn)无明显交叉反应,重复性好、特异性较强,精密度及准确度验证均符合常规质控要求,通过验证确定的准确检测范围为0.0008~0.0160 Lf/mL;检测限度为0.0008 Lf/mL。该方法对DT抗原进行了吸附率的检测,同时检测了10批白喉类毒素原液与《中华人民共和国药典》三部2010年版规定的絮状单位检测方法进行对比,变异系数低于20%。结论建立了白喉类毒素双抗体夹心 ELISA检测方法,为吸附无细胞百白破联合疫苗生产过程中白喉类毒素含量的质量控制提供了有效技术手段。%Objective To develop and preliminary application a double antibody sandwich ELISA in quantitative determi-nation of diphtheria toxoid ( DT ) in DTaP ( Diphtheria, tetanus and acellular pertussis combined vaccine, adsorbed ) . Methods The DT polyclonal antibodies with a high potency were obtained by using DT immunized rabbit antisera, and the detective enzyme labeled antibody as signal in order to develop a double antibody sandwich ELISA in quantitative determi-nation of DT in DTap. The linear range was determined, the repeatability and specificity for the ELISA were verified, and detection limit was determined as well. The preliminary application of the ELISA was performed. Results The best lineari-ty of dose-response curve was found in a range of 0-0. 0160 Lf/mL(r >0. 99). The tested result was

  6. Self-Assembled Conjugated Polymer Nanometer Scale Devices

    Institute of Scientific and Technical Information of China (English)

    Wenping Hu; Hiroshi Nakashima; Keiichi Torimitsu; Yunqi Liu; Daoben Zhu


    @@ 1Introduction Nanometer scale devices, as the next generation devices of electronics, have got a worldwide attention and rapid development recently. Simultaneously, conjugated polymers have been applied in organic electronics successfully because of their outstanding electronic-photonic properties. However, as far as we know few reports have dealt with the fabrication of nanometer scale devices by using conjugated polymers, although the combination of nanometer scale devices and polymers will not only extend conjugated polymers to Nanoelectronics, but also excavate the behaviors of polymer molecules at nano-molecular level, such as the electron transport through polymer molecules. One reason for this case is due to the lack of rigidity for most polymers.It results in the failure to bridge them between electrodes or to stand on substrates, therefore, fails to be characterized by scanning probe microscopy. Another reason is that the non-functionalized end-group of most polymers is impossible to graft on substrates through chemical bonds. Here, we introduce a self-assembled conjugated polymer can be used to fabricate nanodevices by self-assembly. The conjugated polymer is a derivative of poly(p-phenyleneethynylene)s (PPE) with thioacetyl end groups (Fig. 1). In general, it is known that for self-assembling ideal nanojunctions the materials should possess: a) conductivity, b) rigidity (for wiring and bridging between electrodes), and c) connectivity (for covalent attachment to metallic or semiconductor solid surfaces). PPE provides good conductivity owing to its special π-conjugated configuration. It is also believed that in principle PPE molecules possess rigidity because of the presence of the triple bond in their molecules,which prevents the rotation of adjacent phenyl rings with respect to each other.

  7. High-conjugation-efficiency aqueous CdSe quantum dots. (United States)

    Au, Giang H T; Shih, Wan Y; Shih, Wei-Heng


    Quantum dots (QDs) are photoluminescent nanoparticles that can be directly or indirectly coupled with a receptor such as an antibody to specifically image a target biomolecule such as an antigen. Recent studies have shown that QDs can be directly made at room temperature and in an aqueous environment (AQDs) with 3-mercaptopropionic acid (MPA) as the capping ligand without solvent and ligand exchange typically required by QDs made by the organic solvent routes (OQDs). In this study, we have synthesized CdSe AQDs and compared their conjugation efficiency and imaging efficacy with commercial carboxylated OQDs in HT29 colon cancer cells using a primary antibody-biotinylated secondary antibody-streptavidin (SA) sandwich. We showed that the best imaging condition for AQDs occurred when one AQD was bound with 3 ± 0.3 SA with a nominal SA/AQD ratio of 4 corresponding to an SA conjugation efficiency of 75 ± 7.5%. In comparison, for commercial CdSe-ZnS OQDs to achieve 2.7 ± 0.4 bound SAs per OQD for comparable imaging efficacy a nominal SA/OQD ratio of 80 was needed corresponding to an SA conjugation efficiency of 3.4 ± 0.5% for CdSe-ZnS OQDs. The more than 10 times better SA conjugation efficiency of the CdSe AQDs as compared to that of the CdSe-ZnS OQDs was attributed to more capping molecules on the AQD surface as a result of the direct aqueous synthesis. More capping molecules on the AQD surface also allowed the SA-AQD conjugate to be stable in cell culture medium for more than three days without losing their staining capability in a flowing cell culture medium. In contrast, SA-OQD conjugates aggregated in cell culture medium and in phosphate buffer saline solution over time.

  8. Realization of a Dual Transmission Band Conjugate Omega Shaped Metamaterial

    Directory of Open Access Journals (Sweden)

    Asit Kumar Panda


    Full Text Available In this article we propose a new conjugate omega shaped structure for realization of left hand material. This new metamaterial (MTM is designed and simulated using CST MWS. The effective permittivity permeability are extracted from the transmission reflection data obtained by normal incident on the purposed structure. It is shown the purposed MTM exhibits DNG material property and negative refractive index in dual transmission band with wider band in frequency ranges from 3.35-6.37GHz and 12.53-16.7GHZ. The conjugate omegas structures are pseudo-chiral in nature, where both electric magnetic polarization are due to induced electric and magnetic fields.

  9. Synthesis and Characterization of π-Conjugated Dithiol

    Institute of Scientific and Technical Information of China (English)

    Hardy; S.O.Chan


    1 Results Organic compounds are able to act as active components for the preparation of electronics and optoelectronics.Fig.1 A new π-conjugated anthracene-based dithiol compoundA new π-conjugated anthracene-based dithiol compound has been synthesized and its optical properties were determined by UV-vis and PL spectroscopy.Its self-assembled monolayers on a gold surface have been prepared and characterized by spectroscopic ellipsometry and atomic force microscopy.The structures and properties of its SAM...

  10. Synthesis and photocurrent response of porphyrin-containing conjugated polymers

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jinling; LI Binsong; BO Zhishan


    Porphyrin-containing conjugated polymers with fluorene or carbazole as spacer groups were prepared by Sonogashira cross-coupling reactions. The polymers were of high molecular weight and the flexible alkyl chains on fluorene or carbazole units made the conjugated polymers soluble in common organic solvents, such as THF and methylene chloride. The polymers could form high quality durable films from solution casting. Their optical and photocurrent responsive properties were investigated. It was found that the photocurrent response was directly proportional to the content of porphyrin. The incorporation of carbazole units into the polymer chains also gave positive contribution to the photocurrent generation in some extent.

  11. Imaging GABAc Receptors with Ligand-Conjugated Quantum Dots

    Directory of Open Access Journals (Sweden)

    Ian D. Tomlinson


    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.

  12. Side Chain Engineering in Solution-Processable Conjugated Polymers

    KAUST Repository

    Mei, Jianguo


    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.

  13. Emerging applications of conjugated polymers in molecular imaging. (United States)

    Li, Junwei; Liu, Jie; Wei, Chen-Wei; Liu, Bin; O'Donnell, Matthew; Gao, Xiaohu


    In recent years, conjugated polymers have attracted considerable attention from the imaging community as a new class of contrast agent due to their intriguing structural, chemical, and optical properties. Their size and emission wavelength tunability, brightness, photostability, and low toxicity have been demonstrated in a wide range of in vitro sensing and cellular imaging applications, and have just begun to show impact in in vivo settings. In this Perspective, we summarize recent advances in engineering conjugated polymers as imaging contrast agents, their emerging applications in molecular imaging (referred to as in vivo uses in this paper), as well as our perspectives on future research.

  14. Poly(trimethylsilylcyclooctatetraene): A soluble conjugated polyacetylene via olefin metathesis

    Energy Technology Data Exchange (ETDEWEB)

    Ginsburg, E.J.; Gorman, C.B.; Grubbs, R.H.; Marder, S.R. (California Institute of Technology, Pasadena (USA))


    highly conjugated polymers, such as polyacetylene, polythiophene, and poly(p-phenylene vinylene), have been the subject of intensive research due to their intriguing optical and electronic properties. These parent systems are highly desirable for experimental and theoretical studies due to their simplicity. Their intractability, however, has made characterization an arduous task, and insolubility has severely limited their applications. Researchers have successfully circumvented these obstacles by synthesizing soluble alkyl- and alkoxy-substituted polythiphenes and poly(p-phenylene vinylenes). Analogous soluble highly conjugated polyacetylene derivatives have proven more elusive. The authors report here the synthesis of such a polymer using ring-opening metathesis polymerization (ROMP).

  15. Convexity of Spheres in a Manifold without Conjugate Points

    Indian Academy of Sciences (India)

    Akhil Ranjan; Hemangi Shah


    For a non-compact, complete and simply connected manifold without conjugate points, we prove that if the determinant of the second fundamental form of the geodesic spheres in is a radial function, then the geodesic spheres are convex. We also show that if is two or three dimensional and without conjugate points, then, at every point there exists a ray with no focal points on it relative to the initial point of the ray. The proofs use a result from the theory of vector bundles combined with the index lemma.

  16. Integrable Lattice Models for Conjugate $A^{(1)}_n$

    CERN Document Server

    Behrend, R E; Behrend, Roger E.; Evans, David E.


    A new class of $A^{(1)}_n$ integrable lattice models is presented. These are interaction-round-a-face models based on fundamental nimrep graphs associated with the $A^{(1)}_n$ conjugate modular invariants, there being a model for each value of the rank and level. The Boltzmann weights are parameterized by elliptic theta functions and satisfy the Yang-Baxter equation for any fixed value of the elliptic nome q. At q=0, the models provide representations of the Hecke algebra and are expected to lead in the continuum limit to coset conformal field theories with torus partition functions described by the $A^{(1)}_n$ conjugate modular invariants.


    DEFF Research Database (Denmark)


    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....... Subsequently, the immunomodulating substance is also bound in a chemoselective manner, to give a dendrimer conjugate with a well-defined structure and connectivity and containing a precise, pre-determined ratio of carbohydrate to immunomodulating substance. The invention also relates to novel dendrimer...

  18. Product Summability Transform of Conjugate Series of Fourier Series

    Directory of Open Access Journals (Sweden)

    Vishnu Narayan Mishra


    Full Text Available A known theorem, Nigam (2010 dealing with the degree of approximation of conjugate of a signal belonging to Lipξ(t-class by (E,1(C,1 product summability means of conjugate series of Fourier series has been generalized for the weighted W(Lr,ξ(t, (r≥1,(t>0-class, where ξ(t is nonnegative and increasing function of t, by En1Cn1~ which is in more general form of Theorem 2 of Nigam and Sharma (2011.

  19. Peptide π-Electron Conjugates: Organic Electronics for Biology? (United States)

    Ardoña, Herdeline Ann M; Tovar, John D


    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.

  20. A heterostructure composed of conjugated polymer and copper sulfide nanoparticles. (United States)

    Narizzano, Riccardo; Erokhin, Victor; Nicolini, Claudio


    A heterostructure formed by a conjugated polymer and semiconducting nanoparticles was produced. The conjugated polymer was synthesized by oxidative copolymerization of 3-thiopheneacetic acid and 3-hexylthiophene, thus obtaining an amphiphilic polythiophene that allows the formation of a stable polymer layer at the air-water interface. Different numbers of monolayers were deposited on solid substrates. CuS nanoparticles were grown directly in the polymeric matrix using the carboxylic groups as nucleation centers. The reactions were monitored by quartz crystal microbalance, Brewster angle, and fluorescence microscopy. The heterostructure showed increased conductivity as compared to the pristine polymer.

