Science.gov

Sample records for cholesterol-vinyl ether-peg conjugate

  1. Cytoplasmic Delivery of Liposomal Contents Mediated by an Acid-Labile Cholesterol-Vinyl Ether-PEG Conjugate

    PubMed Central

    Boomer, Jeremy A.; Qualls, Marquita M.; Inerowicz, H. Dorota; Haynes, Robert H.; Patri, G.V. Srilaksmi; Kim, Jong-Mok; Thompson, David H.

    2009-01-01

    An acid-cleavable PEG lipid, 1′-(4′-cholesteryloxy-3′-butenyl)-ω-methoxy-polyethylene[112] glycolate (CVEP), has been developed that produces stable liposomes when dispersed as a minor component (0.5–5 mol%) in 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Cleavage of CVEP at mildly acidic pH’s results in dePEGylation of the latently fusogenic DOPE liposomes, thereby triggering the onset of contents release. This paper describes the synthesis of CVEP via a six step sequence starting from the readily available precursors 1,4-butanediol, cholesterol, and mPEG acid. The hydrolysis rates and release kinetics from CVEP:DOPE liposome dispersions as a function of CVEP loading, as well as the cryogenic transmission electron microscopy and pH-dependent monolayer properties of 9:91 CVEP:DOPE mixtures, also are reported. When folate-receptor positive KB cells were exposed to calcein-loaded 5:95 CVEP:DOPE liposomes containing 0.1 mol% folate-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-polyethylene[76] glycolamide (folate-PEG-DSPE), efficient delivery of the calcein cargo to the cytoplasm of the cells was observed as determined by fluorescence microscopy and flow cytometry. Fluorescence resonance energy transfer analysis of lipid mixing in these cells was consistent with membrane-membrane fusion between the liposome and endosomal membranes. PMID:19072698

  2. Adverse eff ects of polymeric nanoparticle poly(ethylene glycol)- block-polylactide methyl ether (PEG-b-PLA) on steroid hormone secretion by porcine granulosa cells.

    PubMed

    Scsukova, Sona; Bujnakova, Mlynarcikova A; Kiss, A; Rollerova, E

    2017-04-25

    Development of nanoparticles (NPs) for biomedical applications, including medical imaging and drug delivery, is currently undergoing a dramatic expansion. Diverse effects of different type NPs relating to mammalian reproductive tissues have been demonstrated. Th e objective of this study was to explore the in vitro effects of polymeric nanoparticle poly(ethylene glycol)-blockpolylactide methyl ether (PEG-b-PLA NPs) on functional state and viability of ovarian granulosa cells (GCs), which play an important role in maintaining ovarian function and female fertility. The GCs isolated from porcine ovarian follicles were incubated with the different concentrations of PEG-b-PLA NPs (PEG average Mn=350 g/mol and PLA average Mn=1000 g/mol; 0.2-100 μg/ml) or poly(ethylene glycol) with an average molecular weight of 300 (PEG-300; 0.2- 40 mg/ml) in the presence or absence of stimulators, follicle-stimulating hormone (FSH; 1 μg/ml), androstenedione (100 nM), forskolin (10 μM) or 8Br-cAMP (100 μM), for different time periods (24, 48, 72 h). At the end of the incubation, progesterone and estradiol levels produced by GCs were measured in the culture media by radioimmunoassay. Th e viability of GCs was determined by the method using a colorimetric assay with MTT. Treatment of GCs with PEG-b-PLA NPs induced a significant decrease in basal as well as FSH-stimulated progesterone secretion above the concentration of 20 and 4 μg/ml, respectively. Moreover, PEG-b-PLA NPs reduced forskolin-stimulated, but not cAMP-stimulated progesterone production by GCs. A dose-dependent inhibition of androstenedione-stimulated estradiol release by GCs was found by the action of PEG-b-PLA NPs. Incubation of GCs with PEG-300 significantly inhibited basal as well as FSH-stimulated progesterone secretion above the concentration of 40 mg/ml. PEG-b-PLA NPs and PEG-300 significantly reduced the viability of GCs at the highest tested concentrations (100 μg/ml and 40 mg/ml, respectively). The obtained

  3. [Conjugated vaccines].

    PubMed

    Fritzell, Bernard

    2005-01-01

    Encapsulated bacterial pathogens (e.g. Haemophilus influenzae type b [Hib], Neisseria meningitidis, or Streptococcus pneumoniae) target infants and young children who have lost any protective anti-capsular antibodies supplied maternally and whose immune systems are ineffective against T-independent antigens such as the polysaccharides of the capsule. The polysaccharide-protein conjugate vaccines overcome this limitation by converting the polysaccharide to a T-dependent antigen, which allows a vaccinated infant to mount a protective immune response. Where conjugated vaccines have been introduced into paediatric vaccination schedules, the incidence of invasive diseases caused by Hib, the group C meningococcus, or the pneumococcus has plummeted by at least 80%, a major public health success. Furthermore, surveillance has demonstrated that the conjugate vaccines provide 'herd protection' through their beneficial impact on nasopharyngeal colonisation among vaccinated children. Promising future approaches include enhancement of the number of capsular serogroups targeted by the meningococcal or pneumococcal conjugate vaccines.

  4. Chlorophyll-a analogues conjugated with aminobenzyl-DTPA as potential bifunctional agents for magnetic resonance imaging and photodynamic therapy.

    PubMed

    Li, Guolin; Slansky, Adam; Dobhal, Mahabeer P; Goswami, Lalit N; Graham, Andrew; Chen, Yihui; Kanter, Peter; Alberico, Ronald A; Spernyak, Joseph; Morgan, Janet; Mazurchuk, Richard; Oseroff, Allan; Grossman, Zachary; Pandey, Ravindra K

    2005-01-01

    A clinically relevant photosensitizer, 3-devinyl-3-(1-hexyloxyethyl)pyropheophorbide-a (HPPH, a chlorophyll-a derivative), was conjugated with Gd(III)-aminobenzyl-diethylenetriaminepentaacetic acid (DTPA), an experimental magnetic resonance (MR) imaging agent. In vivo reflectance spectroscopy confirmed tumor uptake of HPPH-aminobenzyl-Gd(III)-DTPA conjugate was higher than free HPPH administered intraveneously (iv) to C3H mice with subcutaneously (sc) implanted radiation-induced fibrosarcoma (RIF) tumor cells. In other experiments, Sprague-Dawley (SD) rats with sc implanted Ward Colon Carcinoma cells yielded markedly increased MR signal intensities from tumor regions-of-interest (ROIs) 24 h post-iv injection of HPPH-aminobenzyl-Gd(III)-DTPA conjugate as compared to unconjugated HPPH. In both in vitro (RIF tumor cells) and in vivo (mice bearing RIF tumors and rats bearing Ward Colon tumors) the conjugate produced significant increases in tumor conspicuity at 1.5 T and retained therapeutic efficacy following PDT. Also synthesized were a series of novel bifunctional agents containing two Gd(III) atoms per HPPH molecule that remained tumor-avid and PDT-active and yielded improved MR tumor conspicuity compared to their corresponding mono-Gd(III) analogues. Administered iv at a MR imaging dose of 10 micromol/kg, these conjugates produced severe skin phototoxicity. However, by replacing the hexyl group of the pyropheophorbide-a with a tri(ethylene glycol) monomethyl ether (PEG-methyl ether), these conjugates produced remarkable MR tumor enhancement at 8 h post-iv injection, significant tumoricidal activity (80% of mice were tumor-free on day 90), and reduced skin phototoxicity compared to their corresponding hexyl ether analogues. The poor water-solubility characteristic of these conjugates was resolved by incorporation into a liposomal formulation. This paper presents the synthesis of tumor-avid contrast enhancing agents for MR imaging and thus represents an important

  5. Stabilized polyacrylic saccharide protein conjugates

    DOEpatents

    Callstrom, Matthew R.; Bednarski, Mark D.; Gruber, Patrick R.

    1996-01-01

    This invention is directed to water soluble protein polymer conjugates which are stabile in hostile environments. The conjugate comprises a protein which is linked to an acrylic polymer at multiple points through saccharide linker groups.

  6. Stabilized polyacrylic saccharide protein conjugates

    DOEpatents

    Callstrom, M.R.; Bednarski, M.D.; Gruber, P.R.

    1996-02-20

    This invention is directed to water soluble protein polymer conjugates which are stable in hostile environments. The conjugate comprises a protein which is linked to an acrylic polymer at multiple points through saccharide linker groups. 16 figs.

  7. Conjugation in "Escherichia coli"

    ERIC Educational Resources Information Center

    Phornphisutthimas, Somkiat; Thamchaipenet, Arinthip; Panijpan, Bhinyo

    2007-01-01

    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…

  8. DNA-cell conjugates

    SciTech Connect

    Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn

    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.

  9. DNA-cell conjugates

    DOEpatents

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

    2016-05-03

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

  10. Conjugated Polymers in Bioelectronics.

    PubMed

    Inal, Sahika; Rivnay, Jonathan; Suiu, Andreea-Otilia; Malliaras, George G; McCulloch, Iain

    2018-06-19

    The emerging field of organic bioelectronics bridges the electronic world of organic-semiconductor-based devices with the soft, predominantly ionic world of biology. This crosstalk can occur in both directions. For example, a biochemical reaction may change the doping state of an organic material, generating an electronic readout. Conversely, an electronic signal from a device may stimulate a biological event. Cutting-edge research in this field results in the development of a broad variety of meaningful applications, from biosensors and drug delivery systems to health monitoring devices and brain-machine interfaces. Conjugated polymers share similarities in chemical "nature" with biological molecules and can be engineered on various forms, including hydrogels that have Young's moduli similar to those of soft tissues and are ionically conducting. The structure of organic materials can be tuned through synthetic chemistry, and their biological properties can be controlled using a variety of functionalization strategies. Finally, organic electronic materials can be integrated with a variety of mechanical supports, giving rise to devices with form factors that enable integration with biological systems. While these developments are innovative and promising, it is important to note that the field is still in its infancy, with many unknowns and immense scope for exploration and highly collaborative research. The first part of this Account details the unique properties that render conjugated polymers excellent biointerfacing materials. We then offer an overview of the most common conjugated polymers that have been used as active layers in various organic bioelectronics devices, highlighting the importance of developing new materials. These materials are the most popular ethylenedioxythiophene derivatives as well as conjugated polyelectrolytes and ion-free organic semiconductors functionalized for the biological interface. We then discuss several applications and

  11. Semiconductor Phase Conjugation

    DTIC Science & Technology

    1992-05-01

    PL-TR--91- 1082 PL-TR-- AD-A253 684 91- 1082 SEMICONDUCTOR PHASE CONJUGATION lam-Choon Khoo Pennsylvania State University Electrical and Computer... 1082 This final report was prepared by Pennsylvania State University, University Park, Pennsylvania, under Contract F29601-88-K-0028, Job Order 33261B18...10. SPONSORING/ MONITORING AGENCY REPORT NUMBER Phill ips Laboratory PL-TR--91- 1082 Kirtland AFB, NM 87117-6008 11. SUPPLEMENTARY NOTES 12a

  12. Exciton transport in π-conjugated polymers with conjugation defects.

    PubMed

    Meng, Ruixuan; Li, Yuan; Li, Chong; Gao, Kun; Yin, Sun; Wang, Luxia

    2017-09-20

    In π-conjugated polymers for photovoltaic applications, intrinsic conjugation defects are known to play crucial roles in impacting exciton transport after photoexcitation. However, the understanding of the associated microscopic processes still remains limited. Here, we present a theoretical investigation of the effects of different conjugation defects on the dynamics of exciton transport in two linearly coupled poly(p-phenylene vinylene) (PPV) molecules. The model system is constructed by employing an extended version of the Su-Schrieffer-Heeger model and the exciton behaviors are simulated by means of a quantum nonadiabatic dynamics. We identify two types of conjugation defects, i.e., weakening conjugation and strengthening conjugation, which are demonstrated to play different roles in impacting the dynamics of exciton transport in the system. The weakening conjugation acts as an energy well inclined to trap a moving exciton, while the strengthening conjugation acts as an energy barrier inclined to block the exciton. We also systematically simulate both intrachain and interchain dynamics of exciton transport, and find that an exciton could experience a "short-time delaying", "trapping", "blocking", or "hopping" process, which is determined by the defect type, strength, and position. These findings provide a microscopic understanding of how the exciton transport dynamics can be impacted by conjugation defects in an actual polymer system.

  13. Conjugate and method for forming aminomethyl phosphorus conjugates

    DOEpatents

    Katti, Kattesh V.; Berning, Douglas E.; Volkert, Wynn A.; Ketring, Alan R.; Churchill, Robert

    1999-01-01

    A method of forming phosphine-amine conjugates includes reacting a hydroxymethyl phosphine group of an amine-free first molecule with at least one free amine group of a second molecule to covalently bond the first molecule with the second molecule through an aminomethyl phosphorus linkage and the conjugates formed thereby.

  14. Antibody-gold cluster conjugates

    DOEpatents

    Hainfeld, J.F.

    1988-06-28

    Antibody- or antibody fragment-gold cluster conjugates are shown wherein the conjugate size can be about 5.0 nm. Methods and reagents are disclosed in which antibodies or Fab' fragments thereof are covalently bound to a stable cluster of gold atoms. 2 figs.

  15. Glutathione conjugation and contaminant transformation

    USGS Publications Warehouse

    Field, Jennifer A.; Thurman, E.M.

    1996-01-01

    The recent identification of a novel sulfonated metabolite of alachlor in groundwater and metolachlor in soil is likely the result of glutathione conjugation. Glutathione conjugation is an important biochemical reaction that leads, in the case of alachlor, to the formation of a rather difficult to detect, water-soluble, and therefore highly mobile, sulfonated metabolite. Research from weed science, toxicology, and biochemistry is discussed to support the hypothesis that glutathione conjugation is a potentially important detoxification pathway carried out by aquatic and terrestrial plants and soil microorganisms. A brief review of the biochemical basis for glutathione conjugation is presented. We recommend that multidisciplinary research focus on the occurrence and expression of glutathione and its attendant enzymes in plants and microorganisms, relationships between electrophilic substrate structure and enzyme activity, and the potential exploitation of plants and microorganisms that are competent in glutathione conjugation for phytoremediation and bioremediation.

  16. Conjugation in Escherichia coli

    PubMed Central

    Boyer, Herbert

    1966-01-01

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

  17. Star-Shaped Conjugated Systems

    PubMed Central

    Detert, Heiner; Lehmann, Matthias; Meier, Herbert

    2010-01-01

    The present review deals with the preparation and the properties of star-shaped conjugated compounds. Three, four or six conjugated arms are attached to cross-conjugated cores, which consist of single atoms (B, C+, N), benzene or azine rings or polycyclic ring systems, as for example triphenylene or tristriazolotriazine. Many of these shape-persistent [n]star compounds tend to π-stacking and self-organization, and exhibit interesting properties in materials science: Linear and non-linear optics, electrical conductivity, electroluminescence, formation of liquid crystalline phases, etc.

  18. Conjugate Relationships in Basic Electricity.

    ERIC Educational Resources Information Center

    Fisher, Kurt

    1999-01-01

    Presents an organization of seemingly disparate convention and procedure statements and rules of basic electricity into conjugate relationships which can be used to reduce students' memorization loads and improve their understanding. (WRM)

  19. Conjugated polymers: Watching polymers dance

    NASA Astrophysics Data System (ADS)

    Rothberg, Lewis

    2011-06-01

    Single-molecule spectroscopy allows fluctuations of conjugated polymer conformation to be monitored during solvent vapour annealing. Dramatic changes in fluorescence behaviour are observed and interpreted in terms of transformations between extended and collapsed polymer geometries.

  20. Entanglements in Conjugated Polymers

    NASA Astrophysics Data System (ADS)

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

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

  1. Protein carriers of conjugate vaccines

    PubMed Central

    Pichichero, Michael E

    2013-01-01

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

  2. Conjugated Fatty Acid Synthesis

    PubMed Central

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

    2012-01-01

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

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

    DOEpatents

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

    2018-06-05

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

  4. Enhanced photophysics of conjugated polymers

    DOEpatents

    Chen, Liaohai [Darien, IL

    2007-06-12

    A particulate fluorescent conjugated polymer surfactant complex and method of making and using same. The particles are between about 15 and about 50 nm and when formed from a lipsome surfactant have a charge density similar to DNA and are strongly absorbed by cancer cells.

  5. Polyamine-iron chelator conjugate.

    PubMed

    Bergeron, Raymond J; McManis, James S; Franklin, April M; Yao, Hua; Weimar, William R

    2003-12-04

    The current study demonstrates unequivocally that polyamines can serve as vectors for the intracellular delivery of the bidentate chelator 1,2-dimethyl-3-hydroxypyridin-4-one (L1). The polyamine-hydroxypyridinone conjugate 1-(12-amino-4,9-diazadodecyl)-2-methyl-3-hydroxy-4(1H)-pyridinone is assembled from spermine and 3-O-benzylmaltol. The conjugate is shown to form a 3:1 complex with Fe(III) and to be taken up by the polyamine transporter 1900-fold against a concentration gradient. The K(i) of the conjugate is 3.7 microM vs spermidine for the polyamine transporter. The conjugate is also at least 230 times more active in suppressing the growth of L1210 murine leukemia cells than is the parent ligand, decreases the activities of the polyamine biosynthetic enzymes ornithine decarboxylase and S-adenosylmethionine decarboxylase, and upregulates spermidine-spermine N (1)-acetyltransferase. However, the effect on native polyamine pools is a moderate one. These findings are in keeping with the idea that polyamines can also serve as efficient vectors for the intracellular delivery of other iron chelators.

  6. Orderings for conjugate gradient preconditionings

    NASA Technical Reports Server (NTRS)

    Ortega, James M.

    1991-01-01

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

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

    PubMed Central

    Yunus, Ali A.; Lima, Christopher D.

    2009-01-01

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

  8. Enhanced photophysics of conjugated polymers

    DOEpatents

    Chen, Liaohai [Argonne, IL; Xu, Su [Santa Clara, CA; McBranch, Duncan [Santa Fe, NM; Whitten, David [Santa Fe, NM

    2003-05-27

    The addition of oppositely charged surfactant to fluorescent ionic conjugated polymer forms a polymer-surfactant complex that exhibits at least one improved photophysical property. The conjugated polymer is a fluorescent ionic polymer that typically has at least one ionic side chain or moiety that interacts with the specific surfactant selected. The photophysical property improvements may include increased fluorescence quantum efficiency, wavelength-independent emission and absorption spectra, and more stable fluorescence decay kinetics. The complexation typically occurs in a solution of a polar solvent in which the polymer and surfactant are soluble, but it may also occur in a mixture of solvents. The solution is commonly prepared with a surfactant molecule:monomer repeat unit of polymer ratio ranging from about 1:100 to about 1:1. A polymer-surfactant complex precipitate is formed as the ratio approaches 1:1. This precipitate is recoverable and usable in many forms.

  9. Biosensors from conjugated polyelectrolyte complexes

    PubMed Central

    Wang, Deli; Gong, Xiong; Heeger, Peter S.; Rininsland, Frauke; Bazan, Guillermo C.; Heeger, Alan J.

    2002-01-01

    A charge neutral complex (CNC) was formed in aqueous solution by combining an orange light emitting anionic conjugated polyelectrolyte and a saturated cationic polyelectrolyte at a 1:1 ratio (per repeat unit). Photoluminescence (PL) from the CNC can be quenched by both the negatively charged dinitrophenol (DNP) derivative, (DNP-BS−), and positively charged methyl viologen (MV2+). Use of the CNC minimizes nonspecific interactions (which modify the PL) between conjugated polyelectrolytes and biopolymers. Quenching of the PL from the CNC by the DNP derivative and specific unquenching on addition of anti-DNP antibody (anti-DNP IgG) were observed. Thus, biosensing of the anti-DNP IgG was demonstrated. PMID:11756675

  10. Fiber bundle phase conjugate mirror

    DOEpatents

    Ward, Benjamin G.

    2012-05-01

    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.

  11. The Tcp conjugation system of Clostridium perfringens.

    PubMed

    Wisniewski, Jessica A; Rood, Julian I

    2017-05-01

    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. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Subgap Absorption in Conjugated Polymers

    DOE R&D Accomplishments Database

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

    1991-01-01

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

  13. Conjugations with glutathione. The enzymic conjugation of some chlorocyclohexenes

    PubMed Central

    Sims, P.; Grover, P. L.

    1965-01-01

    1. α-3,4,5,6-Tetrachlorocyclohex-1-ene and γ-2,3,4,5,6-pentachlorocyclohex-1-ene are conjugated with glutathione in vitro by a rat-liver enzyme that is probably glutathione S-aryltransferase. 2. Chlorocyclohexane and the α-, β-, γ- and δ-isomers of hexachlorocyclohexane were not substrates for rat-liver glutathione S-aryltransferase. 3. Glutathione-S-aryltransferase activity was present in tissue preparations of houseflies of insecticide-resistant and -susceptible strains. More activity was found in a dieldrin-resistant strain of houseflies fed on dieldrin than in either a dieldrin-resistant strain not fed on dieldrin or a control strain of dieldrin-susceptible houseflies. 4. Housefly soluble supernatant preparations converted S-(2-chloro-4-nitrophenyl)glutathione into the corresponding cysteine and mercapturic acid derivatives. PMID:14333551

  14. Tales of conjugation and sex pheromones

    PubMed Central

    2011-01-01

    This review covers highlights of the author's experience becoming and working as a plasmid biologist. The account chronicles a progression from studies of ColE1 DNA in Escherichia coli to Gram-positive bacteria with an emphasis on conjugation in enterococci. It deals with gene amplification, conjugative transposons and sex pheromones in the context of bacterial antibiotic resistance. PMID:22016844

  15. The Conjugate Acid-Base Chart.

    ERIC Educational Resources Information Center

    Treptow, Richard S.

    1986-01-01

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

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

    ERIC Educational Resources Information Center

    Hill, Malcolm D.

    1988-01-01

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

  17. Approximate error conjugation gradient minimization methods

    DOEpatents

    Kallman, Jeffrey S

    2013-05-21

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

  18. Narrow Band Gap Conjugated Polyelectrolytes.

    PubMed

    Cui, Qiuhong; Bazan, Guillermo C

    2018-01-16

    Two essential structural elements define a class of materials called conjugated polyelectrolytes (CPEs). The first is a polymer framework with an electronically delocalized, π-conjugated structure. This component allows one to adjust desirable optical and electronic properties, for example the range of wavelengths absorbed, emission quantum yields, electron affinity, and ionization potential. The second defining feature is the presence of ionic functionalities, which are usually linked via tethers that can modulate the distance of the charged groups relative to the backbone. These ionic groups render CPEs distinct relative to their neutral conjugated polymer counterparts. Solubility in polar solvents, including aqueous media, is an immediately obvious difference. This feature has enabled the development of optically amplified biosensor protocols and the fabrication of multilayer organic semiconductor devices through deposition techniques using solvents with orthogonal properties. Important but less obvious potential advantages must also be considered. For example, CPE layers have been used to introduce interfacial dipoles and thus modify the effective work function of adjacent electrodes. One can thereby modulate the barriers for charge injection into semiconductor layers and improve the device efficiencies of organic light-emitting diodes and solar cells. With a hydrophobic backbone and hydrophilic ionic sites, CPEs can also be used as dispersants for insoluble materials. Narrow band gap CPEs (NBGCPEs) have been studied only recently. They contain backbones that comprise electron-rich and electron-poor fragments, a combination that leads to intramolecular charge transfer excited states and enables facile oxidation and reduction. One particularly interesting combination is NBGCPEs with anionic sulfonate side groups, for which spontaneous self-doping in aqueous media is observed. That no such doping is observed with cationic NBGCPEs indicates that the interplay

  19. Conjugated Polymers: Catalysts for Photocatalytic Hydrogen Evolution.

    PubMed

    Zhang, Guigang; Lan, Zhi-An; Wang, Xinchen

    2016-12-19

    Conjugated polymers, comprising fully π-conjugated systems, present a new generation of heterogeneous photocatalysts for solar-energy utilization. They have three key features, namely robustness, nontoxicity, and visible-light activity, for photocatalytic processes, thus making them appealing candidates for scale-up. Presented in this Minireview, is a brief summary on the recent development of various promising polymer photocatalysts for hydrogen evolution from aqueous solutions, including linear polymers, planarized polymers, triazine/heptazine polymers, and other related organic conjugated semiconductors, with a particular focus on the rational manipulation in the composition, architectures, and optical and electronic properties that are relevant to photophysical and photochemical properties. Some future trends and prospects for organic conjugated photocatalysts in artificial photosynthesis, by water splitting, are also envisaged. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Conjugated amplifying polymers for optical sensing applications.

    PubMed

    Rochat, Sébastien; Swager, Timothy M

    2013-06-12

    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.

  1. Soluble polymer conjugates for drug delivery.

    PubMed

    Minko, Tamara

    2005-01-01

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

  2. Processing Conjugated-Diene-Containing Polymers

    NASA Technical Reports Server (NTRS)

    Bell, Vernon L.; Havens, Stephen J.

    1987-01-01

    Diels-Alder reaction used to cross-linked thermoplastics. Process uses Diels-Alder reaction to cross-link and/or extend conjugated-diene-containing polymers by reacting them with bis-unsaturated dienophiles results in improved polymer properties. Quantities of diene groups required for cross-linking varies from very low to very high concentrations. Process also used to extend, or build up molecular weights of, low-molecular-weight linear polymers with terminal conjugated dienic groups.

  3. Phase conjugation and time reversal in acoustics

    NASA Astrophysics Data System (ADS)

    Fink, Mathias

    2000-07-01

    This paper compares the different approaches used in acoustics to time reverse or to phase conjugate a wavefield. The basic principle of a time reversal mirror is an extension for broadband pulsed waves to the optical phase conjugated mirror designed for monochromatic waves. However, this equivalence is only valid mathematically and there are some fundamental differences between these two techniques that will be described in this paper.

  4. Emerging roles for conjugated sterols in plants.

    PubMed

    Ferrer, Albert; Altabella, Teresa; Arró, Montserrat; Boronat, Albert

    2017-07-01

    In plants, sterols are found in free form (free sterols, FSs) and conjugated as steryl esters (SEs), steryl glycosides (SGs) and acyl steryl glycosides (ASGs). Conjugated sterols are ubiquitously found in plants but their relative contents highly differ among species and their profile may change in response to developmental and environmental cues. SEs play a central role in membrane sterol homeostasis and also represent a storage pool of sterols in particular plant tissues. SGs and ASGs are main components of the plant plasma membrane (PM) that specifically accumulate in lipid rafts, PM microdomains known to mediate many relevant cellular processes. There are increasing evidences supporting the involvement of conjugated sterols in plant stress responses. In spite of this, very little is known about their metabolism. At present, only a limited number of genes encoding enzymes participating in conjugated sterol metabolism have been cloned and characterized in plants. The aim of this review is to update the current knowledge about the tissue and cellular distribution of conjugated sterols in plants and the enzymes involved in their biosynthesis. We also discuss novel aspects on the role of conjugated sterols in plant development and stress responses recently unveiled using forward- and reverse-genetic approaches. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Estimation of phenolic conjugation by colonic mucosa.

    PubMed Central

    Ramakrishna, B S; Gee, D; Weiss, A; Pannall, P; Roberts-Thomson, I C; Roediger, W E

    1989-01-01

    Conjugation of phenol by the colonic mucosa was assessed in vivo using dialysis tubing containing 1.5 ml of 1 mmol/l acetaminophen (paracetamol) and 10 mmol/l butyrate. These were allowed to equilibrate in the rectum for one hour. The glucuronidated and sulphated conjugates of acetaminophen were measured by high pressure liquid chromatography and bicarbonate concentrations by gas analysis. In 21 subjects without colonic disease sulphate conjugation was observed in all cases, with a mean (SE) of 3.86 (0.66) nmol/hour, while glucuronide conjugation was found in seven of 21 cases. Mean (SE) bicarbonate output of 42.9 (3.9) mumol/hour (n = 21) indicated healthy colonic mucosal metabolism and phenolic sulphation in dialysate and agreed with published sulphation rates obtained with cultured cells of colonic epithelium. Acetaminophen sulphation suggests that the colonic mucosa has an important role in the conjugation of phenols, and the method reported here would be useful in assessing the detoxification capacity of the colonic mucosa in diseases of the rectal mucosa. PMID:2738167

  6. Multicolor Upconversion Nanoparticles for Protein Conjugation

    PubMed Central

    Wilhelm, Stefan; Hirsch, Thomas; Patterson, Wendy M.; Scheucher, Elisabeth; Mayr, Torsten; Wolfbeis, Otto S.

    2013-01-01

    We describe the preparation of monodisperse, lanthanide-doped hexagonal-phase NaYF4 upconverting luminescent nanoparticles for protein conjugation. Their core was coated with a silica shell which then was modified with a poly(ethylene glycol) spacer and N-hydroxysuccinimide ester groups. The nanoparticles were characterized by transmission electron microscopy, Raman spectroscopy, X-ray diffraction, and dynamic light scattering. The N-hydroxysuccinimide ester functionalization renders them highly reactive towards amine nucleophiles (e.g., proteins). We show that such particles can be conjugated to proteins. The protein-reactive UCLNPs and their conjugates to streptavidin and bovine serum albumin display multicolor emissions upon 980-nm continuous wave laser excitation. Surface plasmon resonance studies were carried out to prove bioconjugation and to compare the affinity of the particles for proteins immobilized on a thin gold film. PMID:23606910

  7. Meningococcal conjugate vaccines: optimizing global impact

    PubMed Central

    Terranella, Andrew; Cohn, Amanda; Clark, Thomas

    2011-01-01

    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. PMID:22114508

  8. [Human drug metabolizing enzymes. II. Conjugation enzymes].

    PubMed

    Vereczkey, L; Jemnitz, K; Gregus, Z

    1998-09-01

    In this review we focus on human conjugation enzymes (UDP-glucuronyltransferases, methyl-trasferases, N-acetyl-transferases, O-acetyl-transferases, Amidases/carboxyesterases, sulfotransferases, Glutation-S-transferases and the enzymes involved in the conjugation with amino acids) that participate in the metabolism of xenobiotics. Although conjugation reactions in most of the cases result in detoxication, more and more publications prove that the reactions catalysed by these enzymes very often lead to activated molecules that may attack macromolecules (proteins, RNAs, DNAs), resulting in toxicity (liver, neuro-, embryotoxicity, allergy, carcinogenecity). We have summarised the data available on these enzymes concerning their catalytic profile and specificity, inhibition, induction properties, their possible role in the generation of toxic compounds, their importance in clinical practice and drug development.

  9. Biomedical Applications of Organometal-Peptide Conjugates

    NASA Astrophysics Data System (ADS)

    Metzler-Nolte, Nils

    Peptides are well suited as targeting vectors for the directed delivery of metal-based drugs or probes for biomedical investigations. This chapter describes synthetic strategies for the preparation of conjugates of medically interesting peptides with covalently bound metal complexes. Peptides that were used include neuropeptides (enkephalin, neuropeptide Y, neurotensin), uptake peptides (TAT and poly-Arg), and intracellular localization sequences. To these peptides, a whole variety of transition metal complexes has been attached in recent years by solid-phase peptide synthesis (SPPS) techniques. The metal complex can be attached to the peptide on the resin as part of the SPPS scheme. Alternatively, the metal complex may be attached to the peptide as a postsynthetic modification. Advantages as well as disadvantages for either strategy are discussed. Biomedical applications include radiopharmaceutical applications, anticancer and antibacterial activity, metal-peptide conjugates as targeted CO-releasing molecules, and metal-peptide conjugates in biosensor applications.

  10. Scintillation Reduction using Conjugate-Plane Imaging

    NASA Astrophysics Data System (ADS)

    Vander Haagen, Gary A.

    2017-06-01

    All observatories are plagued by atmospheric turbulence exhibited as star scintillation or "twinkle" whether a high altitude adaptive optics research or a 30 cm amateur telescope. It is well known that these disturbances are caused by wind and temperature driven refractive gradients in the atmosphere and limit the ultimate photometric resolution of land-based facilities. One approach identified by Fuchs (1998) for scintillation noise reduction was to create a conjugate image space at the telescope and focus on the dominant conjugate turbulent layer within that space. When focused on the turbulent layer little or no scintillation exists. This technique is described whereby noise reductions of 6 to 11/1 have been experienced with mathematical and optical bench simulations. Discussed is a proof-of-principle conjugate optical train design for an 80 mm, f-7 telescope.

  11. Conjugate field approaches for active array compensation

    NASA Technical Reports Server (NTRS)

    Acosta, R. J.

    1989-01-01

    Two approaches for calculating the compensating feed array complex excitations are namely, the indirect conjugate field matching (ICFM) and the direct conjugate field matching (DCFM) approach. In the ICFM approach the compensating feed array excitations are determined by considering the transmitting mode and the reciprocity principle. The DCF, in contrast calculates the array excitations by integrating directly the induced surface currents on the reflector under a receiving mode. DCFM allows the reflector to be illuminated by an incident plane wave with a tapered amplitude. The level of taper can effectively control the sidelobe level of the compensated antenna pattern. Both approaches are examined briefly.

  12. Phase Conjugation Scaling for High Energy Lasers.

    DTIC Science & Technology

    1985-05-30

    PFPORT b PfRiOE) C"v’’’ NV Pnase cor, uqatio. scaling for high. energy’ lasers FIna 718 PF RF06MING OR,’ 04EPOPT NUM14EP C 7. AUHRo. CONTRACT QN GRA#%T...nocoo..wy dind ld9ntalY DY OoCw K~b * - High energy lasers ; phase conjugation; stimulated Brillouin scattering,’ infrared waveguides 2. ABSTRACT...coiw on meoe eti if I r’w~ o ldenIr by block n’.inb..) * Phase conjugation of both cv and pulsed 10.6 micron lasers by stimulated * Brillouin

  13. Phase conjugate digital inline holography (PCDIH)

    DOE PAGES

    Guildenbecher, Daniel Robert; Hoffmeister, Kathryn N. Gabet; Kunzler, William Marley; ...

    2018-01-12

    We report digital inline holography (DIH) provides instantaneous three-dimensional (3D) measurements of diffracting objects; however, phase disturbances in the beam path can distort the imaging. In this Letter, a phase conjugate digital inline holography (PCDIH) configuration is proposed for removal of phase disturbances. Brillouin-enhanced four-wave mixing produces a phase conjugate signal that back propagates along the DIH beam path. Finally, the results demonstrate the removal of distortions caused by gas-phase shocks to recover 3D images of diffracting objects.

  14. Phase conjugate digital inline holography (PCDIH)

    SciTech Connect

    Guildenbecher, Daniel Robert; Hoffmeister, Kathryn N. Gabet; Kunzler, William Marley

    We report digital inline holography (DIH) provides instantaneous three-dimensional (3D) measurements of diffracting objects; however, phase disturbances in the beam path can distort the imaging. In this Letter, a phase conjugate digital inline holography (PCDIH) configuration is proposed for removal of phase disturbances. Brillouin-enhanced four-wave mixing produces a phase conjugate signal that back propagates along the DIH beam path. Finally, the results demonstrate the removal of distortions caused by gas-phase shocks to recover 3D images of diffracting objects.

  15. Integrated circuits based on conjugated polymer monolayer.

    PubMed

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

    2018-01-31

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

  16. Conjugal Succession and the American Kinship System.

    ERIC Educational Resources Information Center

    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…

  17. Women experiencing the intergenerationality of conjugal violence.

    PubMed

    Paixão, Gilvânia Patrícia do Nascimento; Gomes, Nadirlene Pereira; Diniz, Normélia Maria Freire; Carvalho e Lira, Margaret Ollinda de Souza; Carvalho, Milca Ramaiane da Silva; da Silva, Rudval Souza

    2015-01-01

    to analyze the family relationship, in childhood and adolescence, of women who experience conjugal violence. 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). 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. 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.

  18. Plasmid transfer by conjugation in Xylella fastidiosa.

    USDA-ARS?s Scientific Manuscript database

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

  19. Bacillus thuringiensis Conjugation in Simulated Microgravity

    NASA Astrophysics Data System (ADS)

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

    2009-10-01

    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.

  20. Compositions for directed alignment of conjugated polymers

    DOEpatents

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

    2016-04-19

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

  1. Integrated circuits based on conjugated polymer monolayer

    SciTech Connect

    Li, Mengmeng; Mangalore, Deepthi Kamath; Zhao, Jingbo

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

  2. Conjugate Gradient Algorithms For Manipulator Simulation

    NASA Technical Reports Server (NTRS)

    Fijany, Amir; Scheid, Robert E.

    1991-01-01

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

  3. Integrated circuits based on conjugated polymer monolayer

    DOE PAGES

    Li, Mengmeng; Mangalore, Deepthi Kamath; Zhao, Jingbo; ...

    2018-01-31

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

  4. Antibody-drug conjugates: Intellectual property considerations

    PubMed Central

    Storz, Ulrich

    2015-01-01

    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. PMID:26292154

  5. Bacillus thuringiensis conjugation in simulated microgravity.

    PubMed

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

    2009-10-01

    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.

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

    PubMed

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

    2018-04-01

    To determine whether family variables, such as type of relationship, years of marriage, existence of offspring, number of members of family, stage of family life cycle, transition between stages, perceived social support, and/or stressful life events are related to conjugal adjustment. A cross-sectional and correlational study using questionnaires. Primary care and hospital units of selected centres in the province of Seville, Spain. Consecutive stratified sampling by quotas of 369 heterosexual couples over 18years of age, who maintained a relationship, with or without children, living in Seville. A self-report questionnaire for the sociodemographic variables, and the abbreviated version of the Dyadic Adjustment Scale, Questionnaire MOS Perceived Social Support, and Social Readjustment Rating Scale, were used. Descriptive and inferential statistics were performed with correlation analysis and multivariate regression. Statistically significant associations were found between conjugal adjustment and marriage years (r=-10: P<.05), stage of family life cycle (F=2.65; P<.05), the transition between stages (RPB=.11; P<.05) and perceived social support (r=.44; P<.001). The regression model showed the predictive power of perceived social support and the family life cycle stage (mature-aged stage) on conjugal adjustment (R2=.21; F=9.9; df=356; P<.001). Couples may be assessed from Primary Care and be provide with resources and support. In addition, it can identify variables that may help improve the conjugal relationship. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  7. Improved conjugation and purification strategies for the preparation of protein-polysaccharide conjugates.

    PubMed

    Suárez, N; Massaldi, H; Franco Fraguas, L; Ferreira, F

    2008-12-12

    A glycoconjugate constituted by the Streptococcus pneumoniae serotype 14 capsular polysaccharide (CPS14) and bovine serum albumin (BSA) was prepared, and the unique properties of Sephadex LH-20 were used to separate the conjugate from the unconjugated material. The strength of this approach consists in its capacity to produce pure polysaccharide-protein conjugate in good yield and free from unconjugated material, a common residual contaminant of this type of immunobiologicals. The CPS14-BSA conjugate prepared via an improved 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP)-activation technique was characterized chemically and its immunogenicity was evaluated in mice. The purified conjugate, unlike the corresponding polysaccharide, produced a T-cell-dependent response in this species.

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

    SciTech Connect

    Xu, Ting; Dong, He; Shu, Jessica

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

  9. High-reflectivity phase conjugation using Brillouin preamplification.

    PubMed

    Ridley, K D; Scott, A M

    1990-07-15

    We describe experiments in which a weak laser pulse is phase conjugated by using a high-gain Brillouin amplifier in front of a stimulated Brillouin scattering phase-conjugate mirror. We observe phase conjugation with signal energies as low as 3 x 10(-13) J and with a maximum reflection coefficient of 2 x 10(8).

  10. Multi-step high-throughput conjugation platform for the development of antibody-drug conjugates.

    PubMed

    Andris, Sebastian; Wendeler, Michaela; Wang, Xiangyang; Hubbuch, Jürgen

    2018-07-20

    Antibody-drug conjugates (ADCs) form a rapidly growing class of biopharmaceuticals which attracts a lot of attention throughout the industry due to its high potential for cancer therapy. They combine the specificity of a monoclonal antibody (mAb) and the cell-killing capacity of highly cytotoxic small molecule drugs. Site-specific conjugation approaches involve a multi-step process for covalent linkage of antibody and drug via a linker. Despite the range of parameters that have to be investigated, high-throughput methods are scarcely used so far in ADC development. In this work an automated high-throughput platform for a site-specific multi-step conjugation process on a liquid-handling station is presented by use of a model conjugation system. A high-throughput solid-phase buffer exchange was successfully incorporated for reagent removal by utilization of a batch cation exchange step. To ensure accurate screening of conjugation parameters, an intermediate UV/Vis-based concentration determination was established including feedback to the process. For conjugate characterization, a high-throughput compatible reversed-phase chromatography method with a runtime of 7 min and no sample preparation was developed. Two case studies illustrate the efficient use for mapping the operating space of a conjugation process. Due to the degree of automation and parallelization, the platform is capable of significantly reducing process development efforts and material demands and shorten development timelines for antibody-drug conjugates. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Phase conjugation of high energy lasers.

    SciTech Connect

    Bliss, David E; Valley, Michael T.; Atherton, Briggs W.

    2013-01-01

    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 conjugatemore » 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.« less

  12. Synthesis and Characterization of Bioactive Tamoxifen-conjugated Polymers

    PubMed Central

    Rickert, Emily L.; Trebley, Joseph P.; Peterson, Anton C.; Morrell, Melinda M.; Weatherman, Ross V.

    2008-01-01

    Macromolecular conjugates of tamoxifen could perhaps be used to circumvent some of the limitations of the extensively used breast cancer drug. To test the feasibility of these conjugates, a 4-hydroxytamoxifen analog was conjugated to a diaminoalkyl linker and then conjugated to activated esters of a poly(methacrylic acid) polymer synthesized by atom transfer radical polymerization. A polymer conjugated to the 4-hydroxytamoxifen analog with a six carbon linker showed high affinity for both estrogen receptor alpha and estrogen receptor beta and potent antagonism of the estrogen receptor in cell-based transcriptional reporter assays. These results suggest that the conjugation of 4-hydroxytamoxifen to a polymer results in a macromolecular conjugate that can display ligand in a manner that can be recognized by estrogen receptor and still act as a potent antiestrogen in cells. PMID:17929966

  13. Ubiquitin in Motion: Structural Studies of the Ubiquitin-Conjugating Enzyme~Ubiquitin Conjugate

    SciTech Connect

    Pruneda, Jonathan N.; Stoll, Kate E.; Bolton, Laura J.