  1. Morroniside cinnamic acid conjugate as an anti-inflammatory agent. (United States)

    Takeda, Yoshinori; Tanigawa, Naomi; Sunghwa, Fortunatus; Ninomiya, Masayuki; Hagiwara, Makoto; Matsushita, Kenji; Koketsu, Mamoru


    A morroniside cinnamic acid conjugate was prepared and evaluated on E-selectin mediated cell-cell adhesion as an important role in inflammatory processes. 7-O-Cinnamoylmorroniside exhibited excellent anti-inflammatory activity (IC(50)=49.3 microM) by inhibiting the expression of E-selectin; further, it was more active than another cinnamic-acid-conjugated iridoid glycoside (harpagoside; IC(50)=88.2 microM), 7-O-methylmorroniside, and morroniside itself. As a result, 7-O-cinnamoylmorroniside was observed to be a potent inhibitor of TNF-alpha-induced E-selectin expression.

  2. Clifford Algebras and Their Decomposition into Conjugate Fermionic Heisenberg Algebras (United States)

    Catto, Sultan; Gürcan, Yasemin; Khalfan, Amish; Kurt, Levent; Kato La, V.


    We discuss a construction scheme for Clifford numbers of arbitrary dimension. The scheme is based upon performing direct products of the Pauli spin and identity matrices. Conjugate fermionic algebras can then be formed by considering linear combinations of the Clifford numbers and the Hermitian conjugates of such combinations. Fermionic algebras are important in investigating systems that follow Fermi-Dirac statistics. We will further comment on the applications of Clifford algebras to Fueter analyticity, twistors, color algebras, M-theory and Leech lattice as well as unification of ancient and modern geometries through them.

  3. Medicinal chemistry of drugs with active metabolites following conjugation. (United States)

    Kalász, Huba; Petroianu, Georg; Hosztafi, Sándor; Darvas, Ferenc; Csermely, Tamás; Adeghate, Ernest; Siddiq, Afshan; Tekes, Kornélia


    Authorities of Drug Administration in the United States of America approved about 5000 drugs for use in the therapy or management of several diseases. About two hundred of these drugs have active metabolites and the knowledge of their medicinal chemistry is important both in medical practice and pharmaceutical research. This review gives a detailed description of the medicinal chemistry of drugs with active metabolites generated after conjugation. This review focused on glucuronide-, acetyl-, sulphate- and phosphate-conjugation of drugs, converting the drug into an active metabolite. This conversion essentially changed the lipophilicity of the drug.

  4. Electronic states of emodin and its conjugate base

    DEFF Research Database (Denmark)

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


    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...

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

    CERN Document Server

    Zhang, Li-Zhi


    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. Light-emitting conjugated polymers with microporous network architecture: interweaving scaffold promotes electronic conjugation, facilitates exciton migration, and improves luminescence. (United States)

    Xu, Yanhong; Chen, Long; Guo, Zhaoqi; Nagai, Atsushi; Jiang, Donglin


    Herein we report a strategy for the design of highly luminescent conjugated polymers by restricting rotation of the polymer building blocks through a microporous network architecture. We demonstrate this concept using tetraphenylethene (TPE) as a building block to construct a light-emitting conjugated microporous polymer. The interlocked network successfully restricted the rotation of the phenyl units, which are the major cause of fluorescence deactivation in TPE, thus providing intrinsic luminescence activity for the polymers. We show positive "CMP effects" that the network promotes π-conjugation, facilitates exciton migration, and improves luminescence activity. Although the monomer and linear polymer analogue in solvents are nonemissive, the network polymers are highly luminescent in various solvents and the solid state. Because emission losses due to rotation are ubiquitous among small chromophores, this strategy can be generalized for the de novo design of light-emitting materials by integrating the chromophores into an interlocked network architecture.

  7. Conjugative Transfer and cis-Mobilization of a Genomic Island by an Integrative and Conjugative Element of Streptococcus agalactiae


    Puymège, Aurore; Bertin, Stéphane; Chuzeville, Sarah; Guédon, Gérard; Payot, Sophie


    Putative integrative and conjugative elements (ICEs), i.e., genomic islands which could excise, self-transfer by conjugation, and integrate into the chromosome of the bacterial host strain, were previously identified by in silico analysis in the sequenced genomes of Streptococcus agalactiae (M. Brochet et al., J. Bacteriol. 190:6913–6917, 2008). We investigated here the mobility of the elements integrated into the 3′ end of a tRNALys gene. Three of the four putative ICEs tested were found to ...

  8. Bioactivation of cysteine conjugates of 1-nitropyrene oxides by cysteine conjugate beta-lyase purified from Peptostreptococcus magnus.


    Kataoka, K; Kinouchi, T; Akimoto, S; Ohnishi, Y


    To determine the role of cysteine conjugate beta-lyase (beta-lyase) in the metabolism of mutagenic nitropolycyclic aromatic hydrocarbons, we determined the effect of beta-lyase on the mutagenicities and DNA binding of cysteine conjugates of 4,5-epoxy-4,5-dihydro-1-nitropyrene (1-NP 4,5-oxide) and 9,10-epoxy-9,10-dihydro-1-nitropyrene (1-NP 9,10-oxide), which are detoxified metabolites of the mutagenic compound 1-nitropyrene. We purified beta-lyase from Peptostreptococcus magnus GAI0663, since...

  9. Synthesis of Bis (silyloxy) Cross-Conjugated Polyenes and Their Sequential Ring Formations via Electrocyclization


    Wada, Eiji; Kanemasa, Shuji; Kimura, Nobuo; KIMURA, Hirohiko; Tsuge, Otohiko


    Presented are the synthesis of several bis(silyloxy) cross-conjugated polyenes and some synthetic utilization of these new types of conjugation systems via thermal or photochemical electrocyclization.

  10. Biodistribution of ~(99)Tc~m Labelled Dextran Conjugates for Sentinel Lymph Node Detection

    Institute of Scientific and Technical Information of China (English)


    Mannosylated dextran conjugates showed high receptor affinity to the receptors on the surface of macrophages in the lymph node. 99Tcm labelled mannosylated dextran conjugates could be used for sentinel lymph node (SLN) detection. In this paper,

  11. 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.


    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 fu

  12. Synthesis and Antiproliferative Activity of Silybin Conjugates with Salinomycin and Monensin. (United States)

    Antoszczak, Michał; Klejborowska, Greta; Kruszyk, Monika; Maj, Ewa; Wietrzyk, Joanna; Huczyński, Adam


    Aiming at development of multitarget drugs for the anticancer treatment, new silybin (SIL) conjugates with salinomycin (SAL) and monensin (MON) were synthesized, in mild esterification conditions, and their antiproliferative activity was studied. The conjugates obtained exhibit anticancer activity against HepG2, LoVo and LoVo/DX cancer cell lines. Moreover, MON-SIL conjugate exhibits higher anticancer potential and better selectivity than the corresponding SAL-SIL conjugate.

  13. Sub-nanometer control of the interlayer spacing in thin films of intercalated rodlike conjugated molecules. (United States)

    Vogel, Jörn-Oliver; Salzmann, Ingo; Opitz, Ricarda; Duhm, Steffen; Nickel, Bert; Rabe, Jürgen P; Koch, Norbert


    Organic molecular beam co-deposition of rodlike conjugated molecules with an alkylated analogue resulted in thin film structures with layers of alternating semiconducting (conjugated molecular parts) and insulating (alkyl parts) character. By varying the alkylated molecule ratio, we could adjust the distance between conjugated layers with sub-nanometer precision, exploiting the mechanical flexibility of the alkyl chains. Furthermore, due to mutual molecular intercalation, mixed layers containing two conjugated moieties with vastly different electronic properties could be fabricated.

  14. Accurate Force Field Development for Modeling Conjugated Polymers. (United States)

    DuBay, Kateri H; Hall, Michelle Lynn; Hughes, Thomas F; Wu, Chuanjie; Reichman, David R; Friesner, Richard A


    The modeling of the conformational properties of conjugated polymers entails a unique challenge for classical force fields. Conjugation imposes strong constraints upon bond rotation. Planar configurations are favored, but the concomitantly shortened bond lengths result in moieties being brought into closer proximity than usual. The ensuing steric repulsions are particularly severe in the presence of side chains, straining angles, and stretching bonds to a degree infrequently found in nonconjugated systems. We herein demonstrate the resulting inaccuracies by comparing the LMP2-calculated inter-ring torsion potentials for a series of substituted stilbenes and bithiophenes to those calculated using standard classical force fields. We then implement adjustments to the OPLS-2005 force field in order to improve its ability to model such systems. Finally, we show the impact of these changes on the dihedral angle distributions, persistence lengths, and conjugation length distributions observed during molecular dynamics simulations of poly[2-methoxy-5-(2'-ethylhexyloxy)-p-phenylene vinylene] (MEH-PPV) and poly 3-hexylthiophene (P3HT), two of the most widely used conjugated polymers.

  15. RPM peptide conjugated bioreducible polyethylenimine targeting invasive colon cancer. (United States)

    Lee, Yeong Mi; Lee, Duhwan; Kim, Jihoon; Park, Hansoo; Kim, Won Jong


    CPIEDRPMC (RPM) peptide is a peptide that specifically targets invasive colorectal cancer, which is one of the leading causes of cancer-related deaths worldwide. In this study, we exploited RPM peptide as a targeting ligand to produce a novel and efficient gene delivery system that could potentially be used to treat invasive colon cancer. In order to achieve enhanced specificity to colon cancer cells, the RPM peptide was conjugated to a bioreducible gene carrier consisting of a reducible moiety of disulfide-crosslinked low molecular weight polyethylenimine, IR820 dye, and polyethylene glycol. Here, we examined the physiochemical properties, cytotoxicity, in vitro transfection efficiency, and in vivo biodistribution of the RPM-conjugated polyplex. Our results showed that the RPM-conjugated gene carrier formed a compact polyplex with pDNA that had low toxicity. Furthermore, the RPM-conjugated polymer not only had higher cellular uptake in invasive colon cancer than the non-targeted polymer, but also showed enhanced transfection efficiency in invasive colon cancer cells in vitro and in vivo.


    Institute of Scientific and Technical Information of China (English)



    Some properties of the preconditioned gradient conjugate method are given.It may happen that loss of significant digits, when the norm of residual is very small. To avoid this, a variant algorithm which does not use the residual is put forward.


    Institute of Scientific and Technical Information of China (English)

    LiuYun; WeiZengxin


    This paper discusses the global convergence of a class of nonmonotone conjugate gradient methods (NM methods) for nonconvex object functions. This class of methods includes the nonmonotone counterpart of modified Polak-Ribiere method and modified Hestenes-Stiefel method as special cases.

  18. Nanobody-photosensitizer conjugates for targeted photodynamic therapy

    NARCIS (Netherlands)

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


    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 t

  19. Synthesis of regioregular pentacene-containing conjugated polymers

    KAUST Repository

    Okamoto, Toshihiro


    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.

  20. A Facile Synthesis of Indole-based Conjugated Derivatives

    Institute of Scientific and Technical Information of China (English)

    LI, Qian-Qian; ZHU, Zhi-Chao; LI,Zhen; QIN, Jin-Gui


    A novel synthetic method was developed for the preparation of indole-based conjugated derivatives with satisfied yields. By applying this strategy, a series of new compounds were prepared conveniently. All the obtained new indole derivatives were characterized by spectroscopic analyse s, giving satisfactory data corresponding to their expected molecular structures.

  1. Synthesis and biological activity of salinomycin conjugates with floxuridine. (United States)

    Huczyński, Adam; Antoszczak, Michał; Kleczewska, Natalia; Lewandowska, Marta; Maj, Ewa; Stefańska, Joanna; Wietrzyk, Joanna; Janczak, Jan; Celewicz, Lech


    As part of our program to develop anticancer agents, we have synthesized new compounds, which are conjugates between well-known anticancer drug, floxuridine and salinomycin which is able to selectivity kill cancer stem cells. The conjugates were obtained in two ways i.e. by copper(I) catalysed click Huisgen cycloaddition reaction performed between 3'-azido-2',3'-dideoxy-5-fluorouridine and salinomycin propargyl amide, and by the ester synthesis starting from salinomycin and floxuridine under mild condition. The compounds obtained were characterized by spectroscopic methods and evaluated for their in vitro cytotoxicity against seven human cancer cell lines as well as antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE). The conjugate obtained by esterification reaction showed a significantly higher antiproliferative activity against the drug-resistant cancer cells and lower toxicity than those of salinomycin and floxuridine towards normal cells, as well as standard anticancer drugs, such as cisplatin and doxorubicin. The conjugate compound revealed also moderate activity against MRSA and MRSE bacterial strains. Very high activity of floxuridine and 5-fluorouracil against MRSA and MRSE has been also observed.

  2. [Conjugal leprosy infection in Japan--case report and review]. (United States)

    Ozaki, Motoaki; Tomoda, Masakazu


    The authors reported a conjugal leprosy infection observed in Japan. The husband, index case, first noticed sensory disturbance at the lower right leg in his forties. He developed edematous swelling with redness of the right hand and forearm at the age of 72 (1989), and then developed multiple erythema and hypesthesia at the extremities. He was diagnosed as BL type leprosy (reactional stage) and treated with multi-drug therapy. His 71-year-old wife developed a few erythema at the right forearm in 1993. She was classified as BT type. The duration of their marriage life was over forty years. The couple did not have consanguinity. No other leprosy patients were found in their lineage. From their clinical courses the authors concluded that the husband infected his wife. According to Japanese literatures, the frequency of conjugal leprosy among new patients in Japan was approximately 1%. There were worldwide observations that the husband often infected the wife, and mostly the index case was multibacillary and the secondary case paucibacillary. The authors reviewed definition and frequency of conjugal leprosy, factors in conjugal infection and leprosy infection among the adults.

  3. Patterning of conjugated polymers for organic optoelectronic devices. (United States)

    Xu, Youyong; Zhang, Fan; Feng, Xinliang


    Conjugated polymers have been attracting more and more attention because they possess various novel electrical, magnetical, and optical properties, which render them useful in modern organic optoelectronic devices. Due to their organic nature, conjugated polymers are light-weight and can be fabricated into flexible appliances. Significant research efforts have been devoted to developing new organic materials to make them competitive with their conventional inorganic counterparts. It is foreseeable that when large-scale industrial manufacture of the devices made from organic conjugated polymers is feasible, they would be much cheaper and have more functions. On one hand, in order to improve the performance of organic optoelectronic devices, it is essential to tune their surface morphologies by techniques such as patterning. On the other hand, patterning is the routine requirement for device processing. In this review, the recent progress in the patterning of conjugated polymers for high-performance optoelectronic devices is summarized. Patterning based on the bottom-up and top-down methods are introduced. Emerging new patterning strategies and future trends for conventional patterning techniques are discussed.

  4. Diazobenzene-containing conjugated polymers as dark quenchers. (United States)

    Wu, Jiatao; Tan, Ying; Xie, Yonghua; Wu, Yi; Zhao, Rui; Jiang, Yuyang; Tan, Chunyan


    The synthesis and photophysical characterization of new conjugated polymers (CPs) with alternating phenylethynylene and diazobenzene (azo-PPE) units were reported, which showed broadened absorption and no measurable fluorescence. Quenching studies showed that azo-PPEs displayed high efficiency over a wide wavelength range.

  5. Tumor targeting of HPMA copolymer conjugates containing sulfadiazine groups

    Institute of Scientific and Technical Information of China (English)

    Jian Chao Yuan; Xiao Li Xie; Xian Wu Zeng; Hong Yun Guo; Cheng Ping Miao


    To develop new tumor targeting macromolecular conjugates,poly(HPMA)-SD-APMA-DTPA (HPMA:N-(2-hydroxypropyl)-methacrylamide; APMA:N-(3-aminopropyl)methacrylamide; DTPA:diethylenetriarninepentaacetic acid; SD:sulfadiazine) was synthesized and characterized.The poly(HPMA)-SD-DTPA conjugates were radiolabeled with the radionuclide 99mTc and tested for uptake by cultured H22 cells in vitro.DTPA-99mTc (radiotracer 1) and poly(HPMA)-DTPA-99mTc (radiotracer 2) were also synthesized and characterized for comparison.The uptake of poly(HPMA)-SD-DTPA-99mTc (radiotracer 3,34.76%) was significantly higher than that of poly(HPMA)-DTPA-99mTc (16.40%),indicating that uptake of the poly(HPMA)-SD-DTPA-99mT was active binding.The uptake of poly(HPMA)-DTPA-99mTc was significantly higher than that of DTPA-99mTc (2.98%),suggesting that uptake of the poly(HPMA)-DTPA-99mT was passive binding.The data suggest thin the poly(HPMA)-SD-APMA-DTPA conjugates might be useful as tumor targeting macromolecular conjugates.

  6. Opto-Electronic Properties of Conjugated Molecular Wires

    NARCIS (Netherlands)

    Grozema, F.C.


    Conjugated polymers are of considerable current interest because of their semi-conducting and light-emitting properties. These properties, combined with their relatively low cost and good processability as compared to inorganic semiconductors, make them attractive candidates for application in plast

  7. Maternal Conjugal Multiplicity and Child Development in Rural Jamaica (United States)

    Dreher, Melanie; Hudgins, Rebekah


    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,…

  8. 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)


    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.)

  9. Conjugal gene transfer between bacteria in soil and rhizosphere.

    NARCIS (Netherlands)

    Smit, E.


    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 GEMs for

  10. Diversity of (dihydro) hydroxycinnamic acid conjugates in Colombian potato tubers

    NARCIS (Netherlands)

    Narvaez Cuenca, C.E.; Vincken, J.P.; Zheng, Chaoya; Gruppen, H.


    In potato tuber, caffeic acid (the predominant hydroxycinnamic acid (HCA)), its conjugates (HCAcs; i.e. chlorogenic acid (ChA), crypto-ChA, and neo-ChA), and anthocyanin-linked HCAs have been extensively described in the literature. In contrast, only little information is available on the occurrence

  11. 1,2-Selective Hydrosilylation of Conjugated Dienes


    Parker, Sarah Elizabeth


    Selective 1,2-hydrosilylation of 1,3-dienes is a challenging problem to solve for transition metal catalysis. Butadiene, specifically, would be a useful substrate because 3-butenylsilane products have promise as superior coupling reagents for hybrid organic/inorganic materials synthesis. In this thesis, we describe the first selective 1,2-hydrosilylation of conjugated dienes, including butadiene.

  12. Adaptive Regularization of Neural Networks Using Conjugate Gradient

    DEFF Research Database (Denmark)

    Goutte, Cyril; Larsen, Jan


    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...

  13. Programmable multimetallic linear nanoassemblies of ruthenium-DNA conjugates


    Irvoas, Joris; Noirot, Arielle; Chouini-Lalanne, Nadia; Reynes, Olivier; Garrigues, Jean-Christophe; Sartor, Valérie


    International audience; A new ruthenium-DNA conjugates family was synthesized, made up of a ruthenium complex bound to one or two identical DNA strands of 14-58 nucleotides. The formation of controlled linear nanoassemblies containing one to seven ruthenium complexes is described.

  14. Bacteriophages Limit the Existence Conditions for Conjugative Plasmids (United States)

    Wood, A. Jamie; Dytham, Calvin; Pitchford, Jonathan W.; Truman, Julie; Spiers, Andrew; Paterson, Steve; Brockhurst, Michael A.


    ABSTRACT Bacteriophages are a major cause of bacterial mortality and impose strong selection on natural bacterial populations, yet their effects on the dynamics of conjugative plasmids have rarely been tested. We combined experimental evolution, mathematical modeling, and individual-based simulations to explain how the ecological and population genetics effects of bacteriophages upon bacteria interact to determine the dynamics of conjugative plasmids and their persistence. The ecological effects of bacteriophages on bacteria are predicted to limit the existence conditions for conjugative plasmids, preventing persistence under weak selection for plasmid accessory traits. Experiments showed that phages drove faster extinction of plasmids in environments where the plasmid conferred no benefit, but they also revealed more complex effects of phages on plasmid dynamics under these conditions, specifically, the temporary maintenance of plasmids at fixation followed by rapid loss. We hypothesized that the population genetic effects of bacteriophages, specifically, selection for phage resistance mutations, may have caused this. Further mathematical modeling and individual-based simulations supported our hypothesis, showing that conjugative plasmids may hitchhike with phage resistance mutations in the bacterial chromosome. PMID:26037122

  15. Abnormal glutathione conjugation in patients with tyrosinaemia type I

    NARCIS (Netherlands)

    Bergman, DJW; PollThe, BT; Smit, GPA; Breimer, DD; Duran, M; Smeitink, JAM


    Previous studies have suggested that tyrosinaemia type I may be associated with reduced glutathione availability due to conjugation of tyrosinaemia-associated reactive intermediates with glutathione. In the present study, the glutathione/glutathione S-transferase system of two tyrosinaemia patients

  16. Novel Bipolar Conjugated Polymer Containing Both Triphenylamine and Oxadizole Units

    Institute of Scientific and Technical Information of China (English)


    A novel bipolar conjugated polymer containing triphenylamine and 1, 3, 4-oxadiazole units was synthesized by Suzuki reaction. Its structure and properties were characterized by NMR, IR, UV-Vis, PL spectroscopy and electrochemical measurement. The photoluminescent spectroscopy and cyclic voltammograms measurement demonstrated that the resulting polymer shows blue emission (477 nm) and possesses both electron and hole-transporting property.

  17. Fullerene–biomolecule conjugates and their biomedicinal applications

    Directory of Open Access Journals (Sweden)

    Yang X


    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

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

    DEFF Research Database (Denmark)

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


    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...... demonstrate how microscopic ordering in the polymer domains controls the conductivity....

  19. Photorefractive dynamic holography using self-pumped phase conjugate beam

    Indian Academy of Sciences (India)

    Arun Anand; C S Narayanamurthy


    Dynamic holography in photorefractive materials using self-pumped phase conjugate beam of the object beam itself as the other writing beam is proposed. Our detailed theoretical analysis shows four-fold increase in the diffraction efficiency of dynamic holograms if recorded using this geometry even in photorefractive crystal like BTO (having low optical activity) without applying external field. Detailed theoretical analysis is given.

  20. Synthesis and optical properties of terminally substituted conjugated polyenes


    Effenberger, Franz; Schlosser, Hubert; Bäuerle, Peter; Maier, Stefan; Port, Helmut; Wolf, Hans Christoph


    Long-chain, conjugated polyenes can function as molecular wires. This is shown by the photophysical properties of polyenes containing naphthyl, anthryl, and tetraphenylporphyrinyl (TPP) terminal groups. When the anthryl group in 1, which is obtainable by a sequence of Wittig reactions, is selectively excited, strong TPP emission is observed.

  1. Facile Synthesis of Chiral Conjugated Polymer Based on BINOL Skeleton

    Institute of Scientific and Technical Information of China (English)


    A new type of chiral conjugated polymers 6a-d has been synthesized by the reaction of (R)-2,2'-dihydroxy-1,1'-binaphthyl-6,6'-dicarbaldehyde 5 with corresponding diamine in the presence of acetic acid.

  2. Enhanced Thermal Stability of Polylactide by Terminal Conjugation Groups (United States)

    Tran, Hang Thi; Matsusaki, Michiya; Akashi, Mitsuru; Vu, Ngo Dinh


    Various acids such as aliphatic or carbocyclic fatty or aromatic acids were successfully conjugated into the ending hydroxyl group of poly( l-lactide) (PLLA). The chemical structures of various acid-PLLAs were confirmed by Fourier transform infrared and proton nuclear magnetic resonance analysis. The crystallinity and solubility of the original PLLA were maintained after the terminal conjugation of various acids. The thermal properties were significantly improved, especially the 10% weight-loss temperature that showed an increase of over 80°C for conjugation of aliphatic or aromatic acids as compared to that of the corresponding original PLLA. In addition, more than 60 wt.% of the aliphatic acid-PLLAs was pyrolyzed, and aromatic acid-PLLAs degraded only about 10 wt.% for 150 min, although the original PLLA was pyrolyzed completely at 250°C for 7 min. The thermal stability of PLLA was controlled by the conjugation of aliphatic or aromatic acids into a chain end. These acid-PLLAs may be useful as materials with high thermal stability for various application fields.