    2011-03-15

    Ubiquitination of proteins provides a powerful and versatile post-translational signal in the eukaryotic cell. The formation of a thioester bond between ubiquitin (Ub) and the active site of a ubiquitin-conjugating enzyme (E2) is critical for the transfer of Ub to substrates. Assembly of a functional ubiquitin ligase (E3) complex poised for Ub transfer involves recognition and binding of an E2~Ub conjugate. Therefore, full characterization of the structure and dynamics of E2~Ub conjugates is required for further mechanistic understanding of Ub transfer reactions. Here we present characterization of the dynamic behavior of E2~Ub conjugates of two human enzymes, UbcH5c~Ub and Ubc13~Ub,more » in solution as determined by nuclear magnetic resonance and small-angle X-ray scattering. Within each conjugate, Ub retains great flexibility with respect to the E2, indicative of highly dynamic species that adopt manifold orientations. The population distribution of Ub conformations is dictated by the identity of the E2: the UbcH5c~Ub conjugate populates an array of extended conformations, and the population of Ubc13~Ub conjugates favors a closed conformation in which the hydrophobic surface of Ub faces helix 2 of Ubc13. Finally, we propose that the varied conformations adopted by Ub represent available binding modes of the E2~Ub species and thus provide insight into the diverse E2~Ub protein interactome, particularly with regard to interaction with Ub ligases.« less

  14. Optical phase conjugation: principles, techniques, and applications

    NASA Astrophysics Data System (ADS)

    He, Guang S.

    2002-05-01

    Over the last three decades, optical phase conjugation (OPC) has been one of the major research subjects in the field of nonlinear optics and quantum electronics. OPC defines usually a special relationship between two coherent optical beams propagating in opposite directions with reversed wave front and identical transverse amplitude distributions. The unique feature of a pair of phase-conjugate beams is that the aberration influence imposed on the forward beam passed through an inhomogeneous or disturbing medium can be automatically removed for the backward beam passed through the same disturbing medium. To date there have been three major technical approaches that can efficiently produce the backward phase-conjugate beam. The first approach is based on the degenerate (or partially degenerate) four-wave mixing processes, the second is based on various backward simulated (Brillouin, Raman, Rayleigh-wing or Kerr) scattering processes, and the third is based on one-photon or multi-photon pumped backward stimulated emission (lasing) processes. Among these three different approaches, there is a common physical mechanism that plays the same essential role in generating a backward phase-conjugate beam, which is the formation of the induced holographic grating and the subsequent wave-front restoration via a backward reading beam. In most experimental studies, certain types of resonance enhancements of induced refractive-index changes are desirable for obtaining higher grating-refraction efficiency. The momentum of OPC studies has recently become even stronger because there are more prospective potentials and achievements for applications. OPC-associated techniques can be successfully utilized in many different application areas: such as high-brightness laser oscillator/amplifier systems, cavity-less lasing devices, laser target-aiming systems, aberration correction for coherent-light transmission and reflection through disturbing media, long distance optical fiber

  15. M-step preconditioned conjugate gradient methods

    NASA Technical Reports Server (NTRS)

    Adams, L.

    1983-01-01

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

  16. Conjugate gradient optimization programs for shuttle reentry

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

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

  17. Conformational Order in Aggregates of Conjugated Polymers

    SciTech Connect

    Jackson, Nicholas E.; Kohlstedt, Kevin L.; Savoie, Brett M.

    With the abundant variety and increasing chemical complexity of conjugated poly-friers proliferating the field of organic semiconductors, it has become increasingly important to correlate the polymer molecular structure with its mesoscale conformational and morphological attributes. For instance, it is unknown which combinations of chemical moieties and periodicities predictably produce mesoscale ordering. Interestingly) not all ordered morphologies result in efficient devices. In this work we have parametrized accurate classical force-fields and used these to compute the conformational and aggregation characteristics of single strands of common conjugated polymers. Molecular dynamics trajectories are shown to reproduce experimentally observed polymeric ordering, concluding that efficientmore » organic photovoltaic devices span a range of polymer conformational classes, and suggesting that the solution-phase morphologies have far-reaching effects. Encouragingly, these simulations indicate that despite the wide-range of conformational classes present in successful devices, local molecular ordering, and not long-range crystallinity, appears to be the necessary requirement for efficient devices. Finally, we examine what makes a "good" solvent for conjugated polymers, concluding that dispersive pi-electron solvent-polymer interactions, and not the electrostatic potential of the backbone interacting with the solvent, are what primarily determine a polymer's solubility in a particular solvent, and consequently its morphological characteristics.« less

  18. Conjugation, characterization and toxicity of lipophosphoglycan-polyacrylic acid conjugate for vaccination against leishmaniasis.

    PubMed

    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

    2013-06-03

    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.

  19. Synthesis, characterization and biological activity of Rhein-cyclodextrin conjugate

    NASA Astrophysics Data System (ADS)

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

    2017-01-01

    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.

  20. Protein/oligonucleotide conjugates as a cell specific PNA carrier.

    PubMed

    Obara, K; Ishihara, T; Akaike, T; Maruyama, A

    2001-01-01

    We have focused on proteineus ligand conjugate with oligonucleotides (ODNs) as a cell-specific delivery vector for peptide nucleic acids (PNAs). Asialofetuin (AF), a hepatocyte-specific proteineus ligand, was conjugated with ODNs that served as binding sites for PNAs. Succinimidyl-transe-4(N-maleimidylmethyl)-cyclohexane-1-carboxylate (SMCC) modified AF was coupled with 5'-thiolated oligodeoxynucleotide (HS-ODN). The resulting conjugate held PNAs with sequence-specific manner. The PNA/DNA conjugate complex has resistance against nucleases in serum. The efficient release of PNA from the complex was observed when the complex was made in contact with a target nucleotide. PNA uptake to hepatocytes was greatly enhanced when hepatocytes was incubated with PNA/conjugate complex. Free AF thoroughly inhibited PNA uptake with the conjugate, evidencing asialoglycoprotein receptor (ASGP-R) mediated endocytosis to be a major-route for the cellular uptake.

  1. Morphological priming by itself: a study of Portuguese conjugations.

    PubMed

    Veríssimo, João; Clahsen, Harald

    2009-07-01

    Does the language processing system make use of abstract grammatical categories and representations that are not directly visible from the surface form of a linguistic expression? This study examines stem-formation processes and conjugation classes, a case of 'pure' morphology that provides insight into the role of grammatical structure in language processing. We report results from a cross-modal priming experiment examining 1st and 3rd conjugation verb forms in Portuguese. Although items were closely matched with respect to a range of non-morphological factors, distinct priming patterns were found for 1st and 3rd conjugation stems. We attribute the observed priming patterns to different representations of conjugational stems, combinatorial morphologically structured ones for 1st conjugation and un-analyzed morphologically unstructured ones for 3rd conjugation stems. Our findings underline the importance of morphology for language comprehension indicating that morphological analysis goes beyond the identification of grammatical morphemes.

  2. Nonspecific Interaction of Streptavidin with Urease-Conjugated Antibodies

    DTIC Science & Technology

    1991-11-01

    11l1llilll li ii________ l__ :’SUFFIELD MEMORANDUM= NO. 1358 NONSPECIFIC INTERACTION OF STREPTAVIDIN WITH UREASE -CONJUGATED ANTIBODIES E LECT- by 92-01626...ESTABLISHMENT SUFFIELD RALSTON ALBERTA Suffield Memorandum No. 1358 Nonspecific Interaction of Streptavidin with Urease -Conjugated Antibodies by H. Gail...mixture, a urease -conjugated antibody. The variations could be diminished by allowing the reagents to stand at room temperature for two to three hours

  3. Minimizing inner product data dependencies in conjugate gradient iteration

    NASA Technical Reports Server (NTRS)

    Vanrosendale, J.

    1983-01-01

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

  4. Subpicosecond Optical Digital Computation Using Conjugate Parametric Generators

    DTIC Science & Technology

    1989-03-31

    Using Phase Conjugate Farametric Generators ..... 12. PERSONAL AUTHOR(S) Alfano, Robert- Eichmann . George; Dorsinville. Roger! Li. Yao 13a. TYPE OF...conjugation-based optical residue arithmetic processor," Y. Li, G. Eichmann , R. Dorsinville, and R. R. Alfano, Opt. Lett. 13, (1988). [2] "Parallel ultrafast...optical digital and symbolic computation via optical phase conjugation," Y. Li, G. Eichmann , R. Dorsinville, Appl. Opt. 27, 2025 (1988). [3

  5. Multiline phase conjugation at 4 microm in germanium.

    PubMed

    Depatie, D; Haueisen, D

    1980-06-01

    Phase conjugation by degenerate four-wave mixing in the 4-microm region in germanium has been observed for both single-line and multiline radiation. By using single-line output of a DF laser at 3.8 microm, X3 has been measured to be 4 X 10(-1) esu. Phase conjugation of multiline laser output has been achieved with an efficiency of 0.03%, a level that is consistent with the susceptibility found for single-line phase conjugation and the assumption of independent conjugation of each line of the multiline output.

  6. Helically assembled π-conjugated polymers with circularly polarized luminescence.

    PubMed

    Watanabe, Kazuyoshi; Akagi, Kazuo

    2014-08-01

    We review the recent progress in the field of helically assembled π -conjugated polymers, focusing on aromatic conjugated polymers with interchain helical π -stacking that exhibit circularly polarized luminescence (CPL). In Part 1, we discuss optically active polymers with white-colored CPL and the amplification of the circular polarization through liquid crystallinity. In Part 2, we focus on the stimuli-responsive CPL that results from changes in the conformation and aggregation state of π -conjugated molecules and polymers. In Part 3, we discuss the self-assembly of achiral cationic π -conjugated polymers into circularly polarized luminescent supramolecular nanostructures with the aid of other chiral molecules.

  7. 2-Deoxystreptamine Conjugates by Truncation–Derivatization of Neomycin

    PubMed Central

    Aslam, M. Waqar; Tabares, Leandro C.; Andreoni, Alessio; Canters, Gerard W.; Rutjes, Floris P.J.T.; van Delft, Floris L.

    2010-01-01

    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. PMID:27713274

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2017-09-20

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

  10. Multicellular Computing Using Conjugation for Wiring

    PubMed Central

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

    2013-01-01

    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

  11. Modeling Transformation and Conjugation in Bacteria Populations

    NASA Astrophysics Data System (ADS)

    Russo, John; Dong, J. J.

    The rise of antibiotic resistance in bacteria populations is a growing threat to medical treatment of diseases. Transformation, where a cell absorbs a plasmid from its environment, and conjugation, direct transfer of a plasmid from one cell to another, are the two main mechanisms of emergence of antibiotic resistance. We model the processes using a combined approach of Kinetic Monte Carlo simulation and differential equations to describe the plasmid-carrying and plasmid-free populations. Through analysis of our results, we characterize the conditions that lead to dominance of the antibiotic resistant population. NSF-DMR #1248387.

  12. Antibody–Drug Conjugates for Cancer Therapy

    PubMed Central

    Parslow, Adam C.; Parakh, Sagun; Lee, Fook-Thean; Gan, Hui K.; Scott, Andrew M.

    2016-01-01

    Antibody–drug conjugates (ADCs) take advantage of the specificity of a monoclonal antibody to deliver a linked cytotoxic agent directly into a tumour cell. The development of these compounds provides exciting opportunities for improvements in patient care. Here, we review the key issues impacting on the clinical success of ADCs in cancer therapy. Like many other developing therapeutic classes, there remain challenges in the design and optimisation of these compounds. As the clinical applications for ADCs continue to expand, key strategies to improve patient outcomes include better patient selection for treatment and the identification of mechanisms of therapy resistance. PMID:28536381

  13. π-Clamp-mediated cysteine conjugation

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  14. Conjugated Microporous Polymers for Heterogeneous Catalysis.

    PubMed

    Zhou, Yun-Bing; Zhan, Zhuang-Ping

    2018-01-04

    Conjugated microporous polymers (CMPs) are a class of crosslinked polymers that combine permanent micropores with π-conjugated skeletons and possess three-dimensional (3D) networks. Compared with conventional materials such as metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), CMPs usually have superior chemical and thermal stability. CMPs have made significant progress in heterogeneous catalysis in the past seven years. With a bottom-up strategy, catalytic moieties can be directly introduced into in the framework to produce heterogeneous CMP catalysts. Higher activity, stability, and selectivity can be obtained with heterogeneous CMP catalysts in comparison with their homogeneous analogs. In addition, CMP catalysts can be easily isolated and recycled. In this review, we focus on CMPs as an intriguing platform for developing various highly efficient and recyclable heterogeneous catalysts in organic reactions. The design, synthesis, and structure of these CMP catalysts are also discussed in this focus review. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Exploring the Charge Transport in Conjugated Polymers.

    PubMed

    Xu, Yong; Sun, Huabin; Li, Wenwu; Lin, Yen-Fu; Balestra, Francis; Ghibaudo, Gerard; Noh, Yong-Young

    2017-11-01

    Conjugated polymers came to an unprecedented epoch that the charge transport is limited only by small disorder within aggregated domains. Accurate evaluation of transport performance is thus vital to optimizing further molecule design. Yet, the routine method by means of the conventional field-effect transistors may not satisfy such a requirement. Here, it is shown that the extrinsic effects of Schottky barrier, access transport through semiconductor bulk, and concurrent ambipolar conduction seriously influence transport analysis. The planar transistors incorporating ohmic contacts free of access and ambipolar conduction afford an ideal access to charge transport. It is found, however, that only the planar transistors operating in low-field regime are reliable to explore the inherent transport properties due to the energetic disorder lowering by the lateral field induced by high drain voltage. This work opens up a robust approach to comprehend the delicate charge transport in conjugated polymers so as to develop high-performance semiconducting polymers for promising plastic electronics. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. [Pneumococcal vaccines. New conjugate vaccines for adults].

    PubMed

    Campins Martí, Magda

    2015-11-01

    Pneumococcal infections are a significant cause of morbidity and mortality, and are one of the 10 leading causes of death worldwide. Children under 2 years have a higher incidence rate, followed by adults over 64 years. The main risk group are individuals with immunodeficiency, and those with anatomical or functional asplenia, but can also affect immunocompetent persons with certain chronic diseases. Significant progress has been made in the last 10 years in the prevention of these infections. Until a few years ago, only the 23-valent non-conjugate pneumococcal vaccine was available. Its results were controversial in terms of efficacy and effectiveness, and with serious limitations on the type of immune response induced. The current possibility of using the 13-valent conjugate vaccine in adults has led to greater expectations in improving the prevention of pneumococcal disease in these age groups. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  17. The multigrid preconditioned conjugate gradient method

    NASA Technical Reports Server (NTRS)

    Tatebe, Osamu

    1993-01-01

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

  18. Bridging disulfides for stable and defined antibody drug conjugates.

    PubMed

    Badescu, George; Bryant, Penny; Bird, Matthew; Henseleit, Korinna; Swierkosz, Julia; Parekh, Vimal; Tommasi, Rita; Pawlisz, Estera; Jurlewicz, Kosma; Farys, Monika; Camper, Nicolas; Sheng, XiaoBo; Fisher, Martin; Grygorash, Ruslan; Kyle, Andrew; Abhilash, Amrita; Frigerio, Mark; Edwards, Jeff; Godwin, Antony

    2014-06-18

    To improve both the homogeneity and the stability of ADCs, we have developed site-specific drug-conjugating reagents that covalently rebridge reduced disulfide bonds. The new reagents comprise a drug, a linker, and a bis-reactive conjugating moiety that is capable of undergoing reaction with both sulfur atoms derived from a reduced disulfide bond in antibodies and antibody fragments. A disulfide rebridging reagent comprising monomethyl auristatin E (MMAE) was prepared and conjugated to trastuzumab (TRA). A 78% conversion of antibody to ADC with a drug to antibody ratio (DAR) of 4 was achieved with no unconjugated antibody remaining. The MMAE rebridging reagent was also conjugated to the interchain disulfide of a Fab derived from proteolytic digestion of TRA, to give a homogeneous single drug conjugated product. The resulting conjugates retained antigen-binding, were stable in serum, and demonstrated potent and antigen-selective cell killing in in vitro and in vivo cancer models. Disulfide rebridging conjugation is a general approach to prepare stable ADCs, which does not require the antibody to be recombinantly re-engineered for site-specific conjugation.

  19. Antimicrobial Peptide-PNA Conjugates Selectively Targeting Bacterial Genes

    DTIC Science & Technology

    2013-07-22

    RXR)4XB and (KFF)3K, were previously reported as a potent permeabilizer against E. coli and MRSA cells (Mellbye, 2009). (RW)4D, a small dendrimeric ...lethal concentration (Liu, 2007). Scheme 1. Synthesis of PNA- dendrimer conjugate. (a) (RW)4D-cysteine (b)Free PNA (C) PNA-(RW)4D conjugates

  20. Enzyme linked immunoassay with stabilized polymer saccharide enzyme conjugates

    DOEpatents

    Callstrom, M.R.; Bednarski, M.D.; Gruber, P.R.

    1997-11-25

    An improvement in enzyme linked immunoassays is disclosed wherein the enzyme is in the form of a water soluble polymer saccharide conjugate which is stable in hostile environments. The conjugate comprises the enzyme which is linked to the polymer at multiple points through saccharide linker groups. 19 figs.

  1. Method for synthesizing peptides with saccharide linked enzyme polymer conjugates

    DOEpatents

    Callstrom, M.R.; Bednarski, M.D.; Gruber, P.R.

    1997-06-17

    A method is disclosed for synthesizing peptides using water soluble enzyme polymer conjugates. The method comprises catalyzing the peptide synthesis with enzyme which has been covalently bonded to a polymer through at least three linkers which linkers have three or more hydroxyl groups. The enzyme is conjugated at lysines or arginines. 19 figs.

  2. Enzyme linked immunoassay with stabilized polymer saccharide enzyme conjugates

    DOEpatents

    Callstrom, Matthew R.; Bednarski, Mark D.; Gruber, Patrick R.

    1997-01-01

    An improvement in enzyme linked immunoassays is disclosed wherein the enzyme is in the form of a water soluble polymer saccharide conjugate which is stable in hostile environments. The conjugate comprises the enzyme which is linked to the polymer at multiple points through saccharide linker groups.

  3. Method for synthesizing peptides with saccharide linked enzyme polymer conjugates

    DOEpatents

    Callstrom, Matthew R.; Bednarski, Mark D.; Gruber, Patrick R.

    1997-01-01

    A method is disclosed for synthesizing peptides using water soluble enzyme polymer conjugates. The method comprises catalyzing the peptide synthesis with enzyme which has been covalently bonded to a polymer through at least three linkers which linkers have three or more hydroxyl groups. The enzyme is conjugated at lysines or arginines.

  4. Responsive Guest Encapsulation of Dynamic Conjugated Microporous Polymers.

    PubMed

    Xu, Lai; Li, Youyong

    2016-06-30

    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.

  5. Chain conformations and phase behavior of conjugated polymers.

    PubMed

    Kuei, Brooke; Gomez, Enrique D

    2016-12-21

    Conjugated polymers may play an important role in various emerging optoelectronic applications because they combine the chemical versatility of organic molecules and the flexibility, stretchability and toughness of polymers with semiconducting properties. Nevertheless, in order to achieve the full potential of conjugated polymers, a clear description of how their structure, morphology, and macroscopic properties are interrelated is needed. We propose that the starting point for understanding conjugated polymers includes understanding chain conformations and phase behavior. Efforts to predict and measure the persistence length have significantly refined our intuition of the chain stiffness, and have led to predictions of nematic-to-isotropic transitions. Exploring mixing between conjugated polymers and small molecules or other polymers has demonstrated tremendous advancements in attaining the needed properties for various optoelectronic devices. Current efforts continue to refine our knowledge of chain conformations and phase behavior and the factors that influence these properties, thereby providing opportunities for the development of novel optoelectronic materials based on conjugated polymers.

  6. In vitro antibody-enzyme conjugates with specific bactericidal activity.

    PubMed

    Knowles, D M; Sulivan, T J; Parker, C W; Williams, R C

    1973-06-01

    IgG with antibacterial antibody opsonic activity was isolated from rabbit antisera produced by intravenous hyperimmunization with several test strains of pneumococci, Group A beta-hemolytic streptococci, Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, and Escherichia coli. Antibody-enzyme conjugates were prepared, using diethylmalonimidate to couple glucose oxidase to IgG antibacterial antibody preparations. Opsonic human IgG obtained from serum of patients with subacute bacterial endocarditis was also conjugated to glucose oxidase. Antibody-enzyme conjugates retained combining specificity for test bacteria as demonstrated by indirect immunofluorescence. In vitro test for bactericidal activity of antibody-enzyme conjugates utilized potassium iodide, lactoperoxidase, and glucose as cofactors. Under these conditions glucose oxidase conjugated to antibody generates hydrogen peroxide, and lactoperoxidase enzyme catalyzes the reduction of hydrogen peroxide with simultaneous oxidation of I(-) and halogenation and killing of test bacteria. Potent in vitro bactericidal activity of this system was repeatedly demonstrated for antibody-enzyme conjugates against pneumococci, streptococci, S. aureus, P. mirabilis, and E. coli. However, no bactericidal effect was demonstrable with antibody-enzyme conjugates and two test strains of P. aeruginosa. Bactericidal activity of antibody-enzyme conjugates appeared to parallel original opsonic potency of unconjugated IgG preparations. Antibody-enzyme conjugates at concentrations as low as 0.01 mg/ml were capable of intense bactericidal activity producing substantial drops in surviving bacterial counts within 30-60 min after initiation of assay. These in vitro bactericidal systems indicate that the concept of antibacterial antibody-enzyme conjugates may possibly be adaptable as a mechanism for treatment of patients with leukocyte dysfunction or fulminant bacteremia.

  7. A Scheme for the Evaluation of Electron Delocalization and Conjugation Efficiency in Linearly π-Conjugated Systems.

    PubMed

    Bruschi, Maurizio; Limacher, Peter A; Hutter, Jürg; Lüthi, Hans Peter

    2009-03-10

    In this study, we present a scheme for the evaluation of electron delocalization and conjugation efficiency in lineraly π-conjugated systems. The scheme, based on the natural bond orbital theory, allows monitoring the evolution of electron delocalization along an extended conjugation path as well as its response to chemical modification. The scheme presented is evaluated and illustrated by means of a computational investigation of π-conjugation in all-trans polyacetylene [PA; H(-CH═CH)n-H], polydiacetylene [PDA, H(-C≡C-CH═CH)n-H], and polytriacetylene [PTA, H(-C≡C-CH═CH-C≡C)n-H] with up to 180 carbon atoms, all related by the number of ethynyl units incorporated in the chain. We are able to show that for short oligomers the incorporation of ethynyl spacers into the PA chain increases the π-delocalization energy, but, on the other hand, reduces the efficiency with which π-electron delocalization is promoted along the backbone. This explains the generally shorter effective conjugation lengths observed for the properties of the polyeneynes (PDA and PTA) relative to the polyenes (PA). It will also be shown that the reduced conjugation efficiency, within the NBO-based model presented in this work, can be related to the orbital interaction pattern along the π-conjugated chain. We will show that the orbital interaction energy pattern is characteristic for the type and the length of the backbone and may therefore serve as a descriptor for linearly π-conjugated chains.

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

    PubMed

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

    2014-04-01

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

  9. Conjugate Heat Transfer Study in Hypersonic Flows

    NASA Astrophysics Data System (ADS)

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

    2018-04-01

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

  10. Designer diatom episomes delivered by bacterial conjugation

    SciTech Connect

    Karas, Bogumil J.; Diner, Rachel E.; Lefebvre, Stephane C.

    Eukaryotic microalgae hold great promise for the bioproduction of fuels and higher value chemicals. However, compared with model genetic organisms such as Escherichia coli and Saccharomyces cerevisiae, characterization of the complex biology and biochemistry of algae and strain improvement has been hampered by the inefficient genetic tools. To date, many algal species are transformable only via particle bombardment, and the introduced DNA is integrated randomly into the nuclear genome. Here we describe the first nuclear episomal vector for diatoms and a plasmid delivery method via conjugation from Escherichia coli to the diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana. We identify amore » yeast-derived sequence that enables stable episome replication in these diatoms even in the absence of antibiotic selection and show that episomes are maintained as closed circles at copy number equivalent to native chromosomes. This highly efficient genetic system facilitates high-throughput functional characterization of algal genes and accelerates molecular phytoplankton research.« less

  11. Designer diatom episomes delivered by bacterial conjugation

    DOE PAGES

    Karas, Bogumil J.; Diner, Rachel E.; Lefebvre, Stephane C.; ...

    2015-04-21

    Eukaryotic microalgae hold great promise for the bioproduction of fuels and higher value chemicals. However, compared with model genetic organisms such as Escherichia coli and Saccharomyces cerevisiae, characterization of the complex biology and biochemistry of algae and strain improvement has been hampered by the inefficient genetic tools. To date, many algal species are transformable only via particle bombardment, and the introduced DNA is integrated randomly into the nuclear genome. Here we describe the first nuclear episomal vector for diatoms and a plasmid delivery method via conjugation from Escherichia coli to the diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana. We identify amore » yeast-derived sequence that enables stable episome replication in these diatoms even in the absence of antibiotic selection and show that episomes are maintained as closed circles at copy number equivalent to native chromosomes. This highly efficient genetic system facilitates high-throughput functional characterization of algal genes and accelerates molecular phytoplankton research.« less

  12. Double diffusive conjugate heat transfer: Part I

    NASA Astrophysics Data System (ADS)

    Azeem, Soudagar, Manzoor Elahi M.

    2018-05-01

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

  13. Targeted Immunomodulation Using Antigen-Conjugated Nanoparticles

    PubMed Central

    McCarthy, Derrick P.; Hunter, Zoe N.; Chackerian, Bryce; Shea, Lonnie D.; Miller, Stephen D.

    2014-01-01

    The growing prevalence of nanotechnology in the fields of biology, medicine and the pharmaceutical industry is confounded by the relatively small amount of data on the impact of these materials on the immune system. In addition to concerns surrounding the potential toxicity of nanoparticle (NP)-based delivery systems, there is also a demand for a better understanding of the mechanisms governing interactions of NPs with the immune system. Nanoparticles can be tailored to suppress, enhance, or subvert recognition by the immune system. This “targeted immunomodulation” can be achieved by delivery of unmodified particles, or by modifying particles to deliver drugs, proteins/peptides or genes to a specific site. In order to elicit the desired, beneficial immune response, considerations should be made at every step of the design process: the NP platform itself, ligands and other modifiers, the delivery route, and the immune cells that will encounter the conjugated NPs can all impact host immune responses. PMID:24616452

  14. Double diffusive conjugate heat transfer: Part II

    NASA Astrophysics Data System (ADS)

    Azeem, Soudagar, Manzoor Elahi M.

    2018-05-01

    Conjugate heat transfer in porous medium is an important study involved in many practical applications. The current study is aimed to investigate the double diffusive flow in a square porous cavity subjected to left vertical surface heating and right vertical surface cooling respectively along with left and right surfaces maintained at high and low concentration. The three governing equations are converted into algebraic form of equations by applying finite element method and solved in iterative manner. The study is focused to investigate the effect of presence of solid inside the cavity with respect to varying buoyancy ratio. It is found that the local heat and mass transfer rate decreases along the height of cavity.

  15. TIL system with nonlinear phase conjugation

    NASA Astrophysics Data System (ADS)

    Khizhnyak, Anatoliy; Markov, Vladimir

    2007-09-01

    Efficient laser beam delivery on a distant target remains a key problem for practical implementation of tactical laser systems. Since the conventional target-in-the-loop (TIL) concept is generally not effective in such operational environments, new solutions are needed. In this report we discuss an innovative approach for effective compensation of laser beam aberrations in TIL systems. It is based on a recently devised technique that combines optical phase conjugation (OPC) with a TIL system for effective hot-spot formation. The proposed method should enable delivery of enhanced density laser energy to a target within a finite number of iteration cycles. Using the model based on an analogy between the TIL system and laser resonator, pointing of the laser beam on the target is performed at the image plane, resulting in reduced hot-spot formation time.

  16. A fast, preconditioned conjugate gradient Toeplitz solver

    NASA Technical Reports Server (NTRS)

    Pan, Victor; Schrieber, Robert

    1989-01-01

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

  17. Conjugated Polymers Atypically Prepared in Water

    PubMed Central

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

    2010-01-01

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

  18. Resistance to Antibody-Drug Conjugates.

    PubMed

    García-Alonso, Sara; Ocaña, Alberto; Pandiella, Atanasio

    2018-05-01

    Antibody-drug conjugates (ADC) are multicomponent molecules constituted by an antibody covalently linked to a potent cytotoxic agent. ADCs combine high target specificity provided by the antibody together with strong antitumoral properties provided by the attached cytotoxic agent. At present, four ADCs have been approved and over 60 are being explored in clinical trials. Despite their effectiveness, resistance to these drugs unfortunately occurs. Efforts to understand the bases underlying such resistance are being carried out with the final purpose of counteracting them. In this review, we report described mechanisms of resistance to ADCs used in the clinic along with other potential ones that may contribute to resistance acquisition. We also discuss strategies to overcome resistance to ADCs. Cancer Res; 78(9); 2159-65. ©2018 AACR . ©2018 American Association for Cancer Research.

  19. WGA-Alexa conjugates for axonal tracing

    PubMed Central

    Levy, Sabrina L.; White, Joshua J.; Lackey, Elizabeth P.; Schwartz, Lindsey; Sillitoe, Roy V.

    2017-01-01

    Anatomical labeling approaches are essential for understanding brain organization. Among these approaches are various methods of performing tract tracing. However, a major hurdle to overcome when marking neurons in vivo is visibility. Poor visibility makes it challenging to image a desired neuronal pathway so that it can be easily differentiated from a closely neighboring pathway. As a result, it becomes impossible to analyze individual projections or their connections. The tracer that is chosen for a given purpose has a major influence on the quality of the tracing. Here, we describe the wheat germ agglutinin (WGA) tracer conjugated to Alexa fluorophores for reliable high-resolution tracing of central nervous system projections. Using the mouse cerebellum as a model system, we implement WGA-Alexa tracing for marking and mapping neural circuits that control motor function. We also show its utility for marking localized regions of the cerebellum after performing single-unit extracellular recordings in vivo. PMID:28398642

  20. Conjugating binary systems for spacecraft thermal control

    NASA Technical Reports Server (NTRS)

    Grodzka, Philomena G.; Dean, William G.; Sisk, Lori A.; Karu, Zain S.

    1989-01-01

    The materials search was directed to liquid pairs which can form hydrogen bonds of just the right strength, i.e., strong enough to give a high heat of mixing, but weak enough to enable phase change to occur. The cursory studies performed in the area of additive effects indicate that Conjugating Binary (CB) performance can probably be fine-tuned by this means. The Fluid Loop Test Systems (FLTS) tests of candidate CBs indicate that the systems Triethylamine (TEA)/water and propionaldehyde/water show close to the ideal, reversible behavior, at least initially. The Quick Screening Tests QSTs and FLTS tests, however, both suffer from rather severe static due either to inadequate stirring or temperature control. Thus it is not possible to adequately evaluate less than ideal CB performers. Less than ideal performers, it should be noted, may have features that make them better practical CBs than ideal performers. Improvement of the evaluation instrumentation is thus indicated.

  1. Near-IR Light-Cleavable Antibody Conjugates and Conjugate Precursors | NCI Technology Transfer Center | TTC

    Cancer.gov

    Researchers at the National Cancer Institute (NCI) developed novel groups of cyanine (Cy) based antibody-drug conjugate (ADC) chemical linkers that undergo photolytic cleavage upon irradiation with near-IR light. By using the fluorescent properties of the Cy linker to monitor localization of the ADC, and subsequent near-IR irradiation of cancerous tissue, drug release could be confined to the tumor microenvironment.

  2. White-Light Phase-Conjugate Mirrors as Distortion Correctors

    NASA Technical Reports Server (NTRS)

    Frazier, Donald; Smith, W. Scott; Abdeldayem, Hossin; Banerjee, Partha

    2010-01-01

    White-light phase-conjugate mirrors would be incorporated into some optical systems, according to a proposal, as means of correcting for wavefront distortions caused by imperfections in large optical components. The proposal was given impetus by a recent demonstration that white, incoherent light can be made to undergo phase conjugation, whereas previously, only coherent light was known to undergo phase conjugation. This proposal, which is potentially applicable to almost any optical system, was motivated by a need to correct optical aberrations of the primary mirror of the Hubble Space telescope. It is difficult to fabricate large optical components like the Hubble primary mirror and to ensure the high precision typically required of such components. In most cases, despite best efforts, the components as fabricated have small imperfections that introduce optical aberrations that adversely affect imaging quality. Correcting for such aberrations is difficult and costly. The proposed use of white-light phase conjugate mirrors offers a relatively simple and inexpensive solution of the aberration-correction problem. Indeed, it should be possible to simplify the entire approach to making large optical components because there would be no need to fabricate those components with extremely high precision in the first place: A white-light phase-conjugate mirror could correct for all the distortions and aberrations in an optical system. The use of white-light phase-conjugate mirrors would be essential for ensuring high performance in optical systems containing lightweight membrane mirrors, which are highly deformable. As used here, "phase-conjugate mirror" signifies, more specifically, an optical component in which incident light undergoes time-reversal phase conjugation. In practice, a phase-conjugate mirror would typically be implemented by use of a suitably positioned and oriented photorefractive crystal. In the case of a telescope comprising a primary and secondary

  3. Aptamer-conjugated nanobubbles for targeted ultrasound molecular imaging.

    PubMed

    Wang, Chung-Hsin; Huang, Yu-Fen; Yeh, Chih-Kuang

    2011-06-07

    Targeted ultrasound contrast agents can be prepared by some specific bioconjugation techniques. The biotin-avidin complex is an extremely useful noncovalent binding system, but the system might induce immunogenic side effects in human bodies. Previous proposed covalently conjugated systems suffered from low conjugation efficiency and complex procedures. In this study, we propose a covalently conjugated nanobubble coupling with nucleic acid ligands, aptamers, for providing a higher specific affinity for ultrasound targeting studies. The sgc8c aptamer was linked with nanobubbles through thiol-maleimide coupling chemistry for specific targeting to CCRF-CEM cells. Further improvements to reduce the required time and avoid the degradation of nanobubbles during conjugation procedures were also made. Several investigations were used to discuss the performance and consistency of the prepared nanobubbles, such as size distribution, conjugation efficiency analysis, and flow cytometry assay. Further, we applied our conjugated nanobubbles to ex vivo ultrasound targeted imaging and compared the resulting images with optical images. The results indicated the availability of aptamer-conjugated nanobubbles in targeted ultrasound imaging and the practicability of using a highly sensitive ultrasound system in noninvasive biological research.

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

    NASA Astrophysics Data System (ADS)

    Titanova, Elena O.; Burygin, Gennady L.

    2016-04-01

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

  5. Mannose-pepstatin conjugates as targeted inhibitors of antigen processing.

    PubMed

    Free, Paul; Hurley, Christopher A; Kageyama, Takashi; Chain, Benjamin M; Tabor, Alethea B

    2006-05-07

    The molecular details of antigen processing, including the identity of the enzymes involved, their intracellular location and their substrate specificity, are still incompletely understood. Selective inhibition of proteolytic antigen processing enzymes such as cathepsins D and E, using small molecular inhibitors such as pepstatin, has proven to be a valuable tool in investigating these pathways. However, pepstatin is poorly soluble in water and has limited access to the antigen processing compartment in antigen presenting cells. We have synthesised mannose-pepstatin conjugates, and neomannosylated BSA-pepstatin conjugates, as tools for the in vivo study of the antigen processing pathway. Conjugation to mannose and to neomannosylated BSA substantially improved the solubility of the conjugates relative to pepstatin. The mannose-pepstatin conjugates showed no reduction in inhibition of cathepsin E, whereas the neomannosylated BSA-pepstatin conjugates showed some loss of inhibition, probably due to steric factors. However, a neomannosylated BSA-pepstatin conjugate incorporating a cleavable disulfide linkage between the pepstatin and the BSA showed the best uptake to dendritic cells and the best inhibition of antigen processing.

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

    PubMed

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

    2014-09-01

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

  7. Molecular diodes based on conjugated diblock co-oligomers.

    PubMed

    Ng, Man-Kit; Lee, Dong-Chan; Yu, Luping

    2002-10-09

    This report describes synthesis and characterization of a molecular diode based upon a diblock conjugated oligomer system. This system consists of two conjugated blocks with opposite electronic demand. The molecular structure exhibits a built-in electronic asymmetry, much like a semiconductor p-n junction. Electrical measurements by scanning tunneling spectroscopy (STS) clearly revealed a pronounced rectifying effect. Definitive proof for the molecular nature of the rectifying effect in this conjugated diblock molecule is provided by control experiments with a structurally similar reference compound.

  8. Derivatized gold clusters and antibody-gold cluster conjugates

    DOEpatents

    Hainfeld, J.F.; Furuya, F.R.

    1994-11-01

    Antibody- or antibody fragment-gold cluster conjugates are shown wherein the conjugate size can be as small as 5.0 nm. Methods and reagents are disclosed in which antibodies, Fab' or F(ab')[sub 2] fragments are covalently bound to a stable cluster of gold atoms. The gold clusters may contain 6, 8, 9, 11, 13, 55 or 67 gold atoms in their inner core. The clusters may also contain radioactive gold. The antibody-cluster conjugates are useful in electron microscopy applications as well as in clinical applications that include imaging, diagnosis and therapy. 7 figs.

  9. Derivatized gold clusters and antibody-gold cluster conjugates

    DOEpatents

    Hainfeld, James F.; Furuya, Frederic R.

    1994-11-01

    Antibody- or antibody fragment-gold cluster conjugates are shown wherein the conjugate size can be as small as 5.0 nm. Methods and reagents are disclosed in which antibodies, Fab' or F(ab').sub.2 fragments thereof are covalently bound to a stable cluster of gold atoms. The gold clusters may contain 6, 8, 9, 11, 13, 55 or 67 gold atoms in their inner core. The clusters may also contain radioactive gold. The antibody-cluster conjugates are useful in electron microscopy applications as well as in clinical applications that include imaging, diagnosis and therapy.

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

    SciTech Connect

    Schanze, Kirk S

    2014-08-05

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

  11. Multilevel Investigation of Charge Transport in Conjugated Polymers.

    PubMed

    Dong, Huanli; Hu, Wenping

    2016-11-15

    Conjugated polymers have attracted the world's attentions since their discovery due to their great promise for optoelectronic devices. However, the fundamental understanding of charge transport in conjugated polymers remains far from clear. The origin of this challenge is the natural disorder of polymers with complex molecular structures in the solid state. Moreover, an effective way to examine the intrinsic properties of conjugated polymers is absent. Optoelectronic devices are always based on spin-coated films. In films, polymers tend to form highly disordered structures at nanometer to micrometer length scales due to the high degree of conformational freedom of macromolecular chains and the irregular interchain entanglement, thus typically resulting in much lower charge transport properties than their intrinsic performance. Furthermore, a subtle change of processing conditions may dramatically affect the film formation-inducing large variations in the morphology, crystallinity, microstructure, molecular packing, and alignment, and finally varying the effective charge transport significantly and leading to great inconsistency over an order of magnitude even for devices based on the same polymer semiconductor. Meanwhile, the charge transport mechanism in conjugated polymers is still unclear and its investigation is challenging based on such complex microstructures of polymers in films. Therefore, how to objectively evaluate the charge transport and probe the charge transport mechanism of conjugated polymers has confronted the world for decades. In this Account, we present our recent progress on multilevel charge transport in conjugated polymers, from disordered films, uniaxially aligned thin films, and single crystalline micro- or nanowires to molecular scale, where a derivative of poly(para-phenylene ethynylene) with thioacetyl end groups (TA-PPE) is selected as the candidate for investigation, which could also be extended to other conjugated polymer systems. Our

  12. Lipid-peptide-polymer conjugates and nanoparticles thereof

    DOEpatents

    Xu, Ting; Dong, He; Shu, Jessica

    2015-06-02

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

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

    PubMed

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

    2017-03-01

    Modification of cellular macromolecules by reactive drug metabolites is considered to play an important role in the initiation of tissue injury by many drugs. Detection and identification of reactive intermediates is often performed by analyzing the conjugates formed after trapping by glutathione (GSH). Although sensitivity of modern mass spectrometrical methods is extremely high, absolute quantification of GSH-conjugates is critically dependent on the availability of authentic references. Although 1 H NMR is currently the method of choice for quantification of metabolites formed biosynthetically, its intrinsically low sensitivity can be a limiting factor in quantification of GSH-conjugates which generally are formed at low levels. In the present study, a simple but sensitive and generic method for absolute quantification of GSH-conjugates is presented. The method is based on quantitative alkaline hydrolysis of GSH-conjugates and subsequent quantification of glutamic acid and glycine by HPLC after precolumn derivatization with o-phthaldialdehyde/N-acetylcysteine (OPA/NAC). Because of the lower stability of the glycine OPA/NAC-derivate, quantification of the glutamic acid OPA/NAC-derivate appeared most suitable for quantification of GSH-conjugates. The novel method was used to quantify the concentrations of GSH-conjugates of diclofenac, clozapine and acetaminophen and quantification was consistent with 1 H NMR, but with a more than 100-fold lower detection limit for absolute quantification. Copyright © 2017. Published by Elsevier B.V.

  14. Enhanced solubility and antioxidant activity of chlorogenic acid-chitosan conjugates due to the conjugation of chitosan with chlorogenic acid.

    PubMed

    Rui, Liyun; Xie, Minhao; Hu, Bing; Zhou, Li; Saeeduddin, Muhammad; Zeng, Xiaoxiong

    2017-08-15

    Chlorogenic acid-chitosan conjugate was synthesized by introducing of chlorogenic acid onto chitosan with the aid of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and hydroxybenzotriazole. The data of UV-vis, FT-IR and NMR for chlorogenic acid-chitosan conjugates demonstrated the successful conjugation of chlorogenic acid with chitosan. Compared to chitosan, chlorogenic acid-chitosan conjugates exhibited increased solubility in distilled water, 1% acetic acid solution (v/v) or 50% ethanol solution (v/v) containing 0.5% acetic acid. Moreover, chlorogenic acid-chitosan conjugates showed dramatic enhancements in metal ion chelating activity, total antioxidant capacity, scavenging activities on 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) and superoxide radicals, inhibitory effects on lipid peroxidation and β-carotene-linoleic acid bleaching, and protective effect on H 2 O 2 -induced oxidative injury of PC12 cells. Particularly, chlorogenic acid-chitosan conjugate exhibited higher inhibitory effects on lipid peroxidation and β-carotene-linoleic acid bleaching than chlorogenic acid. The results suggested that chlorogenic acid-chitosan conjugates could serve as food supplements to enhance the function of foods in future. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2012-12-31

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

  16. Conjugated Polymers/DNA Hybrid Materials for Protein Inactivation.

    PubMed

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

    2016-09-07

    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.

  17. Dehydration Polymerization for Poly(hetero)arene Conjugated Polymers.

    PubMed

    Mirabal, Rafael A; Vanderzwet, Luke; Abuadas, Sara; Emmett, Michael R; Schipper, Derek

    2018-02-18

    The lack of scalable and sustainable methods to prepare conjugated polymers belies their importance in many enabling technologies. Accessing high-performance poly(hetero)arene conjugated polymers by dehydration has remained an unsolved problem in synthetic chemistry and has historically required transitional-metal coupling reactions. Herein, we report a dehydration method that allows access to conjugated heterocyclic materials. By using the technique, we have prepared a series of small molecules and polymers. The reaction avoids using transition metals, proceeds at room temperature, the only required reactant is a simple base and water is the sole by-product. The dehydration reaction is technically simple and provides a sustainable and straightforward method to prepare conjugated heteroarene motifs. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Conjugated Polymers for Flexible Energy Harvesting and Storage.

    PubMed

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

    2018-03-01

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

  19. Scattering from Colloid-Polymer Conjugates with Excluded Volume Effect

    DOE PAGES

    Li, Xin; Sanchez-Diaz, Luis E.; Smith, Gregory Scott; ...

    2015-01-13

    This work presents scattering functions of conjugates consisting of a colloid particle and a self-avoiding polymer chain as a model for protein-polymer conjugates and nanoparticle-polymer conjugates in solution. The model is directly derived from the two-point correlation function with the inclusion of excluded volume effects. The dependence of the calculated scattering function on the geometric shape of the colloid and polymer stiffness is investigated. The model is able to describe the experimental scattering signature of the solutions of suspending hard particle-polymer conjugates and provide additional conformational information. This model explicitly elucidates the link between the global conformation of a conjugatemore » and the microstructure of its constituent components.« less

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

    PubMed

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

    2009-05-20

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

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

    PubMed

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

    1994-02-01

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

  2. Factors contributing to the immunogenicity of meningococcal conjugate vaccines

    PubMed Central

    Bröker, Michael; Berti, Francesco; Costantino, Paolo

    2016-01-01

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

  3. Photoresponsive peptide azobenzene conjugates that specifically interact with platinum surfaces

    NASA Astrophysics Data System (ADS)

    Dinçer, S.; Tamerler, C.; Sarıkaya, M.; Pişkin, E.

    2008-05-01

    The aim of this study is to prepare photoresponsive peptide-azobenzene compounds which interacts with platinum surfaces specifically, in order to create smart surfaces for further novel applications in design of smart biosensors and array platforms. Here, a water-soluble azobenzene molecule, 4-hydroxyazo benzene,4-sulfonic acid was synthesized by diazo coupling reaction. A platinum-specific peptide, originally selected by a phage display technique was chemically synthesized/purchased, and conjugated with the azobenzene compound activated with carbonyldiimidazole. Both azobenzene and its conjugate were characterized (including photoresponsive properties) by FTIR, NMR, and UV-spectrophotometer. The yield of conjugation reaction estimated by ninhydrin assay was about 65%. Peptide incorporation did not restrict the light-sensitivity of azobenzene. Adsorption of both the peptide and its azobenzene conjugate was followed by Quartz Crystal Microbalance (QCM) system. The kinetic evaluations exhibited that both molecules interact platinum surfaces, quite rapidly and strongly.

  4. Synthesis of Mikto-Arm Star Peptide Conjugates.

    PubMed

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

    2018-01-01

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

  5. Injection Seeded/Phase-Conjugated 2-micron Laser System

    NASA Technical Reports Server (NTRS)

    Bai, Yingxin; Yu, Jirong; Petros,M.; Petzar, Paul; Trieu, Bo; Lee, Hyung; Singh, U.; Leyva, V.; Shkunov, V.; Rockwell, D.; hide

    2007-01-01

    For the first time, beam quality improvement of 2 micron laser using a fiber based phase conjugation mirror has been demonstrated. Single frequency operation is necessary to lower threshold. The reflectivity of PCM is approx. 50%.

  6. Gold Nanoparticle Conjugation Enhances the Antiacanthamoebic Effects of Chlorhexidine

    PubMed Central

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

    2015-01-01

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

  7. Tumor-specific novel taxoid-monoclonal antibody conjugates.

    PubMed

    Ojima, Iwao; Geng, Xudong; Wu, Xinyuan; Qu, Chuanxing; Borella, Christopher P; Xie, Hongsheng; Wilhelm, Sharon D; Leece, Barbara A; Bartle, Laura M; Goldmacher, Victor S; Chari, Ravi V J

    2002-12-19

    Taxoids bearing methyldisulfanyl(alkanoyl) groups for taxoid-antibody immunoconjugates were designed, synthesized and their activities evaluated. A highly cytotoxic C-10 methyldisulfanylpropanoyl taxoid was conjugated to monoclonal antibodies recognizing the epidermal growth factor receptor (EGFR) expressed in human squamous cancers. These conjugates were shown to possess remarkable target-specific antitumor activity in vivo against EGFR-expressing A431 tumor xenografts in severe combined immune deficiency mice, resulting in complete inhibition of tumor growth in all the treated mice.

  8. Ferrocene conjugated oligonucleotide for electrochemical detection of DNA base mismatch.

    PubMed

    Hasegawa, Yusuke; Takada, Tadao; Nakamura, Mitsunobu; Yamana, Kazushige

    2017-08-01

    We describe the synthesis, binding, and electrochemical properties of ferrocene-conjugated oligonucleotides (Fc-oligos). The key step for the preparation of Fc-oligos contains the coupling of vinylferrocene to 5-iododeoxyuridine via Heck reaction. The Fc-conjugated deoxyuridine phosphoramidite was used in the Fc-oligonucleotide synthesis. We show that thiol-modified Fc-oligos deposited onto gold electrodes possess potential ability in electrochemical detection of DNA base mismatch. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Enhancing energy transport in conjugated polymers

    NASA Astrophysics Data System (ADS)

    Holmes, Russell J.

    2018-05-01

    The conversion of light into usable chemical energy by plants is enabled by the precise spatial arrangement of light-absorbing photosynthetic systems and associated molecular complexes (1). In organic solar cells, there is also the need to control intermolecular spacing and molecular orientation, as well as thin-film crystallinity and morphology, so as to enable efficient energy migration and photoconversion (2). In an organic solar cell, light absorption creates excitons, tightly bound electron-hole pairs that must be efficiently dissociated into their component charge carriers in order to create an electrical current. Thus, long-range exciton migration must occur from the point of photogeneration to a dissociating site. On page 897 of this issue, Jin et al. (3) report on a conjugated polymer nanofiber system that yields exciton diffusion lengths greater than 200 nm. In comparison, organic solar cells are typically constructed with materials having exciton diffusion lengths one order of magnitude smaller than this value, which limits device thickness and optical absorption. Their approach exploits a sequential synthesis method that enables measurement of this long exciton diffusion length (see the figure).

  10. Linear phase conjugation for atmospheric aberration compensation

    NASA Astrophysics Data System (ADS)

    Grasso, Robert J.; Stappaerts, Eddy A.

    1998-01-01

    Atmospheric induced aberrations can seriously degrade laser performance, greatly affecting the beam that finally reaches the target. Lasers propagated over any distance in the atmosphere suffer from a significant decrease in fluence at the target due to these aberrations. This is especially so for propagation over long distances. It is due primarily to fluctuations in the atmosphere over the propagation path, and from platform motion relative to the intended aimpoint. Also, delivery of high fluence to the target typically requires low beam divergence, thus, atmospheric turbulence, platform motion, or both results in a lack of fine aimpoint control to keep the beam directed at the target. To improve both the beam quality and amount of laser energy delivered to the target, Northrop Grumman has developed the Active Tracking System (ATS); a novel linear phase conjugation aberration compensation technique. Utilizing a silicon spatial light modulator (SLM) as a dynamic wavefront reversing element, ATS undoes aberrations induced by the atmosphere, platform motion or both. ATS continually tracks the target as well as compensates for atmospheric and platform motion induced aberrations. This results in a high fidelity, near-diffraction limited beam delivered to the target.

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    1999-12-01

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

  13. Chimeric Antisense Oligonucleotide Conjugated to α-Tocopherol

    PubMed Central

    Nishina, Tomoko; Numata, Junna; Nishina, Kazutaka; Yoshida-Tanaka, Kie; Nitta, Keiko; Piao, Wenying; Iwata, Rintaro; Ito, Shingo; Kuwahara, Hiroya; Wada, Takeshi; Mizusawa, Hidehiro; Yokota, Takanori

    2015-01-01

    We developed an efficient system for delivering short interfering RNA (siRNA) to the liver by using α-tocopherol conjugation. The α-tocopherol–conjugated siRNA was effective and safe for RNA interference–mediated gene silencing in vivo. In contrast, when the 13-mer LNA (locked nucleic acid)-DNA gapmer antisense oligonucleotide (ASO) was directly conjugated with α-tocopherol it showed markedly reduced silencing activity in mouse liver. Here, therefore, we tried to extend the 5′-end of the ASO sequence by using 5′-α-tocopherol–conjugated 4- to 7-mers of unlocked nucleic acid (UNA) as a “second wing.” Intravenous injection of mice with this α-tocopherol–conjugated chimeric ASO achieved more potent silencing than ASO alone in the liver, suggesting increased delivery of the ASO to the liver. Within the cells, the UNA wing was cleaved or degraded and α-tocopherol was released from the 13-mer gapmer ASO, resulting in activation of the gapmer. The α-tocopherol–conjugated chimeric ASO showed high efficacy, with hepatic tropism, and was effective and safe for gene silencing in vivo. We have thus identified a new, effective LNA-DNA gapmer structure in which drug delivery system (DDS) molecules are bound to ASO with UNA sequences. PMID:25584900

  14. New Generation of Photosensitizers: Conjugates of Chlorin e 6 With Diamond Nanoparticles

    NASA Astrophysics Data System (ADS)

    Lapina, V. A.; Bushuk, S. B.; Pavich, T. A.; Vorobey, A. V.

    2016-07-01

    Conjugates of chlorin e 6 with diamond nanoparticles were synthesized by two methods. The spectral and luminescent properties of the obtained conjugates were studied. It was shown that chlorin e 6 retained its photosensitizing activity in the conjugate. It was established that chlorin e 6 immobilized directly on diamond nanoparticles had higher photosensitizing activity than that conjugated using a spacer. It was observed that chlorin e 6 in the conjugate had higher photolytic stability than the free form.

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

    PubMed

    Vogel, Curtis R; Yang, Qiang

    2006-08-21

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

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

    PubMed

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

    2017-01-01

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

  17. Molecular Approach to Conjugated Polymers with Biomimetic Properties.

    PubMed

    Baek, Paul; Voorhaar, Lenny; Barker, David; Travas-Sejdic, Jadranka

    2018-06-13

    The field of bioelectronics involves the fascinating interplay between biology and human-made electronics. Applications such as tissue engineering, biosensing, drug delivery, and wearable electronics require biomimetic materials that can translate the physiological and chemical processes of biological systems, such as organs, tissues. and cells, into electrical signals and vice versa. However, the difference in the physical nature of soft biological elements and rigid electronic materials calls for new conductive or electroactive materials with added biomimetic properties that can bridge the gap. Soft electronics that utilize organic materials, such as conjugated polymers, can bring many important features to bioelectronics. Among the many advantages of conjugated polymers, the ability to modulate the biocompatibility, solubility, functionality, and mechanical properties through side chain engineering can alleviate the issues of mechanical mismatch and provide better interface between the electronics and biological elements. Additionally, conjugated polymers, being both ionically and electrically conductive through reversible doping processes provide means for direct sensing and stimulation of biological processes in cells, tissues, and organs. In this Account, we focus on our recent progress in molecular engineering of conjugated polymers with tunable biomimetic properties, such as biocompatibility, responsiveness, stretchability, self-healing, and adhesion. Our approach is general and versatile, which is based on functionalization of conjugated polymers with long side chains, commonly polymeric or biomolecules. Applications for such materials are wide-ranging, where we have demonstrated conductive, stimuli-responsive antifouling, and cell adhesive biointerfaces that can respond to external stimuli such as temperature, salt concentration, and redox reactions, the processes that in turn modify and reversibly switch the surface properties. Furthermore, utilizing the

  18. Dosing Schedules for Pneumococcal Conjugate Vaccine

    PubMed Central

    2014-01-01

    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

  19. [Design of next generation antibody drug conjugates].

    PubMed

    Zhu, Gui-Dong; Fu, Yang-Xin

    2013-07-01

    Chemotherapy remains one of the major tools, along with surgery, radiotherapy, and more recently targeted therapy, in the war against cancer. There have appeared a plethora of highly potent cytotoxic drugs but the poor discriminability between cancerous and healthy cells of these agents limits their broader application in clinical settings. Therapeutic antibodies have emerged as an important class of biological anticancer agents, thanks to their ability in specific binding to tumor-associated antigens. While this important class of biologics can be used as single agents for the treatment of cancer through antibody-dependent cell cytotoxicity (ADCC), their therapeutical efficacy is often limited. Antitumor antibody drug conjugates (ADCs) combine the target-specificity of monoclonal antibody (mAb) and the highly active cell-killing drugs, taking advantages of the best characteristics out of both components. Thus, insufficiency of most naked mAbs in cancer therapy has been circumvented by arming the immunoglobulin with cytotoxic drugs. Here mAbs are used as vehicles to transport potent payloads to tumor cells. ADCs contain three main components: antibody, linker and cytotoxics (also frequently referred as payload). Antibodies can recognize and specifically bind to the tumor-specific antigens, leading to an antibody-assisted internalization, and payload release. While ADC has demonstrated tremendous success, a number of practical challenges limit the broader applications of this new class of anticancer therapy, including inefficient cellular uptake, low cytotoxicity, and off-target effects. This review article aims to cover recent advances in optimizing linkers with increased stability in circulation while allowing efficient payload release within tumor cells. We also attempt to provide some practical strategies in resolving the current challenges in this attractive research area, particularly to those new to the field.

  20. Recent advances in conjugated polymers for light emitting devices.

    PubMed

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

    2011-01-01

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

  1. Recent Advances in Conjugated Polymers for Light Emitting Devices

    PubMed Central

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

    2011-01-01

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

  2. Electroactive polymer-peptide conjugates for adhesive biointerfaces.

    PubMed

    Maione, Silvana; Gil, Ana M; Fabregat, Georgina; Del Valle, Luis J; Triguero, Jordi; Laurent, Adele; Jacquemin, Denis; Estrany, Francesc; Jiménez, Ana I; Zanuy, David; Cativiela, Carlos; Alemán, Carlos

    2015-10-15

    Electroactive polymer-peptide conjugates have been synthesized by combining poly(3,4-ethylenedioxythiophene), a polythiophene derivative with outstanding properties, and an Arg-Gly-Asp (RGD)-based peptide in which Gly has been replaced by an exotic amino acid bearing a 3,4-ethylenedioxythiophene ring in the side chain. The incorporation of the peptide at the ends of preformed PEDOT chains has been corroborated by both FTIR and X-ray photoelectron spectroscopy. Although the morphology and topology are not influenced by the incorporation of the peptide at the ends of PEDOT chains, this process largely affects other surface properties. Thus, the wettability of the conjugates is considerably higher than that of PEDOT, independently of the synthetic strategy, whereas the surface roughness only increases when the conjugate is obtained using a competing strategy (i.e. growth of the polymer chains against termination by end capping). The electrochemical activity of the conjugates has been found to be higher than that of PEDOT, evidencing the success of the polymer-peptide links designed by chemical similarity. Density functional theory calculations have been used not only to ascertain the conformational preferences of the peptide but also to interpret the electronic transitions detected by UV-vis spectroscopy. Electroactive surfaces prepared using the conjugates displayed the higher bioactivities in terms of cell adhesion, with the relative viabilities being dependent on the roughness, wettability and electrochemical activity of the conjugate. In addition to the influence of the peptide fragment in the initial cell attachment and subsequent cell spreading and survival, the results indicate that PEDOT promotes the exchange of ions at the conjugate-cell interface.

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

    PubMed

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

    2018-05-04

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

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

    PubMed Central

    Liu, Jing; Li, Ruilian; Jiao, Siming; Feng, Cui; Du, Yuguang

    2018-01-01

    Bacteria biofilm helps bacteria prevent phagocytosis during infection and increase resistance to antibiotics. Staphylococcus aureus is a Gram-positive pathogenic bacterium and is tightly associated with biofilm-related infections, which have led to great threat to human health. Chitosan, the only cationic polysaccharide in nature, has been demonstrated to have antimicrobial and anti-biofilm activities, which, however, require a relative high dosage of chitosan. Moreover, poor water solubility further restricts its applications on anti-infection therapy. Inulins are a group of polysaccharides produced by many types of plants, and are widely used in processed foods. Compared to chitosan, inulin is very soluble in water and possesses a mild antibacterial activity against certain pathogenic bacteria. In order to develop an effective strategy to treat biofilm-related infections, we introduce a method by covalent conjugation of inulin to chitosan. The physicochemical characterization of the inulin–chitosan conjugate was assayed, and the anti-biofilm activity was evaluated against S. aureus biofilm. The results indicated that, as compared to chitosan, this novel polysaccharide–polysaccharide conjugate significantly enhanced activities against S. aureus either in a biofilm or planktonic state. Of note, the conjugate also showed a broad spectrum anti-biofilm activity on different bacteria strains and low cellular toxicity to mammalian cells. These results suggested that chitosan conjugation of inulin was a viable strategy for treatment against biofilm-related infections. This finding may further spread the application of natural polysaccharides on treatments of infectious disease. PMID:29734657

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

    PubMed

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

    2018-05-23

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

  6. Controlling Molecular Ordering in Solution-State Conjugated Polymers

    SciTech Connect

    Zhu, Jiahua; Han, Youngkyu; Kumar, Rajeev

    Rationally encoding molecular interactions that can control the assembly structure and functional expression in solution of conjugated polymers holds 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 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,more » 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.« less

  7. Controlling Molecular Ordering in Solution-State Conjugated Polymers

    DOE PAGES

    Zhu, Jiahua; Han, Youngkyu; Kumar, Rajeev; ...

    2015-07-17

    Rationally encoding molecular interactions that can control the assembly structure and functional expression in solution of conjugated polymers holds 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 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,more » 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.« less

  8. Novel agrochemical conjugates with self-assembling behaviour.

    PubMed

    Liu, Qingtao; Graham, Bim; Hawley, Adrian; Dong, Yao-Da; Boyd, Ben J

    2018-02-15

    That conjugation of agrichemicals to pro-assembly hydrophobic moieties will enable enhanced compatibility and loading with host lyotropic liquid crystalline carrier matrix, and potentially self-assemble in their own right in aqueous environments. A series of lipid-like agrochemical-conjugates were synthesized using specific amphiphilic entities conjugated onto the agrochemicals, picloram and 2,4-dichlorophenoxyacetic acid (2,4-D). The self-assembly behaviour and compatibility of the novel entities when incorporated into phytantriol and monoolein-based liquid crystalline systems were examined using small angle X-ray scattering, cryo-TEM and polarized optical microscopy. Compared to agrochemical-conjugates with simple alkyl ester groups, the esterification of the agrochemicals with amphiphilic groups such as phytantriol and monoolein led to greater structural compatibility and consequently a greater loading of the agrochemicals in the liquid crystalline systems without destabilizing phase structure. Picloram-monoolein and picloram-monoelaidin can self-assemble to form lamellar structures in water. However, certain agrochemical-conjugates such as picloram-monoelaidin and picloram-PEGn-oleate showed poor compatibility with liquid crystalline systems, resulting in phase separation. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Novel conjugates of peptides and conjugated polymers for optoelectronics and neural interfaces

    NASA Astrophysics Data System (ADS)

    Bhagwat, Nandita

    Peptide-polymer conjugates are a novel class of hybrid materials that take advantage of each individual component giving the opportunity to generate materials with unique physical, chemical, mechanical, optical, and electronic properties. In this dissertation peptide-polymer conjugates for two different applications are discussed. The first set of peptide-polymer conjugates were developed as templates to study the intermolecular interactions between electroactive molecules by manipulating the intermolecular distances at nano-scale level. A PEGylated, alpha-helical peptide template was employed to effectively display an array of organic chromophores (oxadiazole containing phenylenevinylene oligomers, Oxa-PPV). Three Oxa-PPV chromophores were strategically positioned on each template, at distances ranging from 6 to 17 A from each other, as dictated by the chemical and structural properties of the peptide. The Oxa-PPV modified PEGylated helical peptides (produced via Heck coupling strategies) were characterized by a variety of spectroscopic methods. Electronic contributions from multiple pairs of chromophores on a scaffold were detectable; the number and relative positioning of the chromophores dictated the absorbance and emission maxima, thus confirming the utility of these polymer--peptide templates for complex presentation of organic chromophores. The rest of the thesis is focused on using poly(3,4-alkylenedioxythiophene) based conjugated polymers as coatings for neural electrodes. This thiophene derivative is of considerable current interest for functionalizing the surfaces of a wide variety of devices including implantable biomedical electronics, specifically neural bio-electrodes. Toward these ends, copolymer films of 3,4-ethylenedioxythiophene (EDOT) with a carboxylic acid functional EDOT (EDOTacid) were electrochemically deposited and characterized as a systematic function of the EDOTacid content (0, 25, 50, 75, and 100%). The chemical surface characterization

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

    PubMed

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

    2004-07-08

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

  11. Thin Films Formed from Conjugated Polymers with Ionic, Water-Soluble Backbones.

    PubMed

    Voortman, Thomas P; Chiechi, Ryan C

    2015-12-30

    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.

  12. Development of an aptamer-ampicillin conjugate for treating biofilms

    SciTech Connect

    Lijuan, Cheng; Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, Changsha, Hunan, 410208; Xing, Yan

    Biofilm formation involves the development of extracellular matrix and initially depends on adherence and tropism by flagellar movement. With the widespread development of antibiotic resistance and tolerance of biofilms, there is a growing need for novel anti-infective strategies. No currently approved medications specifically target biofilms. Aptamers are single-stranded nucleic acid molecules that may bind to their targets with high affinity and affect the target functions. We developed a bifunctional conjugate by linking an aptamer targeting bacterial flagella with ampicillin. We investigated its influence on biofilm prevention and dissolution by ultraviolet–visible spectrophotometry, inverted microscopy, and atomic force microscopy. This conjugate hadmore » distinctive antibacterial activity. Notably, the conjugate was more active than either component, and thus had a synergistic effect against biofilms.« less

  13. Extreme electron polaron spatial delocalization in π-conjugated materials

    DOE PAGES

    Rawson, Jeff; Angiolillo, Paul J.; Therien, Michael J.

    2015-10-28

    The electron polaron, a spin-1/2 excitation, is the fundamental negative charge carrier in π-conjugated organic materials. Large polaron spatial dimensions result from weak electron-lattice coupling and thus identify materials with unusually low barriers for the charge transfer reactions that are central to electronic device applications. In this paper, we demonstrate electron polarons in π-conjugated multiporphyrin arrays that feature vast areal delocalization. This finding is evidenced by concurrent optical and electron spin resonance measurements, coupled with electronic structure calculations that suggest atypically small reorganization energies for one-electron reduction of these materials. Finally, because the electron polaron dimension can be linked tomore » key performance metrics in organic photovoltaics, light-emitting diodes, and a host of other devices, these findings identify conjugated materials with exceptional optical, electronic, and spintronic properties.« less

  14. Aptamer-conjugated nanoparticles for cancer cell detection.

    PubMed

    Medley, Colin D; Bamrungsap, Suwussa; Tan, Weihong; Smith, Joshua E

    2011-02-01

    Aptamer-conjugated nanoparticles (ACNPs) have been used for a variety of applications, particularly dual nanoparticles for magnetic extraction and fluorescent labeling. In this type of assay, silica-coated magnetic and fluorophore-doped silica nanoparticles are conjugated to highly selective aptamers to detect and extract targeted cells in a variety of matrixes. However, considerable improvements are required in order to increase the selectivity and sensitivity of this two-particle assay to be useful in a clinical setting. To accomplish this, several parameters were investigated, including nanoparticle size, conjugation chemistry, use of multiple aptamer sequences on the nanoparticles, and use of multiple nanoparticles with different aptamer sequences. After identifying the best-performing elements, the improvements made to this assay's conditional parameters were combined to illustrate the overall enhanced sensitivity and selectivity of the two-particle assay using an innovative multiple aptamer approach, signifying a critical feature in the advancement of this technique.

  15. Small angle scattering from protein/sugar conjugates

    NASA Astrophysics Data System (ADS)

    Jackson, Andrew; White, John

    2006-11-01

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

  16. Improving Nucleoside Analogs via Lipid Conjugation; Is fatter any better?

    PubMed Central

    Alexander, Peter; Kucera, Gregory; Pardee, Timothy S.

    2016-01-01

    In the past few decades, nucleoside analog drugs have been used to treat a large variety of cancers. These antimetabolite drugs mimic nucleosides and interfere with chain lengthening upon incorporation into the DNA or RNA of actively replicating cells. However, efficient delivery of these drugs is limited due to their pharmacokinetic properties, and tumors often develop drug resistance. In addition, nucleoside analogs are generally hydrophilic, resulting in poor bioavailability and impaired blood-brain barrier penetration. Conjugating these drugs to lipids modifies their pharmacokinetic properties and may improve in vivo efficacy. This review will cover recent advances in the field of conjugation of phospholipids to nucleoside analogs. This includes conjugation of myristic acid, 12-thioethyldodecanoic acid, 5-elaidic acid esters, phosphoramidate, and self-emulsifying formulations. Relevant in vitro and in vivo data will be discussed for each drug, as well as any available data from clinical trials. PMID:26829896

  17. Preparation and characterization of a dextran-amylase conjugate.

    PubMed

    Marshall, J J

    1976-07-01

    Bacillus amyloliquefaciens alpha-amylase was attached to dextran after activation of the polysaccharide by using a modification of the cyanogen bromide method. The soluble dextran-amylase conjugate was purified by molecular-sieve chromatography. The conjugated enzyme has greater stability than the unmodified enzyme at low pH values, during heat treatment, and on removal of calcium ions with a chelating agent. Attachment of dextran to alpha-amylase did not alter the Michaelis constant of the enzyme acting on starch. The polysaccharide-enzyme conjugate probably consists of a cross-linked aggregate of many dextran and many enzyme molecules, in which a proportion of the enzyme molecules, although not inactivated, are unable to express their activity, except after dextranase treatment.

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Vander Haagen, G. A.

    2017-12-01

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

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

    NASA Astrophysics Data System (ADS)

    Chudasama, Vijay; Maruani, Antoine; Caddick, Stephen

    2016-02-01

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

  1. Experiments with conjugate gradient algorithms for homotopy curve tracking

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  4. Repercussions of imprisonment for conjugal violence: discourses of men 1

    PubMed Central

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

    2016-01-01

    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

  5. Investigations of conjugate MSTIDS over the Brazilian sector during daytime

    NASA Astrophysics Data System (ADS)

    Jonah, O. F.; Kherani, E. A.; De Paula, E. R.

    2017-09-01

    This study focuses on the daytime medium-scale traveling ionospheric disturbances (MSTIDs) observed at conjugate hemispheres. It is the first time that the geomagnetical conjugate daytime MSTIDs are observed over the South America sector. To observe the MSTID characteristics, we used detrended total electron content (TEC) derived from Global Navigation Satellite Systems receivers located at Brazilian sector covering the Northern and Southern Hemispheres along the same magnetic meridian. The geographic grid of 1°N to 14°S in latitude and 60°S to 50°S in longitude was selected for this study. The cross-correlation method between two latitudes and longitudes in time was used to observe the propagation of the MSTID waves. The following features are noted: (a) MSTIDs are well developed at both hemispheres; (b) the peak MSTIDs amplitudes vary from one hemisphere to another; hence, we suppose that MSTIDs generated in Southern Hemisphere or Northern Hemisphere mirrored in the conjugate hemisphere; (c) the gravity wave-induced electric fields from one hemisphere map along the field lines and generate the mirrored MSTIDs in the conjugate region. To investigate the hemispheric mapping mechanism, a rough approximation for the integrated field line conductivity ratio of E and F regions is calculated using digisonde E and F region parameters. We noted that during the period of mapping the decrease in E region conductivity results in an increase in total conductivity. This shows that the E region was partially short circuited; hence, electric field generated at F region could map to the conjugate hemisphere during daytime: daytime MSTIDs at conjugate regions; mechanisms responsible for daytime electrified MSTIDs; gravity wave-induced electric field role in daytime MSTIDs.

  6. A universal polysaccharide conjugated vaccine against O111 E. coli

    PubMed Central

    Andrade, Gabrielle R; New, Roger R C; Sant’Anna, Osvaldo A; Williams, Neil A; Alves, Rosely C B; Pimenta, Daniel C; Vigerelli, Hugo; Melo, Bruna S; Rocha, Letícia B; Piazza, Roxane M F; Mendonça-Previato, Lucia; Domingos, Marta O

    2014-01-01

    E. coli O111 strains are responsible for outbreaks of blood diarrhea and hemolytic uremic syndrome throughout the world. Because of their phenotypic variability, the development of a vaccine against these strains which targets an antigen that is common to all of them is quite a challenge. Previous results have indicated, however, that O111 LPS is such a candidate, but its toxicity makes LPS forbidden for human use. To overcome this problem, O111 polysaccharides were conjugated either to cytochrome C or to EtxB (a recombinant B subunit of LT) as carrier proteins. The O111-cytochrome C conjugate was incorporated in silica SBA-15 nanoparticles and administered subcutaneously in rabbits, while the O111-EtxB conjugate was incorporated in VaxcineTM, an oil-based delivery system, and administered orally in mice. The results showed that one year post-vaccination, the conjugate incorporated in silica SBA-15 generated antibodies in rabbits able to inhibit the adhesion of all categories of O111 E. coli to epithelial cells. Importantly, mice immunized orally with the O111-EtxB conjugate in VaxcineTM generated systemic and mucosal humoral responses against all categories of O111 E. coli as well as antibodies able to inhibit the toxic effect of LT in vitro. In summary, the results obtained by using 2 different approaches indicate that a vaccine that targets the O111 antigen has the potential to prevent diarrhea induced by O111 E. coli strains regardless their mechanism of virulence. They also suggest that a conjugated vaccine that uses EtxB as a carrier protein has potential to combat diarrhea induced by ETEC. PMID:25483465

  7. Solar multi-conjugate adaptive optics performance improvement

    NASA Astrophysics Data System (ADS)

    Zhang, Zhicheng; Zhang, Xiaofang; Song, Jie

    2015-08-01

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

  8. Effects of Polymer Conjugation on Hybridization Thermodynamics of Oligonucleic Acids.

    PubMed

    Ghobadi, Ahmadreza F; Jayaraman, Arthi

    2016-09-15

    In this work, we perform coarse-grained (CG) and atomistic simulations to study the effects of polymer conjugation on hybridization/melting thermodynamics of oligonucleic acids (ONAs). We present coarse-grained Langevin molecular dynamics simulations (CG-NVT) to assess the effects of the polymer flexibility, length, and architecture on hybridization/melting of ONAs with different ONA duplex sequences, backbone chemistry, and duplex concentration. In these CG-NVT simulations, we use our recently developed CG model of ONAs in implicit solvent, and treat the conjugated polymer as a CG chain with purely repulsive Weeks-Chandler-Andersen interactions with all other species in the system. We find that 8-100-mer linear polymer conjugation destabilizes 8-mer ONA duplexes with weaker Watson-Crick hydrogen bonding (WC H-bonding) interactions at low duplex concentrations, while the same polymer conjugation has an insignificant impact on 8-mer ONA duplexes with stronger WC H-bonding. To ensure the configurational space is sampled properly in the CG-NVT simulations, we also perform CG well-tempered metadynamics simulations (CG-NVT-MetaD) and analyze the free energy landscape of ONA hybridization for a select few systems. We demonstrate that CG-NVT-MetaD simulation results are consistent with the CG-NVT simulations for the studied systems. To examine the limitations of coarse-graining in capturing ONA-polymer interactions, we perform atomistic parallel tempering metadynamics simulations at well-tempered ensemble (AA-MetaD) for a 4-mer DNA in explicit water with and without conjugation to 8-mer poly(ethylene glycol) (PEG). AA-MetaD simulations also show that, for a short DNA duplex at T = 300 K, a condition where the DNA duplex is unstable, conjugation with PEG further destabilizes DNA duplex. We conclude with a comparison of results from these three different types of simulations and discuss their limitations and strengths.

  9. Novel Synthetic (Poly)Glycerolphosphate-Based Antistaphylococcal Conjugate Vaccine

    PubMed Central

    Chen, Quanyi; Dintaman, Jay; Lees, Andrew; Sen, Goutam; Schwartz, David; Shirtliff, Mark E.; Park, Saeyoung; Lee, Jean C.; Mond, James J.

    2013-01-01

    Staphylococcal infections are a major source of global morbidity and mortality. Currently there exists no antistaphylococcal vaccine in clinical use. Previous animal studies suggested a possible role for purified lipoteichoic acid as a vaccine target for eliciting protective IgG to several Gram-positive pathogens. Since the highly conserved (poly)glycerolphosphate backbone of lipoteichoic acid is a major antigenic target of the humoral immune system during staphylococcal infections, we developed a synthetic method for producing glycerol phosphoramidites to create a covalent 10-mer of (poly)glycerolphosphate for potential use in a conjugate vaccine. We initially demonstrated that intact Staphylococcus aureus elicits murine CD4+ T cell-dependent (poly)glycerolphosphate-specific IgM and IgG responses in vivo. Naive mice immunized with a covalent conjugate of (poly)glycerolphosphate and tetanus toxoid in alum plus CpG-oligodeoxynucleotides produced high secondary titers of serum (poly)glycerolphosphate-specific IgG. Sera from immunized mice enhanced opsonophagocytic killing of live Staphylococcus aureus in vitro. Mice actively immunized with the (poly)glycerolphosphate conjugate vaccine showed rapid clearance of staphylococcal bacteremia in vivo relative to mice similarly immunized with an irrelevant conjugate vaccine. In contrast to purified, natural lipoteichoic acid, the (poly)glycerolphosphate conjugate vaccine itself exhibited no detectable inflammatory activity. These data suggest that a synthetic (poly)glycerolphosphate-based conjugate vaccine will contribute to active protection against extracellular Gram-positive pathogens expressing this highly conserved backbone structure in their membrane-associated lipoteichoic acid. PMID:23649092

  10. Synthesis and biological evaluation of nandrolone-bodipy conjugates.

    PubMed

    Jurášek, Michal; Rimpelová, Silvie; Pavlíčková, Vladimíra; Ruml, Tomáš; Lapčík, Oldřich; Drašar, Pavel B

    2015-05-01

    Here, we report synthesis and biological evaluation of fluorescent nandrolone-3-carboxymethyloxime derivatives conjugated with green-emitting bodipy dye via PEG linkers. All the newly-synthesized compounds were evaluated for their effect on cell proliferation in vitro in MCF-7, LNCaP, PC-3 and HEK 293T model cell lines using WST-1 assay. By means of live-cell fluorescence microscopy, the intracellular localization of nandrolone-bodipy conjugates was revealed in endoplasmic reticulum. Moreover, we performed competitive localization study with nonfluorescent nandrolone, metandrolone, boldenone, trenbolone, and testosterone. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Toward High Performance Photovoltaic Cells based on Conjugated Polymers

    DTIC Science & Technology

    2016-12-26

    AFRL-AFOSR-JP-TR-2016-0103 Toward High Performance Photovoltaic Cells based on Conjugated Polymers Kung-Hwa Wei National Chiao Tung University Final...Conjugated Polymers 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA2386-15-1-4113 5c.  PROGRAM ELEMENT NUMBER 61102F 6. AUTHOR(S) Kung-Hwa Wei 5d.  PROJECT...gap polymer with good packing order as the active layer for a single-junction photovoltaic device. The light absorptions for the small molecule and the

  12. Emerging applications of conjugated polymers in molecular imaging.

    PubMed

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

    2013-10-28

    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.

  13. Live Cell Imaging of a Fluorescent Gentamicin Conjugate

    PubMed Central

    Escobedo, Jorge O.; Chu, Yu-Hsuan; Wang, Qi; Steyger, Peter S.; Strongin, Robert M.

    2012-01-01

    Understanding cellular mechanisms of ototoxic and nephrotoxic drug uptake, intracellular distribution, and molecular trafficking across cellular barrier systems aids the study of potential uptake blockers that preserve sensory and renal function during critical life-saving therapy. Herein we report the design, synthesis characterization and evaluation of a fluorescent conjugate of the aminoglycoside antibiotic gentamicin. Live cell imaging results show the potential utility of this new material. Related gentamicin conjugates studied to date quench in live kindney cells, and have been largely restricted to use in fixed (delipidated) cells. PMID:22545403

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

    PubMed

    Ardoña, Herdeline Ann M; Tovar, John D

    2015-12-16

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

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

    NASA Astrophysics Data System (ADS)

    LI, Can

    2017-09-01

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

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

    PubMed

    Ceriotti, Michele; Bussi, Giovanni; Parrinello, Michele

    2007-08-01

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

  17. Ketopantoyl lactone reductase is a conjugated polyketone reductase.

    PubMed

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

    1989-03-01

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

  18. Conjugate adaptive optics with remote focusing in multiphoton microscopy

    NASA Astrophysics Data System (ADS)

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

    2018-02-01

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

  19. Improving Small Interfering RNA Delivery In Vivo Through Lipid Conjugation.

    PubMed

    Osborn, Maire F; Khvorova, Anastasia

    2018-05-10

    RNA interference (RNAi)-based therapeutics are approaching clinical approval for genetically defined diseases. Current clinical success is a result of significant innovations in the development of chemical architectures that support sustained, multi-month efficacy in vivo following a single administration. Conjugate-mediated delivery has established itself as the most promising platform for safe and targeted small interfering RNA (siRNA) delivery. Lipophilic conjugates represent a major class of modifications that improve siRNA pharmacokinetics and enable efficacy in a broad range of tissues. Here, we review current literature and define key features and limitations of this approach for in vivo modulation of gene expression.

  20. Cyclization Cascades Initiated by 1,6-Conjugate Addition

    PubMed Central

    Brooks, Joshua L.; Frontier, Alison J.

    2012-01-01

    Dienyl diketones containing tethered acetates selectively undergo two different 1,6-conjugate addition-initiated cyclization cascades. One is a 1,6-conjugate addition/cyclization sequence with incorporation of the nucleophile, and the other is catalyzed by DABCO and is thought to proceed via a cyclic acetoxonium intermediate. The reaction behavior of substrates lacking the tethered acetate was also studied. The scope of both types of cyclization cascades, the role of the amine additive, and the factors controlling reactivity and selectivity in the two different reaction pathways is discussed. PMID:23004564

  1. Preliminary experiments on phase conjugation for flow visualization. [barium titanate single crystals

    NASA Technical Reports Server (NTRS)

    Weimer, D.; Howes, W. L.

    1984-01-01

    Barium titanate single crystals are discussed in the context of: the procedure for polarizing a crystal; a test for phase conjugation; transients in the production of phase conjugation; real time readout by a separate laser of a hologram induced within the crystal, including conjugation response times to on-off switching of each beam; and a demonstration of a Twyman-Green interferometer utilizing phase conjugation.

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

    PubMed

    Gavriliuk, V G; Vinnikov, A I

    1997-01-01

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

  3. Effects of Hyaluronic Acid Conjugation on Anti-TNF-alpha Inhibition of Inflammation in Burns

    DTIC Science & Technology

    2014-05-01

    Effects of hyaluronic acid conjugation on anti-TNF-α inhibition of inflammation in burns Emily E. Friedrich1, Liang Tso Sun1, Shanmugasundaram...alone, mixed with hyaluronic acid or conjugated to hyaluronic acid . We found that non-conjugated anti-TNF-α decreased macrophage infiltration to a...greater extent than that conjugated to hyaluronic acid ; however there was little effect on the degree of progression or IL-1β levels. A simple transport

  4. [Conjugal leprosy infection in Japan--case report and review].

    PubMed

    Ozaki, Motoaki; Tomoda, Masakazu

    2012-04-01

    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.

  5. Bacterial meningitis and Haemophilus influenzae type b conjugate vaccine, Malawi.

    PubMed

    McCormick, David W; Molyneux, Elizabeth M

    2011-04-01

    A retrospective database review showed that Haemophilus influenzae type b conjugate vaccine decreased the annual number of cases of H. influenzae type b meningitis in children in Blantyre, Malawi. Among young bacterial meningitis patients, HIV prevalence was high (36.7% during 1997-2009), and pneumococcus was the most common etiologic agent (57% in 2009).

  6. Fatty acid-amino acid conjugates diversification in Lepidopteran caterpillars

    USDA-ARS?s Scientific Manuscript database

    Fatty acid amino acid conjugates (FACs) have been found in Noctuid as well as Sphingid caterpillar oral secretions and especially volicitin [N-(17-hydroxylinolenoyl)-L-Glutamine] and its biochemical precursor, N-linolenoyl-L-glutamine, are known elicitors of induced volatile emissions in corn plants...

  7. Marital Quality and Conjugal Labor Involvement of Rural Couples.

    ERIC Educational Resources Information Center

    Bokemeier, Janet; Maurer, Richard

    1987-01-01

    Examined data from survey of nonmetropolitan households (N=770 couples) to describe conjugal labor involvement of rural couples and to assess relationship between labor involvement and marital quality. Found that, when work situations of both spouses were considered, many couples either had no jobs or more than two jobs. (Author/NB)

  8. Bacterial Meningitis and Haemophilus influenzae Type b Conjugate Vaccine, Malawi

    PubMed Central

    Molyneux, Elizabeth M.