  3. Development of molecular tools to monitor conjugative transfer in rhizobia. (United States)

    Tejerizo, Gonzalo Torres; Bañuelos, Luis Alfredo; Cervantes, Laura; Gaytán, Paul; Pistorio, Mariano; Romero, David; Brom, Susana


    Evolution of bacterial populations has been extensively driven by horizontal transfer events. Conjugative plasmid transfer is considered the principal contributor to gene exchange among bacteria. Several conjugative and mobilizable plasmids have been identified in rhizobia, and two major molecular mechanisms that regulate their transfer have been described, under laboratory conditions. The knowledge of rhizobial plasmid transfer regulation in natural environments is very poor. In this work we developed molecular tools to easily monitor the conjugative plasmid transfer in rhizobia by flow cytometry (FC) or microscopy. 24 cassettes were constructed by combining a variety of promotors, fluorescent proteins and antibiotic resistance genes, and used to tag plasmids and chromosome of donor strains. We were able to detect plasmid transfer after conversion of non-fluorescent recipients into fluorescent transconjugants. Flow cytometry (FC) was optimized to count donor, recipient and transconjugant strains to determine conjugative transfer frequencies. Results were similar, when determined either by FC or by viable counts. Our constructions also allowed the visualization of transconjugants in crosses performed on bean roots. The tools presented here may also be used for other purposes, such as analysis of transcriptional fusions or single-cell tagging. Application of the system will allow the survey of how different environmental conditions or other regulators modulate plasmid transfer in rhizobia.

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

    DEFF Research Database (Denmark)

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


    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...

  5. Homology among tet determinants in conjugative elements of streptococci

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  6. New phenstatin-fatty acid conjugates: synthesis and evaluation. (United States)

    Chen, Jinhui; Brown, David P; Wang, Yi-Jun; Chen, Zhe-Sheng


    New phenstatin-fatty acid conjugates have been synthesized and tested against the KB-3-1, H460, MCF-7 and HEK293 cell lines, with an increase in anti-proliferative activity being observed at the micro-molar level paralleling an increase in un-saturation in the fatty acid component.

  7. Hypothesis: conjugate vaccines may predispose children to autism spectrum disorders. (United States)

    Richmand, Brian J


    The first conjugate vaccine was approved for use in the US in 1988 to protect infants and young children against the capsular bacteria Haemophilus influenzae type b (Hib). Since its introduction in the US, this vaccine has been approved in most developed countries, including Denmark and Israel where the vaccine was added to their national vaccine programs in 1993 and 1994, respectively. There have been marked increases in the reported prevalence of autism spectrum disorders (ASDs) among children in the US beginning with birth cohorts in the late 1980s and in Denmark and Israel starting approximately 4-5 years later. Although these increases may partly reflect ascertainment biases, an exogenous trigger could explain a significant portion of the reported increases in ASDs. It is hypothesized here that the introduction of the Hib conjugate vaccine in the US in 1988 and its subsequent introduction in Denmark and Israel could explain a substantial portion of the initial increases in ASDs in those countries. The continuation of the trend toward increased rates of ASDs could be further explained by increased usage of the vaccine, a change in 1990 in the recommended age of vaccination in the US from 15 to 2 months, increased immunogenicity of the vaccine through changes in its carrier protein, and the subsequent introduction of the conjugate vaccine for Streptococcus pneumoniae. Although conjugate vaccines have been highly effective in protecting infants and young children from the significant morbidity and mortality caused by Hib and S. pneumoniae, the potential effects of conjugate vaccines on neural development merit close examination. Conjugate vaccines fundamentally change the manner in which the immune systems of infants and young children function by deviating their immune responses to the targeted carbohydrate antigens from a state of hypo-responsiveness to a robust B2 B cell mediated response. This period of hypo-responsiveness to carbohydrate antigens coincides

  8. NHS Mediated CdTe Quantum Dots/Albumin Conjugates and Labeling C. Elegans

    Institute of Scientific and Technical Information of China (English)


    Luminescent quantum dots(QDs) are a promising alternative to organic dyes for biomedical assays and imaging.A new conjugation method, NHS mediated conjugating, for QDs and BSA was introduced. The QDs-BSA conjugates were confirmed, and their stability has been proved. Caenorhabditis elegans (C. elegans) were used as animal models, and the imaging of QDs in the organism was studied.

  9. Preliminary Exploration on Properties of the Equidistant Conjugate Points of Higher Dimensional Simplex

    Institute of Scientific and Technical Information of China (English)

    ZENG Jian-guo


    In this paper,the concept of the equidistant conjugate points of a triangle to the n-dimensional Euclidean space is extended.The concept of equidistant conjugate point in high dimensional simplex is defined,and the property of the equidistant conjugate points of a triangle is generalized to high dimensional simplex.

  10. Development and application of nanoparticles synthesized with folic acid-conjugated soy protein (United States)

    In this study, soy protein isolate (SPI) was conjugated with folic acid (FA) to prepare nanoparticles for target-specific drug delivery. Successful conjugation was evidenced by UV spectrophotometry and primary amino group analysis. An increase in count rate by at least 142% was observed in FA-conjug...

  11. Coherent perfect absorption mediated enhancement and optical bistability in phase conjugation

    CERN Document Server

    Reddy, K Nireekshan; Gupta, S Dutta


    We study phase conjugation in a nonlinear composite slab when the counter propagating pump waves are completely absorbed by means of coherent perfect absorption. Under the undepleted pump approximation the coupling constant and the phase conjugated reflectivity are shown to undergo a substantial increase and multivalued response. The effect can be used for efficient switching of the phase conjugated reflectivity in photonic circuits.


    Institute of Scientific and Technical Information of China (English)



    This paper gives a necessary and sufficient condition for a matrix in SL(2, Z) to be conjugate to its inverse. This condition reduces the determination of the conjugation to solving some indeterminate equation of second degree. It yields an algorithm to determine this conjugation in finite steps based on the elementary number theory.

  13. Synthesis and Cytotoxicity of Derivatives of Fluorouracil Conjugated with Three-membered Ring

    Institute of Scientific and Technical Information of China (English)

    WANG, Le; ZHANG, Yunxiao; TAO, Jingchao


    A novel series of 3-membered ring fluorouracil conjugates including cyclopropylmethyl fluorouracil and (2,3- epoxypropyl) fluorouracil conjugates were synthesized via selective protection, and their structures were confirmed by IR, 1H NMR and HRMS. Cytotoxicities in vitro of these conjugates were evaluated. Compounds 7, 8, 12 and 13 have shown cytotoxicities against Ec9706 cells in different degrees.

  14. Catalytic production of conjugated fatty acids and oils. (United States)

    Philippaerts, An; Goossens, Steven; Jacobs, Pierre A; Sels, Bert F


    The reactive double bonds in conjugated vegetable oils are of high interest in industry. Traditionally, conjugated vegetable oils are added to paints, varnishes, and inks to improve their drying properties, while recently there is an increased interest in their use in the production of bioplastics. Besides the industrial applications, also food manufactures are interested in conjugated vegetable oils due to their various positive health effects. While the isomer type is less important for their industrial purposes, the beneficial health effects are mainly associated with the c9,t11, t10,c12 and t9,t11 CLA isomers. The production of CLA-enriched oils as additives in functional foods thus requires a high CLA isomer selectivity. Currently, CLAs are produced by conjugation of oils high in linoleic acid, for example soybean and safflower oil, using homogeneous bases. Although high CLA productivities and very high isomer selectivities are obtained, this process faces many ecological drawbacks. Moreover, CLA-enriched oils can not be produced directly with the homogeneous bases. Literature reports describe many catalytic processes to conjugate linoleic acid, linoleic acid methyl ester, and vegetable oils rich in linoleic acid: biocatalysts, for example enzymes and cells; metal catalysts, for example homogeneous metal complexes and heterogeneous catalysts; and photocatalysts. This Review discusses state-of-the-art catalytic processes in comparison with some new catalytic production routes. For each category of catalytic process, the CLA productivities and the CLA isomer selectivity are compared. Heterogeneous catalysis seems the most attractive approach for CLA production due to its easy recovery process, provided that the competing hydrogenation reaction is limited and the CLA production rate competes with the current homogeneous base catalysis. The most important criteria to obtain high CLA productivity and isomer selectivity are (1) absence of a hydrogen donor, (2

  15. Analysis of vaccination status and its influencing factors of tetanus toxoid vaccine of child-bearing age women in Hainan high-risk areas.%海南省育龄妇女破伤风疫苗接种影响因素调查

    Institute of Scientific and Technical Information of China (English)

    朱坚; 符振旺; 王春雷


    目的 了解影响海南省育龄妇女破伤风类毒素疫苗(TT)接种因素,为制定消除新生儿破伤风方案提供科学依据.方法 选取海南省新生儿破伤风发病较高的4个市县8个乡镇作抽取40个行政村作为问卷调查点.每个调查点随机抽取10名18 ~49岁育龄妇女进行问卷调查.结果 共完成399名育龄妇女问卷调查,大部分群众和育龄妇女对新生儿破伤发病原因和防治相关知识缺乏了解;孕产妇在家分娩率为62.4%,选择在家分娩的主要原因是住院分娩费用太高、交通不便、封建迷信与落后的风俗习惯影响;育龄妇女接种TT主动意识不高,TT接种率为57.79%.,未接种的原因主要有外出打工、怕影响生育、怕影响劳动和收费.群众易于接受宣传形式依次是电视、口头宣传、宣传画和广播.结论 海南省新生儿破伤风高危地区群众和育龄妇女对新生儿破伤发病原因和防治相关知识缺乏了解,育龄妇女TT接种率较低,应加强消毒接生与TT接种的宣传工作.%Objective To know the vaccination status and its influencing factors of tetanus toxoid vaccine of child-bearing age women in neonatal tetanus high-risk areas in Hainan to provide scientific basis for eliminating neonatal tetanus in Hainan province. Methods To choose four villages and towns of two city and county which incidence of neonatal tetanus was highest as investigation sites. Project interview and questionnaire survey in families were taken to investigate information. Results The interview of 218 persons of 24 groups and questionnaire survey of 199 child-bearing age women were completed. Most of the women didn't know the reason and prevention of neonatal tetanus. 62.4% of puerperant gave birth to children at home. The main reasons were high cost in hospital,traffic inconvenience,feudal superstition and backward customs. The active consciousness of child-bearing age women for inoculating tetanus toxoid was not

  16. Conjugative transfer and cis-mobilization of a genomic island by an integrative and conjugative element of Streptococcus agalactiae. (United States)

    Puymège, Aurore; Bertin, Stéphane; Chuzeville, Sarah; Guédon, Gérard; Payot, Sophie


    Putative integrative and conjugative elements (ICEs), i.e., genomic islands which could excise, self-transfer by conjugation, and integrate into the chromosome of the bacterial host strain, were previously identified by in silico analysis in the sequenced genomes of Streptococcus agalactiae (M. Brochet et al., J. Bacteriol. 190:6913-6917, 2008). We investigated here the mobility of the elements integrated into the 3' end of a tRNA(Lys) gene. Three of the four putative ICEs tested were found to excise but only one (ICE_515_tRNA(Lys)) was found to transfer by conjugation not only to S. agalactiae strains but also to a Streptococcus pyogenes strain. Transfer was observed even if recipient cell already carries a related resident ICE or a genomic island flanked by attL and attR recombination sites but devoid of conjugation or recombination genes (CIs-Mobilizable Element [CIME]). The incoming ICE preferentially integrates into the 3' end of the tRNA(Lys) gene (i.e., the attR site of the resident element), leading to a CIME-ICE structure. Transfer of the whole composite element CIME-ICE was obtained, showing that the CIME is mobilizable in cis by the ICE. Therefore, genomic islands carrying putative virulence genes but lacking the mobility gene can be mobilized by a related ICE after site-specific accretion.

  17. 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.