    2011-01-01

    A retrospective database review showed that Haemophilus influenzae type b conjugate vaccine decreased the annual number of cases of H. influenzae type b meningitis in children in Blantyre, Malawi. Among young bacterial meningitis patients, HIV prevalence was high (36.7% during 1997–2009), and pneumococcus was the most common etiologic agent (57% in 2009). PMID:21470461

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

    PubMed

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

    2013-10-29

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

  10. Bispecific small molecule–antibody conjugate targeting prostate cancer

    PubMed Central

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

    2013-01-01

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

  11. Decitabine Nano-conjugate Sensitizing Human Glioblastoma Cells to Temozolomide

    PubMed Central

    Cui, Yi; Naz, Asia; Thompson, David H.; Irudayaraj, Joseph

    2015-01-01

    In this study we developed and characterized a delivery system for the epigenetic demethylating drug, decitabine, to sensitize temozolomide-resistant human glioblastoma multiforme (GBM) cells to alkylating chemotherapy. A poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) based nano-conjugate was fabricated to encapsulate decitabine and achieved a better therapeutic response in GBM cells. After synthesis, the highly efficient uptake process and intracellular dynamics of this nano-conjugate was monitored by single-molecule fluorescence tools. Our experiments demonstrated that, under an acidic pH due to active glycolysis in cancer cells, the PLGA-PEG nano-vector could release the conjugated decitabine at a faster rate, after which the hydrolyzed lactic acid and glycolic acid would further acidify the intracellular microenvironment, thus providing a “positive feedback” to increase the effective drug concentration and realize growth inhibition. In temozolomide-resistant GBM cells, decitabine can potentiate the cytotoxic DNA alkylation by counteracting cytosine methylation and reactivating tumor suppressor genes, such as p53 and p21. Owing to excellent internalization and endo-lysosomal escape enabled by the PLGA-PEG backbone, the encapsulated decitabine exhibited a better anti-GBM potential than free drug molecules. Hence, the synthesized nano-conjugate and temozolomide could act in synergy to deliver a more potent and long-term anti-proliferation effect against malignant GBM cells. PMID:25751281

  12. Approximation of functions and their conjugates in variable Lebesgue spaces

    NASA Astrophysics Data System (ADS)

    Volosivets, S. S.

    2017-01-01

    One-sided Steklov means are used to introduce moduli of continuity of natural order in variable Lp(\\cdot)2π-spaces. A direct theorem of Jackson- Stechkin type and an inverse theorem of Salem-Stechkin type are given. Similar results are obtained for the conjugate functions. Bibliography: 24 titles.

  13. Synthesis and characterization of radiolabeled 17ß-estradiol conjugates

    USDA-ARS?s Scientific Manuscript database

    The use of radioactive tracers for environmental fate and transport studies of emerging contaminants, especially for those that are labile, offers convenience in tracking study compounds and their metabolites and in calculating mass-balances. The contribution of conjugated forms of natural steroid h...

  14. A nanodiamond-fluorescein conjugate for cell studies

    NASA Astrophysics Data System (ADS)

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

    2018-03-01

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

  15. Patterning of conjugated polymers for organic optoelectronic devices.

    PubMed

    Xu, Youyong; Zhang, Fan; Feng, Xinliang

    2011-05-23

    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. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Diazobenzene-containing conjugated polymers as dark quenchers.

    PubMed

    Wu, Jiatao; Tan, Ying; Xie, Yonghua; Wu, Yi; Zhao, Rui; Jiang, Yuyang; Tan, Chunyan

    2013-12-18

    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.

  17. Recent Advances in Conjugated Polymer Materials for Disease Diagnosis.

    PubMed

    Lv, Fengting; Qiu, Tian; Liu, Libing; Ying, Jianming; Wang, Shu

    2016-02-10

    The extraordinary optical amplification and light-harvesting properties of conjugated polymers impart sensing systems with higher sensitivity, which meets the primary demands of early cancer diagnosis. Recent advances in the detection of DNA methylation and mutation with polyfluorene derivatives based fluorescence resonance energy transfer (FRET) as a means to modulate fluorescent responses attest to the great promise of conjugated polymers as powerful tools for the clinical diagnosis of diseases. To facilitate the ever-changing needs of diagnosis, the development of detection approaches and FRET signal analysis are highlighted in this review. Due to their exceptional brightness, excellent photostability, and low or absent toxicity, conjugated polymers are verified as superior materials for in-vivo imaging, and provide feasibility for future clinical molecular-imaging applications. The integration of conjugated polymers with clinical research has shown profound effects on diagnosis for the early detection of disease-related biomarkers, as well as in-vivo imaging, which leads to a multidisciplinary scientific field with perspectives in both basic research and application issues. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed

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

    2012-12-01

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

  19. Conjugate-Gradient Algorithms For Dynamics Of Manipulators

    NASA Technical Reports Server (NTRS)

    Fijany, Amir; Scheid, Robert E.

    1993-01-01

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

  20. Parallel conjugate gradient algorithms for manipulator dynamic simulation

    NASA Technical Reports Server (NTRS)

    Fijany, Amir; Scheld, Robert E.

    1989-01-01

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

  1. Fate of glucuronide conjugated estradiol in the environment

    USDA-ARS?s Scientific Manuscript database

    The fate and transport of conjugated reproductive hormones, which are polar compared to parent hormones, are little understood. Laboratory bench-scale soil (Hamar; Sandy, mixed, frigid typic Endoaquolls) sorption studies were conducted using [14C] 17ß-estradiol-3-glucuronide for a range of concentra...

  2. The Response to Conjugal Violence in Substance Abuse Treatment Settings.

    ERIC Educational Resources Information Center

    Brown, Thomas G.; Caplan, Thomas; Seraganian, Peter; Werk, Annette

    The linkage between conjugal violence and substance abuse is well established. The evidence suggests that little coordination exists among the therapeutic communities positioned to treat co-existing problems. A survey was conducted in Quebec with professionals representing 57 substance abuse treatment centers, 38 of which were public. Questions…

  3. From Support to Control: A Configurational Perspective on Conjugal Quality

    ERIC Educational Resources Information Center

    Widmer, Eric D.; Giudici, Francesco; Le Goff, Jean-Marie; Pollien, Alexandre

    2009-01-01

    The topic of conjugal quality provides an empirical illustration of the relevance of the configurational perspective on families. On the basis of a longitudinal sample of 1,534 couples living in Switzerland drawn from the study "Social Stratification, Cohesion and Conflict in Contemporary Families," we show that various types of…

  4. Organometallic conjugates of the drug sulfadoxine for combatting antimicrobial resistance

    USDA-ARS?s Scientific Manuscript database

    Fourteen new RuII, RhIII and IrIII complexes conjugated to the antimalarial drug sulfadoxine functionalised with either a pyridylimino- or quinolylimino- group to allow N,N’-chelation ligands have been synthesized and characterized. The effect of the arene/Cpx, planarity of imino group on sulfadoxin...

  5. Negative dendritic effect on enzymatic hydrolysis of dendrimer conjugates.

    PubMed

    Zhou, Zhengwei; Cong, Mei; Li, Mengyao; Tintaru, Aura; Li, Jia; Yao, Jianhua; Xia, Yi; Peng, Ling

    2018-06-08

    Dendrimers possess intriguing "dendritic effects", which are unique characteristics that stem from the dendrimer generation and size. Here we report a "negative dendritic effect" observed during enzymatic hydrolysis of dendrimer conjugates. Such negative dendritic effects, though rarely reported, may be explored for tailored and generation-dependent drug release.

  6. Catalytic asymmetric conjugate addition of Grignard reagents to chromones.

    PubMed

    Vila, Carlos; Hornillos, Valentín; Fañanás-Mastral, Martín; Feringa, Ben L

    2013-07-07

    A highly regio- and enantioselective copper catalysed direct conjugate addition of Grignard reagents to chromones has been developed taking advantage of the reduced reactivity of the resulting magnesium enolates. This methodology tolerates a broad scope of alkyl Grignards including secondary alkyl magnesium reagents as well as functionalised chromones.

  7. Generalized matrix summability of a conjugate derived Fourier series.

    PubMed

    Mursaleen, M; Alotaibi, Abdullah

    2017-01-01

    The study of infinite matrices is important in the theory of summability and in approximation. In particular, Toeplitz matrices or regular matrices and almost regular matrices have been very useful in this context. In this paper, we propose to use a more general matrix method to obtain necessary and sufficient conditions to sum the conjugate derived Fourier series.

  8. Women experiencing the intergenerationality of conjugal violence1

    PubMed Central

    Paixão, Gilvânia Patrícia do Nascimento; Gomes, Nadirlene Pereira; Diniz, Normélia Maria Freire; Lira, Margaret Ollinda de Souza Carvalho e; Carvalho, Milca Ramaiane da Silva; da Silva, Rudval Souza

    2015-01-01

    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. PMID:26487137

  9. Maternal Conjugal Multiplicity and Child Development in Rural Jamaica

    ERIC Educational Resources Information Center

    Dreher, Melanie; Hudgins, Rebekah

    2010-01-01

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

  10. Homology among tet determinants in conjugative elements of streptococci.

    PubMed Central

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

    1981-01-01

    A mutation to tetracycline sensitivity in a resistant strain of Streptococcus pneumoniae was shown by several criteria to be due to a point mutation in the conjugative omega (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. PMID:6270063

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

    ERIC Educational Resources Information Center

    Verissimo, Joao; Clahsen, Harald

    2009-01-01

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

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

    PubMed

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

    2018-04-15

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

  13. Microwave phase conjugation using artificial nonlinear microwave surfaces

    NASA Astrophysics Data System (ADS)

    Chang, Yian

    1997-09-01

    A new technique is developed and demonstrated to simulate nonlinear materials in the microwave and millimeter wave regime. Such materials are required to extend nonlinear optical techniques into longer wavelength areas. Using an array of antenna coupled mixers as an artificial nonlinear surface, we have demonstrated two-dimensional free space microwave phase conjugation at 10 GHz. The basic concept is to replace the weak nonlinearity of electron distribution in a crystal with the strong nonlinear V-I response of a P-N junction. This demnstration uses a three-wave mixing method with the effective nonlinear susceptibility χ(2) provided by an artificial nonlinear surface. The pump signal at 2ω (20 GHz) can be injected to the mixing elements electrically or optically. Electrical injection was first used to prove the concept of artificial nonlinear surfaces. However, due to the loss and size of microwave components, electrical injection is not practical for an array of artificial nonlinear surfaces, as would be needed in a three-dimensional free space phase conjugation setup. Therefore optical injection was implemented to carry the 2ω microwave pump signal in phase to all mixing elements. In both cases, two-dimensional free space phase conjugation was observed by directly measuring the electric field amplitude and phase distribution. The electric field wavefronts exhibited retro-directivity and auto- correction characteristics of phase conjugation. This demonstration surface also shows a power gain of 10 dB, which is desired for potential communication applications.

  14. Factors affecting conjugated linoleic acid content in milk and meat.

    PubMed

    Dhiman, Tilak R; Nam, Seung-Hee; Ure, Amy L

    2005-01-01

    Conjugated linoleic acid (CLA) has been recently studied mainly because of its potential in protecting against cancer, atherogenesis, and diabetes. Conjugated linoleic acid (CLA) is a collective term for a series of conjugated dienoic positional and geometrical isomers of linoleic acid, which are found in relative abundance in milk and tissue fat of ruminants compared with other foods. The cis-9, trans-11 isomer is the principle dietary form of CLA found in ruminant products and is produced by partial ruminal biohydrogenation of linoleic acid or by endogenous synthesis in the tissues themselves. The CLA content in milk and meat is affected by several factors, such as animal's breed, age, diet, and management factors related to feed supplements affecting the diet. Conjugated linoleic acid in milk or meat has been shown to be a stable compound under normal cooking and storage conditions. Total CLA content in milk or dairy products ranges from 0.34 to 1.07% of total fat. Total CLA content in raw or processed beef ranges from 0.12 to 0.68% of total fat. It is currently estimated that the average adult consumes only one third to one half of the amount of CLA that has been shown to reduce cancer in animal studies. For this reason, increasing the CLA contents of milk and meat has the potential to raise the nutritive and therapeutic values of dairy products and meat.

  15. Development and application of nanoparticles synthesized with folic acid-conjugated soy protein

    USDA-ARS?s Scientific Manuscript database

    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...

  16. High-power beam steering using phase conjugation through Brillouin-induced four-wave mixing.

    PubMed

    Jones, D C; Cook, G; Ridley, K D; Scott, A M

    1991-10-15

    We report an experimental demonstration of a beam-steering concept. A high-reflectivity phase-conjugate mirror is used to steer a high-power phase-conjugate beam using a low-power signal beam. The high reflectivity phase conjugation is achieved using Brillouin-induced four-wave mixing in a cell containing carbon disulfide.

  17. Hypothesis: conjugate vaccines may predispose children to autism spectrum disorders.

    PubMed

    Richmand, Brian J

    2011-12-01

    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

  18. Impact of linker and conjugation chemistry on antigen binding, Fc receptor binding and thermal stability of model antibody-drug conjugates

    PubMed Central

    Acchione, Mauro; Kwon, Hyewon; Jochheim, Claudia M.; Atkins, William M.

    2012-01-01

    Antibody-drug conjugates (ADCs) with biotin as a model cargo tethered to IgG1 mAbs via different linkers and conjugation methods were prepared and tested for thermostability and ability to bind target antigen and Fc receptor. Most conjugates demonstrated decreased thermostability relative to unconjugated antibody, based on DSC, with carbohydrate and amine coupled ADCs showing the least effect compared with thiol coupled conjugates. A strong correlation between biotin-load and loss of stability is observed with thiol conjugation to one IgG scaffold, but the stability of a second IgG scaffold is relatively insensitive to biotin load. The same correlation for amine coupling was less significant. Binding of antibody to antigen and Fc receptor was investigated using surface plasmon resonance. None of the conjugates exhibited altered antigen affinity. Fc receptor FcγIIb (CD32b) interactions were investigated using captured antibody conjugate. Protein G and Protein A, known inhibitors of Fc receptor (FcR) binding to IgG, were also used to extend the analysis of the impact of conjugation on Fc receptor binding. H10NPEG4 was the only conjugate to show significant negative impact to FcR binding, which is likely due to higher biotin-load compared with the other ADCs. The ADC aHISNLC and aHISTPEG8 demonstrated some loss in affinity for FcR, but to much lower extent. The general insensitivity of target binding and effector function of the IgG1 platform to conjugation highlight their utility. The observed changes in thermostability require consideration for the choice of conjugation chemistry, depending on the system being pursued and particular application of the conjugate. PMID:22531451

  19. A Conserved Helicase Processivity Factor Is Needed for Conjugation and Replication of an Integrative and Conjugative Element

    PubMed Central

    Thomas, Jacob; Lee, Catherine A.; Grossman, Alan D.

    2013-01-01

    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. PMID:23326247

  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.

    PubMed

    Tabatabaee Amid, Bahareh; Mirhosseini, Hamed

    2014-01-01

    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. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. In Vitro and In Vivo Evaluation of Cysteine and Site Specific Conjugated Herceptin Antibody-Drug Conjugates

    PubMed Central

    Jackson, Dowdy; Atkinson, John; Guevara, Claudia I.; Zhang, Chunying; Kery, Vladimir; Moon, Sung-Ju; Virata, Cyrus; Yang, Peng; Lowe, Christine; Pinkstaff, Jason; Cho, Ho; Knudsen, Nick; Manibusan, Anthony; Tian, Feng; Sun, Ying; Lu, Yingchun; Sellers, Aaron; Jia, Xiao-Chi; Joseph, Ingrid; Anand, Banmeet; Morrison, Kendall; Pereira, Daniel S.; Stover, David

    2014-01-01

    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. PMID:24454709

  2. Axial range of conjugate adaptive optics in two-photon microscopy

    PubMed Central

    Paudel, Hari P.; Taranto, John; Mertz, Jerome; Bifano, Thomas

    2015-01-01

    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. PMID:26367938

  3. Axial range of conjugate adaptive optics in two-photon microscopy.

    PubMed

    Paudel, Hari P; Taranto, John; Mertz, Jerome; Bifano, Thomas

    2015-08-10

    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.

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

    PubMed

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

    2017-11-15

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

  5. Nanohybrid conjugated polyelectrolytes: highly photostable and ultrabright nanoparticles

    NASA Astrophysics Data System (ADS)

    Darwish, Ghinwa H.; Karam, Pierre

    2015-09-01

    We present a general and straightforward one-step approach to enhance the photophysical properties of conjugated polyelectrolytes. Upon complexation with an amphiphilic polymer (polyvinylpyrrolidone), an anionic conjugated polyelectrolyte (poly[5-methoxy-2-(3-sulfopropoxy)-1,4-phenylenevinylene]) was prepared into small nanoparticles with exceptional photostability and brightness. The polymer fluorescence intensity was enhanced by 23 -fold and could be easily tuned by changing the order of addition. Single molecule experiments revealed a complete suppression of blinking. In addition, after only losing 18% of the original intensity, a remarkable amount of photons were emitted per particle (~109, on average). This number is many folds greater than popular organic fluorescent dyes. We believe that an intimate contact between the two polymers is shielding the conjugated polyelectrolyte from the destructive photooxidation. The prepared nanohybrid particles will prove instrumental in single particle based fluorescent assays and can serve as a probe for the current state-of-the-art bioimaging fluorescence techniques.We present a general and straightforward one-step approach to enhance the photophysical properties of conjugated polyelectrolytes. Upon complexation with an amphiphilic polymer (polyvinylpyrrolidone), an anionic conjugated polyelectrolyte (poly[5-methoxy-2-(3-sulfopropoxy)-1,4-phenylenevinylene]) was prepared into small nanoparticles with exceptional photostability and brightness. The polymer fluorescence intensity was enhanced by 23 -fold and could be easily tuned by changing the order of addition. Single molecule experiments revealed a complete suppression of blinking. In addition, after only losing 18% of the original intensity, a remarkable amount of photons were emitted per particle (~109, on average). This number is many folds greater than popular organic fluorescent dyes. We believe that an intimate contact between the two polymers is shielding the

  6. Novel anticancer polymeric conjugates of activated nucleoside analogs

    PubMed Central

    Senanayake, Thulani H.; Warren, Galya; Vinogradov, Serguei V.

    2011-01-01

    Inherent or therapy-induced drug resistance is a major clinical setback in cancer treatment. The extensive usage of cytotoxic nucleobases and nucleoside analogs in chemotherapy also results in the development of specific mechanisms of drug resistance; such as nucleoside transport or activation deficiencies. These drugs are prodrugs; and being converted into the active mono-, di- and triphosphates inside cancer cells following administration, they affect nucleic acid synthesis, nucleotide metabolism, or sensitivity to apoptosis. Previously, we have actively promoted the idea that the nanodelivery of active nucleotide species, e.g. 5′-triphosphates of nucleoside analogs, can enhance drug efficacy and reduce nonspecific toxicity. In this study we report the development of a novel type of drug nanoformulations, polymeric conjugates of nucleoside analogs, which are capable of the efficient transport and sustained release of phosphorylated drugs. These drug conjugates have been synthesized, starting from cholesterol-modified mucoadhesive polyvinyl alcohol or biodegradable dextrin, by covalent attachment of nucleoside analogs through a tetraphosphate linker. Association of cholesterol moieties in aqueous media resulted in intramolecular polymer folding and the formation of small nanogel particles containing 0.5 mmol/g of a 5′-phosphorylated nucleoside analog, e.g. 5-fluoro-2′-deoxyuridine (floxuridine, FdU), an active metabolite of anticancer drug 5-fluorouracyl (5-FU). The polymeric conjugates demonstrated rapid enzymatic release of floxuridine 5′-phosphate and much slower drug release under hydrolytic conditions (pH 1.0–7.4). Among the panel of cancer cell lines, all studied polymeric FdU-conjugates demonstrated an up to 50 times increased cytotoxicity in human prostate cancer PC-3, breast cancer MCF-7 and MDA-MB-231 cells, and more than 100 times higher efficacy against cytarabine-resistant human T-lymphoma (CEM/araC/8) and gemcitabine-resistant follicular

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

    NASA Astrophysics Data System (ADS)

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

    2008-07-01

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

  8. Water-soluble luminescent quantum dots and biomolecular conjugates thereof and related compositions and methods of use

    DOEpatents

    Nie, Shuming; Chan, Warren C. W.; Emory, Stephen

    2007-03-20

    The present invention provides a water-soluble luminescent quantum dot, a biomolecular conjugate thereof and a composition comprising such a quantum dot or conjugate. Additionally, the present invention provides a method of obtaining a luminescent quantum dot, a method of making a biomolecular conjugate thereof, and methods of using a biomolecular conjugate for ultrasensitive nonisotopic detection in vitro and in vivo.

  9. Water-soluble luminescent quantum dots and biomolecular conjugates thereof and related compositions and method of use

    DOEpatents

    Nie, Shuming; Chan, Warren C. W.; Emory, Steven R.

    2002-01-01

    The present invention provides a water-soluble luminescent quantum dot, a biomolecular conjugate thereof and a composition comprising such a quantum dot or conjugate. Additionally, the present invention provides a method of obtaining a luminescent quantum dot, a method of making a biomolecular conjugate thereof, and methods of using a biomolecular conjugate for ultrasensitive nonisotopic detection in vitro and in vivo.

  10. Application of Conjugate Gradient methods to tidal simulation

    USGS Publications Warehouse

    Barragy, E.; Carey, G.F.; Walters, R.A.

    1993-01-01

    A harmonic decomposition technique is applied to the shallow water equations to yield a complex, nonsymmetric, nonlinear, Helmholtz type problem for the sea surface and an accompanying complex, nonlinear diagonal problem for the velocities. The equation for the sea surface is linearized using successive approximation and then discretized with linear, triangular finite elements. The study focuses on applying iterative methods to solve the resulting complex linear systems. The comparative evaluation includes both standard iterative methods for the real subsystems and complex versions of the well known Bi-Conjugate Gradient and Bi-Conjugate Gradient Squared methods. Several Incomplete LU type preconditioners are discussed, and the effects of node ordering, rejection strategy, domain geometry and Coriolis parameter (affecting asymmetry) are investigated. Implementation details for the complex case are discussed. Performance studies are presented and comparisons made with a frontal solver. ?? 1993.

  11. Discovery of a conjugative megaplasmid in Bifidobacterium breve.

    PubMed

    Bottacini, Francesca; O'Connell Motherway, Mary; Casey, Eoghan; McDonnell, Brian; Mahony, Jennifer; Ventura, Marco; van Sinderen, Douwe

    2015-01-01

    Bifidobacterium breve is a common and sometimes very abundant inhabitant of the human gut. Genome sequencing of B. breve JCM 7017 revealed the presence of an extrachromosomal element, designated pMP7017 consisting of >190 kb, thus representing the first reported bifidobacterial megaplasmid. In silico characterization of this element revealed several genomic features supporting a stable establishment of the megaplasmid in its host, illustrated by predicted CRISPR-Cas functions that are known to protect the host against intrusion of foreign DNA. Interestingly, pMP7017 is also predicted to encode a conjugative DNA transfer apparatus and, consistent with this notion, we demonstrate here the conjugal transfer of pMP7017 to representative strains of B. breve and B. longum subsp. longum. We also demonstrate the presence of a megaplasmid with homology to pMP7017 in three B. longum subsp. longum strains. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. Discovery of a Conjugative Megaplasmid in Bifidobacterium breve

    PubMed Central

    Bottacini, Francesca; O'Connell Motherway, Mary; Casey, Eoghan; McDonnell, Brian; Mahony, Jennifer; Ventura, Marco

    2014-01-01

    Bifidobacterium breve is a common and sometimes very abundant inhabitant of the human gut. Genome sequencing of B. breve JCM 7017 revealed the presence of an extrachromosomal element, designated pMP7017 consisting of >190 kb, thus representing the first reported bifidobacterial megaplasmid. In silico characterization of this element revealed several genomic features supporting a stable establishment of the megaplasmid in its host, illustrated by predicted CRISPR-Cas functions that are known to protect the host against intrusion of foreign DNA. Interestingly, pMP7017 is also predicted to encode a conjugative DNA transfer apparatus and, consistent with this notion, we demonstrate here the conjugal transfer of pMP7017 to representative strains of B. breve and B. longum subsp. longum. We also demonstrate the presence of a megaplasmid with homology to pMP7017 in three B. longum subsp. longum strains. PMID:25326305

  13. Two New PRP Conjugate Gradient Algorithms for Minimization Optimization Models

    PubMed Central

    Yuan, Gonglin; Duan, Xiabin; Liu, Wenjie; Wang, Xiaoliang; Cui, Zengru; Sheng, Zhou

    2015-01-01

    Two new PRP conjugate Algorithms are proposed in this paper based on two modified PRP conjugate gradient methods: the first algorithm is proposed for solving unconstrained optimization problems, and the second algorithm is proposed for solving nonlinear equations. The first method contains two aspects of information: function value and gradient value. The two methods both possess some good properties, as follows: 1)β k ≥ 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. PMID:26502409

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

    PubMed

    Patterson, James T; Isaacson, Jason; Kerwin, Lisa; Atassi, Ghazi; Duggal, Rohit; Bresson, Damien; Zhu, Tong; Zhou, Heyue; Fu, Yanwen; Kaufmann, Gunnar F

    2017-12-15

    Bioconjugate formats provide alternative strategies for antigen targeting with bispecific antibodies. Here, PSMA-targeted Fab conjugates were generated using different bispecific formats. Interchain disulfide bridging of an αCD3 Fab enabled installation of either the PSMA-targeting small molecule DUPA (SynFab) or the attachment of an αPSMA Fab (BisFab) by covalent linkage. Optimization of the reducing conditions was critical for selective interchain disulfide reduction and good bioconjugate yield. Activity of αPSMA/CD3 Fab conjugates was tested by in vitro cytotoxicity assays using prostate cancer cell lines. Both bispecific formats demonstrated excellent potency and antigen selectivity. Copyright © 2017. Published by Elsevier Ltd.

  15. Quantum dot conjugates in a sub-micrometer fluidic channel

    DOEpatents

    Stavis, Samuel M.; Edel, Joshua B.; Samiee, Kevan T.; Craighead, Harold G.

    2010-04-13

    A nanofluidic channel fabricated in fused silica with an approximately 500 nm square cross section was used to isolate, detect and identify individual quantum dot conjugates. The channel enables the rapid detection of every fluorescent entity in solution. A laser of selected wavelength was used to excite multiple species of quantum dots and organic molecules, and the emission spectra were resolved without significant signal rejection. Quantum dots were then conjugated with organic molecules and detected to demonstrate efficient multicolor detection. PCH was used to analyze coincident detection and to characterize the degree of binding. The use of a small fluidic channel to detect quantum dots as fluorescent labels was shown to be an efficient technique for multiplexed single molecule studies. Detection of single molecule binding events has a variety of applications including high throughput immunoassays.

  16. Quantum dot conjugates in a sub-micrometer fluidic channel

    DOEpatents

    Stavis, Samuel M [Ithaca, NY; Edel, Joshua B [Brookline, MA; Samiee, Kevan T [Ithaca, NY; Craighead, Harold G [Ithaca, NY

    2008-07-29

    A nanofluidic channel fabricated in fused silica with an approximately 500 nm square cross section was used to isolate, detect and identify individual quantum dot conjugates. The channel enables the rapid detection of every fluorescent entity in solution. A laser of selected wavelength was used to excite multiple species of quantum dots and organic molecules, and the emission spectra were resolved without significant signal rejection. Quantum dots were then conjugated with organic molecules and detected to demonstrate efficient multicolor detection. PCH was used to analyze coincident detection and to characterize the degree of binding. The use of a small fluidic channel to detect quantum dots as fluorescent labels was shown to be an efficient technique for multiplexed single molecule studies. Detection of single molecule binding events has a variety of applications including high throughput immunoassays.

  17. Exploring the origin of high optical absorption in conjugated polymers.

    PubMed

    Vezie, Michelle S; Few, Sheridan; Meager, Iain; Pieridou, Galatia; Dörling, Bernhard; Ashraf, Raja Shahid; Goñi, Alejandro R; Bronstein, Hugo; McCulloch, Iain; Hayes, Sophia C; Campoy-Quiles, Mariano; Nelson, Jenny

    2016-07-01

    The specific optical absorption of an organic semiconductor is critical to the performance of organic optoelectronic devices. For example, higher light-harvesting efficiency can lead to higher photocurrent in solar cells that are limited by sub-optimal electrical transport. Here, we compare over 40 conjugated polymers, and find that many different chemical structures share an apparent maximum in their extinction coefficients. However, a diketopyrrolopyrrole-thienothiophene copolymer shows remarkably high optical absorption at relatively low photon energies. By investigating its backbone structure and conformation with measurements and quantum chemical calculations, we find that the high optical absorption can be explained by the high persistence length of the polymer. Accordingly, we demonstrate high absorption in other polymers with high theoretical persistence length. Visible light harvesting may be enhanced in other conjugated polymers through judicious design of the structure.

  18. Wavelet methods in multi-conjugate adaptive optics

    NASA Astrophysics Data System (ADS)

    Helin, T.; Yudytskiy, M.

    2013-08-01

    The next generation ground-based telescopes rely heavily on adaptive optics for overcoming the limitation of atmospheric turbulence. In the future adaptive optics modalities, like multi-conjugate adaptive optics (MCAO), atmospheric tomography is the major mathematical and computational challenge. In this severely ill-posed problem, a fast and stable reconstruction algorithm is needed that can take into account many real-life phenomena of telescope imaging. We introduce a novel reconstruction method for the atmospheric tomography problem and demonstrate its performance and flexibility in the context of MCAO. Our method is based on using locality properties of compactly supported wavelets, both in the spatial and frequency domains. The reconstruction in the atmospheric tomography problem is obtained by solving the Bayesian MAP estimator with a conjugate-gradient-based algorithm. An accelerated algorithm with preconditioning is also introduced. Numerical performance is demonstrated on the official end-to-end simulation tool OCTOPUS of European Southern Observatory.

  19. Preparation of Conjugates of Cytotoxic Lupane Triterpenes with Biotin.

    PubMed

    Soural, Miroslav; Hodon, Jiri; Dickinson, Niall J; Sidova, Veronika; Gurska, Sona; Dzubak, Petr; Hajduch, Marian; Sarek, Jan; Urban, Milan

    2015-12-16

    To better understand the mechanism of action of antitumor triterpenes, we are developing methods to identify their molecular targets. A promising method is based on combination of quantitative proteomics with SILAC and uses active compounds anchored to magnetic beads via biotin-streptavidin interaction. We developed a simple and fast solid-phase synthetic technique to connect terpenes to biotin through a linker. Betulinic acid was biotinylated from three different conjugation sites for use as a standard validation tool since many molecular targets of this triterpene are already known. Then, a set of four other cytotoxic triterpenoids was biotinylated. Biotinylated terpenes were similarly cytotoxic to their nonbiotinylated parents, which suggests that the target identification should not be influenced by linker or biotin. The developed solid-phase synthetic approach is the first attempt to use solid-phase synthesis to connect active triterpenes to biotin and is applicable as a general procedure for routine conjugation of triterpenes with other molecules of choice.

  20. Extending the construct validity of dependency among conjugally bereaved adults.

    PubMed

    Denckla, Christy A; Bornstein, Robert F; Mancini, Anthony D; Bonanno, George A

    2015-06-01

    The Relationship Profile Test is a widely used measure of dependency, detachment, and healthy dependency that has been examined in both clinical and nonclinical settings, though researchers have yet to validate this measure among conjugally bereaved adults. The present study examines the construct validity of a three-facet model of dependency-detachment by comparing relationships among self-report, semistructured interview-rated, and knowledgeable informant-rated functioning among conjugally bereaved adults. Participants (N = 112) included bereaved adults (M = 51.1 years; SD = 9.7) who had experienced the loss of a spouse 1.5 to 3 years prior to taking part in this study. Findings indicate adequate psychometric properties and theoretically expected associations with various measures of wellness and health including satisfaction with life, coping flexibility, somatic complaints, and ego resiliency. Results draw attention to adaptive correlates of dependency, suggesting potentially beneficial mental health interventions. © The Author(s) 2014.

  1. Extending the Construct Validity of Dependency Among Conjugally Bereaved Adults

    PubMed Central

    Denckla, Christy A.; Bornstein, Robert F.; Mancini, Anthony D.; Bonanno, George A.

    2017-01-01

    The Relationship Profile Test is a widely used measure of dependency, detachment, and healthy dependency that has been examined in both clinical and nonclinical settings, though researchers have yet to validate this measure among conjugally bereaved adults. The present study examines the construct validity of a three-facet model of dependency–detachment by comparing relationships among self-report, semistructured interview–rated, and knowledgeable informant–rated functioning among conjugally bereaved adults. Participants (N = 112) included bereaved adults (M = 51.1 years; SD = 9.7) who had experienced the loss of a spouse 1.5 to 3 years prior to taking part in this study. Findings indicate adequate psychometric properties and theoretically expected associations with various measures of wellness and health including satisfaction with life, coping flexibility, somatic complaints, and ego resiliency. Results draw attention to adaptive correlates of dependency, suggesting potentially beneficial mental health interventions. PMID:25038214

  2. Polythiophenes Comprising Conjugated Pendants for Polymer Solar Cells: A Review

    PubMed Central

    Wang, Hsing-Ju; Chen, Chih-Ping; Jeng, Ru-Jong

    2014-01-01

    Polythiophene (PT) is one of the widely used donor materials for solution-processable polymer solar cells (PSCs). Much progress in PT-based PSCs can be attributed to the design of novel PTs exhibiting intense and broad visible absorption with high charge carrier mobility to increase short-circuit current density (Jsc), along with low-lying highest occupied molecular orbital (HOMO) levels to achieve large open circuit voltage (Voc) values. A promising strategy to tailor the photophysical properties and energy levels via covalently attaching electron donor and acceptor pendants on PTs backbone has attracted much attention recently. The geometry, electron-donating capacity, and composition of conjugated pendants are supposed to be the crucial factors in adjusting the conformation, energy levels, and photovoltaic performance of PTs. This review will go over the most recent approaches that enable researchers to obtain in-depth information in the development of PTs comprising conjugated pendants for PSCs. PMID:28788575

  3. Gel Electrophoresis of Gold-DNA Nano-Conjugates

    SciTech Connect

    Pellegrino, T.; Sperling, R.A.; Alivisatos, A.P.

    2006-01-10

    Single stranded DNA of different lengths and different amounts was attached to colloidal phosphine stabilized Au nanoparticles. The resulting conjugates were investigated in detail by a gel electrophoresis study based on 1200 gels. We demonstrate how these experiments help to understand the binding of DNA to Au particles. In particular we compare specific attachment of DNA via gold-thiol bonds with nonspecific adsorption of DNA. The maximum number of DNA molecules that can be bound per particle was determined. We also compare several methods to used gel electrophoresis for investigating the effective diameter of DNA-Au conjugates, such as using a calibrationmore » curve of particles with known diameters and Ferguson plots.« less

  4. Time reversal and charge conjugation in an embedding quantum simulator.

    PubMed

    Zhang, Xiang; Shen, Yangchao; Zhang, Junhua; Casanova, Jorge; Lamata, Lucas; Solano, Enrique; Yung, Man-Hong; Zhang, Jing-Ning; Kim, Kihwan

    2015-08-04

    A quantum simulator is an important device that may soon outperform current classical computations. A basic arithmetic operation, the complex conjugate, however, is considered to be impossible to be implemented in such a quantum system due to the linear character of quantum mechanics. Here, we present the experimental quantum simulation of such an unphysical operation beyond the regime of unitary and dissipative evolutions through the embedding of a quantum dynamics in the electronic multilevels of a (171)Yb(+) ion. We perform time reversal and charge conjugation, which are paradigmatic examples of antiunitary symmetry operators, in the evolution of a Majorana equation without the tomographic knowledge of the evolving state. Thus, these operations can be applied regardless of the system size. Our approach offers the possibility to add unphysical operations to the toolbox of quantum simulation, and provides a route to efficiently compute otherwise intractable quantities, such as entanglement monotones.

  5. Process for crosslinking and extending conjugated diene-containing polymers

    NASA Technical Reports Server (NTRS)

    Bell, Vernon L. (Inventor); Havens, Stephen J. (Inventor)

    1977-01-01

    A process using a Diels-Alder reaction which increases the molecular weight and/or crosslinks polymers by reacting the polymers with bisunsaturated dienophiles is developed. The polymer comprises at least 75% by weight based on the reaction product, has a molecular weight of at least 5000 and a plurality of conjugated 1,3-diene systems incorporated into the molecular structure. A dienophile reaction with the conjugated 1,3-diene of the polymer is at least 1% by weight based on the reaction product. Examples of the polymer include polyesters, polyamides, polyethers, polysulfones and copolymers. The bisunsaturated dienophiles may include bis-maleimides, bis maleic and bis tumaric esters and amides. This method for expanding the molecular weight chains of the polymers, preferable thermoplastics, is advantageous for processing or fabricating thermoplastics. A low molecular weight thermoplastic is converted to a high molecular weight plastic having improved strength and toughness for use in the completed end use article.

  6. Unusual Internal Electron Transfer in Conjugated Radical Polymers.

    PubMed

    Li, Fei; Gore, Danielle N; Wang, Shaoyang; Lutkenhaus, Jodie L

    2017-08-07

    Nitroxide-containing organic radical polymers (ORPs) have captured attention for their high power and fast redox kinetics. Yet a major challenge is the polymer's aliphatic backbone, resulting in a low electronic conductivity. Recent attempts that replace the aliphatic backbone with a conjugated one have not met with success. The reason for this is not understood until now. We examine a family of polythiophenes bearing nitroxide radical groups, showing that while both species are electrochemically active, there exists an internal electron transfer mechanism that interferes with stabilization of the polymer's fully oxidized form. This finding directs the future design of conjugated radical polymers in energy storage and electronics, where careful attention to the redox potential of the backbone relative to the organic radical species is needed. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. [The profile of female victims of conjugal violence].

    PubMed

    Vasseur, Philippe

    2004-12-18

    To define the profile of female victims of conjugal violence examined in the Legal Medicine emergency unit of the Hotel-Dieu hospital in Paris. A self-administered questionnaire with 15 questions was distributed to 100 victims. The 100 victims replied: 86 cases of violence took place usually in the home, 78 episodes of violence were multiple and complaints were rarely lodged after the first episodes. Mental and sexual violence were severe and unrecognized. Eighty women interviewed suffered from mental violence. In 43 cases, alcohol played a determining role in the onset of such violence. Female victims of conjugal violence do not have a specific profile. The law of silence persists, but the increase in the number of complaints from North African and African women is encouraging for the future.

  8. Jasmonic acid-amino acid conjugation enzyme assays.

    PubMed

    Rowe, Martha L; Staswick, Paul E

    2013-01-01

    Jasmonic acid (JA) is activated for signaling by its conjugation to isoleucine (Ile) through an amide linkage. The Arabidopsis thaliana JASMONIC ACID RESISTANT1 (JAR1) enzyme carries out this Mg-ATP-dependent reaction in two steps, adenylation of the free carboxyl of JA, followed by condensation of the activated group to Ile. This chapter details the protocols used to detect and quantify the enzymatic activity obtained from a glutathione-S-transferase:JAR1 fusion protein produced in Escherichia coli, including an isotope exchange assay for the adenylation step and assays for the complete reaction that involve the high-performance liquid chromatography quantitation of adenosine monophosphate, a stoichiometric by-product of the reaction, and detection of the conjugation product by thin-layer chromatography or gas -chromatography/mass spectrometry.

  9. Fourier domain preconditioned conjugate gradient algorithm for atmospheric tomography.

    PubMed

    Yang, Qiang; Vogel, Curtis R; Ellerbroek, Brent L

    2006-07-20

    By 'atmospheric tomography' we mean the estimation of a layered atmospheric turbulence profile from measurements of the pupil-plane phase (or phase gradients) corresponding to several different guide star directions. We introduce what we believe to be a new Fourier domain preconditioned conjugate gradient (FD-PCG) algorithm for atmospheric tomography, and we compare its performance against an existing multigrid preconditioned conjugate gradient (MG-PCG) approach. Numerical results indicate that on conventional serial computers, FD-PCG is as accurate and robust as MG-PCG, but it is from one to two orders of magnitude faster for atmospheric tomography on 30 m class telescopes. Simulations are carried out for both natural guide stars and for a combination of finite-altitude laser guide stars and natural guide stars to resolve tip-tilt uncertainty.

  10. Modified conjugate gradient method for diagonalizing large matrices.

    PubMed

    Jie, Quanlin; Liu, Dunhuan

    2003-11-01

    We present an iterative method to diagonalize large matrices. The basic idea is the same as the conjugate gradient (CG) method, i.e, minimizing the Rayleigh quotient via its gradient and avoiding reintroducing errors to the directions of previous gradients. Each iteration step is to find lowest eigenvector of the matrix in a subspace spanned by the current trial vector and the corresponding gradient of the Rayleigh quotient, as well as some previous trial vectors. The gradient, together with the previous trial vectors, play a similar role as the conjugate gradient of the original CG algorithm. Our numeric tests indicate that this method converges significantly faster than the original CG method. And the computational cost of one iteration step is about the same as the original CG method. It is suitable for first principle calculations.

  11. Two New PRP Conjugate Gradient Algorithms for Minimization Optimization Models.

    PubMed

    Yuan, Gonglin; Duan, Xiabin; Liu, Wenjie; Wang, Xiaoliang; Cui, Zengru; Sheng, Zhou

    2015-01-01

    Two new PRP conjugate Algorithms are proposed in this paper based on two modified PRP conjugate gradient methods: the first algorithm is proposed for solving unconstrained optimization problems, and the second algorithm is proposed for solving nonlinear equations. The first method contains two aspects of information: function value and gradient value. The two methods both possess some good properties, as follows: 1) βk ≥ 0 2) the search direction has the trust region property without the use of any line search method 3) the search direction has sufficient descent property without the use of any line search method. Under some suitable conditions, we establish the global convergence of the two algorithms. We conduct numerical experiments to evaluate our algorithms. The numerical results indicate that the first algorithm is effective and competitive for solving unconstrained optimization problems and that the second algorithm is effective for solving large-scale nonlinear equations.

  12. Optimised deconjugation of androgenic steroid conjugates in bovine urine.

    PubMed

    Pedersen, Mikael; Frandsen, Henrik L; Andersen, Jens H

    2017-04-01

    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.

  13. Phase conjugation of Nd:YAG laser radiation

    NASA Astrophysics Data System (ADS)

    Chen, Jun

    1988-06-01

    The phase conjugation of Nd:YAG laser radiation by four-wave mixing in silicon and by stimulated Brillouin scattering in acetone and other organic liquids was experimentally and theoretically investigated. Due to nonlinear absorption in Si a saturation of the reflection of the phase conjugator was theoretically predicted, and experimentally observed. It is theoretically and experimentally shown that the radiation profile behind the Si-sample is annular due to defocusing. The experiments show that CS2 and acetone have the lowest thresholds for stimulated Brillouin scattering. A laser resonator was built using a Brillouin cell and two normal mirrors; the emitted laser beam is insensitive to phase perturbations in the resonator, and has a pulse duration of 5 ns and a pulse energy of 220 m.

  14. All solid-state SBS phase conjugate mirror

    DOEpatents

    Dane, Clifford B.; Hackel, Lloyd A.

    1999-01-01

    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.

  15. Time reversal and charge conjugation in an embedding quantum simulator

    PubMed Central

    Zhang, Xiang; Shen, Yangchao; Zhang, Junhua; Casanova, Jorge; Lamata, Lucas; Solano, Enrique; Yung, Man-Hong; Zhang, Jing-Ning; Kim, Kihwan

    2015-01-01

    A quantum simulator is an important device that may soon outperform current classical computations. A basic arithmetic operation, the complex conjugate, however, is considered to be impossible to be implemented in such a quantum system due to the linear character of quantum mechanics. Here, we present the experimental quantum simulation of such an unphysical operation beyond the regime of unitary and dissipative evolutions through the embedding of a quantum dynamics in the electronic multilevels of a 171Yb+ ion. We perform time reversal and charge conjugation, which are paradigmatic examples of antiunitary symmetry operators, in the evolution of a Majorana equation without the tomographic knowledge of the evolving state. Thus, these operations can be applied regardless of the system size. Our approach offers the possibility to add unphysical operations to the toolbox of quantum simulation, and provides a route to efficiently compute otherwise intractable quantities, such as entanglement monotones. PMID:26239028

  16. Truncated Autoinducing Peptide Conjugates Selectively Recognize and Kill Staphylococcus aureus.

    PubMed

    Tsuchikama, Kyoji; Shimamoto, Yasuhiro; Anami, Yasuaki

    2017-06-09

    The accessory gene regulator (agr) of Staphylococcus aureus coordinates various pathogenic events and is recognized as a promising therapeutic target for virulence control. S. aureus utilizes autoinducing peptides (AIPs), cyclic-peptide signaling molecules, to mediate the agr system. Despite the high potency of synthetic AIP analogues in agr inhibition, the potential of AIP molecules as a delivery vehicle for antibacterial agents remains unexplored. Herein, we report that truncated AIP scaffolds can be fused with fluorophore and cytotoxic photosensitizer molecules without compromising their high agr inhibitory activity, binding affinity to the receptor AgrC, or cell specificity. Strikingly, a photosensitizer-AIP conjugate exhibited 16-fold greater efficacy in a S. aureus cell-killing assay than a nontargeting analogue. These findings highlight the potential of truncated AIP conjugates as useful chemical tools for in-depth biological studies and as effective anti-S. aureus agents.

  17. Conjugated polymer sensors built on pi-extended borasiloxane cages.

    PubMed

    Liu, Wenjun; Pink, Maren; Lee, Dongwhan

    2009-06-24

    An efficient 2 + 2 cyclocondensation with dihydroxysilane converted simple arylboronic acids to bifunctional borasiloxane cage molecules, which were subsequently electropolymerized to furnish air-stable thin films. The extended [p,pi]-conjugation that defines the rigid backbone of this new conjugated polymer (CP) motif gives rise to longer-wavelength UV-vis transitions upon oxidative doping, the spectral window and intensity of which can be modified by interaction with Lewis basic reagents. Notably, this boron-containing CP undergoes a rapid and reversible color change from green to orange upon exposure to volatile amine samples under ambient conditions. This direct naked-eye detection scheme can best be explained by invoking the reversible B-N dative bond formation that profoundly influences the p-pi* orbital overlap.

  18. All solid-state SBS phase conjugate mirror

    DOEpatents

    Dane, C.B.; Hackel, L.A.

    1999-03-09

    A stimulated Brillouin scattering (SBS) phase conjugate laser mirror uses a solid-state nonlinear gain medium instead of the conventional liquid or high pressure gas medium. The concept has been effectively demonstrated using common optical-grade fused silica. An energy threshold of 2.5 mJ and a slope efficiency of over 90% were achieved, resulting in an overall energy reflectivity of >80% for 15 ns, 1 um laser pulses. The use of solid-state materials is enabled by a multi-pass resonant architecture which suppresses transient fluctuations that would otherwise result in damage to the SBS medium. This all solid state phase conjugator is safer, more reliable, and more easily manufactured than prior art designs. It allows nonlinear wavefront correction to be implemented in industrial and defense laser systems whose operating environments would preclude the introduction of potentially hazardous liquids or high pressure gases. 8 figs.

  19. Phase-conjugate holographic lithography based on micromirror array recording.

    PubMed

    Lim, Yongjun; Hahn, Joonku; Lee, Byoungho

    2011-12-01

    We present phase-conjugate holographic lithography with a hologram recorded by a digital micromirror device (DMD) and a telecentric lens. In our lithography system, a phase-conjugate hologram is applied instead of conventional masks or reticles to form patterns. This method has the advantage of increasing focus range, and it is applicable to the formation of patterns on fairly uneven surfaces. The hologram pattern is dynamically generated by the DMD, and its resolution is mainly determined by the demagnification of the telecentric lens. We experimentally demonstrate that our holographic lithographic system has a large focus range, and it is feasible to make a large-area hologram by stitching each pattern generated by the DMD without a falling off in resolution. © 2011 Optical Society of America

  20. Facial expressions of emotion and the course of conjugal bereavement.

    PubMed

    Bonanno, G A; Keltner, D

    1997-02-01

    The common assumption that emotional expression mediates the course of bereavement is tested. Competing hypotheses about the direction of mediation were formulated from the grief work and social-functional accounts of emotional expression. Facial expressions of emotion in conjugally bereaved adults were coded at 6 months post-loss as they described their relationship with the deceased; grief and perceived health were measured at 6, 14, and 25 months. Facial expressions of negative emotion, in particular anger, predicted increased grief at 14 months and poorer perceived health through 25 months. Facial expressions of positive emotion predicted decreased grief through 25 months and a positive but nonsignificant relation to perceived health. Predictive relations between negative and positive emotional expression persisted when initial levels of self-reported emotion, grief, and health were statistically controlled, demonstrating the mediating role of facial expressions of emotion in adjustment to conjugal loss. Theoretical and clinical implications are discussed.

  1. Developing Novel Conjugate HIV-1 Subunit Therapeutic Vaccines.

    DTIC Science & Technology

    1996-06-01

    significant CD4-binding was observed for gpl20-KLH conjugates prepared using 1 -ethyl- 3 -( 3 - dimethylaminopropyl )carbodiimide hydrochloride (EDC). EDC...Management and Budget, Paperwork Reduction Project (0704-0188), Washington, DC 20503. 1 . AGENCY USE ONLY (Leave blank) 2. REPORT DATE 3 . REPORT TYPE AND...FOREWORD 3 TABLE OF CONTENTS 4 INTRODUCTION 5 RESULTS 6 Specific Aim # 1 : Production and characterization of HIV-JlV and HIV-1jR_ gp120 6 Development and

  2. Ultrafast polarisation spectroscopy of photoinduced charges in a conjugated polymer

    SciTech Connect

    Bakulin, A A; Loosdrecht, P van; Pshenichnikov, M S

    2009-07-31

    Tunable optical parametric generators and amplifiers (OPA), proposed and developed by Akhmanov and his colleagues, have become the working horses in exploration of dynamical processes in physics, chemistry, and biology. In this paper, we demonstrate the possibility of using ultrafast polarisation-sensitive two-colour spectroscopy, performed with a set of two OPAs, to study charge photogeneration and transport in conjugated polymers and their donor-acceptor blends. (special issue devoted to the 80th birthday of S.A. Akhmanov)

  3. CO2 Push-Pull Dual (Conjugate) Faults Injection Simulations

    DOE Data Explorer

    Oldenburg, Curtis (ORCID:0000000201326016); Lee, Kyung Jae; Doughty, Christine; Jung, Yoojin; Borgia, Andrea; Pan, Lehua; Zhang, Rui; Daley, Thomas M.; Altundas, Bilgin; Chugunov, Nikita

    2017-07-20

    This submission contains datasets and a final manuscript associated with a project simulating carbon dioxide push-pull into a conjugate fault system modeled after Dixie Valley- sensitivity analysis of significant parameters and uncertainty prediction by data-worth analysis. Datasets include: (1) Forward simulation runs of standard cases (push & pull phases), (2) Local sensitivity analyses (push & pull phases), and (3) Data-worth analysis (push & pull phases).

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

    DTIC Science & Technology

    2008-03-01

    cavity or in an external amplifier. Since pumping is never a perfectly efficient process, some heat will be introduced, and for very high pump powers...modes it supports, and the incident pump power. While theoretical investigations of SBS PCMs have been conducted by a num- ber of authors, the model...predictions about the phase conjugate fidelity that could be expected from a given pump intensity input coupled into a specific fiber. A numerical

  5. Asymmetric conjugate addition of Grignard reagents to pyranones.

    PubMed

    Mao, Bin; Fañanás-Mastral, Martín; Feringa, Ben L

    2013-01-18

    An efficient enantioselective synthesis of lactones was developed based on the catalytic asymmetric conjugate addition (ACA) of alkyl Grignard reagents to pyranones. The use of 2H-pyran-2-one for the first time in the ACA with Grignard reagents allows for a variety of further transformations to access highly versatile building blocks such as β-alkyl substituted aldehydes or β-bromo-γ-alkyl substituted alcohols with excellent regio- and stereoselectivity.

  6. Ferritin-Polymer Conjugates: Grafting Chemistry and Self-Assembly

    DTIC Science & Technology

    2009-10-26

    a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. a...Chemoselective modification of M13 bacteriophage and cell imaging We systematically investigated the chemical modification of three kinds of reactive...tyrosine residues, on M13 surface. The reactivity for each group was identified by conjugation with small fluorescent molecules. Furthermore, the

  7. Conjugate-like immunogens produced as protein capsular matrix vaccines.

    PubMed

    Thanawastien, Ann; Cartee, Robert T; Griffin, Thomas J; Killeen, Kevin P; Mekalanos, John J

    2015-03-10

    Capsular polysaccharides are the primary antigenic components involved in protective immunity against encapsulated bacterial pathogens. Although immunization of adolescents and adults with polysaccharide antigens has reduced pathogen disease burden, pure polysaccharide vaccines have proved ineffective at conferring protective immunity to infants and the elderly, age cohorts that are deficient in their adaptive immune responses to such antigens. However, T-cell-independent polysaccharide antigens can be converted into more potent immunogens by chemically coupling to a "carrier protein" antigen. Such "conjugate vaccines" efficiently induce antibody avidity maturation, isotype switching, and immunological memory in immunized neonates. These immune responses have been attributed to T-cell recognition of peptides derived from the coupled carrier protein. The covalent attachment of polysaccharide antigens to the carrier protein is thought to be imperative to the immunological properties of conjugate vaccines. Here we provide evidence that covalent attachment to carrier proteins is not required for conversion of T-independent antigens into T-dependent immunogens. Simple entrapment of polysaccharides or a d-amino acid polymer antigen in a cross-linked protein matrix was shown to be sufficient to produce potent immunogens that possess the key characteristics of conventional conjugate vaccines. The versatility and ease of manufacture of these antigen preparations, termed protein capsular matrix vaccines (PCMVs), will likely provide improvements in the manufacture of vaccines designed to protect against encapsulated microorganisms. This in turn could improve the availability of such vaccines to the developing world, which has shown only a limited capacity to afford the cost of conventional conjugate vaccines.

  8. DNA Replication During Conjugal Transfer of R1162

    DTIC Science & Technology

    2002-01-01

    transport out of the cell. This idea is stimulated by the similarity between the intermediates of single-stranded phage DNA replication and conjugative...the tra gene clusters ( Miele et al., 1991). The protein is not required for replication of the plasmid, and it seems to be dispensable for transfer...donor, in order to reattach to the transport mechanism prior to the start of a new round of transfer. Rolling circle replication itself might also be

  9. Comparison of genetic algorithms with conjugate gradient methods

    NASA Technical Reports Server (NTRS)

    Bosworth, J. L.; Foo, N. Y.; Zeigler, B. P.

    1972-01-01

    Genetic algorithms for mathematical function optimization are modeled on search strategies employed in natural adaptation. Comparisons of genetic algorithms with conjugate gradient methods, which were made on an IBM 1800 digital computer, show that genetic algorithms display superior performance over gradient methods for functions which are poorly behaved mathematically, for multimodal functions, and for functions obscured by additive random noise. Genetic methods offer performance comparable to gradient methods for many of the standard functions.

  10. Conjugated Organosilicon Materials for Organic Electronics and Photonics

    NASA Astrophysics Data System (ADS)

    Ponomarenko, Sergei A.; Kirchmeyer, Stephan

    In this chapter different types of conjugated organosilicon materials possessing luminescent and/or semiconducting properties will be described. Such macromolecules have various topologies and molecular structures: linear, branched and hyperbranched oligomers, polymers, and dendrimers. Specific synthetic approaches to access these structures will be discussed. Special attention is devoted to the role of silicon in these structures and its influence on their optical and electrical properties, leading to their potential application in the emerging areas of organic and hybrid electronics.

  11. Functional conjugated pyridines via main-group element tuning.

    PubMed

    Stolar, Monika; Baumgartner, Thomas

    2018-03-29

    Pyridine-based materials have seen widespread attention for the development of n-type organic materials. In recent years, the incorporation of main-group elements has also explored significant advantages for the development and tunability of organic conjugated materials. The unique chemical and electronic structure of main-group elements has led to several enhancements in conventional organic materials. This Feature article highlights recent main-group based pyridine materials by discussing property enhancements and application in organic electronics.

  12. A conjugate heat transfer procedure for gas turbine blades.

    PubMed

    Croce, G

    2001-05-01

    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.

  13. Collagen-Gold Nanoparticle Conjugates for Versatile Biosensing

    PubMed Central

    Unser, Sarah; Holcomb, Samuel; Cary, ReJeana; Sagle, Laura

    2017-01-01

    Integration of noble metal nanoparticles with proteins offers promising potential to create a wide variety of biosensors that possess both improved selectivity and versatility. The multitude of functionalities that proteins offer coupled with the unique optical properties of noble metal nanoparticles can allow for the realization of simple, colorimetric sensors for a significantly larger range of targets. Herein, we integrate the structural protein collagen with 10 nm gold nanoparticles to develop a protein-nanoparticle conjugate which possess the functionality of the protein with the desired colorimetric properties of the nanoparticles. Applying the many interactions that collagen undergoes in the extracellular matrix, we are able to selectively detect both glucose and heparin with the same collagen-nanoparticle conjugate. Glucose is directly detected through the cross-linking of the collagen fibrils, which brings the attached nanoparticles into closer proximity, leading to a red-shift in the LSPR frequency. Conversely, heparin is detected through a competition assay in which heparin-gold nanoparticles are added to solution and compete with heparin in the solution for the binding sites on the collagen fibrils. The collagen-nanoparticle conjugates are shown to detect both glucose and heparin in the physiological range. Lastly, glucose is selectively detected in 50% mouse serum with the collagen-nanoparticle devices possessing a linear range of 3–25 mM, which is also within the physiologically relevant range. PMID:28212282

  14. An Integrated Solution for Performing Thermo-fluid Conjugate Analysis

    NASA Technical Reports Server (NTRS)

    Kornberg, Oren

    2009-01-01

    A method has been developed which integrates a fluid flow analyzer and a thermal analyzer to produce both steady state and transient results of 1-D, 2-D, and 3-D analysis models. The Generalized Fluid System Simulation Program (GFSSP) is a one dimensional, general purpose fluid analysis code which computes pressures and flow distributions in complex fluid networks. The MSC Systems Improved Numerical Differencing Analyzer (MSC.SINDA) is a one dimensional general purpose thermal analyzer that solves network representations of thermal systems. Both GFSSP and MSC.SINDA have graphical user interfaces which are used to build the respective model and prepare it for analysis. The SINDA/GFSSP Conjugate Integrator (SGCI) is a formbase graphical integration program used to set input parameters for the conjugate analyses and run the models. The contents of this paper describes SGCI and its thermo-fluids conjugate analysis techniques and capabilities by presenting results from some example models including the cryogenic chill down of a copper pipe, a bar between two walls in a fluid stream, and a solid plate creating a phase change in a flowing fluid.

  15. Oriented conjugation of single-domain antibodies and quantum dots.

    PubMed

    Brazhnik, Kristina; Nabiev, Igor; Sukhanova, Alyona

    2014-01-01

    Nanoparticle-based biodetection routinely employs monoclonal antibodies (mAbs) for targeting. However, the large size of mAbs limits the number of ligands per nanoparticle and severely restricts the bioavailability and distribution of these probes in a sample. Furthermore, conventional conjugation techniques provide nanoprobes with irregular orientation of mAbs on the nanoparticle surface and often provoke mAb unfolding. Here, we describe a protocol for engineering a new generation of ultrasmall diagnostic nanoprobes through oriented conjugation of semiconductor quantum dots (QDs) with 13 kDa single-domain antibodies (sdAbs) derived from llama immunoglobulin G (IgG). The sdAbs are conjugated with QDs in a highly oriented manner via an additional cysteine residue specifically integrated into the sdAb C-terminus. The resultant nanoprobes are <12 nm in diameter, ten times smaller in volume compared to the known alternatives. They have been proved highly efficient in flow cytometry and immunuhistochemical diagnostics. This approach can be easily extended to other semiconductor and plasmonic nanoparticles.

  16. Radialenes are minimally conjugated cyclic π-systems

    NASA Astrophysics Data System (ADS)

    Dias, Jerry Ray

    2017-03-01

    Conjugation energy (CE) in benzene is larger than its aromatic stabilisation energy (ASE). A far-reaching conclusion offered by this work is that per π-electron, CE is energetically larger than aromaticity. If a diene has a doubly degenerate HOMO, then its Diels-Alder reaction will be kinetically faster than a similar diene with a nondegenerate HOMO. The topological conjugation energy (TCE) for the radialene, monocyclic, dendralene, and linear polyene series has quite different trends. Radialenes are minimally conjugated cyclic systems with the TCE/No. π-bond = 0.432 β; the members of the dendralene series approach this same value from smaller values with increasing size. With increasing size, the members of the monocyclic and linear polyene series have, respectively, decreasing and increasing TCE/No. π-bond values approaching 0.547 β. Topological resonance energy (TRE) for radialenes, dendralenes, and linear polyenes all have TRE = 0, and the TRE/π-electron for monocyclic polyenes has alternating declining values between antiaromatic (-0.3066 β, -0.07435 β, -0.03287 β, …) and aromatic (0.04543 β, 0.01594 β, 0.00807 β, …). For benzene, TRE/No. π-bond = 0.0909 β and TCE/No. π-bond = 0.576 β.

  17. Fatty acid conjugation enhances the activities of antimicrobial peptides.

    PubMed

    Li, Zhining; Yuan, Penghui; Xing, Meng; He, Zhumei; Dong, Chuanfu; Cao, Yongchang; Liu, Qiuyun

    2013-04-01

    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.

  18. Naphthobischalcogenadiazole Conjugated Polymers: Emerging Materials for Organic Electronics.

    PubMed

    Osaka, Itaru; Takimiya, Kazuo

    2017-07-01

    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. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Laser radiation wavefront conjugation in fiber optic lightguides

    NASA Astrophysics Data System (ADS)

    Chertkov, A. A.

    1986-02-01

    Wavefront conjugation precision during stimulated brillouin scattering is investigated in a monofiber with spatially homogeneous and inhomogeneous beams at lambda = 106 micrometer. A Q-modulated YAG:Nd sup 3+ laser with initial transmission of 25% was employed as the radiation source. The energy of the incident and reflected radiation was measured by means of F-28 photoelements outputting their signals to an S8-12 oscilloscope. The behavior of the coefficient of reflection from the stimulated Brillouin scattering mirror as a function of the amount by which the pumping energy exceeded the threshold was found to be the same for all types of fibers, and to be independent of astigmatism and angular beam divergence. The wavefront conjugation quality as a function of the energy level was also the same for all of the lightguides employed: quartz, silicate and silicate-quartz. The good wavefront conjugation observed for astigmatic and spatially inhomogeneous beams make it possible to compensate satisfactorily for inhomogeneities in the distorting wavefront of the beam.

  20. Peptide-Drug Conjugate: A Novel Drug Design Approach.

    PubMed

    Ma, Liang; Wang, Chao; He, Zihao; Cheng, Biao; Zheng, Ling; Huang, Kun

    2017-01-01

    More than 100 years ago, German physician Paul Ehrlich first proposed the concept of selectively delivering "magic bullets" to tumors through targeting agents. The targeting therapy with antibody-drug conjugates (ADCs) and peptide-drug conjugate (PDCs), which are usually composed of monoclonal antibodies or peptides, toxic payloads and cleavage/ noncleavage linkers, has been extensively studied for decades. The conjugates enable selective delivery of cytotoxic payloads to target cells, which results in improved efficacy, reduced systemic toxicity and improved pharmacokinetics (PK)/pharmacodynamics (PD) compared with traditional chemotherapy. PDC and ADC share similar concept, but with vastly different structures and properties. Humanized antibodies introduce high specificity and prolonged half-life, while small molecule weight peptides exhibit higher drug loading and enhanced tissue penetration capacity, and the flexible linear or cyclic peptides are also modified more easily. In this review, the principles of design, synthesis approaches and the latest advances of PDCs are summarized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Conjugal intimacy, gender and modernity in contemporary China.

    PubMed

    Liu, Jieyu; Bell, Eona; Zhang, Jiayu

    2017-12-15

    The new generation of modernity theorists have forecast the democratization of gender relations within intimate relationships in late-modern times. Chinese society has undergone rapid and dramatic changes in its unique trajectory of political, social and economic reform. Using China as an example of a region which has been largely ignored in contemporary social theory, this article enters the debate to contest the extent to which conjugal relationships are democratized in line with modernity. We further test the assertion that modern marriages are characterized by increased self-disclosure and communication between partners. Data from a national survey on Chinese families is analysed in relation to the level of self-disclosure between husbands and wives; gender division of housework; household decision-making; and home ownership. We highlight the impact of gender, cohort and location (urban, rural or migrant) on experiences of modernity and draw attention to the material, social and cultural factors which continue to shape conjugal relations in contemporary Chinese society. Based on our findings, we contest the argument that disclosing intimacy between intimate partners is a defining characteristic of modern relationships, and suggest that other social factors may condition degrees of self-disclosure in marriage. Similarly, we question the extent to which heterosexual conjugal equality is attained: the cultural practices and values of patrilineal family organization, together with material circumstances, continue to influence marital relations in China. © London School of Economics and Political Science 2017.

  2. Moving force identification based on modified preconditioned conjugate gradient method

    NASA Astrophysics Data System (ADS)

    Chen, Zhen; Chan, Tommy H. T.; Nguyen, Andy

    2018-06-01

    This paper develops a modified preconditioned conjugate gradient (M-PCG) method for moving force identification (MFI) by improving the conjugate gradient (CG) and preconditioned conjugate gradient (PCG) methods with a modified Gram-Schmidt algorithm. The method aims to obtain more accurate and more efficient identification results from the responses of bridge deck caused by vehicles passing by, which are known to be sensitive to ill-posed problems that exist in the inverse problem. A simply supported beam model with biaxial time-varying forces is used to generate numerical simulations with various analysis scenarios to assess the effectiveness of the method. Evaluation results show that regularization matrix L and number of iterations j are very important influence factors to identification accuracy and noise immunity of M-PCG. Compared with the conventional counterpart SVD embedded in the time domain method (TDM) and the standard form of CG, the M-PCG with proper regularization matrix has many advantages such as better adaptability and more robust to ill-posed problems. More importantly, it is shown that the average optimal numbers of iterations of M-PCG can be reduced by more than 70% compared with PCG and this apparently makes M-PCG a preferred choice for field MFI applications.

  3. Nanohybrid conjugated polyelectrolytes: highly photostable and ultrabright nanoparticles.

    PubMed

    Darwish, Ghinwa H; Karam, Pierre

    2015-10-07

    We present a general and straightforward one-step approach to enhance the photophysical properties of conjugated polyelectrolytes. Upon complexation with an amphiphilic polymer (polyvinylpyrrolidone), an anionic conjugated polyelectrolyte (poly[5-methoxy-2-(3-sulfopropoxy)-1,4-phenylenevinylene]) was prepared into small nanoparticles with exceptional photostability and brightness. The polymer fluorescence intensity was enhanced by 23 -fold and could be easily tuned by changing the order of addition. Single molecule experiments revealed a complete suppression of blinking. In addition, after only losing 18% of the original intensity, a remarkable amount of photons were emitted per particle (∼10(9), on average). This number is many folds greater than popular organic fluorescent dyes. We believe that an intimate contact between the two polymers is shielding the conjugated polyelectrolyte from the destructive photooxidation. The prepared nanohybrid particles will prove instrumental in single particle based fluorescent assays and can serve as a probe for the current state-of-the-art bioimaging fluorescence techniques.

  4. 3D Display Using Conjugated Multiband Bandpass Filters

    NASA Technical Reports Server (NTRS)

    Bae, Youngsam; White, Victor E.; Shcheglov, Kirill

    2012-01-01

    Stereoscopic display techniques are based on the principle of displaying two views, with a slightly different perspective, in such a way that the left eye views only by the left eye, and the right eye views only by the right eye. However, one of the major challenges in optical devices is crosstalk between the two channels. Crosstalk is due to the optical devices not completely blocking the wrong-side image, so the left eye sees a little bit of the right image and the right eye sees a little bit of the left image. This results in eyestrain and headaches. A pair of interference filters worn as an optical device can solve the problem. The device consists of a pair of multiband bandpass filters that are conjugated. The term "conjugated" describes the passband regions of one filter not overlapping with those of the other, but the regions are interdigitated. Along with the glasses, a 3D display produces colors composed of primary colors (basis for producing colors) having the spectral bands the same as the passbands of the filters. More specifically, the primary colors producing one viewpoint will be made up of the passbands of one filter, and those of the other viewpoint will be made up of the passbands of the conjugated filter. Thus, the primary colors of one filter would be seen by the eye that has the matching multiband filter. The inherent characteristic of the interference filter will allow little or no transmission of the wrong side of the stereoscopic images.

  5. Nano-assembly of nanodiamonds by conjugation to actin filaments.

    PubMed

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

    2016-03-01

    Fluorescent nanodiamonds (NDs) are remarkable objects. They possess unique mechanical and optical properties combined with high surface areas and controllable surface reactivity. They are non-toxic and hence suited for use in biological environments. NDs are also readily available and commercially inexpensive. Here, the exceptional capability of controlling and tailoring their surface chemistry is demonstrated. Small, bright diamond nanocrystals (size ˜30 nm) are conjugated to protein filaments of actin (length ˜3-7 µm). The conjugation to actin filaments is extremely selective and highly target-specific. These unique features, together with the relative simplicity of the conjugation-targeting method, make functionalised nanodiamonds a powerful and versatile platform in biomedicine and quantum nanotechnologies. Applications ranging from using NDs as superior biological markers to, potentially, developing novel bottom-up approaches for the fabrication of hybrid quantum devices that would bridge across the bio/solid-state interface are presented and discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Bioanalysis of antibody-drug conjugates: American Association of Pharmaceutical Scientists Antibody-Drug Conjugate Working Group position paper.

    PubMed

    Gorovits, Boris; Alley, Stephen C; Bilic, Sanela; Booth, Brian; Kaur, Surinder; Oldfield, Phillip; Purushothama, Shobha; Rao, Chetana; Shord, Stacy; Siguenza, Patricia

    2013-05-01

    Antibody-drug conjugates (ADCs) typically consist of a cytotoxic drug covalently bound to an antibody by a linker. These conjugates have the potential to substantially improve efficacy and reduce toxicity compared with cytotoxic small-molecule drugs. Since ADCs are generally complex heterogeneous mixtures of multiple species, these novel therapeutic products present unique bioanalytical challenges. The growing number of ADCs being developed across the industry suggests the need for alignment of the bioanalytical methods or approaches used to assess the multiple species and facilitate consistent interpretation of the bioanalytical data. With limited clinical data, the current strategies that can be used to provide insight into the relationship between the multiple species and the observed clinical safety and efficacy are still evolving. Considerations of the bioanalytical strategies for ADCs based on the current industry practices that take into account the complexity and heterogeneity of ADCs are discussed.

  7. Evaluation of hyaluronic acid-protein conjugates for polymer masked-unmasked protein therapy.

    PubMed

    Ferguson, Elaine L; Alshame, Alshame M J; Thomas, David W

    2010-12-15

    Bioresponsive polymers may effectively be utilized to enhance the circulation time and stability of biologically active proteins and peptides, while reducing their immunogenicity and toxicity. Recently, dextrin-epidermal growth factor (EGF) conjugates, which make use of the Polymer-masked UnMasked Protein Therapy (PUMPT) concept, have been developed and shown potential as modulators of impaired wound healing. This study investigated the potential of PUMPT using hyaluronic acid (HA) conjugates to mask activity and enhance protein stability, while allowing restoration of biological activity following triggered degradation. HA fragments (Mw ∼90,000g/mol), obtained by acid hydrolysis of Rooster comb HA, were conjugated to trypsin as a model enzyme or to EGF as a model growth factor. Conjugates contained 2.45 and 0.98% (w/w) trypsin or EGF, respectively, and contained <5% free protein. HA conjugation did not significantly alter trypsin's activity. However, incubation of the conjugate with physiological concentrations of HAase increased its activity to ∼145% (p<0.001) that of the free enzyme. In contrast, when HA-EGF conjugates were tested in vitro, no effect on cell proliferation was seen, even in the presence of HAase. HA conjugates did not display typical masking/unmasking behavior, HA-trypsin conjugates exhibited ∼52% greater stability in the presence of elastase, compared to free trypsin, demonstrating the potential of HA conjugates for further development as modulators of tissue repair. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Molecular engineering of phosphole-based conjugated materials

    NASA Astrophysics Data System (ADS)

    Ren, Yi

    The work in this thesis focuses on the molecular engineering of phosphorus-based conjugated materials. In the first part (Chapters Two and Three), new phosphorus-based conjugated systems were designed and synthesized to study the effect of the heteroelement on the electronic properties of the π-conjugated systems. The second part (Chapters Four and Five) deals with the self-assembly features of specifically designed phosphorus-based conjugated systems. In Chapter Two, electron-poor and electron-rich aromatic substituents were introduced to the dithienophosphole core in order to balance the electron-accepting and electron-donating character of the systems. Furthermore, an intriguing intramolecular charge transfer process could be observed between two dithienophosphole cores in a bridged bisphosphole-system. In Chapter Three, a secondary heteroelement (Si, P, S) was incorporated in the phosphorus-based conjugated systems. Extensive structure-property studies revealed that the secondary heteroelement can effectively manipulate the communication in phosphinine-based systems. The study of a heterotetracene system allowed for selectively applying distinct heteroatom (S/P) chemistries, which offers a powerful tool for the modification of the electronic structure of the system. More importantly, the heteroatom-specific electronic nature (S/P) can be utilized to selectively control different photophysical aspects (energy gap and fluorescence quantum yield). Furthermore, additional molecular engineering of the heterotetracene provided access to well-defined 1D microstructures, which opened the door for designing multi-functional self-assembled phosphorus-based materials. In Chapter Four, the self-organizing phosphole-lipid system is introduced, which combines the features of phospholipids with the electronics of phospholes. Its amphiphilic nature induces intriguing self-assembly features - liquid crystal and soft crystal architectures, both exhibiting well

  9. Design and characterization of nanomaterial-biomolecule conjugates

    NASA Astrophysics Data System (ADS)

    Yim, Tae-Jin

    In the field of nanobiotechnology, nanoscale dimensions result in physical properties that differ from more conventional bulk material state. The integration of nanomaterials with biomolecules has begun to be used for unique physical properties, and for biological specific recognition, thereby leading to novel nanomaterial-biomolecule conjugates. The direction of this dissertation is to develop biocatalytic nanomaterial-biomolecule conjugates and to characterize them. For this, biological catalysts are employed to combine with nanomaterials. Two large parts include functional ization of nanomaterials with biomolecules and assembly of nanomaterials using a biological catalyst. First part of this thesis work is the exploration of the biocatalytic properties of nanomaterial-biomolecule conjugates. Si nanocolumns have higher surface area which leads more amount of biocatalytis immobilization than flat Si wafer with the same projected area. The enhanced activity of soybean peroxidase (SBP) immobilized onto Si nanocolumns as novel nanostructured supports is focused. Next, the catalytic activity of immobilized DNAzyme onto multiwalled carbon nanotubes (MWNTs) is compared to that in solution phase, and multiple turnovers are examined. The relationship between hybridization efficiency and activity is investigated as a function of surface density of DNAzyme on MWNTs. Then, cellular delivery of silica nanoparticle-protein conjugates is visually confirmed and therefore the intracellular function of a protein delivered by silica nanoparticle-protein conjugates is proved. For one example of the intracellular function, stable SBP immobilized onto silica nanoparticles to activate a prodrug is demonstrated. Second part of this thesis work is the formation of nanostructured materials through the enzymatic assembly of single-walled carbon nanotubes (SWNTs). Enzymatic polymerization of a phenol compound is applied to the bridging of two or more SWNTs functionalized with phenol

  10. Interactions of Nitroxide-Conjugated and Non-Conjugated Glycodendrimers with Normal and Cancer Cells and Biocompatibility Studies.

    PubMed

    Andreozzi, Elisa; Antonelli, Antonella; Cangiotti, Michela; Canonico, Barbara; Sfara, Carla; Pianetti, Anna; Bruscolini, Francesca; Sahre, Karin; Appelhans, Dietmar; Papa, Stefano; Ottaviani, Maria Francesca

    2017-02-15

    Poly(propyleneimine) glycodendrimers fully modified with maltose units were administered to different cancer cell lines and their effect on cell viability was evaluated by using MTS assay and flow cytometry. The mechanism of dendrimer-cell interactions was investigated by the electron paramagnetic resonance (EPR) technique by using a new nitroxide-conjugated glycodendrimer. The nitroxide groups did not modify both the biological properties (cell viability and apoptosis degree) of the dendrimers in the presence of the cells and the dendrimer-cell interactions. Since this class of dendrimers is already known to be biocompatible for human healthy cells, noncancer cells such as human peripheral blood mononuclear cells (PBMCs) and macrophages were also treated with the glycodendrimer, and EPR spectra of the nitroxide-conjugated glycodendrimer were compared for cancer and noncancer cells. It was found that this dendrimer selectively affects the cell viability of tumor cells, while, surprisingly, PBMC proliferation is induced. Moreover, H-bond-active glycodendrimer-cell interactions were different for the different cancer cell lines and noncancer cells. The nitroxide-conjugated glycodendrimer was able to interact with the cell membrane and eventually cross it, getting in contact with cytosol antioxidants. This study helps to clarify the potential anticancer effect of this class of dendrimers opening to future applications of these macromolecules as new antitumor agents.

  11. Doxorubicin-loaded microgels composed of cinnamic acid-gelatin conjugate and cinnamic acid-Pluronic F127 conjugate.

    PubMed

    Zhang, Hong; Kim, Jin-Chul

    2016-01-01

    Microgels were prepared by cinnamic acid-gelatin (type B) conjugate (CA-GelB) and cinnamic acid-Pluronic F127 conjugate (CA-Plur). (1)H NMR confirmed that CA was conjugated to gelatin and the gelatin to CA residue molar ratio was estimated to be 1:4.7 by a colorimetric method. CA-Plur of which the CA residue to Plur molar ratio was 1.2:1 was used as a thermo-sensitive polymer. The CA residues of CA-Plur/CA-GelB mixture were readily photo-dimerized to form microgels by UV irradiation. The isoelectric point of the microgel was found to be pH 5.8 and the hydrodynamic diameter decreased when the suspension temperature increased. The microgel could hardly retard the release of doxorubicin (DOX) at pH 3.0 and pH 5.0, but it could suppress and control the release at pH 7.4 possibly due to electrostatic attraction. Meanwhile, the release of DOX at pH 7.4 was less suppressed when the medium temperature was higher, possibly because of thermal thinning of Pluronic chain layer.

  12. Preclinical manufacture of anti-HER2 liposome-inserting, scFv-PEG-lipid conjugate. 2. Conjugate micelle identity, purity, stability, and potency analysis.

    PubMed

    Nellis, David F; Giardina, Steven L; Janini, George M; Shenoy, Shilpa R; Marks, James D; Tsai, Richard; Drummond, Daryl C; Hong, Keelung; Park, John W; Ouellette, Thomas F; Perkins, Shelley C; Kirpotin, Dmitri B

    2005-01-01

    Analytical methods optimized for micellar F5cys-MP-PEG(2000)-DPSE protein-lipopolymer conjugate are presented. The apparent micelle molecular weight, determined by size exclusion chromatography, ranged from 330 to 960 kDa. The F5cys antibody and conjugate melting points, determined by differential scanning calorimetry, were near 82 degrees C. Traditional methods for characterizing monodisperse protein species were inapplicable to conjugate analysis. The isoelectric point of F5cys (9.2) and the conjugate (8.9) were determined by capillary isoelectric focusing (cIEF) after addition of the zwitterionic detergent CHAPS to the buffer. Conjugate incubation with phospholipase B selectively removed DSPE lipid groups and dispersed the conjugate prior to separation by chromatographic methods. Alternatively, adding 2-propanol (29.4 vol %) and n-butanol (4.5 vol %) to buffers for salt-gradient cation exchange chromatography provided gentler, nonenzymatic dispersion, resulting in well-resolved peaks. This method was used to assess stability, identify contaminants, establish lot-to-lot comparability, and determine the average chromatographic purity (93%) for conjugate lots, described previously. The F5cys amino acid content was confirmed after conjugation. The expected conjugate avidity for immobilized HER-2/neu was measured by bimolecular interaction analysis (BIAcore). Mock therapeutic assemblies were made by conjugate insertion into preformed doxorubicin-encapsulating liposomes for antibody-directed uptake of doxorubicin by HER2-overexpressing cancer cells in vitro. Together these developed assays established that the manufacturing method as described in the first part of this study consistently produced F5cys-MP-PEG(2000)-DSPE having sufficient purity, stability, and functionality for use in preclinical toxicology investigations.

  13. Systemic aspects of conjugal resilience in couples with a child facing cancer and marrow transplantation

    PubMed Central

    Martin, Julie; Péloquin, Katherine; Vachon, Marie-France; Duval, Michel; Sultan, Serge

    2016-01-01

    Introduction The negative impact of paediatric cancer on parents is well known and is even greater when intensive treatments are used. This study aimed to describe how couples whose child has received a transplant for the treatment of leukaemia view conjugal resilience and to evaluate the role of we-ness as a precursor of conjugal adjustment. Methods Four parental couples were interviewed. Interviews were analysed in two ways: inductive thematic analysis and rating of verbal content with the We-ness Coding Scale. Results Participants report that conjugal resilience involves the identification of the couple as a team and cohesion in the couple. Being a team generates certain collaborative interactions that lead to conjugal resilience. A sense of we-ness in parents is associated with fluctuation in the frequency of themes. Discussion Participants’ vision of conjugal resilience introduced novel themes. The sense of we-ness facilitates cohesion and the process of conjugal resilience. PMID:27687510

  14. Systemic aspects of conjugal resilience in couples with a child facing cancer and marrow transplantation.

    PubMed

    Martin, Julie; Péloquin, Katherine; Vachon, Marie-France; Duval, Michel; Sultan, Serge

    The negative impact of paediatric cancer on parents is well known and is even greater when intensive treatments are used. This study aimed to describe how couples whose child has received a transplant for the treatment of leukaemia view conjugal resilience and to evaluate the role of we-ness as a precursor of conjugal adjustment. Four parental couples were interviewed. Interviews were analysed in two ways: inductive thematic analysis and rating of verbal content with the We-ness Coding Scale . Participants report that conjugal resilience involves the identification of the couple as a team and cohesion in the couple. Being a team generates certain collaborative interactions that lead to conjugal resilience. A sense of we-ness in parents is associated with fluctuation in the frequency of themes. Participants' vision of conjugal resilience introduced novel themes. The sense of we-ness facilitates cohesion and the process of conjugal resilience.

  15. Direct protein-protein conjugation by genetically introducing bioorthogonal functional groups into proteins.

    PubMed

    Kim, Sanggil; Ko, Wooseok; Sung, Bong Hyun; Kim, Sun Chang; Lee, Hyun Soo

    2016-11-15

    Proteins often function as complex structures in conjunction with other proteins. Because these complex structures are essential for sophisticated functions, developing protein-protein conjugates has gained research interest. In this study, site-specific protein-protein conjugation was performed by genetically incorporating an azide-containing amino acid into one protein and a bicyclononyne (BCN)-containing amino acid into the other. Three to four sites in each of the proteins were tested for conjugation efficiency, and three combinations showed excellent conjugation efficiency. The genetic incorporation of unnatural amino acids (UAAs) is technically simple and produces the mutant protein in high yield. In addition, the conjugation reaction can be conducted by simple mixing, and does not require additional reagents or linker molecules. Therefore, this method may prove very useful for generating protein-protein conjugates and protein complexes of biochemical significance. Copyright © 2016. Published by Elsevier Ltd.

  16. A penalized linear and nonlinear combined conjugate gradient method for the reconstruction of fluorescence molecular tomography.

    PubMed

    Shang, Shang; Bai, Jing; Song, Xiaolei; Wang, Hongkai; Lau, Jaclyn

    2007-01-01

    Conjugate gradient method is verified to be efficient for nonlinear optimization problems of large-dimension data. In this paper, a penalized linear and nonlinear combined conjugate gradient method for the reconstruction of fluorescence molecular tomography (FMT) is presented. The algorithm combines the linear conjugate gradient method and the nonlinear conjugate gradient method together based on a restart strategy, in order to take advantage of the two kinds of conjugate gradient methods and compensate for the disadvantages. A quadratic penalty method is adopted to gain a nonnegative constraint and reduce the illposedness of the problem. Simulation studies show that the presented algorithm is accurate, stable, and fast. It has a better performance than the conventional conjugate gradient-based reconstruction algorithms. It offers an effective approach to reconstruct fluorochrome information for FMT.