  18. In vitro and in vivo evaluation of cysteine and site specific conjugated herceptin antibody-drug conjugates.

    Directory of Open Access Journals (Sweden)

    Dowdy Jackson

    Full Text Available Antibody drug conjugates (ADCs are monoclonal antibodies designed to deliver a cytotoxic drug selectively to antigen expressing cells. Several components of an ADC including the selection of the antibody, the linker, the cytotoxic drug payload and the site of attachment used to attach the drug to the antibody are critical to the activity and development of the ADC. The cytotoxic drugs or payloads used to make ADCs are typically conjugated to the antibody through cysteine or lysine residues. This results in ADCs that have a heterogeneous number of drugs per antibody. The number of drugs per antibody commonly referred to as the drug to antibody ratio (DAR, can vary between 0 and 8 drugs for a IgG1 antibody. Antibodies with 0 drugs are ineffective and compete with the ADC for binding to the antigen expressing cells. Antibodies with 8 drugs per antibody have reduced in vivo stability, which may contribute to non target related toxicities. In these studies we incorporated a non-natural amino acid, para acetyl phenylalanine, at two unique sites within an antibody against Her2/neu. We covalently attached a cytotoxic drug to these sites to form an ADC which contains two drugs per antibody. We report the results from the first direct preclinical comparison of a site specific non-natural amino acid anti-Her2 ADC and a cysteine conjugated anti-Her2 ADC. We report that the site specific non-natural amino acid anti-Her2 ADCs have superior in vitro serum stability and preclinical toxicology profile in rats as compared to the cysteine conjugated anti-Her2 ADCs. We also demonstrate that the site specific non-natural amino acid anti-Her2 ADCs maintain their in vitro potency and in vivo efficacy against Her2 expressing human tumor cell lines. Our data suggests that site specific non-natural amino acid ADCs may have a superior therapeutic window than cysteine conjugated ADCs.

  19. Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants. (United States)

    Garcia-Knight, Miguel A; Nduati, Eunice; Hassan, Amin S; Gambo, Faith; Odera, Dennis; Etyang, Timothy J; Hajj, Nassim J; Berkley, James Alexander; Urban, Britta C; Rowland-Jones, Sarah L


    Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of vaccine efficacy

  20. Stabilization of water in oil in water (W/O/W) emulsion using whey protein isolate-conjugated durian seed gum: enhancement of interfacial activity through conjugation process. (United States)

    Tabatabaee Amid, Bahareh; Mirhosseini, Hamed


    The present work was conducted to investigate the effect of purification and conjugation processes on functional properties of durian seed gum (DSG) used for stabilization of water in oil in water (W/O/W) emulsion. Whey protein isolate (WPI) was conjugated to durian seed gum through the covalent linkage. In order to prepare WPI-DSG conjugate, covalent linkage of whey protein isolate to durian seed gum was obtained by Maillard reaction induced by heating at 60 °C and 80% (±1%) relative humidity. SDS-polyacrylamide gel electrophoresis was used to test the formation of the covalent linkage between whey protein isolate and durian seed gum after conjugation process. In this study, W/O/W stabilized by WPI-conjugated DSG A showed the highest interface activity and lowest creaming layer among all prepared emulsions. This indicated that the partial conjugation of WPI to DSG significantly improved its functional characteristics in W/O/W emulsion. The addition of WPI-conjugated DSG to W/O/W emulsion increased the viscosity more than non-conjugated durian seed gum (or control). This might be due to possible increment of the molecular weight after linking the protein fraction to the structure of durian seed gum through the conjugation process.

  1. Digital phase conjugate mirror by parallel arrangement of two phase-only spatial light modulators. (United States)

    Shibukawa, Atsushi; Okamoto, Atsushi; Goto, Yuta; Honma, Satoshi; Tomita, Akihisa


    In a conventional digital phase conjugation system, only the phase of an input light is time-reversed. This deteriorates phase conjugation fidelity and restricts application fields to specific cases only when the input light has uniformly-distributed scattered wavefront. To overcome these difficulties, we present a digital phase conjugate mirror based on parallel alignment of two phase-only spatial light modulators (SLMs), in which both amplitude and phase of the input light can be time-reversed. Experimental result showed that, in the phase conjugation through a holographic diffuser with diffusion angle of 0.5 degree, background noises decrease to 65% by our digital phase conjugation mirror.

  2. Axial range of conjugate adaptive optics in two-photon microscopy

    CERN Document Server

    Paudel, Hari P; Mertz, Jerome; Bifano, Thomas


    We describe an adaptive optics technique for two-photon microscopy in which the deformable mirror used for aberration compensation is positioned in a plane conjugate to the plane of the aberration. We demonstrate in a proof-of-principle experiment that this technique yields a large field of view advantage in comparison to standard pupil-conjugate adaptive optics. Further, we show that the extended field of view in conjugate AO is maintained over a relatively large axial translation of the deformable mirror with respect to the conjugate plane. We conclude with a discussion of limitations and prospects for the conjugate AO technique in two-photon biological microscopy.

  3. Separation of polyamines, conjugated to DNA, by reversed-phase high-performance liquid chromatography. (United States)

    Mateos, J L; Reyes, A; Vicente, C; Legaz, M E


    Genomic DNA was isolated from the lichen Evernia prunastri in order to analyze by high-performance liquid chromatography the occurrence of polyamines conjugated to the macromolecule. The acid-insoluble (PH) fraction of this DNA contained mainly conjugated spermidine, although small amounts of free putrescine and spermidine were also present. The PH fraction of DNA also contained conjugated evernic acid, the main phenol produced by this lichen species. Conjugation of polyamines to calf thymus DNA was carried out under in vitro conditions. Conjugation was to spermidine and mainly to spermine and produced DNA compactation. Evernic acid enhanced the action of polyamines in order to produce DNA aggregation.

  4. Adenosine conjugated lipidic nanoparticles for enhanced tumor targeting. (United States)

    Swami, Rajan; Singh, Indu; Jeengar, Manish Kumar; Naidu, V G M; Khan, Wahid; Sistla, Ramakrishna


    Delivering chemotherapeutics by nanoparticles into tumor is impeded majorly by two factors: nonspecific targeting and inefficient penetration. Targeted delivery of anti-cancer agents solely to tumor cells introduces a smart strategy because it enhances the therapeutic index compared with untargeted drugs. The present study was performed to investigate the efficiency of adenosine (ADN) to target solid lipid nanoparticles (SLN) to over expressing adenosine receptor cell lines such as human breast cancer and prostate cancer (MCF-7 and DU-145 cells), respectively. SLN were prepared by emulsification and solvent evaporation process using docetaxel (DTX) as drug and were characterized by various techniques like dynamic light scattering, differential scanning calorimeter and transmission electron microscopy. DTX loaded SLNs were surface modified with ADN, an adenosine receptors ligand using carbodiimide coupling. Conjugation was confirmed using infrared spectroscopy and quantified using phenol-sulfuric acid method. Conjugated SLN were shown to have sustained drug release as compared to unconjugated nanoparticles and drug suspension. Compared with free DTX and unconjugated SLN, ADN conjugated SLN showed significantly higher cytotoxicity of loaded DTX, as evidenced by in vitro cell experiments. The IC50 was 0.41 μg/ml for native DTX, 0.30 μg/ml for unconjugated SLN formulation, and 0.09 μg/ml for ADN conjugated SLN formulation in MCF-7 cell lines. Whereas, in DU-145, there was 2 fold change in IC50 of ADN-SLN as compared to DTX. IC50 was found to be 0.44 μg/ml for free DTX, 0.39 μg/ml for unconjugated SLN and 0.22 μg/ml for ADN-SLN. Annexin assay and cell cycle analysis assay further substantiated the cell cytotoxicity. Fluorescent cell uptake and competitive ligand-receptor binding assay corroborated the receptor mediated endocytosis pathway indicated role of adenosine receptors in internalization of conjugated particles. Pharmacokinetic studies of lipidic

  5. A comparison of chemiluminescent acridinium dimethylphenyl ester labels with different conjugation sites. (United States)

    Natrajan, Anand; Wen, David


    Chemiluminescent acridinium dimethylphenyl esters are highly sensitive labels that are used in automated assays for clinical diagnosis. Light emission from these labels and their conjugates is triggered by treatment with alkaline peroxide. Conjugation of acridinium ester labels is normally done at the phenol. During the chemiluminescent reaction of these acridinium esters, the phenolic ester is cleaved and the light emitting acridone moiety is liberated from its conjugate partner. In the current study, we report the synthesis of three new acridinium esters with conjugation sites at the acridinium nitrogen and compare their properties with that of a conventional acridinium ester with a conjugation site at the phenol. Our study is the first that provides a direct comparison of the emissive properties of acridinium dimethylphenyl esters (free labels and protein conjugates) with different conjugation sites, one where the light emitting acridone remains attached to its conjugate partner versus conventional labeling which results in cleavage of the acridone from the conjugate. Our results indicate that the conjugation at the acridinium nitrogen, which also alters how the acridinium ring and phenol are oriented with respect to the protein surface, has a minimal impact on emission kinetics and emission spectra. However, this mode of conjugation to three different proteins led to a significant increase in light yield which should be useful for improving the assay sensitivity.

  6. Synthesis and biological evaluation of benzimidazole-oxindole conjugates as microtubule-targeting agents. (United States)

    Kamal, Ahmed; Nagaseshadri, B; Nayak, V Lakshma; Srinivasulu, Vunnam; Sathish, Manda; Kapure, Jeevak Sopanrao; Suresh Reddy, C


    A series of benzimidazole-oxindole conjugates were synthesized and evaluated for their cytotoxic activity. The cytotoxicity assay results suggest that conjugates 5c and 5p exhibit promising cytotoxicity against human breast cancer cell line (MCF-7). The Cell cycle analysis revealed that these conjugates induced cell cycle arrest at G2/M phase in MCF-7 cells. The tubulin polymerization assay results suggested that these conjugates inhibit tubulin polymerization with IC50 values 1.12 and 1.59μM respectively. Immunofluorescence analysis also suggested that these conjugates effectively inhibited the microtubule assembly in MCF-7 cells. Further, molecular docking studies indicated that these conjugates 5c and 5p interact and binds efficiently with the tubulin protein. By and large, the results demonstrated that these benzimidazole-oxindole conjugates possess cytotoxic property by inhibiting the tubulin polymerization.

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

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, Rameshwer; Thomas, Thommey P; Desai, Ankur M; Kotlyar, Alina; Park, Steve J; Baker, James R Jr [Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, 9220 MSRB III, Box 0648, Ann Arbor, MI 48109 (United States)], E-mail:, E-mail:


    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.

  8. Phase conjugator with two coherent beams in a BaTiO3: Ce crystal

    Institute of Scientific and Technical Information of China (English)

    武建劳; 谢平; 戴建华; 张洪钧


    A phase conjugator which includes two coherent beams that are incident upon one of a-faces of a BaTiO3: Ce crystal without internal reflection is performed experimentally. Based on the four-wave mixing, the mechanism of this conjugator is investigated numerically. in comparison with the cor-responding self-pumped phase conjugator, the phase-conjugate behavior of this conjugator is estab-lished much more quickly, its phase conjugate reflectivity is greater in some cases and the intensity threshold is lower by over two orders of magnitude. The configuration of this conjugator is easy to per-form because the output response exists over a wide range of angular and lateral positions of the two incident beams on the crystal.

  9. Implementation of Modified Conjugate Gradient Algorithm and Analysis of Convergence in Electromagnetic Tomography Lab System

    Directory of Open Access Journals (Sweden)

    Li Liu


    Full Text Available Electromagnetic tomography technology is a new process tomography technology. The aim of this study is to develop a new image reconstruction algorithm suitable to electromagnetic tomography and verify its convergence. The advantages and development of electromagnetic tomography technology and image reconstruction algorithms are introduced briefly. Based on conjugate gradient algorithm, modified conjugate gradient algorithm for Electromagnetic Tomography (EMT is proposed. Convergence of the modified conjugate gradient algorithm is analyzed. In the light of the lab electromagnetic tomography system, modified conjugate gradient algorithm for reconstructing images is verified. By evaluation of image error and the relevance, regularization algorithm, Landweber algorithm, conjugate gradient algorithm and modified conjugate gradient algorithm are compared. It can draw the conclusion that for different flow patterns, modified conjugate gradient algorithm is superior to other algorithms in the 8 coils electromagnetic tomography lab system.

  10. Quantum dot conjugates in a sub-micrometer fluidic channel (United States)

    Stavis, Samuel M.; Edel, Joshua B.; Samiee, Kevan T.; Craighead, Harold G.