  17. Protein-Polymer Conjugates: Synthetic Approaches by Controlled Radical Polymerizations & Interesting Applications

    PubMed Central

    Grover, Gregory N.; Maynard, Heather D.

    2011-01-01

    Protein-polymer conjugates are of interest to researchers in diverse fields. Attachment of polymers to proteins results in improved pharmacokinetics, which is important in medicine. From an engineering standpoint, conjugates are exciting because they exhibit properties of both the biomolecules and synthetic polymers. This allows the activity of the protein to be altered or tuned, a key aspect in therapeutic design, anchoring conjugates to surfaces, and utilizing these materials for supramolecular self-assembly. Thus, there is broad interest in straightforward synthetic methods to make protein-polymer conjugates. Controlled radical polymerization (CRP) techniques have emerged as excellent strategies to make conjugates because the resulting polymers have narrow molecular weight distributions, targeted molecular weights, and attach to specific sites on proteins. Herein, recent advances in the synthesis and application of protein-polymer conjugates by CRP are highlighted. PMID:21071260

  18. Novel amphiphilic PEG-hydroxycamptothecin conjugates as glutathione-responsive prodrug nanocapsules for cancer chemotherapy

    NASA Astrophysics Data System (ADS)

    Guo, Na; Hao, Tiantian; Shang, Xiuzhuan; Zhang, Tianle; Liu, Huan; Zhang, Qian; Wang, Jing; Jiang, Du; Rong, Yao; Teng, Yuou; Yu, Peng

    2017-06-01

    A series of novel hydroxycamptothecin (HCPT) conjugates ( 13a-14d), which contained a polyethylene glycol moiety and disulfide bond, were designed and synthesized in five to six steps, with overall yields of 20-39%. The anticancer activities and toxicities of these new conjugates were evaluated using an in vitro MTT assay in K562, HepG2, and HT-29 cell lines and HUVECs. The conjugates displayed enhanced antitumor activity and reduced toxicity in comparison with their parent molecule, HCPT. Among these conjugates, compound 13a exhibited 100-fold better selectivity to the tumor cells than to HUVECs. TEM and DLS experiments demonstrated that 13a formed nanosized micelles with a diameter of approximately 200 nm in aqueous solution and that the conjugate could undergo glutathione-responsive degradation to release HCPT at the tumor site. The improved potency and reduced toxicity of these conjugates may be caused by the enhanced permeation and retention (EPR) effect of nanoparticles.

  19. Optimization of condition for conjugation of enrofloxacin to enzymes in chemiluminescence enzyme immunoassay.

    PubMed

    Yu, Songcheng; Yu, Fei; Zhang, Hongquan; Qu, Lingbo; Wu, Yongjun

    2014-06-05

    In this study, in order to find out a proper method for conjugation of enrofloxacin to label enzymes, two methods were compared and carbodiimide condensation was proved to be better. The results showed that the binding ratio of enrofloxacin and alkaline phosphatase (ALP) was 8:1 and that of enrofloxacin and horseradish peroxidase (HRP) was 5:1. This indicated that conjugate synthesized by carbodiimide condensation was fit for chemiluminescence enzyme immunoassay (CLEIA). Furthermore, data revealed that dialysis time was an important parameter for conjugation and 6days was best. Buffer to dilute conjugate had little effect on CLEIA. The storage condition for conjugates was also studied and it was shown that the conjugate was stable at 4°C with no additive up to 30days. These data were valuable for establishing CLEIA to quantify enrofloxacin. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Optimization of condition for conjugation of enrofloxacin to enzymes in chemiluminescence enzyme immunoassay

    NASA Astrophysics Data System (ADS)

    Yu, Songcheng; Yu, Fei; Zhang, Hongquan; Qu, Lingbo; Wu, Yongjun

    2014-06-01

    In this study, in order to find out a proper method for conjugation of enrofloxacin to label enzymes, two methods were compared and carbodiimide condensation was proved to be better. The results showed that the binding ratio of enrofloxacin and alkaline phosphatase (ALP) was 8:1 and that of enrofloxacin and horseradish peroxidase (HRP) was 5:1. This indicated that conjugate synthesized by carbodiimide condensation was fit for chemiluminescence enzyme immunoassay (CLEIA). Furthermore, data revealed that dialysis time was an important parameter for conjugation and 6 days was best. Buffer to dilute conjugate had little effect on CLEIA. The storage condition for conjugates was also studied and it was shown that the conjugate was stable at 4 °C with no additive up to 30 days. These data were valuable for establishing CLEIA to quantify enrofloxacin.

  1. Degradable conjugated polymers for the selective sorting of semiconducting carbon nanotubes

    DOEpatents

    Gopalan, Padma; Arnold, Michael Scott; Kansiusarulsamy, Catherine Kanimozhi; Brady, Gerald Joseph; Shea, Matthew John

    2018-04-10

    Conjugated polymers composed of bi-pyridine units linked to 9,9-dialkyl fluorenyl-2,7-diyl units via imine linkages along the polymer backbone are provided. Also provided are semiconducting single-walled carbon nanotubes coated with the conjugated polymers and methods of sorting and separating s-SWCNTs from a sample comprising a mixture of s-SWCNTs and metallic single-walled carbon nanotubes using the conjugated polymers.

  2. Intramolecular Charge Transfer of Conjugated Liquid Crystal Ferrocene Macromolecules - Synthesis and Characterization

    DTIC Science & Technology

    2016-04-12

    AFRL-AFOSR-CL-TR-2016-0012 Intramolecular Charge Transfer of Conjugated Liquid Crystal Ferrocene Macromolecules Ronald Ziolo CIQA Final Report 07/07...3. DATES COVERED (From - To)  15 Aug 2014 to 14 Jan 2016 4. TITLE AND SUBTITLE Intramolecular Charge Transfer of Conjugated Liquid Crystal Ferrocene...characterization of a new series of conjugated macromolecules bearing ferrocene as a highly efficient electron donor material coupled to 2,5-di(alcoxy) benzene

  3. Nonlinear propagation of phase-conjugate focused sound beams in water

    NASA Astrophysics Data System (ADS)

    Brysev, A. P.; Krutyansky, L. M.; Preobrazhensky, V. L.; Pyl'nov, Yu. V.; Cunningham, K. B.; Hamilton, M. F.

    2000-07-01

    Nonlinear propagation of phase-conjugate, focused, ultrasound beams is studied. Measurements are presented of harmonic amplitudes along the axis and in the focal plane of the conjugate beam, and of the waveform and spectrum at the focus. A maximum peak pressure of 3.9 MPa was recorded in the conjugate beam. The measurements are compared with simulations based on the KZK equation, and satisfactory agreement is obtained.

  4. Particle-in-a-box model of exciton absorption and electroabsorption in conjugated polymers

    NASA Astrophysics Data System (ADS)

    Pedersen, Thomas G.

    2000-12-01

    The recently proposed particle-in-a-box model of one-dimensional excitons in conjugated polymers is applied in calculations of optical absorption and electroabsorption spectra. It is demonstrated that for polymers of long conjugation length a superposition of single exciton resonances produces a line shape characterized by a square-root singularity in agreement with experimental spectra near the absorption edge. The effects of finite conjugation length on both absorption and electroabsorption spectra are analyzed.

  5. Preparation and testing of a Haemophilus influenzae Type b/Hepatitis B surface antigen conjugate vaccine.

    PubMed

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

    2015-03-24

    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. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2016-12-08

    to know the consequences that men experience related to incarceration by conjugal violence. qualitative study on 20 men in jail and indicted in criminal processes related to conjugal violence in a Court specialized in Family and Domestic Violence against women. The interviews were classified based on Collective Subject Discourse method, using NVIVO(r) software. the collective discourse shows that the experience of preventive imprisonment starts a process of family dismantling, social stigma, financial hardship and psycho-emotional symptoms such as phobia, depression, hypertension, and headaches. due to the physical, mental and social consequences of the conjugal violence-related imprisonment experience, it is urgent to look carefully into the somatization process as well as to the prevention strategies regarding this process. conhecer as repercussões da prisão por violência conjugal para os homens. estudo qualitativo com 20 homens que foram presos e respondem a processo criminal por violência conjugal em uma Vara de Violência Doméstica e Familiar contra a Mulher. As entrevistas foram categorizadas com base no método do Discurso do Sujeito Coletivo, com auxílio do software NVIVO(r). o discurso coletivo revela que a vivência da prisão preventiva desencadeia desagregação familiar, estigma social, dificuldades financeiras e sintomatologia de caráter psicoemocional, como fobia, depressão, hipertensão e cefaleia. diante das repercussões físicas, mentais e sociais de experienciar a prisão em decorrência de violência conjugal, urge um olhar acerca do processo de somatização do vivido, da mesma maneira que estratégias de prevenção do fenômeno. conocer las repercusiones de prisión, por violencia conyugal, en los hombres. estudio cualitativo con 20 hombres que fueron presos y responden por caso criminal de violencia conyugal, en una Juzgado de Violencia Doméstica y Familiar contra la Mujer. Las entrevistas fueron categorizadas con base en el m

  7. Doxorubicin conjugated to D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS): conjugation chemistry, characterization, in vitro and in vivo evaluation.

    PubMed

    Cao, Na; Feng, Si-Shen

    2008-10-01

    To develop a polymer-anticancer drug conjugate, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was employed as a carrier of doxorubicin (DOX) to enhance its therapeutic effects and reduce its side effects. Doxorubicin was chemically conjugated to TPGS. The molecular structure, drug loading efficiency, drug release kinetics and stability of the conjugate were characterized. The cellular uptake, intracellular distribution, and cytotoxicity were accessed by using MCF-7 breast cancer cells and C6 glioma cells as in vitro cell model. The conjugate showed higher cellular uptake efficiency and broader distribution within the cells. Judged by IC(50), the conjugate was found 31.8, 69.6, 84.1% more effective with MCF-7 cells and 43.9, 87.7, 42.2% more effective with C6 cells than the parent drug after 24, 48, 72 h culture, respectively. The in vivo pharmacokinetics and biodistribution were investigated after an i.v. administration at 5 mg DOX/kg body weight in rats. Promisingly, 4.5-fold increase in the half-life and 24-fold increase in the area-under-the-curve (AUC) of DOX were achieved for the TPGS-DOX conjugate compared with the free DOX. The drug level in heart, gastric and intestine was significantly reduced, which is an indication of reduced side effects. Our TPGS-DOX conjugate showed great potential to be a prodrug of higher therapeutic effects and fewer side effects than DOX itself.

  8. Water-soluble polymer–drug conjugates for combination chemotherapy against visceral leishmaniasis

    PubMed Central

    Nicoletti, Salvatore; Seifert, Karin; Gilbert, Ian H.

    2010-01-01

    There is a need for new safe, effective and short-course treatments for leishmaniasis; one strategy is to use combination chemotherapy. Polymer–drug conjugates have shown promise for the delivery of anti-leishmanial agents such as amphotericin B. In this paper, we report on the preparation and biological evaluation of polymer–drug conjugates of N-(2-hydroxypropyl)methacrylamide (HPMA), amphotericin B and alendronic acid. The combinatorial polymer–drug conjugates were effective anti-leishmanial agents in vitro and in vivo, but offered no advantage over the single poly(HPMA)–amphotericin B conjugates. PMID:20338769

  9. Reduced T cell response to beta-lactoglobulin by conjugation with acidic oligosaccharides.

    PubMed

    Yoshida, Tadashi; Sasahara, Yoshimasa; Miyakawa, Shunpei; Hattori, Makoto

    2005-08-24

    We have previously reported that the conjugation of beta-lactoglobulin (beta-LG) with alginic acid oligosaccharide (ALGO) and phosphoryl oligosaccharides reduced the immunogenicity of beta-LG. In addition, those conjugates showed higher thermal stability and improved emulsifying properties than those of native beta-LG. We examine in this study the effect of conjugation on the T cell response. Our results demonstrate that the T cell response was reduced when mice were immunized with the conjugates. The findings obtained from an experiment using overlapping synthetic peptides show that novel epitopes were not generated by conjugation. One of the mechanisms for the reduced T cell response to the conjugates was found to be the reduced susceptibility of the conjugates to processing enzymes for antigen presentation. We further clarify that the beta-LG-ALGO conjugate modulated the immune response to Th1 dominance. We consider that this property of the beta-LG-ALGO conjugate would be effective for preventing food allergy as well as by its reduced immunogenicity. Our observations indicate that the method used in this study could be applied to various protein allergens to achieve reduced allergenicity with multiple improvements in their properties.

  10. Cholesterol-conjugated supramolecular assemblies of low generations polyamidoamine dendrimers for enhanced EGFP plasmid DNA transfection

    NASA Astrophysics Data System (ADS)

    Golkar, Nasim; Samani, Soliman Mohammadi; Tamaddon, Ali Mohammad

    2016-05-01

    Aimed to prepare an enhanced gene delivery system with low cytotoxicity and high transfection efficiency, various cholesterol-conjugated derivates of low generation polyamidoamine (PAMAM) dendrimers were prepared. The conjugates were characterized by TNBS assay, FTIR, and 1H-NMR spectroscopy. Self-assembly of the dendrimer conjugates (G1-Chol, G2-Chol, and G3-Chol) was investigated by pyrene assay. Following formation of the complexes between enhanced green fluorescence protein plasmid and the dendrimer conjugates at various N (primary amine)/P (phosphate) mole ratios, plasmid condensation, biologic stability, cytotoxicity, and protein expression were investigated. The conjugates self-assembled into micellar dispersions with the critical micelle concentration values (<50 µg/ml) depending on the dendrimer generation and cholesterol/amine mole ratio. Cholesterol conjugation resulted in higher resistance of the condensed plasmid DNA in a competition assay with heparin sulfate. Also, the transfection efficiency was determined higher for the cholesterol conjugates than unmodified dendrimers in HepG2 cells, showing the highest for G2-Chol at 40 % degree of cholesterol modification (G2-Chol40 %) among various dendrimer generations. Interestingly, such conjugate showed a complete protection of plasmid against serum nucleases. Our results confirmed that the cholesterol conjugation to PAMAM dendrimers of low generations bearing little cytotoxicity improves their several physicochemical and biological characteristics required for an enhanced delivery of plasmid DNA into cells.

  11. Photo-induced conjugation of tetrazoles to modified and native proteins.

    PubMed

    Siti, Winna; Khan, Amit Kumar; de Hoog, Hans-Peter M; Liedberg, Bo; Nallani, Madhavan

    2015-03-21

    Bio-orthogonal chemistry has been widely used for conjugation of polymer molecules to proteins. Here, we demonstrate the conjugation of polyethylene glycol (PEG) to bovine beta-lactoglobulin (BLG) by photo-induced cyclo-addition of tetrazole-appended PEG and allyl-modified BLG. During the course of the investigation, a significant side-reaction was found to occur for the conjugation of PEG-tetrazole to native BLG. Further exploration of the underlying chemistry reveals that the presence of a tryptophan residue is sufficient for conjugation of tetrazole-modified molecules.

  12. Molecules with enhanced electronic polarizabilities based on defect-like states in conjugated polymers

    NASA Technical Reports Server (NTRS)

    Beratan, David N. (Inventor)

    1991-01-01

    Highly conjugated organic polymers typically have large non-resonant electronic susceptibilities, which give the molecules unusual optical properties. To enhance these properties, defects are introduced into the polymer chain. Examples include light doping of the conjugated polymer and synthesis, conjugated polymers which incorporate either electron donating or accepting groups, and conjugated polymers which contain a photoexcitable species capable of reversibly transferring its electron to an acceptor. Such defects in the chain permit enhancement of the second hyperpolarizability by at least an order of magnitude.

  13. Efficient conjugate gradient algorithms for computation of the manipulator forward dynamics

    NASA Technical Reports Server (NTRS)

    Fijany, Amir; Scheid, Robert E.

    1989-01-01

    The applicability of conjugate gradient algorithms for computation of the manipulator forward dynamics is investigated. The redundancies in the previously proposed conjugate gradient algorithm are analyzed. A new version is developed which, by avoiding these redundancies, achieves a significantly greater efficiency. A preconditioned conjugate gradient algorithm is also presented. A diagonal matrix whose elements are the diagonal elements of the inertia matrix is proposed as the preconditioner. In order to increase the computational efficiency, an algorithm is developed which exploits the synergism between the computation of the diagonal elements of the inertia matrix and that required by the conjugate gradient algorithm.

  14. Recent progress in the development of polysaccharide conjugates of docetaxel and paclitaxel

    PubMed Central

    Roy, Aniruddha; Bhattacharyya, Mousumi; Ernsting, Mark J.; May, Jonathan P; Li, Shyh-Dar

    2014-01-01

    Taxanes are one of the most potent and broadest spectrum chemotherapeutics used clinically, but also induce significant side effects. Different strategies have been developed to produce a safer taxane formulation. Development of polysaccharide drug conjugates has increased in the recent years due to the demonstrated biocompatibility, biodegradability, safety and low cost of the biopolymers. This review focuses on polysaccharide taxane conjugates and provides an overview on various conjugation strategies and their effect on the efficacy. Detailed analyses on the designing factors of an effective polysaccharide drug conjugate are provided with a discussion on the future direction of this field. PMID:24652678

  15. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative) test...

  16. 21 CFR 862.1187 - Conjugated sulfolithocholic acid (SLCG) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1187 Conjugated sulfolithocholic acid (SLCG) test system. (a) Identification. A...

  17. 21 CFR 862.1187 - Conjugated sulfolithocholic acid (SLCG) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1187 Conjugated sulfolithocholic acid (SLCG) test system. (a) Identification. A...

  18. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative) test...

  19. Protein-protein conjugate nanoparticles for malaria antigen delivery and enhanced immunogenicity

    PubMed Central

    Scaria, Puthupparampil V.; Jones, David S.; Barnafo, Emma; Fischer, Elizabeth R.; Anderson, Charles; MacDonald, Nicholas J.; Lambert, Lynn; Rausch, Kelly M.; Narum, David L.

    2017-01-01

    Chemical conjugation of polysaccharide to carrier proteins has been a successful strategy to generate potent vaccines against bacterial pathogens. We developed a similar approach for poorly immunogenic malaria protein antigens. Our lead candidates in clinical trials are the malaria transmission blocking vaccine antigens, Pfs25 and Pfs230D1, individually conjugated to the carrier protein Exoprotein A (EPA) through thioether chemistry. These conjugates form nanoparticles that show enhanced immunogenicity compared to unconjugated antigens. In this study, we examined the broad applicability of this technology as a vaccine development platform, by comparing the immunogenicity of conjugates prepared by four different chemistries using different malaria antigens (PfCSP, Pfs25 and Pfs230D1), and carriers such as EPA, TT and CRM197. Several conjugates were synthesized using thioether, amide, ADH and glutaraldehyde chemistries, characterized for average molecular weight and molecular weight distribution, and evaluated in mice for humoral immunogenicity. Conjugates made with the different chemistries, or with different carriers, showed no significant difference in immunogenicity towards the conjugated antigens. Since particle size can influence immunogenicity, we tested conjugates with different average size in the range of 16–73 nm diameter, and observed greater immunogenicity of smaller particles, with significant differences between 16 and 73 nm particles. These results demonstrate the multiple options with respect to carriers and chemistries that are available for protein-protein conjugate vaccine development. PMID:29281708

  20. In Vitro Structural and Functional Evaluation of Gold Nanoparticles Conjugated Antibiotics

    NASA Astrophysics Data System (ADS)

    Saha, Biswarup; Bhattacharya, Jaydeep; Mukherjee, Ananda; Ghosh, Anup Kumar; Santra, Chitta Ranjan; Dasgupta, Anjan K.; Karmakar, Parimal

    2007-12-01

    Bactericidal efficacy of gold nanoparticles conjugated with ampicillin, streptomycin and kanamycin were evaluated. Gold nanoparticles (Gnps) were conjugated with the antibiotics during the synthesis of nanoparticles utilizing the combined reducing property of antibiotics and sodium borohydride. The conjugation of nanoparticles was confirmed by dynamic light scattering (DLS) and electron microscopic (EM) studies. Such Gnps conjugated antibiotics showed greater bactericidal activity in standard agar well diffusion assay. The minimal inhibitory concentration (MIC) values of all the three antibiotics along with their Gnps conjugated forms were determined in three bacterial strains, Escherichia coli DH5α, Micrococcus luteus and Staphylococcus aureus. Among them, streptomycin and kanamycin showed significant reduction in MIC values in their Gnps conjugated form whereas; Gnps conjugated ampicillin showed slight decrement in the MIC value compared to its free form. On the other hand, all of them showed more heat stability in their Gnps conjugated forms. Thus, our findings indicated that Gnps conjugated antibiotics are more efficient and might have significant therapeutic implications.

  1. 21 CFR 862.1187 - Conjugated sulfolithocholic acid (SLCG) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1187 Conjugated sulfolithocholic acid (SLCG) test system. (a) Identification. A...

  2. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative) test...

  3. 21 CFR 862.1187 - Conjugated sulfolithocholic acid (SLCG) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1187 Conjugated sulfolithocholic acid (SLCG) test system. (a) Identification. A...

  4. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative) test...

  5. 21 CFR 862.1187 - Conjugated sulfolithocholic acid (SLCG) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1187 Conjugated sulfolithocholic acid (SLCG) test system. (a) Identification. A...

  6. 21 CFR 862.1115 - Urinary bilirubin and its conjugates (nonquantitative) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1115 Urinary bilirubin and its conjugates (nonquantitative) test...

  7. Multifunctional adhesive polymers: Preactivated thiolated chitosan-EDTA conjugates.

    PubMed

    Netsomboon, Kesinee; Suchaoin, Wongsakorn; Laffleur, Flavia; Prüfert, Felix; Bernkop-Schnürch, Andreas

    2017-02-01

    The aim of this study was to synthesis preactivated thiolated chitosan-EDTA (Ch-EDTA-cys-2MNA) conjugates exhibiting in particular high mucoadhesive, cohesive and chelating properties. Thiol groups were coupled with chitosan by carbodiimide reaction and further preactivated by attachment with 2-mercaptonicotinic acid (2MNA) via disulfide bond formation. Determinations of primary amino and sulfhydryl groups were performed by TNBS and Ellman's tests, respectively. Cytotoxicity was screened by resazurin assay in Caco-2 cells. Mucoadhesive properties and bivalent cation binding capacity with Mg 2+ and Ca 2+ in comparison to chitosan-EDTA (Ch-EDTA) and thiolated Ch-EDTA (Ch-EDTA-cys) were evaluated. Determination of 2MNA and total sulfhydryl groups indicated that 80% of thiol groups were preactivated. The results from cytotoxicity studies demonstrated that Ch-EDTA-cys and Ch-EDTA-cys-2MNA were not toxic to the cells at the polymer test concentration of 0.25% (w/v) while cell viability decreased by increasing the concentration of Ch-EDTA. Although EDTA molecule was modified by thiolation and preactivation, approximately 50% of chelating properties of the conjugates were maintained compared to Ch-EDTA. Ch-EDTA-cys-2MNA adhered on freshly excised porcine intestinal mucosa up to 6h while Ch-EDTA adhered for just 1h. According to the combination of mucoadhesive and chelating properties of the conjugates synthesized in this study, Ch-EDTA-cys-2MNA might be useful for various mucosal drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Crosslinked polymer nanoparticles containing single conjugated polymer chains

    NASA Astrophysics Data System (ADS)

    Ponzio, Rodrigo A.; Marcato, Yésica L.; Gómez, María L.; Waiman, Carolina V.; Chesta, Carlos A.; Palacios, Rodrigo E.

    2017-06-01

    Conjugated polymer nanoparticles are widely used in fluorescent labeling and sensing, as they have mean radii between 5 and 100 nm, narrow size dispersion, high brightness, and are photochemically stable, allowing single particle detection with high spatial and temporal resolution. Highly crosslinked polymers formed by linking individual chains through covalent bonds yield high-strength rigid materials capable of withstanding dissolution by organic solvents. Hence, the combination of crosslinked polymers and conjugated polymers in a nanoparticulated material presents the possibility of interesting applications that require the combined properties of constituent polymers and nanosized dimension. In the present work, F8BT@pEGDMA nanoparticles composed of poly(ethylene glycol dimethacrylate) (pEGDMA; a crosslinked polymer) and containing the commercial conjugated polymer poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT) were synthesized and characterized. Microemulsion polymerization was applied to produce F8BT@pEDGMA particles with nanosized dimensions in a ∼25% yield. Photophysical and size distribution properties of F8BT@pEDGMA nanoparticles were evaluated by various methods, in particular single particle fluorescence microscopy techniques. The results demonstrate that the crosslinking/polymerization process imparts structural rigidity to the F8BT@pEDGMA particles by providing resistance against dissolution/disintegration in organic solvents. The synthesized fluorescent crosslinked nanoparticles contain (for the most part) single F8BT chains and can be detected at the single particle level, using fluorescence microscopy, which bodes well for their potential application as molecularly imprinted polymer fluorescent nanosensors with high spatial and temporal resolution.

  9. Immunologic memory in Haemophilus influenzae type b conjugate vaccine failure.

    PubMed

    McVernon, J; Johnson, P D R; Pollard, A J; Slack, M P E; Moxon, E R

    2003-05-01

    To compare the convalescent antibody response to invasive Haemophilus influenzae type b (Hib) disease between conjugate vaccine immunised and unimmunised children, to look for evidence of priming for immunologic memory. Unmatched case-control study in the UK and Eire 1992-2001 and Victoria, Australia 1988-1990. A total of 93 children were identified as having invasive Hib disease following three doses of conjugate vaccine in infancy through post licensure surveillance throughout the UK and Eire; 92 unvaccinated children admitted to an Australian paediatric hospital with invasive Hib disease were used as historical controls. Convalescent serum was taken for measurement of Hib antibody concentration, and clinical information relating to potential disease risk factors was collected. The geometric mean concentrations of convalescent Hib antibodies were compared between immunised and unimmunised children, using raw and adjusted data. Hib conjugate vaccine immunised children had higher serum Hib antibody responses to disease (geometric mean concentration (GMC) 10.81 microg/ml (95% CI 6.62 to 17.66) than unimmunised children (1.06 microg/ml (0.61 to 1.84)) (p < 0.0001). However, following adjustment for the significant confounding influences of age at presentation and timing of serum collection, a difference persisted only in children presenting with meningitis (vaccinated GMC 3.78 microg/ml (2.78 to 5.15); unvaccinated GMC 1.48 microg/ml (0.90 to 2.21); p = 0.003). Higher antibody responses to invasive Hib disease in vaccinated children with meningitis reflect priming for immunologic memory by the vaccine. Although a majority of children in the UK are protected from Hib disease by immunisation, the relative roles of immunologic memory and other immune mechanisms in conferring protection remain unclear.

  10. Immunologic memory in Haemophilus influenzae type b conjugate vaccine failure

    PubMed Central

    McVernon, J; Johnson, P; Pollard, A; Slack, M; Moxon, E

    2003-01-01

    Aims: To compare the convalescent antibody response to invasive Haemophilus influenzae type b (Hib) disease between conjugate vaccine immunised and unimmunised children, to look for evidence of priming for immunologic memory. Methods: Unmatched case-control study in the UK and Eire 1992–2001 and Victoria, Australia 1988–1990. A total of 93 children were identified as having invasive Hib disease following three doses of conjugate vaccine in infancy through post licensure surveillance throughout the UK and Eire; 92 unvaccinated children admitted to an Australian paediatric hospital with invasive Hib disease were used as historical controls. Convalescent serum was taken for measurement of Hib antibody concentration, and clinical information relating to potential disease risk factors was collected. The geometric mean concentrations of convalescent Hib antibodies were compared between immunised and unimmunised children, using raw and adjusted data. Results: Hib conjugate vaccine immunised children had higher serum Hib antibody responses to disease (geometric mean concentration (GMC) 10.81 µg/ml (95% CI 6.62 to 17.66) than unimmunised children (1.06 µg/ml (0.61 to 1.84)) (p < 0.0001). However, following adjustment for the significant confounding influences of age at presentation and timing of serum collection, a difference persisted only in children presenting with meningitis (vaccinated GMC 3.78 µg/ml (2.78 to 5.15); unvaccinated GMC 1.48 µg/ml (0.90 to 2.21); p = 0.003). Conclusions: Higher antibody responses to invasive Hib disease in vaccinated children with meningitis reflect priming for immunologic memory by the vaccine. Although a majority of children in the UK are protected from Hib disease by immunisation, the relative roles of immunologic memory and other immune mechanisms in conferring protection remain unclear. PMID:12716702

  11. Economic evaluation of second generation pneumococcal conjugate vaccines in Norway.

    PubMed

    Robberstad, Bjarne; Frostad, Carl R; Akselsen, Per E; Kværner, Kari J; Berstad, Aud K H

    2011-11-03

    A seven valent pneumococcal conjugate vaccine (PCV7) was introduced in the Norwegian childhood immunization programme in 2006, and since then the incidence of invasive pneumococcal disease has declined substantially. Recently, two new second generation pneumococcal conjugate vaccines have become available, and an update of the economic evidence is needed. The aim of this study was to estimate incremental costs, health effects and cost-effectiveness of the pneumococcal conjugate vaccines PCV7, PCV13 and PHiD-CV in Norway. We used a Markov model to estimate costs and epidemiological burden of pneumococcal- and NTHi-related diseases (invasive pneumococcal disease (IPD), Community Acquired Pneumonia (CAP) and acute otitis media (AOM)) for a specific birth cohort. Using the most relevant evidence and assumptions for a Norwegian setting, we calculated incremental costs, health effects and cost-effectiveness for different vaccination strategies. In addition we performed sensitivity analyses for key parameters, tested key assumptions in scenario analyses and explored overall model uncertainty using probabilistic sensitivity analysis. The model predicts that both PCV13 and PHiD-CV provide more health gains at a lower cost than PCV7. Differences in health gains between the two second generation vaccines are small for invasive pneumococcal disease but larger for acute otitis media and myringotomy procedures. Consequently, PHiD-CV saves more disease treatment costs and indirect costs than PCV13. This study predicts that, compared to PVC13, PHiD-CV entails lower costs and greater benefits if the latter is measured in terms of quality adjusted life years. PVC13 entails more life years gained than PHiD-CV, but those come at a cost of NOK 3.1 million (∼€0.4 million) per life year. The results indicate that PHiD-CV is cost-effective compared to PCV13 in the Norwegian setting. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Optical Control of Living Cells Electrical Activity by Conjugated Polymers.

    PubMed

    Martino, Nicola; Bossio, Caterina; Vaquero Morata, Susana; Lanzani, Guglielmo; Antognazza, Maria Rosa

    2016-01-28

    Hybrid interfaces between organic semiconductors and living tissues represent a new tool for in-vitro and in-vivo applications. In particular, conjugated polymers display several optimal properties as substrates for biological systems, such as good biocompatibility, excellent mechanical properties, cheap and easy processing technology, and possibility of deposition on light, thin and flexible substrates. These materials have been employed for cellular interfaces like neural probes, transistors for excitation and recording of neural activity, biosensors and actuators for drug release. Recent experiments have also demonstrated the possibility to use conjugated polymers for all-optical modulation of the electrical activity of cells. Several in-vitro study cases have been reported, including primary neuronal networks, astrocytes and secondary line cells. Moreover, signal photo-transduction mediated by organic polymers has been shown to restore light sensitivity in degenerated retinas, suggesting that these devices may be used for artificial retinal prosthesis in the future. All in all, light sensitive conjugated polymers represent a new approach for optical modulation of cellular activity. In this work, all the steps required to fabricate a bio-polymer interface for optical excitation of living cells are described. The function of the active interface is to transduce the light stimulus into a modulation of the cell membrane potential. As a study case, useful for in-vitro studies, a polythiophene thin film is used as the functional, light absorbing layer, and Human Embryonic Kidney (HEK-293) cells are employed as the biological component of the interface. Practical examples of successful control of the cell membrane potential upon stimulation with light pulses of different duration are provided. In particular, it is shown that both depolarizing and hyperpolarizing effects on the cell membrane can be achieved depending on the duration of the light stimulus. The reported

  13. Solving large mixed linear models using preconditioned conjugate gradient iteration.

    PubMed

    Strandén, I; Lidauer, M

    1999-12-01

    Continuous evaluation of dairy cattle with a random regression test-day model requires a fast solving method and algorithm. A new computing technique feasible in Jacobi and conjugate gradient based iterative methods using iteration on data is presented. In the new computing technique, the calculations in multiplication of a vector by a matrix were recorded to three steps instead of the commonly used two steps. The three-step method was implemented in a general mixed linear model program that used preconditioned conjugate gradient iteration. Performance of this program in comparison to other general solving programs was assessed via estimation of breeding values using univariate, multivariate, and random regression test-day models. Central processing unit time per iteration with the new three-step technique was, at best, one-third that needed with the old technique. Performance was best with the test-day model, which was the largest and most complex model used. The new program did well in comparison to other general software. Programs keeping the mixed model equations in random access memory required at least 20 and 435% more time to solve the univariate and multivariate animal models, respectively. Computations of the second best iteration on data took approximately three and five times longer for the animal and test-day models, respectively, than did the new program. Good performance was due to fast computing time per iteration and quick convergence to the final solutions. Use of preconditioned conjugate gradient based methods in solving large breeding value problems is supported by our findings.

  14. Peptide/protein-polymer conjugates: synthetic strategies and design concepts.

    PubMed

    Gauthier, Marc A; Klok, Harm-Anton

    2008-06-21

    This feature article provides a compilation of tools available for preparing well-defined peptide/protein-polymer conjugates, which are defined as hybrid constructs combining (i) a defined number of peptide/protein segments with uniform chain lengths and defined monomer sequences (primary structure) with (ii) a defined number of synthetic polymer chains. The first section describes methods for post-translational, or direct, introduction of chemoselective handles onto natural or synthetic peptides/proteins. Addressed topics include the residue- and/or site-specific modification of peptides/proteins at Arg, Asp, Cys, Gln, Glu, Gly, His, Lys, Met, Phe, Ser, Thr, Trp, Tyr and Val residues and methods for producing peptides/proteins containing non-canonical amino acids by peptide synthesis and protein engineering. In the second section, methods for introducing chemoselective groups onto the side-chain or chain-end of synthetic polymers produced by radical, anionic, cationic, metathesis and ring-opening polymerization are described. The final section discusses convergent and divergent strategies for covalently assembling polymers and peptides/proteins. An overview of the use of chemoselective reactions such as Heck, Sonogashira and Suzuki coupling, Diels-Alder cycloaddition, Click chemistry, Staudinger ligation, Michael's addition, reductive alkylation and oxime/hydrazone chemistry for the convergent synthesis of peptide/protein-polymer conjugates is given. Divergent approaches for preparing peptide/protein-polymer conjugates which are discussed include peptide synthesis from synthetic polymer supports, polymerization from peptide/protein macroinitiators or chain transfer agents and the polymerization of peptide side-chain monomers.

  15. Biomacromolecule conjugated nanofiber scaffold for salivary gland tissue engineering

    NASA Astrophysics Data System (ADS)

    Jayarathanam, Kavitha

    Xerostomia or dry mouth, resulting from loss of salivary gland secretion can be alleviated by tissue engineering approaches to restore glandular cell function. Engineering an artificial salivary gland structure requires closely mimicking the natural environment, both physically and functionally, to promote epithelial cell proliferation, monolayer formation and apico-basal polarization. While the physical structure of the salivary gland extracellular matrix (ECM) can be reconstructed using biocompatible nanofiber scaffolds, the chemical signals from ECM macromolecules are equally involved in the gland morphogenesis. In these glands, Hyaluronic acid (HA), a biomacromolecule that is a major component of the ECM, plays a crucial role in recruiting growth factors to improve cell viability and growth in these glands. Another molecule of interest that improved salivary epithelial cell viability and apico-basal differentiation is laminin, a major protein found in the basement membrane. We hypothesize that these biomacromolecules, when conjugated nanofiber scaffolds, will provide the essential chemical signals that promote cell viability, proliferation, polarity in the salivary cell line of interest. These morphological changes will in turn promote the secretory function (salivary production). The nanofiber scaffold consisting of poly(lactic-co-glycolic)acid is conjugated with HA using a polyethylene glycol (PEG) diamine crosslinker. This conjugation was confirmed using fluorescence spectrometry, water contact angle test and immunocytochemistry analysis using confocal microscopy. The effect of HA in promoting cell survival in-vitro was established with MTT assay using SIMS (mouse submandibular immortalized ductal SIMS cells) cells. The effect of HA in improving the apico - basal polarity of SIMS cells will be assessed. Chemical modification of synthetic nanopolymeric scaffolds with ECM molecules e.g., HA, laminin are the next step towards developing "smart scaffolds", that

  16. Conjugal amyotrophic lateral sclerosis: a case report from Scotland.

    PubMed

    Fernandes, P M; Macleod, M R; Bateman, A; Abrahams, S; Pal, S

    2017-03-29

    Conjugal amyotrophic lateral sclerosis is rare, with significant effects on psychological and care needs. We report a case of conjugal amyotrophic lateral sclerosis disease from central Scotland. This case is particularly unusual as both patients were diagnosed within an 18-month period and experienced the disease simultaneously, with similar symptomatology and progression. Patient A was a 71-year-old man who presented with unilateral arm weakness and wasting. Patient B was a 68-year-old woman who presented with unilateral shoulder and elbow weakness. Diagnosis of amyotrophic lateral sclerosis was made within a few months of presentation in both cases, based on typical clinical symptomatology together with supportive neurophysiological testing. Interventions included enteral feeding and non-invasive ventilation. The time period between symptom onset and death was 5 years for Patient A and 3.5 years for Patient B. This case illustrates two main points: the care issues surrounding cases of conjugal neurological disease, and the psychological issues in these patients. There are significant care issues arising when co-habiting couples both develop severe functionally limiting neurological diseases at the same time. The more slowly progressive nature of Patient A's disease may be at least partially explained by the support he was able to receive from Patient B before she developed symptoms. Secondly, there are important psychological effects of living with someone with the same - but more advanced - progressive and incurable neurological disease. Thus, Patient B was reluctant to have certain interventions that she had observed being given to her husband. Lastly, no plausible shared environmental risk factors were identified, implying that the co-occurrence of ALS in this couple was a random association.

  17. Numerical Modeling of Conjugate Heat Transfer in Fluid Network

    NASA Technical Reports Server (NTRS)

    Majumdar, Alok

    2004-01-01

    Fluid network modeling with conjugate heat transfer has many applications in Aerospace engineering. In modeling unsteady flow with heat transfer, it is important to know the variation of wall temperature in time and space to calculate heat transfer between solid to fluid. Since wall temperature is a function of flow, a coupled analysis of temperature of solid and fluid is necessary. In cryogenic applications, modeling of conjugate heat transfer is of great importance to correctly predict boil-off rate in propellant tanks and chill down of transfer lines. In TFAWS 2003, the present author delivered a paper to describe a general-purpose computer program, GFSSP (Generalized Fluid System Simulation Program). GFSSP calculates flow distribution in complex flow circuit for compressible/incompressible, with or without heat transfer or phase change in all real fluids or mixtures. The flow circuit constitutes of fluid nodes and branches. The mass, energy and specie conservation equations are solved at the nodes where as momentum conservation equations are solved at the branches. The proposed paper describes the extension of GFSSP to model conjugate heat transfer. The network also includes solid nodes and conductors in addition to fluid nodes and branches. The energy conservation equations for solid nodes solves to determine the temperatures of the solid nodes simultaneously with all conservation equations governing fluid flow. The numerical scheme accounts for conduction, convection and radiation heat transfer. The paper will also describe the applications of the code to predict chill down of cryogenic transfer line and boil-off rate of cryogenic propellant storage tank.

  18. Benzimidazole--ibuprofen/mesalamine conjugates: potential candidates for multifactorial diseases.

    PubMed

    Bansal, Yogita; Kaur, Maninder; Silakari, Om

    2015-01-07

    Ibuprofen (IB) and mesalamine (MES) are commonly used NSAIDs whereas benzimidazole (BZ) and 2-aminobenzimidazole (ABZ) are important pharmacophore for immunomodulatory activities. In the present study, IB and MES were coupled with variedly substituted BZ or ABZ nucleus to synthesize IB-BZ (2a-2e), IB-ABZ (3a-3e), MES-BZ (4a-4e) and MES-ABZ (5a-5e) chimeric conjugates as novel compounds that could elicit both anti-inflammatory and immunomodulatory activities. Each compound retained the anti-inflammatory activity of the parent NSAID. The BZ conjugates (2 and 4) were found immunostimulatory whereas the ABZ conjugates (3 and 5) were immunosuppressive. Each compound also exhibited good antioxidant activity, which is attributed to the electron rich BZ and ABZ nuclei. Compound 2a, 2e, 3a, 3e and 5b exhibited the most significant anti-inflammatory and immunomodulatory activities. Hence, these were evaluated for in vivo acute gastric ulcerogenicity. The compounds were safe to gastric mucosa, probably due to masking of the free -COOH group of IB and MES, and/or to the BZ nucleus itself. A benzoyl group at 5-position of BZ and ABZ incurred maximum immunostimulatory activity. In contrast, a -NO2 group incurred the maximum immunosuppressive action. Docking analysis revealed the compounds to be more selective towards COX-2 enzyme, which support the gastroprotective activity. These results suggest that the compounds can be taken as lead for development of new drugs for the treatment of immune related inflammatory disorders, such as cancer and rheumatoid arthritis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  19. Ferrocene-oligonucleotide conjugates for electrochemical probing of DNA.

    PubMed Central

    Ihara, T; Maruo, Y; Takenaka, S; Takagi, M

    1996-01-01

    Toward the development of a universal, sensitive and convenient method of DNA (or RNA) detection, electrochemically active oligonucleotides were prepared by covalent linkage of a ferrocenyl group to the 5'-aminohexyl-terminated synthetic oligonucleotides. Using these electrochemically active probes, we have been able to demonstrate the detection of DNA and RNA at femtomole levels by HPLC equipped with an ordinary electrochemical detector (ECD) [Takenaka,S., Uto,Y., Kondo,H., Ihara,T. and Takagi,M. (1994) Anal. Biochem., 218, 436-443]. Thermodynamic and electrochemical studies of the interaction between the probes and the targets are presented here. The thermodynamics obtained revealed that the conjugation stabilizes the triple-helix complexes by 2-3 kcal mol-1 (1-2 orders increment in binding constant) at 298 K, which corresponds to the effect of elongation of additional several base triplets. The main cause of this thermodynamic stabilization by the conjugation is likely to be the overall conformational change of whole structure of the conjugate rather than the additional local interaction. The redox potential of the probe was independent of the target structure, which is either single- or double stranded. However, the potential is slightly dependent (with a 10-30 mV negative shift on complexation) on the extra sequence in the target, probably because the individual sequence is capable of contacting or interacting with the ferrocenyl group in a slightly different way from each other. This small potential shift itself, however, does not cause any inconvenience on practical applications in detecting the probes by using ECD. These results lead to the conclusion that the redox-active probes are very useful for the microanalysis of nucleic acids due to the stability of the complexes, high detection sensitivity and wide applicability to the target structures (DNA and RNA; single- and double strands) and the sequences. PMID:8932383

  20. p-aminophenol nephrotoxicity: biosynthesis of toxic glutathione conjugates.

    PubMed

    Klos, C; Koob, M; Kramer, C; Dekant, W

    1992-07-01

    p-Aminophenol causes necrosis of the pars recta of the proximal tubules in rats, and its nephrotoxicity may be due to glutathione-dependent bioactivation reactions. We have investigated the hepatic metabolism of p-aminophenol in Wistar rats and the cytotoxicity of formed glutathione S-conjugates in rat renal epithelial cells. After ip application of p-aminophenol (100 mg/kg), the following metabolites were identified in rat bile: 4-amino-2-(glutathion-S-yl)phenol, 4-amino-3-(glutathion-S-yl)-phenol, 4-amino-2,5-bis(glutathion-S-yl)phenol, 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol, an aminophenol conjugate (likely a sulfate or glucuronide), acetaminophen glucuronide, and 3-(glutathion-S-yl)acetaminophen. 4-Amino-3-(glutathion-S-yl)phenol, 4-amino-2,5-bis(glutathion-S-yl)phenol, and 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol induced a dose- and time-dependent loss of cell viability in rat kidney cortical cells. Cell killing was significantly reduced by inhibition of gamma-glutamyl transpeptidase with Acivicin. p-Aminophenol was also toxic to renal epithelial cells. Coincubation of p-aminophenol with tetraethylammonium bromide, a competitive inhibitor of the organic cation transporter, and with SKF-525A, an inhibitor of cytochrome P450, protected cells from p-aminophenol-induced toxicity. p-Aminophenol would thus be accumulated in the kidney mainly by organic cation transport systems, which are concentrated in the S-1 segment of the proximal tubule. However, p-aminophenol toxicity in vivo is directed toward the S-2 and S-3 segments, which are rich in gamma-glutamyl transpeptidase. These results and the observation that biliary cannulation and glutathione depletion reduce p-aminophenol nephrotoxicity suggest that the biosynthesis of toxic glutathione conjugates is responsible for p-aminophenol nephrotoxicity in vivo. The aminophenol glutathione S-conjugates formed induce p-aminophenol nephrotoxicity by a pathway dependent on gamma-glutamyl transpeptidase.

  1. Ferritin conjugates as specific magnetic labels. Implications for cell separation.

    PubMed Central

    Odette, L L; McCloskey, M A; Young, S H

    1984-01-01

    Concanavalin A coupled to the naturally occurring iron storage protein ferritin is used to label rat erythrocytes and increase the cells' magnetic susceptibility. Labeled cells are introduced into a chamber containing spherical iron particles and the chamber is placed in a uniform 5.2 kG (gauss) magnetic field. The trajectory of cells in the inhomogeneous magnetic field around the iron particles and the polar distributions of cells bound to the iron particles compare well with the theoretical predictions for high gradient magnetic systems. On the basis of these findings we suggest that ferritin conjugated ligands can be used for selective magnetic separation of labeled cells. Images FIGURE 2 PMID:6743752

  2. Self-Adjuvanting Glycopeptide Conjugate Vaccine against Disseminated Candidiasis

    PubMed Central

    Xin, Hong; Cartmell, Jonathan; Bailey, Justin J.; Dziadek, Sebastian; Bundle, David R.; Cutler, Jim E.

    2012-01-01

    Our research on pathogenesis of disseminated candidiasis led to the discovery that antibodies specific for Candida albicans cell surface β-1, 2–mannotriose [β-(Man)3] protect mice. A 14 mer peptide Fba, which derived from the N-terminal portion of the C. albicans cytosolic/cell surface protein fructose-bisphosphate aldolase, was used as the glycan carrier and resulted in a novel synthetic glycopeptide vaccine β-(Man)3-Fba. By a dendritic cell-based immunization approach, this conjugate induced protective antibody responses against both the glycan and peptide parts of the vaccine. In this report, we modified the β-(Man)3-Fba conjugate by coupling it to tetanus toxoid (TT) in order to improve immunogenicity and allow for use of an adjuvant suitable for human use. By new immunization procedures entirely compatible with human use, the modified β-(Man)3-Fba-TT was administered either alone or as a mixture made with alum or monophosphoryl lipid A (MPL) adjuvants and given to mice by a subcutaneous (s.c.) route. Mice vaccinated with or, surprisingly, without adjuvant responded well by making robust antibody responses. The immunized groups showed a high degree of protection against a lethal challenge with C. albicans as evidenced by increased survival times and reduced kidney fungal burden as compared to control groups that received only adjuvant or DPBS buffer prior to challenge. To confirm that induced antibodies were protective, sera from mice immunized against the β-(Man)3-Fba-TT conjugate transferred protection against disseminated candidiasis to naïve mice, whereas C. albicans-absorbed immune sera did not. Similar antibody responses and protection induced by the β-(Man)3-Fba-TT vaccine was observed in inbred BALB/c and outbred Swiss Webster mice. We conclude that addition of TT to the glycopeptide conjugate results in a self-adjuvanting vaccine that promotes robust antibody responses without the need for additional adjuvant, which is novel and represents a

  3. Studies of Phase-Conjugate Optical Device Concepts

    DTIC Science & Technology

    1991-04-01

    09/30/90 1991, APRIL 127 I&. SUPPLEMENTARY NOTAT11ON 17. COSATI CODES 18. SUBJECT TERMS fCondnue on~e ow twmInocemy and Iknffyby block numbw) FIELD ...coherent; beams 3 and 4 are also mutually gratings are identical, i.e., coherent. But beams 2 and 3 (or 2 and 4) are mutually incoherent. The electric field ...Introduction Science Center Optical phase conjugation has been an active field of research for nearly two decades. 1 One of the more unusual additions to the

  4. Weighted graph based ordering techniques for preconditioned conjugate gradient methods

    NASA Technical Reports Server (NTRS)

    Clift, Simon S.; Tang, Wei-Pai

    1994-01-01

    We describe the basis of a matrix ordering heuristic for improving the incomplete factorization used in preconditioned conjugate gradient techniques applied to anisotropic PDE's. Several new matrix ordering techniques, derived from well-known algorithms in combinatorial graph theory, which attempt to implement this heuristic, are described. These ordering techniques are tested against a number of matrices arising from linear anisotropic PDE's, and compared with other matrix ordering techniques. A variation of RCM is shown to generally improve the quality of incomplete factorization preconditioners.

  5. Neighbor effect in complexation of a conjugated polymer.

    PubMed

    Sosorev, Andrey; Zapunidi, Sergey

    2013-09-19

    Charge-transfer complex (CTC) formation between a conjugated polymer and low-molecular-weight organic acceptor is proposed to be driven by the neighbor effect. Formation of a CTC on the polymer chain results in an increased probability of new CTC formation near the existing one. We present an analytical model for CTC distribution considering the neighbor effect, based on the principles of statistical mechanics. This model explains the experimentally observed threshold-like dependence of the CTC concentration on the acceptor content in a polymer:acceptor blend. It also allows us to evaluate binding energies of the complexes.

  6. Conjugate gradient coupled with multigrid for an indefinite problem

    NASA Technical Reports Server (NTRS)

    Gozani, J.; Nachshon, A.; Turkel, E.

    1984-01-01

    An iterative algorithm for the Helmholtz equation is presented. This scheme was based on the preconditioned conjugate gradient method for the normal equations. The preconditioning is one cycle of a multigrid method for the discrete Laplacian. The smoothing algorithm is red-black Gauss-Seidel and is constructed so it is a symmetric operator. The total number of iterations needed by the algorithm is independent of h. By varying the number of grids, the number of iterations depends only weakly on k when k(3)h(2) is constant. Comparisons with a SSOR preconditioner are presented.

  7. A finite element conjugate gradient FFT method for scattering

    NASA Technical Reports Server (NTRS)

    Collins, Jeffery D.; Ross, Dan; Jin, J.-M.; Chatterjee, A.; Volakis, John L.

    1991-01-01

    Validated results are presented for the new 3D body of revolution finite element boundary integral code. A Fourier series expansion of the vector electric and mangnetic fields is employed to reduce the dimensionality of the system, and the exact boundary condition is employed to terminate the finite element mesh. The mesh termination boundary is chosen such that is leads to convolutional boundary operatores of low O(n) memory demand. Improvements of this code are discussed along with the proposed formulation for a full 3D implementation of the finite element boundary integral method in conjunction with a conjugate gradiant fast Fourier transformation (CGFFT) solution.

  8. Synthesis and study of conjugated polymers containing Di- or Triphenylamine

    SciTech Connect

    Sukwattanasinitt, M.

    1996-06-21

    This thesis consists of two separate parts. The first part addresses the synthesis and study of conjugated polymers containing di- or triphenylamine. Two types of polymers: linear polymers and dendrimers, were synthesized. The polymers were characterized by NMR, IR, UV, GPC, TGA and DSC. Electronic and optical properties of the polymers were studied through the conductivity measurements and excitation- emission spectra. the second part of this thesis deals with a reaction of electron-rich acetylenes with TCNE. The discovery of the reaction from charge transfer complex studies and the investigation of this reaction on various electron-rich acetylenes are presented.

  9. Unsteady conjugate heat transfer analysis for impinging jet cooling

    NASA Astrophysics Data System (ADS)

    Tejero, F.; Flaszyński, P.; Szwaba, R.; Telega, J.

    2016-10-01

    The paper presents the numerical investigations of the heat transfer on a flat plate cooled by a single impinging jet. The thermal conductivity of the plate was modified from a high thermal case (steel -λ= 35 W/m/K) to a low one (steel alloy Inconel -λ= 9.8 W/m/K). The numerical simulations results are compared with the experimental data from the Institute of Fluid-Flow Machinery Polish Academy of Sciences, Gdansk (Poland). The numerical simulations are carried out by means of Ansys/Fluent and k-ω SST turbulence model and the temperature evolution on the target plate is investigated by conjugated heat transfer computations.

  10. Methods for calculating conjugate problems of heat transfer

    NASA Astrophysics Data System (ADS)

    Kalinin, E. K.; Dreitser, G. A.; Kostiuk, V. V.; Berlin, I. I.

    Methods are examined for calculating various conjugate problems of heat transfer in channels and closed vessels in cases of single-phase and two-phase flow in steady and unsteady conditions. The single-phase-flow studies involve the investigation of gaseous and liquid heat-carriers in pipes, annular and plane channels, and pipe bundles in cases of cooling and heating. General relationships are presented for heat transfer in cases of film, transition, and nucleate boiling, as well as for boiling crises. Attention is given to methods for analyzing the filling and cooling of conduits and tanks by cryogenic liquids; and ways to intensify heat transfer in these conditions are examined.

  11. Nanowire-nanoparticle conjugate photolytic devices for renewable hydrogen production

    NASA Astrophysics Data System (ADS)

    Maclaskey, Sean Kelly

    A clean energy driven economy requires renewable production of zero--emission fuels, such as hydrogen (H2). Photocatalytic generation of H2 is one such method to fulfill this demand. Photocatalytic water splitting is an electrochemical process driven by solar energy to produce H2. Although there have been many investigations on photocatalytic water splitting, the number of concepts utilizing visible light is limited. In the present study, H2 evolution from water splitting is demonstrated using the novel concept of nanowire--nanoparticle (NW--NP) conjugate devices irradiated by visible light. Photolytic nanodevice suspensions are fabricated via sol--gel synthesis of vanadium oxyhydrate (V3O 7·H2O) NWs, followed by solution chemistry with HAuCl 4 for reduction of gold (Au) NPs on the NW surfaces. Characterization of nanodevices was performed via TEM, SEM, and optical spectroscopy. Products of photolysis were quantified and analyzed by Gas Chromatography (GC). The performance of the nanowire--nanoparticle conjugate devices was compared with previous photolytic device designs by the use of quantum and internal conversion efficiencies (QE and ICE, respectively). The present thesis demonstrates photocatalytic production of H2 using V3O7·H 2O NW -- Au NP conjugate devices under 470 nm excitation. The "photolytic nanodevice suspension in water" concept poses the potential for scalable H2 production, in addition to the provision for a low--cost technique due to fabrication by sol--gel synthesis and solution chemistry. The V3O7·H2O aerogel, a recently discovered semiconductor material, is found to be a suitable photoanode due to its narrow band gap energy of 2.18 eV, and its stability during photolysis. The diameters of the V3O7·H2O NWs are found to be 12 nm (+/- 2.4 nm) from SEM images. The decoration of NWs with Au NPs is verified by TEM imaging and Au NPs are estimated to be 7.5 nm (+/- 2.2 nm) in size. After decoration of NWs by Au NPs, a near--field enhancement

  12. Heat Shock-Enhanced Conjugation Efficiency in Standard Campylobacter jejuni Strains

    PubMed Central

    Zeng, Ximin; Ardeshna, Devarshi

    2015-01-01

    Campylobacter jejuni, the leading bacterial cause of human gastroenteritis in the United States, displays significant strain diversity due to horizontal gene transfer. Conjugation is an important horizontal gene transfer mechanism contributing to the evolution of bacterial pathogenesis and antimicrobial resistance. It has been observed that heat shock could increase transformation efficiency in some bacteria. In this study, the effect of heat shock on C. jejuni conjugation efficiency and the underlying mechanisms were examined. With a modified Escherichia coli donor strain, different C. jejuni recipient strains displayed significant variation in conjugation efficiency ranging from 6.2 × 10−8 to 6.0 × 10−3 CFU per recipient cell. Despite reduced viability, heat shock of standard C. jejuni NCTC 11168 and 81-176 strains (e.g., 48 to 54°C for 30 to 60 min) could dramatically enhance C. jejuni conjugation efficiency up to 1,000-fold. The phenotype of the heat shock-enhanced conjugation in C. jejuni recipient cells could be sustained for at least 9 h. Filtered supernatant from the heat shock-treated C. jejuni cells could not enhance conjugation efficiency, which suggests that the enhanced conjugation efficiency is independent of secreted substances. Mutagenesis analysis indicated that the clustered regularly interspaced short palindromic repeats system and the selected restriction-modification systems (Cj0030/Cj0031, Cj0139/Cj0140, Cj0690c, and HsdR) were dispensable for heat shock-enhanced conjugation in C. jejuni. Taking all results together, this study demonstrated a heat shock-enhanced conjugation efficiency in standard C. jejuni strains, leading to an optimized conjugation protocol for molecular manipulation of this organism. The findings from this study also represent a significant step toward elucidation of the molecular mechanism of conjugative gene transfer in C. jejuni. PMID:25911489

  13. Tumor targeting of gene expression through metal-coordinated conjugation with dextran.

    PubMed

    Hosseinkhani, Hossein; Aoyama, Teruyoshi; Ogawa, Osamu; Tabata, Yasuhiko

    2003-03-07

    Tumor targeting of plasmid DNA was achieved through the conjugation of dextran derivatives with chelate residues based on metal coordination. Diethylenetriamine pentaacetic acid (DTPA), spermidine (Sd), and spermine (Sm) were chemically introduced to the hydroxyl groups of dextran to obtain dextran-DTPA, dextran-Sd and dextran-Sm derivatives. Conjugation of the dextran derivative by Zn(2+) coordination decreased the apparent size of the plasmid DNA, depending on the derivative type. The negative zeta potential of plasmid DNA became almost 0 mV after Zn(2+)-coordinated conjugation with dextran-Sm. When the dextran derivative-plasmid DNA conjugates with Zn(2+) coordination were intravenously injected subcutaneously into mice bearing Meth-AR-1 fibrosarcoma, the dextran-Sm-plasmid DNA conjugate significantly enhanced the level of gene expression in the tumor, in contrast to the conjugate of other dextran derivatives and free plasmid DNA. The enhanced gene expression produced by the Zn(2+)-coordinated dextran-Sm-plasmid DNA conjugate was specific to the tumor, whereas a simple mixture of dextran-Sm and plasmid DNA was not effective. The level of gene expression depended on the percentage of chelate residues introduced, the mixing weight ratio of the plasmid DNA/Sm residue used for conjugate preparation, and the plasmid DNA dose. A fluorescent microscopic study revealed that localization of plasmid DNA in the tumor tissue was observed only after injection of the dextran-Sm-plasmid DNA conjugate with Zn(2+) coordination. In addition, the gene expression induced by the conjugate lasted for more than 10 days after the injection. We conclude that Zn(2+)-coordinated dextran-Sm conjugation is a promising way to enable plasmid DNA to target the tumor in gene expression as well as to prolong the duration of gene expression.

  14. Reductive nanocomplex encapsulation of cRGD-siRNA conjugates for enhanced targeting to cancer cells

    PubMed Central

    Zhang, Yanfen; Yang, Xiantao; Ma, Yuan; Guan, Zhu; Wu, Yun; Zhang, Lihe; Yang, Zhenjun

    2017-01-01

    In this study, through covalent conjugation and lipid material entrapment, a combined modification strategy was established for effective delivery of small interfering RNA (siRNA). Single strands of siRNA targeting to BRAFV600E gene (siMB3) conjugated with cRGD peptide at 3′-terminus or 5′-terminus via cleavable disulfide bond was synthesized and then annealed with corresponding strands to obtain single and bis-cRGD-siRNA conjugates. A cationic lipid material (CLD) developed by our laboratory was mixed with the conjugates to generate nanocomplexes; their uniformity and electrical property were revealed by particle size and zeta potential measurement. Compared with CLD/siBraf, CLD/cRGD-siBraf achieved higher cell uptake and more excellent tumor-targeting ability, especially 21 (sense-5′/antisense-3″-cRGD-congjugate) nanocomplex. Moreover, they can regulate multiple pathways to varying degree and reduce acidification of endosome. Compared with the gene silencing of different conjugates, single or bis-cRGD-conjugated siRNA showed little differences except 22 (5/5) which cRGD was conjugated at 5′-terminus of antisense strand and sense strand. However bis-cRGD conjugate 21 nanocomplex exhibited better specific target gene silencing at multiple time points. Furthermore, the serum stabilities of the bis-cRGD conjugates were higher than those of the single-cRGD conjugates. In conclusion, all these data suggested that CLD/bis-conjugates, especially CLD/21, can be an effective system for delivery of siRNA to target BRAFV600E gene for therapy of melanoma. PMID:29042774

  15. Heat Shock-Enhanced Conjugation Efficiency in Standard Campylobacter jejuni Strains.

    PubMed

    Zeng, Ximin; Ardeshna, Devarshi; Lin, Jun

    2015-07-01

    Campylobacter jejuni, the leading bacterial cause of human gastroenteritis in the United States, displays significant strain diversity due to horizontal gene transfer. Conjugation is an important horizontal gene transfer mechanism contributing to the evolution of bacterial pathogenesis and antimicrobial resistance. It has been observed that heat shock could increase transformation efficiency in some bacteria. In this study, the effect of heat shock on C. jejuni conjugation efficiency and the underlying mechanisms were examined. With a modified Escherichia coli donor strain, different C. jejuni recipient strains displayed significant variation in conjugation efficiency ranging from 6.2 × 10(-8) to 6.0 × 10(-3) CFU per recipient cell. Despite reduced viability, heat shock of standard C. jejuni NCTC 11168 and 81-176 strains (e.g., 48 to 54°C for 30 to 60 min) could dramatically enhance C. jejuni conjugation efficiency up to 1,000-fold. The phenotype of the heat shock-enhanced conjugation in C. jejuni recipient cells could be sustained for at least 9 h. Filtered supernatant from the heat shock-treated C. jejuni cells could not enhance conjugation efficiency, which suggests that the enhanced conjugation efficiency is independent of secreted substances. Mutagenesis analysis indicated that the clustered regularly interspaced short palindromic repeats system and the selected restriction-modification systems (Cj0030/Cj0031, Cj0139/Cj0140, Cj0690c, and HsdR) were dispensable for heat shock-enhanced conjugation in C. jejuni. Taking all results together, this study demonstrated a heat shock-enhanced conjugation efficiency in standard C. jejuni strains, leading to an optimized conjugation protocol for molecular manipulation of this organism. The findings from this study also represent a significant step toward elucidation of the molecular mechanism of conjugative gene transfer in C. jejuni. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Conjugated Polymer for Voltage-Controlled Release of Molecules.

    PubMed

    Liu, Shenghua; Fu, Ying; Li, Guijun; Li, Li; Law, Helen Ka-Wai; Chen, Xianfeng; Yan, Feng

    2017-09-01

    Conjugated polymers are attractive in numerous biological applications because they are flexible, biocompatible, cost-effective, solution-processable, and electronic/ionic conductive. One interesting application is for controllable drug release, and this has been realized previously using organic electronic ion pumps. However, organic electronic ion pumps show high operating voltages and limited transportation efficiency. Here, the first report of low-voltage-controlled molecular release with a novel organic device based on a conjugated polymer poly(3-hexylthiophene) is presented. The releasing rate of molecules can be accurately controlled by the duration of the voltage applied on the device. The use of a handy mobile phone to remotely control the releasing process and its application in delivering an anticancer drug to treat cancer cells are also successfully demonstrated. The working mechanism of the device is attributed to the unique switchable permeability of poly(3-hexylthiophene) in aqueous solutions under a bias voltage that can tune the wettability of poly(3-hexylthiophene) via oxidation or reduction processes. The organic devices are expected to find many promising applications for controllable drug delivery in biological systems. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Analysis of phase conjugation in a turbid medium

    NASA Astrophysics Data System (ADS)

    Hollmann, Joseph L.; Cantero, Sergio; Tseng, Snow; DiMarzio, Charles A.

    2014-03-01

    The ability to focus light in most tissue degrades quickly with depth due to high optical scattering. Recently, researchers have found they can concentrate light tightly despite these scattering effects by using a guidestar and optical phase conjugation to focus light to greater distances in tissue. An optical or probe signal is transmitted through a scattering medium and its resulting wavefront is detected. The wavefront is then conjugated and utilized as a new optical source or delivery wave that focuses back to the guidestar's location with minimal scattering. The power in the delivery wave may be greatly increased for enhanced energy delivery at the focus. Modulation by an ultrasound (US) beam may be utilized to generate the guidestar dynamically and allow for US-resolution at depths of several millimeters. The delivery wave is successful at focusing light back at the guidestar because it creates constructive interference at the desired focus. However, if the phases of the field contributions change, we expect the delivered power at the focus to be reduced. This paper will analyze the robustness of this method when the probe beam is at one wavelength and the delivery wave is at another. This will allow us to characterize the deleterious effects of varying the phase contributions at the focus.

  18. Concanavalin A conjugated biodegradable nanoparticles for oral insulin delivery

    NASA Astrophysics Data System (ADS)

    Hurkat, Pooja; Jain, Aviral; Jain, Ashish; Shilpi, Satish; Gulbake, Arvind; Jain, Sanjay K.

    2012-11-01

    Major research issues in oral protein delivery include the stabilization of protein in delivery devices which could increase its oral bioavailability. The study deals with development of oral insulin delivery system utilizing biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles and modifying its surface with Concanavalin A to increase lymphatic uptake. Surface-modified PLGA nanoparticles were characterized for conjugation efficiency of ligand, shape and surface morphology, particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro drug release. Stability of insulin in the developed formulation was confirmed by SDS-PAGE, and integrity of entrapped insulin was assessed using circular dichroism spectrum. Ex vivo study was performed on Wistar rats, which exhibited the higher intestinal uptake of Con A conjugated nanoparticles. In vivo study performed on streptozotocin-induced diabetic rats which indicate that a surface-modified nanoparticle reduces blood glucose level effectively within 4 h of its oral administration. In conclusion, the present work resulted in successful production of Con A NPs bearing insulin with sustained release profile, and better absorption and stability. The Con A NPs showed high insulin uptake, due to its relative high affinity for non-reducing carbohydrate residues i.e., fucose present on M cells and have the potential for oral insulin delivery in effective management of Type 1 diabetes condition.

  19. Coherent chirped pulse laser network with Mickelson phase conjugator.

    PubMed

    Okulov, A Yu

    2014-04-10

    The mechanisms of nonlinear phase-locking of a large fiber amplifier array are analyzed. The preference is given to the most suitable configuration for a coherent coupling of thousands of fundamental spatial mode fiber beams into a single smooth beam ready for chirped pulse compression. It is shown that a Michelson phase-conjugating configuration with double passage through an array of fiber amplifiers has the definite advantage compared to a one-way fiber array coupled in a Mach-Zehnder configuration. Regardless of the amount of synchronized fiber amplifiers, the Michelson phase-conjugating interferometer is expected to do a perfect compensation of the phase-piston errors and collimation of backwardly amplified fiber beams on an entrance/output beam splitter. In both configurations, the nonlinear transformation of the stretched pulse envelope, due to gain saturation, is capable of randomizing the position of chirp inside an envelope; thus it may reduce the visibility of the interference pattern at an output beam splitter. Certain advantages are inherent to the sech-form temporal envelope because of the exponential precursor and self-similar propagation in gain medium. The Gaussian envelope is significantly compressed in a deep gain saturation regime, and the frequency chirp position inside pulse envelope is more deformed.

  20. Intracellular Delivery System for Antibody–Peptide Drug Conjugates

    PubMed Central

    Berguig, Geoffrey Y; Convertine, Anthony J; Frayo, Shani; Kern, Hanna B; Procko, Erik; Roy, Debashish; Srinivasan, Selvi; Margineantu, Daciana H; Booth, Garrett; Palanca-Wessels, Maria Corinna; Baker, David; Hockenbery, David; Press, Oliver W; Stayton, Patrick S

    2015-01-01

    Antibodies armed with biologic drugs could greatly expand the therapeutic potential of antibody–drug conjugates for cancer therapy, broadening their application to disease targets currently limited by intracellular delivery barriers. Additional selectivity and new therapeutic approaches could be realized with intracellular protein drugs that more specifically target dysregulated pathways in hematologic cancers and other malignancies. A multifunctional polymeric delivery system for enhanced cytosolic delivery of protein drugs has been developed that incorporates endosomal-releasing activity, antibody targeting, and a biocompatible long-chain ethylene glycol component for optimized safety, pharmacokinetics, and tumor biodistribution. The pH-responsive polymeric micelle carrier, with an internalizing anti-CD22 monoclonal targeting antibody, effectively delivered a proapoptotic Bcl-2 interacting mediator (BIM) peptide drug that suppressed tumor growth for the duration of treatment and prolonged survival in a xenograft mouse model of human B-cell lymphoma. Antitumor drug activity was correlated with a mechanistic induction of the Bcl-2 pathway biomarker cleaved caspase-3 and a marked decrease in the Ki-67 proliferation biomarker. Broadening the intracellular target space by more effective delivery of protein/peptide drugs could expand the repertoire of antibody–drug conjugates to currently undruggable disease-specific targets and permit tailored drug strategies to stratified subpopulations and personalized medicines. PMID:25669432

  1. Implementing biological logic gates using gold nanoparticles conjugated to fluorophores

    NASA Astrophysics Data System (ADS)

    Barnoy, Eran A.; Popovtzer, Rachela; Fixler, Dror

    2018-02-01

    We describe recent research in which we explored biologically relevant logic gates using gold nanoparticles (GNPs) conjugated to fluorophores and tracing the results remotely by time-domain fluorescence lifetime imaging microscopy (FLIM). GNPs have a well-known effect on nearby fluorophores in terms of their fluorescence intensity (FI - increase or decrease) as well as fluorescence lifetime (FLT). We have designed a few bio-switch systems in which the FLIMdetected fluorescence varies after biologically relevant stimulation. Some of our tools include fluorescein diacetate (FDA) which can be activated by either esterases or pH, peptide chains cleavable by caspase 3, and the polymer polyacrylic acid which varies in size based on surrounding pH. After conjugating GNPs to chosen fluorophores, we have successfully demonstrated the logic gates of NOT, AND, OR, NAND, NOR, and XOR by imaging different stages of activation. These logic gates have been demonstrated both in solutions as well as within cultured cells, thereby possibly opening the door for nanoparticulate in vivo smart detection. While these initial probes are mainly tools for intelligent detection systems, they lay the foundation for logic gates functioning in conjunction so as to lead to a form of in vivo biological computing, where the system would be able to release proper treatment options in specific situations without external influence.

  2. Complexation of amyloid fibrils with charged conjugated polymers.

    PubMed

    Ghosh, Dhiman; Dutta, Paulami; Chakraborty, Chanchal; Singh, Pradeep K; Anoop, A; Jha, Narendra Nath; Jacob, Reeba S; Mondal, Mrityunjoy; Mankar, Shruti; Das, Subhadeep; Malik, Sudip; Maji, Samir K

    2014-04-08

    It has been suggested that conjugated charged polymers are amyloid imaging agents and promising therapeutic candidates for neurological disorders. However, very less is known about their efficacy in modulating the amyloid aggregation pathway. Here, we studied the modulation of Parkinson's disease associated α-synuclein (AS) amyloid assembly kinetics using conjugated polyfluorene polymers (PF, cationic; PFS, anionic). We also explored the complexation of these charged polymers with the various AS aggregated species including amyloid fibrils and oligomers using multidisciplinary biophysical techniques. Our data suggests that both polymers irrespective of their different charges in the side chains increase the fibrilization kinetics of AS and also remarkably change the morphology of the resultant amyloid fibrils. Both polymers were incorporated/aligned onto the AS amyloid fibrils as evident from electron microscopy (EM) and atomic force microscopy (AFM), and the resultant complexes were structurally distinct from their pristine form of both polymers and AS supported by FTIR study. Additionally, we observed that the mechanism of interactions between the polymers with different species of AS aggregates were markedly different.

  3. Fluorescent nanodiamond-bacteriophage conjugates maintain host specificity.

    PubMed

    Trinh, Jimmy T; Alkahtani, Masfer H; Rampersaud, Isaac; Rampersaud, Arfaan; Scully, Marlan; Young, Ryland F; Hemmer, Philip; Zeng, Lanying

    2018-06-01

    Rapid identification of specific bacterial strains within clinical, environmental, and food samples can facilitate the prevention and treatment of disease. Fluorescent nanodiamonds (FNDs) are being developed as biomarkers in biology and medicine, due to their excellent imaging properties, ability to accept surface modifications, and lack of toxicity. Bacteriophages, the viruses of bacteria, can have exquisite specificity for certain hosts. We propose to exploit the properties of FNDs and phages to develop phages conjugated with FNDs as long-lived fluorescent diagnostic reagents. In this study, we develop a simple procedure to create such fluorescent probes by functionalizing the FNDs and phages with streptavidin and biotin, respectively. We find that the FND-phage conjugates retain the favorable characteristics of the individual components and can discern their proper host within a mixture. This technology may be further explored using different phage/bacteria systems, different FND color centers and alternate chemical labeling schemes for additional means of bacterial identification and new single-cell/virus studies. © 2018 Wiley Periodicals, Inc.

  4. Dielectrophoresis of gold nanoparticles conjugated to DNA origami structures

    PubMed Central

    Wiens, Matthew; Lakatos, Mathias; Heerwig, Andreas; Ostermaier, Frieder; Haufe, Nora

    2016-01-01

    Summary DNA nanostructures are promising construction materials to bridge the gap between self-assembly of functional molecules and conventional top-down fabrication methods in nanotechnology. Their positioning onto specific locations of a microstructured substrate is an important task towards this aim. Here we study manipulation and positioning of pristine and of gold nanoparticle-conjugated tubular DNA origami structures using ac dielectrophoresis. The dielectrophoretic behavior was investigated employing fluorescence microscopy. For the pristine origami, a significant dielectrophoretic response was found to take place in the megahertz range, whereas, due to the higher polarizability of the metallic nanoparticles, the nanoparticle/DNA hybrid structures required a lower electrical field strength and frequency for a comparable trapping at the edges of the electrode structure. The nanoparticle conjugation additionally resulted in a remarkable alteration of the DNA structure arrangement. The growth of linear, chain-like structures in between electrodes at applied frequencies in the megahertz range was observed. The long-range chain formation is caused by a local, gold nanoparticle-induced field concentration along the DNA nanostructures, which in turn, creates dielectrophoretic forces that enable the observed self-alignment of the hybrid structures. PMID:27547612

  5. Aptamer conjugated silver nanoparticles for the detection of interleukin 6

    NASA Astrophysics Data System (ADS)

    Locke, Andrea K.; Norwood, Nicole; Marks, Haley L.; Schechinger, Monika; Jackson, George W.; Graham, Duncan; Coté, Gerard L.

    2016-03-01

    The controlled assembly of plasmonic nanoparticles by a molecular binding event has emerged as a simple yet sensitive methodology for protein detection. Metallic nanoparticles (NPs) coated with functionalized aptamers can be utilized as biosensors by monitoring changes in particle optical properties, such as the LSPR shift and enhancement of the SERS spectra, in the presence of a target protein. Herein we test this method using two modified aptamers selected for the protein biomarker interleukin 6, an indicator of the dengue fever virus and other diseases including certain types of cancers, diabetes, and even arthritis. IL6 works by inducing an immunological response within the body that can be either anti-inflammatory or pro-inflammatory. The results show that the average hydrodynamic diameter of the NPs as measured by Dynamic Light Scattering was ~42 nm. After conjugation of the aptamers, the peak absorbance of the AgNPs shifted from 404 to 408 nm indicating a surface modification of the NPs due to the presence of the aptamer. Lastly, preliminary results were obtained showing an increase in SERS intensity occurs when the IL-6 protein was introduced to the conjugate solution but the assay will still need to be optimized in order for it to be able to monitor varying concentration changes within and across the desired range.

  6. Genetic engineering and chemical conjugation of potato virus X.

    PubMed

    Lee, Karin L; Uhde-Holzem, Kerstin; Fischer, Rainer; Commandeur, Ulrich; Steinmetz, Nicole F

    2014-01-01

    Here we report the genetic engineering and chemical modification of potato virus X (PVX) for the presentation of various peptides, proteins, and fluorescent dyes, or other chemical modifiers. Three different ways of genetic engineering are described and by these means, peptides are successfully expressed not only when the foot and mouth disease virus (FMDV) 2A sequence or a flexible glycine-serine linker is included, but also when the peptide is fused directly to the PVX coat protein. When larger proteins or unfavorable peptide sequences are presented, a partial fusion via the FMDV 2A sequence is preferable. When these PVX chimeras retain the ability to assemble into viral particles and are thus able to infect plants systemically, they can be utilized to inoculate susceptible plants for isolation of sufficient amounts of virus particles for subsequent chemical modification. Chemical modification is required for the display of nonbiological ligands such as fluorophores, polymers, and small drug compounds. We present three methods of chemical bioconjugation. For direct conjugation of small chemical modifiers to solvent exposed lysines, N-hydroxysuccinimide chemistry can be applied. Bio-orthogonal reactions such as copper-catalyzed azide-alkyne cycloaddition or hydrazone ligation are alternatives to achieve more efficient conjugation (e.g., when working with high molecular weight or insoluble ligands). Furthermore, hydrazone ligation offers an attractive route for the introduction of pH-cleavable cargos (e.g., therapeutic molecules).

  7. Quantum and electromagnetic propagation with the conjugate symmetric Lanczos method.

    PubMed

    Acevedo, Ramiro; Lombardini, Richard; Turner, Matthew A; Kinsey, James L; Johnson, Bruce R

    2008-02-14

    The conjugate symmetric Lanczos (CSL) method is introduced for the solution of the time-dependent Schrodinger equation. This remarkably simple and efficient time-domain algorithm is a low-order polynomial expansion of the quantum propagator for time-independent Hamiltonians and derives from the time-reversal symmetry of the Schrodinger equation. The CSL algorithm gives forward solutions by simply complex conjugating backward polynomial expansion coefficients. Interestingly, the expansion coefficients are the same for each uniform time step, a fact that is only spoiled by basis incompleteness and finite precision. This is true for the Krylov basis and, with further investigation, is also found to be true for the Lanczos basis, important for efficient orthogonal projection-based algorithms. The CSL method errors roughly track those of the short iterative Lanczos method while requiring fewer matrix-vector products than the Chebyshev method. With the CSL method, only a few vectors need to be stored at a time, there is no need to estimate the Hamiltonian spectral range, and only matrix-vector and vector-vector products are required. Applications using localized wavelet bases are made to harmonic oscillator and anharmonic Morse oscillator systems as well as electrodynamic pulse propagation using the Hamiltonian form of Maxwell's equations. For gold with a Drude dielectric function, the latter is non-Hermitian, requiring consideration of corrections to the CSL algorithm.

  8. Method of Conjugate Radii for Solving Linear and Nonlinear Systems

    NASA Technical Reports Server (NTRS)

    Nachtsheim, Philip R.

    1999-01-01

    This paper describes a method to solve a system of N linear equations in N steps. A quadratic form is developed involving the sum of the squares of the residuals of the equations. Equating the quadratic form to a constant yields a surface which is an ellipsoid. For different constants, a family of similar ellipsoids can be generated. Starting at an arbitrary point an orthogonal basis is constructed and the center of the family of similar ellipsoids is found in this basis by a sequence of projections. The coordinates of the center in this basis are the solution of linear system of equations. A quadratic form in N variables requires N projections. That is, the current method is an exact method. It is shown that the sequence of projections is equivalent to a special case of the Gram-Schmidt orthogonalization process. The current method enjoys an advantage not shared by the classic Method of Conjugate Gradients. The current method can be extended to nonlinear systems without modification. For nonlinear equations the Method of Conjugate Gradients has to be augmented with a line-search procedure. Results for linear and nonlinear problems are presented.

  9. Displacement of polarons by vibrational modes in doped conjugated polymers

    NASA Astrophysics Data System (ADS)

    Anderson, M.; Ramanan, C.; Fontanesi, C.; Frick, A.; Surana, S.; Cheyns, D.; Furno, M.; Keller, T.; Allard, S.; Scherf, U.; Beljonne, D.; D'Avino, G.; von Hauff, E.; Da Como, E.

    2017-10-01

    Organic pi-conjugated polymers are deemed to be soft materials with strong electron-phonon coupling, which results in the formation of polarons, i.e., charge carriers dressed by self-localized distortion of the nuclei. Universal signatures for polarons are optical resonances below the band gap and intense vibrational modes (IVMs), both found in the infrared (IR) spectral region. Here, we study p -doped conjugated homo- and copolymers by combining first-principles modelling and optical spectroscopy from the far-IR to the visible. Polaronic IVMs are found to feature absorption intensities comparable to purely electronic transitions and, most remarkably, show only loose resemblance to the Raman or IR-active modes of the neutral polymer. The IVM frequency is dramatically scaled down (up to 50%) compared to the backbone carbon-stretching modes in the pristine polymers. The very large intensity of IVMs is associated with displacement of the excess positive charge along the backbone driven by specific vibrational modes. We propose a quantitative picture for the identification of these polaron shifting modes that solely based on structural information, directly correlates with their IR intensity. This finding finally discloses the elusive microscopic mechanism behind the huge IR intensity of IVMs in doped polymeric semiconductors.

  10. Fluorescent and colorimetric ion probes based on conjugated oligopyrroles.

    PubMed

    Ding, Yubin; Tang, Yunyu; Zhu, Weihong; Xie, Yongshu

    2015-03-07

    Metal ions and anions play important roles in many industrial and biochemical processes, and thus it is highly desired to detect them in the relevant systems. Small organic molecule based sensors for selective and sensitive detection of target ions show the advantages of low cost, high sensitivity and convenient implementation. In this area, pyrrole has incomparable advantages. It can be easily incorporated into linear and macrocyclic conjugated structures such as dipyrrins, porphyrins, and N-confused porphyrins, which may utilize the imino N and amino NH moieties for binding metal ions and anions, respectively. In this tutorial review, we focus on representative examples to describe the design, syntheses, sensing mechanisms, and applications of the conjugated oligopyrroles. These compounds could be used as colorimetric or fluorescent ion probes, with the advantages of vivid colour and fluorescence changes, easy structural modification and functionalization, and tunable emission wavelengths. Compared with normal porphyrins, simple di- and tripyrrins, as well as some porphyrinoids are more suitable for designing fluorescence "turn-on" metal probes, because they may exhibit flexible confirmations, and metal coordination will improve the rigidity, resulting in vivid fluorescence enhancement. It is noteworthy that the oligopyrrolic moieties may simultaneously act as the binding unit as well as the reporting moiety, which simplifies the design and syntheses of the probes.

  11. Conjugate Compressible Fluid Flow and Heat Transfer in Ducts

    NASA Technical Reports Server (NTRS)

    Cross, M. F.

    2011-01-01

    A computational approach to modeling transient, compressible fluid flow with heat transfer in long, narrow ducts is presented. The primary application of the model is for analyzing fluid flow and heat transfer in solid propellant rocket motor nozzle joints during motor start-up, but the approach is relevant to a wide range of analyses involving rapid pressurization and filling of ducts. Fluid flow is modeled through solution of the spatially one-dimensional, transient Euler equations. Source terms are included in the governing equations to account for the effects of wall friction and heat transfer. The equation solver is fully-implicit, thus providing greater flexibility than an explicit solver. This approach allows for resolution of pressure wave effects on the flow as well as for fast calculation of the steady-state solution when a quasi-steady approach is sufficient. Solution of the one-dimensional Euler equations with source terms significantly reduces computational run times compared to general purpose computational fluid dynamics packages solving the Navier-Stokes equations with resolved boundary layers. In addition, conjugate heat transfer is more readily implemented using the approach described in this paper than with most general purpose computational fluid dynamics packages. The compressible flow code has been integrated with a transient heat transfer solver to analyze heat transfer between the fluid and surrounding structure. Conjugate fluid flow and heat transfer solutions are presented. The author is unaware of any previous work available in the open literature which uses the same approach described in this paper.