    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.

  11. Preparation of Conjugates of Cytotoxic Lupane Triterpenes with Biotin. (United States)

    Soural, Miroslav; Hodon, Jiri; Dickinson, Niall J; Sidova, Veronika; Gurska, Sona; Dzubak, Petr; Hajduch, Marian; Sarek, Jan; Urban, Milan


    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.

  12. Supramolecular helices: chirality transfer from conjugated molecules to structures. (United States)

    Yang, Yang; Zhang, Yajie; Wei, Zhixiang


    Different scales of chirality endow a material with many excellent properties and potential applications. In this review, using π-conjugated molecules as functional building blocks, recent progress on supramolecular helices inspired by biological helicity is summarized. First, induced chirality on conjugated polymers and small molecules is introduced. Molecular chirality can be amplified to nanostructures, superstructures, and even macroscopic structures by a self-assembly process. Then, the principles for tuning the helicity of supramolecular chirality, as well as formation of helical heterojunctions, are summarized. Finally, the potential applications of chiral structures in chiral sensing and organic electronic devices are critically reviewed. Due to recent progress in chiral structures, an interdisciplinary area called "chiral electronics" is expected to gain wide popularity in the near future.

  13. Metabolic interactions between vitamin A and conjugated linoleic acid. (United States)

    Carta, Gianfranca; Murru, Elisabetta; Cordeddu, Lina; Ortiz, Berenice; Giordano, Elena; Belury, Martha A; Quadro, Loredana; Banni, Sebastiano


    Lipid-soluble molecules share several aspects of their physiology due to their common adaptations to a hydrophilic environment, and may interact to regulate their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA) is a fatty acid with a conjugated diene structure that is found in low concentrations in ruminant products and available as a nutritional supplement. CLA has been shown to increase tissue levels of retinol (vitamin A alcohol) and its sole specific circulating carrier protein retinol-binding protein (RBP or RBP4). However, the precise mechanism of this action has not been elucidated yet. Here, we provide a summary of the current knowledge in this specific area of research and speculate that retinol and CLA may compete for catabolic pathways modulated by the activity of PPAR-α and RXR heterodimer. We also present preliminary data that may position PPAR-α at the crossroads between the metabolism of lipids and vitamin A.

  14. Optimised deconjugation of androgenic steroid conjugates in bovine urine. (United States)

    Pedersen, Mikael; Frandsen, Henrik L; Andersen, Jens H


    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 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 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 in ethyl acetate were used for deconjugation and the extract was purified by solid-phase extraction. The final extract was evaporated to dryness, re-dissolved and analysed by LC-MS/MS.

  15. Wavelet methods in multi-conjugate adaptive optics (United States)

    Helin, T.; Yudytskiy, M.


    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.

  16. Detection of Lectins by Saccharide-gold Nanoparticle Conjugates

    Institute of Scientific and Technical Information of China (English)

    HOU Qiong; WANG Jin-e; LIU Xia; LI Xiao-kun; MA Li-na; DUAN Wu-biao; WANG Zhen-xin


    A general functionalization strategy was reported,which enables one to conjugate saccharide(SA) on gold nanoparticle(GNP) surface without affecting SA properties.First,disulfide phenylboronic acid(Bor) functionalized GNPs(Bor@GNPs) were synthesized by the reaction of citrate stabilized GNPs of 13 nm in diameter with the mixture of Bor and pentapeptide(Cys-Ala-Leu-Asn-Asn,CALNN).Subsequently,the SA-GNP conjugates(SA@GNPs) were prepared by coupling SA to the GNP surface via the reaction of phenylboronic acid(PBA) with the cis-diol configuration in SA.The interactions of three SA@GNPs with three lectins have been analyzed by UV-visible spectroscopic and transmission electronic microscopic(TEM) techniques,respectively.The experimental results demonstrate that SA@GNPs can efficiently bind to lectins and show a great promise as optical probes for monitoring specific affinities of lectins for SA,and detecting lectins with high sensitivity.

  17. Exploring the origin of high optical absorption in conjugated polymers

    KAUST Repository

    Vezie, Michelle S.


    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.

  18. Coherent chirped pulse laser network with Mickelson phase-conjugator

    CERN Document Server

    Okulov, A Yu


    The mechanisms of nonlinear phase-locking of a large fiber amplifier array are analyzed. The preference is given to configuration most suitable for a coherent coupling of a thousands of a fundamental spatial mode fiber beams into a single smooth beam ready for chirped pulse compression. It is shown that Michelson phase conjugating configuration with double passage through array of fiber amplifiers have the definite advantages compared to one-way fiber array coupled in a Mach-Zehnder configuration. Regardless to amount of synchronized fiber amplifiers Michelson phase-conjugating interferometer is expected to do a perfect compensation of the phase-piston errors and collimation of backwardly amplified fiber beams on entrance/output beamsplitter. In both configurations the nonlinear transformation of the stretched pulse envelope due to gain saturation is capable to randomize the position of chirp inside envelope thus it may reduce the visibility of interference pattern at output beamsplitter. A certain advantages...

  19. Pomeron-Quark Coupling from Charge Conjugation Invariance

    Institute of Scientific and Technical Information of China (English)

    ZHOU Li-Juan; WU Qing; MA Wei-Xing; GU Yun-Ting


    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 IG JPC = 0+ 2++ and total decay width Γtot ≌ 100 MeV, which lies on the soft Pomeron trajectory αp = 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, γμ, of the soft Pomeron to quark is successful in dealing with Pomeron physics.

  20. Marine Antibody–Drug Conjugates: Design Strategies and Research Progress (United States)

    Wang, Yu-Jie; Li, Yu-Yan; Liu, Xiao-Yu; Lu, Xiao-Ling; Cao, Xin; Jiao, Bing-Hua


    Antibody–drug conjugates (ADCs), constructed with monoclonal antibodies (mAbs), linkers, and natural cytotoxins, are innovative drugs developed for oncotherapy. Owing to the distinctive advantages of both chemotherapy drugs and antibody drugs, ADCs have obtained enormous success during the past several years. The development of highly specific antibodies, novel marine toxins’ applications, and innovative linker technologies all accelerate the rapid R&D of ADCs. Meanwhile, some challenges remain to be solved for future ADCs. For instance, varieties of site-specific conjugation have been proposed for solving the inhomogeneity of DARs (Drug Antibody Ratios). In this review, the usages of various natural toxins, especially marine cytotoxins, and the development strategies for ADCs in the past decade are summarized. Representative ADCs with marine cytotoxins in the pipeline are introduced and characterized with their new features, while perspective comments for future ADCs are proposed. PMID:28098746

  1. 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.

  2. Recent Advances in Boron-Containing Conjugated Porous Polymers

    Directory of Open Access Journals (Sweden)

    Feng Qiu


    Full Text Available Porous polymers, integrating the advantages of porous materials and conventional polymers, have been well developed and exhibited tremendous attention in the fields of material, chemistry and biology. Of these, boron-containing conjugated porous polymers, featuring tunable geometric structures, unique Lewis acid boron centers and very rich physical properties, such as high specific surface, chargeable scaffold, strong photoluminescence and intramolecular charge transfer, have emerged as one of the most promising functional materials for optoelectronics, catalysis and sensing, etc. Furthermore, upon thermal treatment, some of them can be effectively converted to boron-doped porous carbon materials with good electrochemical performance in energy storage and conversion, extensively enlarging the applicable scope of such kinds of polymers. In this review, the synthetic approaches, structure analyses and various applications of the boron-containing conjugated porous polymers reported very recently are summarized.

  3. Self-Consistent Study of Conjugated Aromatic Molecular Transistors (United States)

    Wang, Jing; Liang, Yun-Ye; Chen, Hao; Wang, Peng; Note, R.; Mizuseki, H.; Kawazoe, Y.


    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.

  4. All solid-state SBS phase conjugate mirror (United States)

    Dane, C.B.; Hackel, L.A.


    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.

  5. Water-soluble, electroactive, and photoluminescent quaterthiophene-dinucleotide conjugates. (United States)

    Alesi, Silvia; Brancolini, Giorgia; Melucci, Manuela; Capobianco, Massimo Luigi; Venturini, Alessandro; Camaioni, Nadia; Barbarella, Giovanna


    Quaterthiophene-dinucleotide conjugates 5'TA3'-t4-3'AT5', 5'AA3'-t4-3'AA5', and 5'TT3'-t4-3'TT5' (TA: thymidine-adenosine, AA: adenosine-adenosine, TT: thymidine-thymidine) were synthesized and analyzed by a combination of spectroscopy and microscopy, electrical characterization, and theoretical calculations. Circular dichroism (CD) experiments demonstrated a transfer of chirality from the dinucleotides to quaterthiophene at high ionic strength and in cast films. The films were photoluminescent and electroactive. CD and photoluminescence spectra and current density/voltage plots (measured under dynamic vacuum) displayed significant variation on changing the dinucleotide scaffold. Molecular mechanics and molecular dynamics calculations indicated that the conformation and packing modes of the conjugates are the result of a balance between intra- and intermolecular nucleobase-thiophene stacking interactions and intramolecular hydrogen bonding between the nucleobases.

  6. Wavelet methods in multi-conjugate adaptive optics

    CERN Document Server

    Helin, Tapio


    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 domain. 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 simul...

  7. Conjugated Molecules for the Smart Filtering of Intense Radiations

    Directory of Open Access Journals (Sweden)

    Danilo Dini


    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.

  8. Remark on charge conjugation in the non relativistic limit

    CERN Document Server

    Cabo-Montes de Oca, Alejandro; Rojas, H P; Socolovsky, M


    We study the non relativistic limit of the charge conjugation operation $\\cal C$ in the context of the Dirac equation coupled to an electromagnetic field. The limit is well defined and, as in the relativistic case, $\\cal C$, $\\cal P$ (parity) and $\\cal T$ (time reversal) are the generators of a matrix group isomorphic to a semidirect sum of the dihedral group of eight elements and $\\Z_2$. The existence of the limit is supported by an argument based in quantum field theory. Finally, if one complexifies the Lorentz group and therefore the galilean spacetime $x_\\mu$, then the explicit form of the matrix for $\\cal C$ allows to interpret it, in this context, as the complex conjugation of the spatial coordinates: $\\vec{x} \\to \\vec{x}^*$. This result is natural in a fiber bundle description.

  9. Metabolic Interactions between Vitamin A and Conjugated Linoleic Acid

    Directory of Open Access Journals (Sweden)

    Gianfranca Carta


    Full Text Available Lipid-soluble molecules share several aspects of their physiology due to their common adaptations to a hydrophilic environment, and may interact to regulate their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA is a fatty acid with a conjugated diene structure that is found in low concentrations in ruminant products and available as a nutritional supplement. CLA has been shown to increase tissue levels of retinol (vitamin A alcohol and its sole specific circulating carrier protein retinol-binding protein (RBP or RBP4. However, the precise mechanism of this action has not been elucidated yet. Here, we provide a summary of the current knowledge in this specific area of research and speculate that retinol and CLA may compete for catabolic pathways modulated by the activity of PPAR-α and RXR heterodimer. We also present preliminary data that may position PPAR-α at the crossroads between the metabolism of lipids and vitamin A.

  10. Bioanalytical approaches for characterizing catabolism of antibody-drug conjugates. (United States)

    Saad, Ola M; Shen, Ben-Quan; Xu, Keyang; Khojasteh, S Cyrus; Girish, Sandhya; Kaur, Surinder


    The in vivo stability and catabolism of antibody-drug conjugates (ADCs) directly impact their PK, efficacy and safety, and metabolites of the cytotoxic or small molecule drug component of an ADC can further complicate these factors. This perspective highlights the importance of understanding ADC catabolism and the associated bioanalytical challenges. We evaluated different bioanalytical approaches to qualitatively and quantitatively characterize ADC catabolites. Here we review and discuss the rationale and experimental strategies used to design bioanalytical assays for characterization of ADC catabolism and supporting ADME studies during ADC clinical development. This review covers both large and small molecule approaches, and uses examples from Kadcyla® (T-DM1) and a THIOMAB™ antibody-drug conjugate to illustrate the process.

  11. Helical peptide-polyamine and -polyether conjugates as synthetic ionophores. (United States)

    Benincasa, Monica; Francescon, Marco; Fregonese, Massimo; Gennaro, Renato; Pengo, Paolo; Rossi, Paola; Scrimin, Paolo; Tecilla, Paolo


    Two new synthetic ionophores in which the hydrophobic portion is represented by a short helical Aib-peptide (Aib=α-amino-isobutyric acid) and the hydrophilic one is a poly-amino (1a) or a polyether (1b) chain have been prepared. The two conjugates show a high ionophoric activity in phospholipid membranes being able to efficiently dissipate a pH gradient and, in the case of 1b, to transport Na(+) across the membrane. Bioactivity evaluation of the two conjugates shows that 1a has a moderate antimicrobial activity against a broad spectrum of microorganisms and it is able to permeabilize the inner and the outer membrane of Escherichia coli cells.

  12. Conjugation and the periodic system of the elements (United States)

    Shorygin, P. P.; Burshtein, Konstantin Ya


    The knowledge of the characteristics and mechanisms of the interaction of the active centres of complex molecules is of primary importance for the development of theoretical and applied organic chemistry, promotes a more productive utilisation of the enormous amount of experimental data available, facilitates predictions and the search for new routes to and new varieties of the synthesis, industrial technology, and applications of organic compounds, and leads to more complete ideas about their functions in chemical, physical, and physiological processes. The studies in this field have been subjected to a critical survey and attention has been paid to the possibility of distinguishing different forms of the mutual influence of atomic groups, the establishment of correlations between different parameters of conjugation and of the role of relativistic effects, the characteristics of conjugation systems incorporating heteroatoms from different groups in the Periodic System, and the study of the evolution of excited molecules. The bibliography includes 188 references.

  13. Application of Conjugate Gradient methods to tidal simulation (United States)

    Barragy, E.; Carey, G.F.; Walters, R.A.


    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.

  14. Synthesis of arylenealkyne conjugated macrocycles containing a long alkylene bridge

    Institute of Scientific and Technical Information of China (English)

    Xiaohong CHENG; Sigurd HOEGER


    The synthesis of the first two arylenealkyne conjugated macrocycles containing a long alkylene bridge via Glaser coupling of template-directed tetra-acetylenes was reported. Tetraacetylene intermediates with complex structures were constructed rapidly via quadruple Hagihara coupling of monoprotected bisace-tylenes to appropriate tetraiodides and subsequent desilylation. The characterization of such compounds was carried out by NMR, GPC and UV-Vis spectra. Unfortunately, the two compounds were not liquid crystals and had no biaxial nematic mesophase character as expected,

  15. Design and synthesis of multivalent neoglycoconjugates by click conjugations

    Directory of Open Access Journals (Sweden)

    Feiqing Ding


    Full Text Available A highly stereoselective BF3∙OEt2-promoted tandem hydroamination/glycosylation on glycal scaffolds has been developed to form propargyl 3-tosylamino-2,3-dideoxysugars in a one-pot manner. Subsequent construction of multivalent 3-tosylamino-2,3-dideoxyneoglycoconjugates with potential biochemical applications was presented herein involving click conjugations as the key reaction step. The copper-catalyzed regioselective click reaction was tremendously accelerated with assistance of microwave irradiation.

  16. Plasmon-Polaron Coupling in Conjugated Polymer on Infrared Nanoantennas. (United States)

    Wang, Zilong; Zhao, Jun; Frank, Bettina; Ran, Qiandong; Adamo, Giorgio; Giessen, Harald; Soci, Cesare


    We propose and demonstrate a novel type of coupling between polarons in a conjugated polymer and localized surface plasmons in infrared (IR) nanoantennas. The near-field interaction between plasmons and polarons is revealed by polarized photoinduced absorption measurements, probing mid-IR polaron transitions, and infrared-active vibrational modes of the polymer, which directly gauge the density of photogenerated charge carriers. This work proves the possibility of tuning the polaronic properties of organic semiconductors with plasmonic nanostructures.

  17. Measuring the gain dynamics in a conjugated polymer film

    CERN Document Server

    Van den Berg, S A; Hooft, G W; Eliel, E R


    We present a simple method for measuring the gain decay time in a conjugated polymer film by optically exciting the film with two mutually delayed ultrashort pump pulses. When the pump is set at such a power level that amplified spontaneous emission marginally develops along the polymer waveguide, the total output emitted from its edge decays exponentially as a function of the interpulse delay. The corresponding decay time represents the decay time of the gain of the polymer material.

  18. Wavelet methods in multi-conjugate adaptive optics


    Helin, T; Yudytskiy, M.


    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 m...

  19. DNA-Conjugated Organic Chromophores in DNA Stacking Interactions

    DEFF Research Database (Denmark)

    Filichev, Vyacheslav V.; Pedersen, Erik Bjerregaard


    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...

  20. Stress Intensity of Antiplane Conjugate Cracks in Cubic Quasicrystal

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lei


    Based on the theory of Muskhelishvili, the general solutions for stress and strain of conjugate cracks in cubic quasicrystal are obtained, with which the stress intensity factors of cubic quasicrystal at crack tips and the stress distribution functions of phonon and phason fields are given. The results show that though phason field is coupled with phonon field by constitutive equations, the stress intensity factors are not coupled with any other factors.

  1. Optical phase conjugation in atomic beams and vapors (United States)

    Donoghue, John James


    Optical phase conjugation in atomic beams and vapors using alkali metal atoms as the nonlinear medium is examined. The significance of the sodium system is that the nonlinear gain is high due to the hyperfine system, which behaves as a Raman system. The gains observed were larger than 100 in cases involving two separate pump lasers. The gain is also seen to be more complicated than a Raman system. The frequency of the beams is examined for three separate configurations. We examine a self pumped configuration, an externally pumped configuration consisting of two pump lasers and a probe, and a ring configuration. The observed gain in a self pumped configuration is a result of a mixture of a three level Mollow type gain and a Raman gain. The initial cavity laser is a result of the Mollow gain, and the conjugate produced is seen to arise from the interaction of the cavity beams with the initial pump beam to produce the conjugate. In the externally pumped scheme, the gain is due to Coherent Population Trapping (CPT) in a double-Λ Raman system. There is an equilibrium that is obtained that is responsible for the high gains observed in this particular setup. The bandwidth of the ground state two photon induced coherence is less than the natural lifetime, indicating CPT as the gain mechanism. In the ring configuration, we observed two separate gains. There is a forward and a backward gain. These two oscillations occur together for a 430 MHZ bandwidth which coincides with the observed width of the phase conjugate oscillation. The design of our vapor cells is discussed in depth. The heat pipe configuration, necessary to successfully conduct these experiments is shown in detail. The design of our atomic beams is also discussed.

  2. Invasive pneumococcal infection despite 7-valent conjugated vaccine

    Directory of Open Access Journals (Sweden)

    Sebastien Joye


    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.

  3. Optical phase conjugation in semiconductor-doped glasses (United States)

    Roussignol, P.; Ricard, D.; Rustagi, K. C.; Flytzanis, C.


    We have studied optical phase conjugation in two types of semiconductor-doped glasses. Corning 3.68 and Schott OG 530 at λ = 0.532 μm using picosecond pulses. We observe a slow nonlinearity in agreement with the slow decay of luminescence. The saturation of the reflectivity is strongly correlated with the absorption saturation of these glasses and may be interpreted in terms of a three-level system model.

  4. A conjugate heat transfer procedure for gas turbine blades. (United States)

    Croce, G


    A conjugate heat transfer procedure, allowing for the use of different solvers on the solid and fluid domain(s), is presented. Information exchange between solid and fluid solution is limited to boundary condition values, and this exchange is carried out at any pseudo-time step. Global convergence rate of the procedure is, thus, of the same order of magnitude of stand-alone computations.

  5. Antifungal activity of amphotericin B conjugated to carbon nanotubes. (United States)

    Benincasa, Monica; Pacor, Sabrina; Wu, Wei; Prato, Maurizio; Bianco, Alberto; Gennaro, Renato


    Amphotericin B (AMB) has long been considered the most effective drug in the treatment of serious invasive fungal infections. There are, however, major limitations to its use, due to several adverse effects, including acute infusional reactions and, most relevant, a dose-dependent nephrotoxicity. At least some of these effects are attributed to the aggregation of AMB as a result of its poor water solubility. To overcome this problem, reformulated versions of the drug have been developed, including a micellar dispersion of AMB with sodium deoxycholate (AMBD), its encapsulation into liposomes, or its incorporation into lipidic complexes. The development of nanobiotechnologies provides novel potential drug delivery systems that make use of nanomaterials such as functionalized carbon nanotubes (f-CNTs), which are emerging as an innovative and efficient tool for the transport and cellular translocation of therapeutic molecules. In this study, we prepared two conjugates between f-CNTs and AMB. The antifungal activity of these conjugates was tested against a collection of reference and clinical fungal strains, in comparison to that of AMB alone or AMBD. Measured minimum inhibition concentration (MIC) values for f-CNT-AMB conjugates were either comparable to or better than those displayed by AMB and AMBD. Furthermore, AMBD-resistant Candida strains were found to be susceptible to f-CNT-AMB 1. Additional studies, aimed at understanding the mechanism of action of the conjugates, suggest a nonlytic mechanism, since the compounds show a major permeabilizing effect on the tested fungal strains only after extended incubation. Interestingly, the f-CNT-AMB 1 does not show any significant toxic effect on Jurkat cells at antifungal concentrations.

  6. Linkers Having a Crucial Role in Antibody–Drug Conjugates


    Jun Lu; Feng Jiang; Aiping Lu; Ge Zhang


    Antibody–drug conjugates (ADCs) comprised of a desirable monoclonal antibody, an active cytotoxic drug and an appropriate linker are considered to be an innovative therapeutic approach for targeted treatment of various types of tumors and cancers, enhancing the therapeutic parameter of the cytotoxic drug and reducing the possibility of systemic cytotoxicity. An appropriate linker between the antibody and the cytotoxic drug provides a specific bridge, and thus helps the antibody to selectively...

  7. Decomposition Theorems and Conjugate Pair in DK Spaces

    Institute of Scientific and Technical Information of China (English)

    Ji Zhen ZHOU; Yu Tian WU


    Let K be a right-continuous and nondecreasing function. A function f analytic in the unit disk D belongs to the space DK if ?D|f?(z)|2K(1-|z|2)dA(z)<∞. Decomposition theorems for DK spaces are established in this paper. As an application, we obtain a characterization of interpolation by functions in DK spaces. Furthermore, we characterize functions in DK spaces by conjugate pairs.

  8. Conjugated polymelectrolyte assembly at water-oil interfaces (United States)

    Liu, Feng; Huang, Caili; Thomas, Russell; Russell Team

    Conjugated polyelectrolytes featured with conjugated backbone and functional side chains are interesting optoelectronic materials and widely used to modify electrodes in electronic devices such as light emitting diodes and solar cells to enhance device performance. Conjugated polyelectrolyte can be designed to have alternating hydrophilic and hydrophobic side chains, and thus inducing interesting surface and interface properties. In this work, we using polyfluorene based material, to study its behavior at water-toluene interface. The aliphatic side-chains will favorably interact with toluene, and amine side-chains will interact with water, making this material a good surfactant. At interface the polymer chain is stretched to a Janus type of geometry. Flattened molecules will assemble into ultra thin films via pi-pi intermolecular stacking, and thus creating barriers between liquids. When liquid volume is reduced, jamming at interface will show up. These properties are strongly affected by the environment of the liquids, such as temperature and PH values, and polyelectrolyte diffusion to interfaces. This study leads to new methods to structure liquids using single component, which can be extended to applications such as electro-spinning or fabricate flow devices.

  9. Compatibilization of All-Conjugated Polymer Blends for Organic Photovoltaics. (United States)

    Lombeck, Florian; Sepe, Alessandro; Thomann, Ralf; Friend, Richard H; Sommer, Michael


    Compatibilization of an immiscible binary blend comprising a conjugated electron donor and a conjugated electron acceptor polymer with suitable electronic properties upon addition of a block copolymer (BCP) composed of the same building blocks is demonstrated. Efficient compatibilization during melt-annealing is feasible when the two polymers are immiscible in the melt, i.e. above the melting point of ∼250 °C of the semicrystalline donor polymer P3HT. To generate immiscibility at these high temperatures, the acceptor polymer PCDTBT is equipped with fluorinated side chains leading to an increased Flory-Huggins interaction parameter. Compatibilization in bulk and thin films is demonstrated, showing that the photovoltaic performance of pristine microphase separated and nanostructured BCPs can also be obtained for compatibilized blend films containing low contents of 10-20 wt % BCP. Thermodynamically stable domain sizes range between several tens of microns for pure blends and ∼10 nm for pure block copolymers. In addition to controlling domain size, the amount of block copolymer added dictates the ratio of edge-on and face-on P3HT crystals, with compatibilized films showing an increasing amount of face-on P3HT crystals with increasing amount of compatibilizer. This study demonstrates the prerequisites and benefits of compatibilizing all-conjugated semicrystalline polymer blends for organic photovoltaics.

  10. Microfluidic Crystal Engineering of π-Conjugated Polymers. (United States)

    Wang, Gang; Persson, Nils; Chu, Ping-Hsun; Kleinhenz, Nabil; Fu, Boyi; Chang, Mincheol; Deb, Nabankur; Mao, Yimin; Wang, Hongzhi; Grover, Martha A; Reichmanis, Elsa


    Very few studies have reported oriented crystallization of conjugated polymers directly in solution. Here, solution crystallization of conjugated polymers in a microfluidic system is found to produce tightly π-stacked fibers with commensurate improved charge transport characteristics. For poly(3-hexylthiophene) (P3HT) films, processing under flow caused exciton bandwidth to decrease from 140 to 25 meV, π-π stacking distance to decrease from 3.93 to 3.72 Å and hole mobility to increase from an average of 0.013 to 0.16 cm(2) V(-1) s(-1), vs films spin-coated from pristine, untreated solutions. Variation of the flow rate affected thin-film structure and properties, with an intermediate flow rate of 0.25 m s(-1) yielding the optimal π-π stacking distance and mobility. The flow process included sequential cooling followed by low-dose ultraviolet irradiation that promoted growth of conjugated polymer fibers. Image analysis coupled with mechanistic interpretation supports the supposition that "tie chains" provide for charge transport pathways between nanoaggregated structures. The "microfluidic flow enhanced semiconducting polymer crystal engineering" was also successfully applied to a representative electron transport polymer and a nonhalogenated solvent. The process can be applied as a general strategy and is expected to facilitate the fabrication of high-performance electrically active polymer devices.

  11. Facile biosynthesis, separation and conjugation of gold nanoparticles to doxorubicin (United States)

    Kumar, S. Anil; Peter, Yves-Alain; Nadeau, Jay L.


    Particle shape and size determine the physicochemical and optoelectronic properties of nanoscale materials, including optical absorption, fluorescence, and electric and magnetic moments. It is thus desirable to be able to synthesize and separate various particle shapes and sizes. Biosynthesis using microorganisms has emerged as a more ecologically friendly, simpler, and more reproducible alternative to chemical synthesis of metal and semiconductor nanoparticles, allowing the generation of rare forms such as triangles. Here we show that the plant pathogenic fungus Helminthosporum solani, when incubated with an aqueous solution of chloroaurate ions, produces a diverse mixture of extracellular gold nanocrystals in the size range from 2 to 70 nm. A plurality are polydisperse spheres, but a significant number are homogeneously sized rods, triangles, pentagons, pyramids, and stars. The particles can be separated according to their size and shape by using a sucrose density gradient in a tabletop microcentrifuge, a novel and facile approach to nanocrystal purification. Conjugation to biomolecules can be performed without further processing, as illustrated with the smallest fraction of particles which were conjugated to the anti-cancer drug doxorubicin (Dox) and taken up readily into HEK293 cells. The cytotoxicity of the conjugates was comparable to that of an equivalent concentration of Dox.

  12. Non-covalent interactions between carbon nanotubes and conjugated polymers. (United States)

    Tuncel, Dönüs


    Carbon nanotubes (CNTs) are interest to many different disciplines including chemistry, physics, biology, material science and engineering because of their unique properties and potential applications in various areas spanning from optoelectronics to biotechnology. However, one of the drawbacks associated with these materials is their insolubility which limits their wide accessibility for many applications. Various approaches have been adopted to circumvent this problem including modification of carbon nanotube surfaces by non-covalent and covalent attachments of solubilizing groups. Covalent approach modification may alter the intrinsic properties of carbon nanotubes and, in turn make them undesirable for many applications. On the other hand, a non-covalent approach helps to improve the solubility of CNTs while preserving their intrinsic properties. Among many non-covalent modifiers of CNTs, conjugated polymers are receiving increasing attention and highly appealing because of a number of reasons. To this end, the aim of this feature article is to review the recent results on the conjugated polymer-based non-covalent functionalization of CNTs with an emphasis on the effect of conjugated polymers in the dispersibility/solubility, optical, thermal and mechanical properties of carbon nanotubes as well as their usage in the purification and isolation of a specific single-walled nanotube from the mixture of the various tubes.

  13. Genome modifications and cloning using a conjugally transferable recombineering system

    Directory of Open Access Journals (Sweden)

    Mohammad J Hossain


    Full Text Available The genetic modification of primary bacterial disease isolates is challenging due to the lack of highly efficient genetic tools. Herein we describe the development of a modified PCR-based, λ Red-mediated recombineering system for efficient deletion of genes in Gram-negative bacteria. A series of conjugally transferrable plasmids were constructed by cloning an oriT sequence and different antibiotic resistance genes into recombinogenic plasmid pKD46. Using this system we deleted ten different genes from the genomes of Edwardsiella ictaluri and Aeromonas hydrophila. A temperature sensitive and conjugally transferable flp recombinase plasmid was developed to generate markerless gene deletion mutants. We also developed an efficient cloning system to capture larger bacterial genetic elements and clone them into a conjugally transferrable plasmid for facile transferring to Gram-negative bacteria. This system should be applicable in diverse Gram-negative bacteria to modify and complement genomic elements in bacteria that cannot be manipulated using available genetic tools.

  14. Naphthobischalcogenadiazole Conjugated Polymers: Emerging Materials for Organic Electronics. (United States)

    Osaka, Itaru; Takimiya, Kazuo


    π-Conjugated polymers are an important class of materials for organic electronics. In the past decade, numerous polymers with donor-acceptor molecular structures have been developed and used as the active materials for organic devices, such as organic field-effect transistors (OFETs) and organic photovoltaics (OPVs). The choice of the building unit is the primary step for designing the polymers. Benzochalcogenadiazoles (BXzs) are one of the most familiar acceptor building units studied in this area. As their doubly fused system, naphthobischalcogenadiazoles (NXzs), i.e., naphthobisthiadiazole (NTz), naphthobisoxadiazole (NOz), and naphthobisselenadiazole (NSz) are emerging building units that provide interesting electronic properties and highly self-assembling nature for π-conjugated polymers. With these fruitful features, π-conjugated polymers based on these building units demonstrate great performances in OFETs and OPVs. In particular, in OPVs, NTz-based polymers have exhibited more than 10% efficiency, which is among the highest values reported so far. In this Progress Report, the synthesis, properties, and structures of NXzs and their polymers is summarized. The device performance is also highlighted and the structure-property relationships of the polymers are discussed.

  15. How Geometric Distortions Scatter Electronic Excitations in Conjugated Macromolecules. (United States)

    Shi, Tian; Li, Hao; Tretiak, Sergei; Chernyak, Vladimir Y


    Effects of disorder and exciton-phonon interactions are the major factors controlling photoinduced dynamics and energy-transfer processes in conjugated organic semiconductors, thus defining their electronic functionality. All-atom quantum-chemical simulations are potentially capable of describing such phenomena in complex "soft" organic structures, yet they are frequently computationally restrictive. Here we efficiently characterize how electronic excitations in branched conjugated molecules interact with molecular distortions using the exciton scattering (ES) approach as a fundamental principle combined with effective tight-binding models. Molecule geometry deformations are incorporated to the ES view of electronic excitations by identifying the dependence of the Frenkel-type exciton Hamiltonian parameters on the characteristic geometry parameters. We illustrate our methodology using two examples of intermolecular distortions, bond length alternation and single bond rotation, which constitute vibrational degrees of freedom strongly coupled to the electronic system in a variety of conjugated systems. The effect on excited-state electronic structures has been attributed to localized variation of exciton on-site energies and couplings. As a result, modifications of the entire electronic spectra due to geometric distortions can be efficiently and accurately accounted for with negligible numerical cost. The presented approach can be potentially extended to model electronic structures and photoinduced processes in bulk amorphous polymer materials.

  16. An Integrated Solution for Performing Thermo-fluid Conjugate Analysis (United States)

    Kornberg, Oren


    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.

  17. Meeting the challenge: prevention of pneumococcal disease with conjugate vaccines

    Directory of Open Access Journals (Sweden)

    Echániz-Avilés Irma Gabriela


    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:

  18. Fatty acid conjugation enhances the activities of antimicrobial peptides. (United States)

    Li, Zhining; Yuan, Penghui; Xing, Meng; He, Zhumei; Dong, Chuanfu; Cao, Yongchang; Liu, Qiuyun


    Antimicrobial peptides are small molecules that play a crucial role in innate immunity in multi-cellular organisms, and usually expressed and secreted constantly at basal levels to prevent infection, but local production can be augmented upon an infection. The clock is ticking as rising antibiotic abuse has led to the emergence of many drug resistance bacteria. Due to their broad spectrum antibiotic and antifungal activities as well as anti-viral and anti-tumor activities, efforts are being made to develop antimicrobial peptides into future microbial agents. This article describes some of the recent patents on antimicrobial peptides with fatty acid conjugation. Potency and selectivity of antimicrobial peptide can be modulated with fatty acid tails of variable length. Interaction between membranes and antimicrobial peptides was affected by fatty acid conjugation. At concentrations above the critical miscelle concentration (CMC), propensity of solution selfassembly hampered binding of the peptide to cell membranes. Overall, fatty acid conjugation has enhanced the activities of antimicrobial peptides, and occasionally it rendered inactive antimicrobial peptides to be bioactive. Antimicrobial peptides can not only be used as medicine but also as food additives.

  19. Comparative assay of fluorescent antibody test results among twelve European National Reference Laboratories using various anti-rabies conjugates

    DEFF Research Database (Denmark)

    Robardet, E.; Andrieu, S.; Rasmussen, Thomas Bruun


    brain tissues infected with various lyssavirus species as well as negative samples were analyzed blindly using a standardized FAT procedure. Conjugates B, C, D, and E were found to be significantly more effective than conjugate A for GS7 (French RABV) diluted samples (1/8 and 1/100) while the frequency...... of concordant results of conjugates C and D differ significantly from conjugates A, B and E for CVS 27. For detection of EBLV-1 strains, conjugates C and D also presented a significantly lower frequency of discordant results compared to conjugates A, B and E. Conjugates B, C and D were found to be significantly...

  20. Coordinate-Space Solver for Superfluid Many-Fermion Systems with Shifted Conjugate Orthogonal Conjugate Gradient Method

    CERN Document Server

    Jin, Shi; Roche, Kenneth; Wlazłowski, Gabriel


    Self-consistent approaches to superfluid many-fermion systems in 3-dimensions (and subsequent time-dependent approaches) require a large number of diagonalizations of very large dimension hermitian matrices, which results in enormous computational costs. We present an approach based on the shifted conjugate-orthogonal conjugate-gradient (COCG) method for the evaluation of the Green's function, from which we subsequently extract various densities (particle number, spin, current, kinetic energy, etc.) of a nuclear system needed in self-consistent approaches. The approach eschews the construction of the quasiparticle wavefunctions and their corresponding quasiparticle energies, which are never explicitly needed in any density functional approaches. As benchmarks we present calculations for nuclei with axial symmetry, including the ground state of spherical (magic or semi-magic) and axially deformed nuclei, the saddle-point in the $^{240}$Pu constrained fission path, and a vortex in the neutron star crust.