  12. Guanidinylated Neomycin Conjugation Enhances Intranasal Enzyme Replacement in the Brain.

    PubMed

    Tong, Wenyong; Dwyer, Chrissa A; Thacker, Bryan E; Glass, Charles A; Brown, Jillian R; Hamill, Kristina; Moremen, Kelley W; Sarrazin, Stéphane; Gordts, Philip L S M; Dozier, Lara E; Patrick, Gentry N; Tor, Yitzhak; Esko, Jeffrey D

    2017-12-06

    Iduronidase (IDUA)-deficient mice accumulate glycosaminoglycans in cells and tissues and exhibit many of the same neuropathological symptoms of patients suffering from Mucopolysaccharidosis I. Intravenous enzyme-replacement therapy for Mucopolysaccharidosis I ameliorates glycosaminoglycan storage and many of the somatic aspects of the disease but fails to treat neurological symptoms due to poor transport across the blood-brain barrier. In this study, we examined the delivery of IDUA conjugated to guanidinoneomycin (GNeo), a molecular transporter. GNeo-IDUA and IDUA injected intravenously resulted in reduced hepatic glycosaminoglycan accumulation but had no effect in the brain due to fast clearance from the circulation. In contrast, intranasally administered GNeo-IDUA entered the brain rapidly. Repetitive intranasal treatment with GNeo-IDUA reduced glycosaminoglycan storage, lysosome size and number, and neurodegenerative astrogliosis in the olfactory bulb and primary somatosensory cortex, whereas IDUA was less effective. The enhanced efficacy of GNeo-IDUA was not the result of increased nose-to-brain delivery or enzyme stability, but rather due to more efficient uptake into neurons and astrocytes. GNeo conjugation also enhanced glycosaminoglycan clearance by intranasally delivered sulfamidase to the brain of sulfamidase-deficient mice, a model of Mucopolysaccharidosis IIIA. These findings suggest the general utility of the guanidinoglycoside-based delivery system for restoring missing lysosomal enzymes in the brain. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  13. Conjugative plasmids: vessels of the communal gene pool

    PubMed Central

    Norman, Anders; Hansen, Lars H.; Sørensen, Søren J.

    2009-01-01

    Comparative whole-genome analyses have demonstrated that horizontal gene transfer (HGT) provides a significant contribution to prokaryotic genome innovation. The evolution of specific prokaryotes is therefore tightly linked to the environment in which they live and the communal pool of genes available within that environment. Here we use the term supergenome to describe the set of all genes that a prokaryotic ‘individual’ can draw on within a particular environmental setting. Conjugative plasmids can be considered particularly successful entities within the communal pool, which have enabled HGT over large taxonomic distances. These plasmids are collections of discrete regions of genes that function as ‘backbone modules’ to undertake different aspects of overall plasmid maintenance and propagation. Conjugative plasmids often carry suites of ‘accessory elements’ that contribute adaptive traits to the hosts and, potentially, other resident prokaryotes within specific environmental niches. Insight into the evolution of plasmid modules therefore contributes to our knowledge of gene dissemination and evolution within prokaryotic communities. This communal pool provides the prokaryotes with an important mechanistic framework for obtaining adaptability and functional diversity that alleviates the need for large genomes of specialized ‘private genes’. PMID:19571247

  14. Light and dark-activated biocidal activity of conjugated polyelectrolytes.

    PubMed

    Ji, Eunkyung; Corbitt, Thomas S; Parthasarathy, Anand; Schanze, Kirk S; Whitten, David G

    2011-08-01

    This Spotlight on Applications provides an overview of a research program that has focused on the development and mechanistic study of cationic conjugated polyelectrolytes (CPEs) that function as light- and dark-active biocidal agents. Investigation has centered on poly-(phenylene ethynylene) (PPE) type conjugated polymers that are functionalized with cationic quaternary ammonium solubilizing groups. These polymers are found to interact strongly with Gram-positive and Gram-negative bacteria, and upon illumination with near-UV and visible light act to rapidly kill the bacteria. Mechanistic studies suggest that the cationic PPE-type polymers efficiently sensitize singlet oxygen ((1)O(2)), and this cytotoxic agent is responsible for initiating the sequence of events that lead to light-activated bacterial killing. Specific CPEs also exhibit dark-active antimicrobial activity, and this is believed to arise due to interactions between the cationic/lipophilic polymers and the negatively charged outer membrane characteristic of Gram-negative bacteria. Specific results are shown where a cationic CPE with a degree of polymerization of 49 exhibits pronounced light-activated killing of E. coli when present in the cell suspension at a concentration of 1 μg mL(-1).

  15. Material Selection for Microchannel Heatsink: Conjugate Heat Transfer Simulation

    NASA Astrophysics Data System (ADS)

    Uday Kumar, A.; Javed, Arshad; Dubey, Satish K.

    2018-04-01

    Heat dissipation during the operation of electronic devices causes rise in temperature, which demands an effective thermal management for their performance, life and reliability. Single phase liquid cooling in microchannels is an effective and proven technology for electronics cooling. However, due to the ongoing trends of miniaturization and developments in the microelectronics technology, the future needs of heat flux dissipation rate are expected to rise to 1 kW/cm2. Air cooled systems are unable to meet this demand. Hence, liquid cooled heatsinks are preferred. This paper presents conjugate heat transfer simulation of single phase flow in microchannels with application to electronic cooling. The numerical model is simulated for different materials: copper, aluminium and silicon as solid and water as liquid coolant. The performances of microchannel heatsink are analysed for mass flow rate range of 20-40 ml/min. The investigation has been carried out on same size of electronic chip and heat flux in order to have comparative study of different materials. This paper is divided into two sections: fabrication techniques and numerical simulation for different materials. In the first part, a brief discussion of fabrication techniques of microchannel heatsink have been presented. The second section presents conjugate heat transfer simulation and parametric investigation for different material microchannel heatsink. The presented study and findings are useful for selection of materials for microchannel heatsink.

  16. Improved QD-BRET conjugates for detection and imaging

    SciTech Connect

    Xing Yun; So, Min-kyung; Koh, Ai Leen

    2008-08-01

    Self-illuminating quantum dots, also known as QD-BRET conjugates, are a new class of quantum dot bioconjugates which do not need external light for excitation. Instead, light emission relies on the bioluminescence resonance energy transfer from the attached Renilla luciferase enzyme, which emits light upon the oxidation of its substrate. QD-BRET combines the advantages of the QDs (such as superior brightness and photostability, tunable emission, multiplexing) as well as the high sensitivity of bioluminescence imaging, thus holding the promise for improved deep tissue in vivo imaging. Although studies have demonstrated the superior sensitivity and deep tissue imaging potential, the stability ofmore » the QD-BRET conjugates in biological environment needs to be improved for long-term imaging studies such as in vivo cell tracking. In this study, we seek to improve the stability of QD-BRET probes through polymeric encapsulation with a polyacrylamide gel. Results show that encapsulation caused some activity loss, but significantly improved both the in vitro serum stability and in vivo stability when subcutaneously injected into the animal. Stable QD-BRET probes should further facilitate their applications for both in vitro testing as well as in vivo cell tracking studies.« less

  17. Lower Critical Solution Temperature (LCST) and drug conjugation of polyacetal

    NASA Astrophysics Data System (ADS)

    de Silva, Chathuranga; Samanta, Sanjoy; Leophairatana, Porakrit; Koberstein, Jeffrey

    There has been an increasing focus in polymer research for materials that can efficiently deliver therapeutics to a pre-identified solid tumor target. Due to their unique properties, stimuli responsive polymers (SRPs) have been of particular interest. One such novel SRP is a polyacetal-based copolymer (PAC). PAC shows a remarkable temperature response (LCST) that is linearly dependent on composition. Here, we discuss the fundamental physical origins of this LCST behavior, exhibited by this polymer. Our results indicate that the observed LCST scales linearly with the number of carbon and oxygen atoms in the polymer repeat units, allowing for precise control over the LCST. We design PAC to include cancer therapeutics in its polymer-backbone, utilizing strategies to modify step-growth polymerization to obtain, for the first time, temperature-responsive main-chain drug conjugates. The temperature response in these main-chain drug conjugates allow for effective delivery of therapeutics to the tumor site, followed by acid-hydrolysis in acidic local tumor environments, to release pristine therapeutics directly at the tumor site. Due to these reasons, we foresee PAC to be in the forefront of soft-matter SRP drug-delivery systems.

  18. Functional Characterization of Corynebacterium glutamicum Mycothiol S-Conjugate Amidase

    PubMed Central

    Si, Meiru; Long, Mingxiu; Chaudhry, Muhammad Tausif; Xu, Yixiang; Zhang, Pan; Zhang, Lei; Shen, Xihui

    2014-01-01

    The present study focuses on the genetic and biochemical characterization of mycothiol S-conjugate amidase (Mca) of Corynebacterium glutamicum. Recombinant C. glutamicum Mca was heterologously expressed in Escherichia coli and purified to apparent homogeneity. The molecular weight of native Mca protein determined by gel filtration chromatography was 35 kDa, indicating that Mca exists as monomers in the purification condition. Mca showed amidase activity with mycothiol S-conjugate of monobromobimane (MSmB) in vivo while mca mutant lost the ability to cleave MSmB. In addition, Mca showed limited deacetylase activity with N-acetyl-D-glucosamine (GlcNAc) as substrate. Optimum pH for amidase activity was between 7.5 and 8.5, while the highest activity in the presence of Zn2+ confirmed Mca as a zinc metalloprotein. Amino acid residues conserved among Mca family members were located in C. glutamicum Mca and site-directed mutagenesis of these residues indicated that Asp14, Tyr137, His139 and Asp141 were important for activity. The mca deletion mutant showed decreased resistance to antibiotics, alkylating agents, oxidants and heavy metals, and these sensitive phenotypes were recovered in the complementary strain to a great extent. The physiological roles of Mca in resistance to various toxins were further supported by the induced expression of Mca in C. glutamicum under various stress conditions, directly under the control of the stress-responsive extracytoplasmic function-sigma (ECF-σ) factor SigH. PMID:25514023

  19. Current safety issues with quadrivalent meningococcal conjugate vaccines.

    PubMed

    Myers, Tanya R; McNeil, Michael M

    2018-05-04

    Invasive meningococcal disease, although rare, can present as sudden, life-threatening disease with high risk of mortality or severe long-term sequelae. The main prevention strategy for invasive meningococcal disease in the United States is the routine vaccination of adolescents and other persons at increased risk of meningococcal disease with quadrivalent meningococcal conjugate vaccines. Two such vaccines are currently licensed and available in the United States, Menactra® (Sanofi Pasteur) and Menveo® (GlaxoSmithKline), and usage in the adolescent population has steadily increased since their introduction. Although early reports raised concerns about a possible association of Menactra with Guillain-Barré syndrome, a comprehensive safety review determined that if such risk existed it was no more than 0.66 cases per 1 million vaccinations. More recently, a study found an elevated risk of Bell's palsy when Menveo was administered concomitantly with other vaccines but no association was found when the vaccine was administered alone. In this commentary, we describe the current state of knowledge with respect to the safety of quadrivalent meningococcal conjugate vaccines, and we identify potential areas for safety research for these vaccines.

  20. Fluorogenic reaction-based prodrug conjugates as targeted cancer theranostics.

    PubMed

    Lee, Min Hee; Sharma, Amit; Chang, Min Jung; Lee, Jinju; Son, Subin; Sessler, Jonathan L; Kang, Chulhun; Kim, Jong Seung

    2018-01-02

    Theranostic systems are receiving ever-increasing attention due to their potential therapeutic utility, imaging enhancement capability, and promise for advancing the field of personalized medicine, particularly as it relates to the diagnosis, staging, and treatment of cancer. In this Tutorial Review, we provide an introduction to the concepts of theranostic drug delivery effected via use of conjugates that are able to target cancer cells selectively, provide cytotoxic chemotherapeutics, and produce readily monitored imaging signals in vitro and in vivo. The underlying design concepts, requiring the synthesis of conjugates composed of imaging reporters, masked chemotherapeutic drugs, cleavable linkers, and cancer targeting ligands, are discussed. Particular emphasis is placed on highlighting the potential benefits of fluorogenic reaction-based targeted systems that are activated for both imaging and therapy by cellular entities, e.g., thiols, reactive oxygen species and enzymes, which are present at relatively elevated levels in tumour environments, physiological characteristics of cancer, e.g., hypoxia and acidic pH. Also discussed are systems activated by an external stimulus, such as light. The work summarized in this Tutorial Review will help define the role fluorogenic reaction-based, cancer-targeting theranostics may have in advancing drug discovery efforts, as well as improving our understanding of cellular uptake and drug release mechanisms.

  1. Investigation of conjugate circular arcs in rocket nozzle contour design

    NASA Astrophysics Data System (ADS)

    Schomberg, K.; Olsen, J.; Neely, A.; Doig, G.

    2018-05-01

    The use of conjugate circular arcs in rocket nozzle contour design has been investigated by numerically comparing three existing sub-scale nozzles to a range of equivalent arc-based contour designs. Three performance measures were considered when comparing nozzle designs: thrust coefficient, nozzle exit wall pressure, and a transition between flow separation regimes during the engine start-up phase. In each case, an equivalent arc-based contour produced an increase in the thrust coefficient and exit wall pressure of up to 0.4 and 40% respectively, in addition to suppressing the transition between a free and restricted shock separation regime. A general approach to arc-based nozzle contour design has also been presented to outline a rapid and repeatable process for generating sub-scale arc-based contours with an exit Mach number of 3.8-5.4 and a length between 60 and 100% of a 15° conical nozzle. The findings suggest that conjugate circular arcs may represent a viable approach for producing sub-scale rocket nozzle contours, and that a further investigation is warranted between arc-based and existing full-scale rocket nozzles.

  2. Graphite-Conjugated Rhenium Catalysts for Carbon Dioxide Reduction

    SciTech Connect

    Oh, Seokjoon; Gallagher, James R.; Miller, Jeffrey T.

    2016-02-17

    Condensation of fac-Re(5,6-diamino-1,10-phenanthroline)(CO)(3)Cl to o-quinone edge defects on graphitic carbon surfaces generates graphite-conjugated rhenium (GCC-Re) catalysts that are highly active for CO2 reduction to CO in acetonitrile electrolyte. X-ray photo-electron and X-ray absorption spectroscopies establish the formation of surface-bound Re centers with well-defined coordination environments. GCC-Re species on glassy carbon surfaces display catalytic currents greater than 50 mA cm(-2) with 96 +/- 3% Faradaic efficiency for CO production. Normalized for the number of Re active sites, GCC-Re catalysts exhibit higher turnover frequencies than that of a soluble molecular analogue, fac-Re(1,10-phenanthroline)(CO)(3)Cl, and turnover numbers greater than 12,000. In contrast to themore » molecular analogue, GCC-Re surfaces display a Tafel slope of 150 mV/decade, indicative of a catalytic mechanism involving rate-limiting one-electron transfer. This work establishes graphite conjugation as a powerful strategy for generating well-defined, tunable, heterogeneous electrocatalysts on ubiquitous graphitic carbon surfaces.« less

  3. Direct heteroarylation polymerization: guidelines for defect-free conjugated polymers.

    PubMed

    Bura, Thomas; Beaupré, Serge; Légaré, Marc-André; Quinn, Jesse; Rochette, Etienne; Blaskovits, J Terence; Fontaine, Frédéric-Georges; Pron, Agnieszka; Li, Yuning; Leclerc, Mario

    2017-05-01

    Direct (hetero)arylation polymerization (DHAP) has emerged as a valuable and atom-economical alternative to traditional cross-coupling methods for the synthesis of low-cost and efficient conjugated polymers for organic electronics. However, when applied to the synthesis of certain (hetero)arene-based materials, a lack of C-H bond selectivity has been observed. To prevent such undesirable side-reactions, we report the design and synthesis of new, bulky, phosphine-based ligands that significantly enhance selectivity of the DHAP process for both halogenated and non-halogenated electron-rich and electron-deficient thiophene-based comonomers. To better understand the selectivity issues, density functional theory (DFT) calculations have been performed on various halogenated and non-halogenated electron-rich and electron-deficient thiophene-based comonomers. Calculations showed that the presence of bromine atoms decreases the energy of activation ( E a ) of the adjacent C-H bonds, allowing undesirable β-defects for some brominated aromatic units. Both calculations and the new ligands should lead to the rational design of monomers and methods for the preparation of defect-free conjugated polymers from DHAP.

  4. Do π-conjugative effects facilitate SN2 reactions?

    PubMed

    Wu, Chia-Hua; Galabov, Boris; Wu, Judy I-Chia; Ilieva, Sonia; Schleyer, Paul von R; Allen, Wesley D

    2014-02-26

    Rigorous quantum chemical investigations of the SN2 identity exchange reactions of methyl, ethyl, propyl, allyl, benzyl, propargyl, and acetonitrile halides (X = F(-), Cl(-)) refute the traditional view that the acceleration of SN2 reactions for substrates with a multiple bond at Cβ (carbon adjacent to the reacting Cα center) is primarily due to π-conjugation in the SN2 transition state (TS). Instead, substrate-nucleophile electrostatic interactions dictate SN2 reaction rate trends. Regardless of the presence or absence of a Cβ multiple bond in the SN2 reactant in a series of analogues, attractive Cβ(δ(+))···X(δ(-)) interactions in the SN2 TS lower net activation barriers (E(b)) and enhance reaction rates, whereas repulsive Cβ(δ(-))···X(δ(-)) interactions increase E(b) barriers and retard SN2 rates. Block-localized wave function (BLW) computations confirm that π-conjugation lowers the net activation barriers of SN2 allyl (1t, coplanar), benzyl, propargyl, and acetonitrile halide identity exchange reactions, but does so to nearly the same extent. Therefore, such orbital interactions cannot account for the large range of E(b) values in these systems.

  5. Crystallization-driven assembly of conjugated-polymer-based nanostructures

    SciTech Connect

    Hayward, Ryan C.

    2016-10-15

    The goal of this project has been to improve our ability to simultaneously control the organization, and therefore the opto-electronic properties, of conjugated-polymer based materials across three different length-scales: 1) the molecular scale, in the sense of controlling growth and functionalization of highly crystalline semiconducting organic materials capable of efficient charge transport, 2) the nanoscale, in terms of positioning n- and p-type materials with domain sizes comparable to exciton diffusion lengths (~ 10 nm) to facilitate charge separation, and 3) the colloidal scale, such that well-defined crystalline nanoscale building blocks can be hierarchically organized into device layers. As described inmore » more detail below, the project was successful in generating powerful new approaches to, and improved fundamental understanding of, processing and self-assembly of organic and hybrid semiconducting materials across all three length-scales. Although the goals of the project were formulated with primarily photovoltaic architectures in mind, the outcomes of the project have significant implications for a variety of conjugated-polymer-based devices including field-effect-transistors for sensors and logic devices, as well as potentially thermoelectrics and battery electrode materials. The project has resulted in 10 peer-reviewed publications to date [1-10], with several additional manuscripts currently in preparation.« less

  6. Comparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNa delivery in SMMC-7721 cells

    PubMed Central

    Deng, Li; Zhang, Yingying; Ma, Lulu; Jing, Xiaolong; Ke, Xingfa; Lian, Jianhao; Zhao, Qiang; Yan, Bo; Zhang, Jinfeng; Yao, Jianzhong; Chen, Jianming

    2013-01-01

    Background Targeted liposome-polycation-DNA complex (LPD), mainly conjugated with antibodies using functionalized PEG derivatives, is an effective nanovector for systemic delivery of small interference RNA (siRNA). However, there are few studies reporting the effect of different conjugation linkers on LPD for gene silencing. To clarify the influence of antibody conjugation linkers on LPD, we prepared two different immunoliposomes to deliver siRNA in which DSPE-PEG-COOH and DSPE-PEG-MAL, the commonly used PEG derivative linkers, were used to conjugate anti-EGFR Fab’ with the liposome. Methods First, 600 μg of anti-EGFR Fab’ was conjugated with 28.35 μL of a micelle solution containing DSPE-PEG-MAL or DSPE-PEG-COOH, and then post inserted into the prepared LPD. Various liposome parameters, including particle size, zeta potential, stability, and encapsulation efficiency were evaluated, and the targeting ability and gene silencing activity of TLPD-FPC (DSPE-PEG-COOH conjugated with Fab’) was compared with that of TLPD-FPM (DSPE-PEG-MAL conjugated with Fab’) in SMMC-7721 hepatocellular carcinoma cells. Results There was no significant difference in particle size between the two TLPDs, but the zeta potential was significantly different. Further, although there was no significant difference in siRNA encapsulation efficiency, cell viability, or serum stability between TLPD-FPM and TLPD-FPC, cellular uptake of TLPD-FPM was significantly greater than that of TLPD-FPC in EGFR-overexpressing SMMC-7721 cells. The luciferase gene silencing efficiency of TLPD-FPM was approximately three-fold high than that of TLPD-FPC. Conclusion Different conjugation linkers whereby antibodies are conjugated with LPD can affect the physicochemical properties of LPD and antibody conjugation efficiency, thus directly affecting the gene silencing effect of TLPD. Immunoliposomes prepared by DSPE-PEG-MAL conjugation with anti-EGFR Fab’ are more effective than TLPD containing DSPE

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

    PubMed

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

    2014-09-01

    Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; stability of curcumin-diclofenac conjugate in gastrointestinal fluids and in vitro efficacy have been evaluated. In vivo bioavailability of curcumin-diclofenac conjugate and curcumin in Sprague-Dawley rats, and antiarthritic activity of curcumin-diclofenac conjugate, curcumin and diclofenac in modified streptococcal cell wall-induced arthritis model in Balb/c mice to mimic rheumatoid arthritis in humans have also been studied. In all of the above studies, curcumin-diclofenac conjugate exhibited enhanced stability as compared to curcumin; its activity was twice that of diclofenac in inhibiting thermal protein denaturation taken as a measure of in vitro antiinflammatory activity; it enhanced the bioavailability of curcumin by more than five folds, and significantly (P<0.01) alleviated the symptoms of arthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin.

  8. Dai-Kou type conjugate gradient methods with a line search only using gradient.

    PubMed

    Huang, Yuanyuan; Liu, Changhe

    2017-01-01

    In this paper, the Dai-Kou type conjugate gradient methods are developed to solve the optimality condition of an unconstrained optimization, they only utilize gradient information and have broader application scope. Under suitable conditions, the developed methods are globally convergent. Numerical tests and comparisons with the PRP+ conjugate gradient method only using gradient show that the methods are efficient.

  9. ß-Lactoglobulin-chlorogenic acid conjugate-based nanoparticle for delivery of (-)-epigallocatechin-3-gallate

    USDA-ARS?s Scientific Manuscript database

    ß-Lactoglobulin (BLG)-chlorogenic acid (CA) conjugates were generated with a free radical induced grafting method. BLG-CA conjugates showed better antioxidant activities than that of BLG. The antioxidant activity increased with the increase of CA substitution. The particle sizes of (-)-epigallocatec...

  10. Physicochemical properties of β-carotene emulsions stabilized by chlorogenic acid-lactoferrin-glucose/polydextrose conjugates.

    PubMed

    Liu, Fuguo; Wang, Di; Xu, Honggao; Sun, Cuixia; Gao, Yanxiang

    2016-04-01

    In this study, the influence of chlorogenic acid (CA)-lactoferrin (LF)-glucose (Glc) conjugate and CA-LF-polydextrose (PD) conjugate on the physicochemical characteristics of β-carotene emulsions was investigated. Novel emulsifiers were formed during Maillard reaction between CA-LF conjugate and Glc/PD. The physicochemical properties of β-carotene emulsions were characterized by droplet size, ζ-potential, rheological behavior, transmission changes during centrifugal sedimentation and β-carotene degradation. Results showed that the covalent attachment of Glc or PD to CA-LF conjugate effectively increased the hydrophilicity of the oil droplets surfaces and strengthened the steric repulsion between the oil droplets. Glucose was better than polydextrose for the conjugation with CA-LF conjugate to stabilize β-carotene emulsions. In comparison with LF and CA-LF-Glc/PD mixtures, CA-LF-Glc/PD ternary conjugates exhibited better emulsifying properties and improved physical stability of β-carotene emulsions during the freeze-thaw treatment. In addition, CA-LF-Glc/PD conjugates significantly enhanced chemical stability of β-carotene in the emulsions against ultraviolet light exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. The Obscure World of Integrative and Mobilizable Elements, Highly Widespread Elements that Pirate Bacterial Conjugative Systems

    PubMed Central

    Guédon, Gérard; Libante, Virginie; Coluzzi, Charles; Payot, Sophie

    2017-01-01

    Conjugation is a key mechanism of bacterial evolution that involves mobile genetic elements. Recent findings indicated that the main actors of conjugative transfer are not the well-known conjugative or mobilizable plasmids but are the integrated elements. This paper reviews current knowledge on “integrative and mobilizable elements” (IMEs) that have recently been shown to be highly diverse and highly widespread but are still rarely described. IMEs encode their own excision and integration and use the conjugation machinery of unrelated co-resident conjugative element for their own transfer. Recent studies revealed a much more complex and much more diverse lifecycle than initially thought. Besides their main transmission as integrated elements, IMEs probably use plasmid-like strategies to ensure their maintenance after excision. Their interaction with conjugative elements reveals not only harmless hitchhikers but also hunters that use conjugative elements as target for their integration or harmful parasites that subvert the conjugative apparatus of incoming elements to invade cells that harbor them. IMEs carry genes conferring various functions, such as resistance to antibiotics, that can enhance the fitness of their hosts and that contribute to their maintenance in bacterial populations. Taken as a whole, IMEs are probably major contributors to bacterial evolution. PMID:29165361

  12. Molecular design of light-harvesting photosensitizers: effect of varied linker conjugation on interfacial electron transfer

    SciTech Connect

    Jiang, Jianbing; Swierk, John R.; Hedstrom, Svante

    2016-06-30

    Here, interfacial electron transfer dynamics of a series of photosensitizers bound to TiO 2 via linkers of varying conjugation strength are explored by spectroscopic and computational techniques. Injection and recombination depend on the extent of conjugation in the linker, where the LUMO delocalization determines the injection dynamics but both the HOMO and HOMO–1 are involved in recombination.

  13. Photogeneration of Charge Carriers in Bilayer Assemblies of Conjugated Rigid-Rod Polymers

    DTIC Science & Technology

    1994-07-08

    photoinduced electron transfer and exciplex formation at the bilayer interface. Thus photocarrier generation on photoexcitation of the conjugated rigid...rod polymers in the bilayer occurs by photoinduced electron transfer, forming intermolecular exciplexes which dissociate efficiently in electric field...photogeneration, conjugated rigid-rod polymers, is. MACI COD bilayer assemblies, electron transfer, exciplexes . 11. SEOJUTY CLASUICA 10. 51(11MIE CLASSIMIAVION

  14. Excited-State Complexes of Conjugated Polymers: Novel Photophysical Processes and Optoelectronic Materials.

    DTIC Science & Technology

    1995-03-20

    corresponding excited-state complexes were only recently discovered. The results of our extensive studies of intermolecular excimers and exciplexes of many...the luminescence of conjugated polymers. The luminescence and charge photogeneration in exciplexes of conjugated polymers with donor triarylamines will also be presented. jg

  15. Conjugated Gammadion Chiral Metamaterial with Uniaxial Optical Activity and Negative Refractive Index

    DTIC Science & Technology

    2011-01-10

    in Fig. 4, we discuss a procedure of transmutation from the simple -particle chiral element to the conjugated gammadion chiral metamaterial. The...the transmutation from the simple -particle chiral element to the conjugated gammadion chiral metamaterial. The procedure shows how the magnetic or

  16. Dynamical Approach to Multiequilibria Problems for Mixtures of Acids and Their Conjugated Bases

    ERIC Educational Resources Information Center

    Glaser, Rainer E.; Delarosa, Marco A.; Salau, Ahmed Olasunkanmi; Chicone, Carmen

    2014-01-01

    Mathematical methods are described for the determination of steady-state concentrations of all species in multiequilibria systems consisting of several acids and their conjugated bases in aqueous solutions. The main example consists of a mixture of a diprotic acid H[subscript 2]A, a monoprotic acid HB, and their conjugate bases. The reaction…

  17. The Use of Conjugate Charts in Transfer Reactions: A Unified Approach

    ERIC Educational Resources Information Center

    Allnutt, Michael I.

    2007-01-01

    Redox reactions can be conveniently discussed in terms of the relative strengths of the oxidant, the reductant, and their conjugates; a conjugate chart is a most convenient and useful way of doing this. A similar chart for acids and bases is proposed, which can be applied in the same manner. (Contains 7 figures and 2 tables.)

  18. Inhomogeneity in the excited-state torsional disorder of a conjugated macrocycle.

    PubMed

    Yang, Jaesung; Ham, Sujin; Kim, Tae-Woo; Park, Kyu Hyung; Nakao, Kazumi; Shimizu, Hideyuki; Iyoda, Masahiko; Kim, Dongho

    2015-03-12

    The photophysics of conjugated polymers has generally been explained based on the interactions between the component conjugated chromophores in a tangled chain. However, conjugated chromophores are entities with static and dynamic structural disorder, which directly affects the conjugated polymer photophysics. Here we demonstrate the impact of chain structure torsional disorder on the spectral characteristics for a macrocyclic oligothiophene 1, which is obscured in conventional linear conjugated chromophores by diverse structural disorders such as those in chromophore size and shape. We used simultaneous multiple fluorescence parameter measurement for a single molecule and quantum-mechanical calculations to show that within the fixed conjugation length across the entire ring an inhomogeneity from torsional disorder in the structure of 1 plays a crucial role in causing its energetic disorder, which affords the spectral broadening of ∼220 meV. The torsional disorder in 1 fluctuated on the time scale of hundreds of milliseconds, typically accompanied by spectral drifts on the order of ∼10 meV. The fluctuations could generate torsional defects and change the electronic structure of 1 associated with the ring symmetry. These findings disclose the fundamental nature of conjugated chromophore that is the most elementary spectroscopic unit in conjugated polymers and suggest the importance of engineering structural disorder to optimize polymer-based device photophysics. Additionally, we combined defocused wide-field fluorescence microscopy and linear dichroism obtained from the simultaneous measurements to show that 1 emits polarized light with a changing polarization direction based on the torsional disorder fluctuations.

  19. Potential Large-Scale Production of Conjugated Soybean Oil Catalyzed by Photolyzed Iodine in Hexanes

    USDA-ARS?s Scientific Manuscript database

    A laboratory apparatus is described for the production of conjugated soybean oil (SBO) in pound quantities via irradiation with visible-light. Under our reaction conditions, quantitative conversions (determined by NMR spectroscopy) of SBO to conjugated SBO, in hexanes at reflux temperatures, were a...

  20. Photosensitizer conjugated iron oxide nanoparticles for simultaneous in vitro magneto-fluorescent imaging guided photodynamic therapy.

    PubMed

    Nafiujjaman, Md; Revuri, Vishnu; Nurunnabi, Md; Cho, Kwang Jae; Lee, Yong-Kyu

    2015-04-04

    In this study, photosensitizer conjugated iron oxide nanoparticles were strategically designed and prepared for simultaneous PDT and dual-mode fluorescence/MR imaging. The MRI contrast agent Fe3O4 was modified by APTES to functionalize the surface and further to link with heparin-pheophorbide-A conjugates.

  1. Formation of primary sperm conjugates in a haplogyne spider (Caponiidae, Araneae) with remarks on the evolution of sperm conjugation in spiders.

    PubMed

    Lipke, Elisabeth; Michalik, Peter

    2012-11-01

    Sperm conjugation, where two or more sperm are physically united, is a rare but widespread pheno-menon across the animal kingdom. One group well known for its different types of sperm conjugation are spiders. Particularly, haplogyne spiders show a high diversity of sperm traits. Besides individual cleistospermia, primary (synspermia) and secondary (coenospermia, "spermatophore") sperm conjugation occurs. However, the evolution of sperm conjugates and sperm is not understood in this group. Here, we look at how sperm are transferred in Caponiidae (Haplogynae) in pursuit of additional information about the evolution of sperm transfer forms in spiders. Additionally, we investigated the male reproductive system and spermatozoa using light- and transmission electron-microscopy and provide a 3D reconstruction of individual as of well as conjugated spermatozoa. Mature spermatozoa are characterized by an extremely elongated, helical nucleus resulting in the longest spider sperm known to date. At the end of spermiogenesis, synspermia are formed by complete fusion of four spermatids. Thus, synspermia might have evolved early within ecribellate Haplogynae. The fused sperm cells are surrounded by a prominent vesicular area. The function of the vesicular area remains still unknown but might be correlated with the capacitation process inside the female. Further phylogenetic and functional implications of the spermatozoa and sperm conjugation are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Quantitative studies of sulphate conjugation by isolated rat liver cells using [35S]sulphate.

    PubMed

    Dawson, J; Knowles, R G; Pogson, C I

    1991-06-21

    We have developed a simple, rapid and sensitive method for the study of sulphate conjugation in isolated liver cells based on the incorporation of 35S from [35S]sulphate. Excess [35S]sulphate is removed by a barium precipitation procedure, leaving [35S]sulphate conjugates in solution. We have used this method to examine the kinetics of sulphation of N-acetyl-p-aminophenol (acetaminophen), 4-nitrophenol and 1-naphthol in isolated rat liver cells. The efficiency of recovery of the sulphate conjugates was greater than 86%. The method is applicable to the quantitative study of sulphate conjugation of any substrate which forms a sulphate conjugate that is soluble in the presence of barium, without the need for standards or radiolabelled sulphate acceptors.

  3. Functional properties of nisin-carbohydrate conjugates formed by radiation induced Maillard reaction

    NASA Astrophysics Data System (ADS)

    Muppalla, Shobita R.; Sonavale, Rahul; Chawla, Surinder P.; Sharma, Arun

    2012-12-01

    Nisin-carbohydrate conjugates were prepared by irradiating nisin either with glucose or dextran. Increase in browning and formation of intermediate products was observed with a concomitant decrease in free amino and reducing sugar groups indicating occurrence of the Maillard reaction catalyzed by irradiation. Nisin-carbohydrate conjugates showed a broad spectrum antibacterial activity against Gram negative bacteria (Escherichia coli, Pseudomonas fluorescence) as well as Gram positive bacteria (Staphylococcus aureus, Bacillus cereus). Results of antioxidant assays, including that of DPPH radical-scavenging activity and reducing power, showed that the nisin-dextran conjugates possessed better antioxidant potential than nisin-glucose conjugate. These results suggested that it was possible to enhance the functional properties of nisin by preparing radiation induced conjugates suitable for application in food industry.

  4. Conjugation of curcumin onto hyaluronic acid enhances its aqueous solubility and stability.

    PubMed

    Manju, S; Sreenivasan, K

    2011-07-01

    Polymer-drug conjugates have gained much attention largely to circumvent lower drug solubility and to enhance drug stability. Curcumin is widely known for its medicinal properties including its anticancer efficacy. One of the serious drawbacks of curcumin is its poor water solubility which leads to reduced bioavailability. With a view to address these issues, we synthesized hyaluronic acid-curcumin (HA-Cur) conjugate. The drug conjugate was characterized using FT-IR, NMR, Dynamic light scattering and TEM techniques. The conjugates, interestingly found to assembles as micelles in aqueous phase. The formation of micelles seems to improve the stability of the drug in physiological pH. We also assessed cytotoxicity of the conjugate using L929 fibroblast cells and quantified by MTT assay. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Targeting Tumor Associated Phosphatidylserine with New Zinc Dipicolylamine-Based Drug Conjugates.

    PubMed

    Liu, Yu-Wei; Shia, Kak-Shan; Wu, Chien-Huang; Liu, Kuan-Liang; Yeh, Yu-Cheng; Lo, Chen-Fu; Chen, Chiung-Tong; Chen, Yun-Yu; Yeh, Teng-Kuang; Chen, Wei-Han; Jan, Jiing-Jyh; Huang, Yu-Chen; Huang, Chen-Lung; Fang, Ming-Yu; Gray, Brian D; Pak, Koon Y; Hsu, Tsu-An; Huang, Kuan-Hsun; Tsou, Lun K

    2017-07-19

    A series of zinc(II) dipicolylamine (ZnDPA)-based drug conjugates have been synthesized to probe the potential of phosphatidylserine (PS) as a new antigen for small molecule drug conjugate (SMDC) development. Using in vitro cytotoxicity and plasma stability studies, PS-binding assay, in vivo pharmacokinetic studies, and maximum tolerated dose profiles, we provided a roadmap and the key parameters required for the development of the ZnDPA based drug conjugate. In particular, conjugate 24 induced tumor regression in the COLO 205 xenograft model and exhibited a more potent antitumor effect with a 70% reduction of cytotoxic payload compared to that of the marketed irinotecan when dosed at the same regimen. In addition to the validation of PS as an effective pharmacodelivery target for SMDC, our work also provided the foundation that, if applicable, a variety of therapeutic agents could be conjugated in the same manner to treat other PS-associated diseases.

  6. Molecularly precise dendrimer-drug conjugates with tunable drug release for cancer therapy.

    PubMed

    Zhou, Zhuxian; Ma, Xinpeng; Murphy, Caitlin J; Jin, Erlei; Sun, Qihang; Shen, Youqing; Van Kirk, Edward A; Murdoch, William J

    2014-10-06

    The structural preciseness of dendrimers makes them perfect drug delivery carriers, particularly in the form of dendrimer-drug conjugates. Current dendrimer-drug conjugates are synthesized by anchoring drug and functional moieties onto the dendrimer peripheral surface. However, functional groups exhibiting the same reactivity make it impossible to precisely control the number and the position of the functional groups and drug molecules anchored to the dendrimer surface. This structural heterogeneity causes variable pharmacokinetics, preventing such conjugates to be translational. Furthermore, the highly hydrophobic drug molecules anchored on the dendrimer periphery can interact with blood components and alter the pharmacokinetic behavior. To address these problems, we herein report molecularly precise dendrimer-drug conjugates with drug moieties buried inside the dendrimers. Surprisingly, the drug release rates of these conjugates were tailorable by the dendrimer generation, surface chemistry, and acidity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Diketopyrrolopyrrole-based Conjugated Polymers Bearing Branched Oligo(Ethylene Glycol) Side Chains for Photovoltaic Devices.

    PubMed

    Chen, Xingxing; Zhang, Zijian; Ding, Zicheng; Liu, Jun; Wang, Lixiang

    2016-08-22

    Conjugated polymers are essential for solution-processable organic opto-electronic devices. In contrast to the great efforts on developing new conjugated polymer backbones, research on developing side chains is rare. Herein, we report branched oligo(ethylene glycol) (OEG) as side chains of conjugated polymers. Compared with typical alkyl side chains, branched OEG side chains endowed the resulting conjugated polymers with a smaller π-π stacking distance, higher hole mobility, smaller optical band gap, higher dielectric constant, and larger surface energy. Moreover, the conjugated polymers with branched OEG side chains exhibited outstanding photovoltaic performance in polymer solar cells. A power conversion efficiency of 5.37 % with near-infrared photoresponse was demonstrated and the device performance could be insensitive to the active layer thickness. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Photophysicochemical behaviour and antimicrobial properties of monocarboxy Mg (II) and Al (III) phthalocyanine-magnetite conjugates

    NASA Astrophysics Data System (ADS)

    Idowu, Mopelola Abidemi; Xego, Solami; Arslanoglu, Yasin; Mark, John; Antunes, Edith; Nyokong, Tebello

    2018-03-01

    Asymmetric Mg (II) or Al (III) phthalocyanine (containing a COOH group and 3-pyridylsulfanyl units) was conjugated via an amide bond to amino functionalized magnetic nanoparticle (AIMN) to form MgPc-AIMN or AlPc-AIMN conjugate, and characterized. The photophysicochemical behaviour of the phthalocyanine-AIMN conjugates was investigated and compared to the asymmetric Pcs and to the simple mixture of Pc with AIMNs without a chemical bond, (MPc-AIMN (mixed)). The directed covalent linkage of AIMNs to the asymmetrical metallopthalocyanines afforded improvements in the singlet oxygen (VΔ) and triplet state quantum yield (VT) as well as singlet oxygen lifetimes for the MPcs-AIMN-linked conjugates compared to MPc-AIMN (mixed) and MPcs alone. The asymmetric phthalocyanines and their conjugates showed effective antimicrobial activity against Escherichia coli bacteria under illumination.

  9. Programmable Regulation of DNA Conjugation to Gold Nanoparticles via Strand Displacement.

    PubMed

    Zhang, Cheng; Wu, Ranfeng; Li, Yifan; Zhang, Qiang; Yang, Jing

    2017-10-31

    Methods for conjugating DNA to gold nanoparticles (AuNPs) have recently attracted considerable attention. The ability to control such conjugation in a programmable way is of great interest. Here, we have developed a logic-based method for manipulating the conjugation of thiolated DNA species to AuNPs via cascading DNA strand displacement. Using this method, several logic-based operation systems are established and up to three kinds of DNA signals are introduced at the same time. In addition, a more sensitive catalytic logic-based operation is also achieved based on an entropy-driven process. In the experiment, all of the DNA/AuNPs conjugation results are verified by agrose gel. This strategy promises great potential for automatically conjugating DNA stands onto label-free gold nanoparticles and can be extended to constructing DNA/nanoparticle devices for applications in diagnostics, biosensing, and molecular robotics.

  10. Preparation and high-resolution microscopy of gold cluster labeled nucleic acid conjugates and nanodevices

    PubMed Central

    Powell, Richard D.; Hainfeld, James F.

    2013-01-01

    Nanogold and undecagold are covalently linked gold cluster labels which enable the identification and localization of biological components with molecular precision and resolution. They can be prepared with different reactivities, which means they can be conjugated to a wide variety of molecules, including nucleic acids, at specific, unique sites. The location of these sites can be synthetically programmed in order to preserve the binding affinity of the conjugate and impart novel characteristics and useful functionality. Methods for the conjugation of undecagold and Nanogold to DNA and RNA are discussed, and applications of labeled conjugates to the high-resolution microscopic identification of binding sites and characterization of biological macromolecular assemblies are described. In addition to providing insights into their molecular structure and function, high-resolution microscopic methods also show how Nanogold and undecagold conjugates can be synthetically assembled, or self-assemble, into supramolecular materials to which the gold cluster labels impart useful functionality. PMID:20869258

  11. Conjugated organic framework with three-dimensionally ordered stable structure and delocalized π clouds

    NASA Astrophysics Data System (ADS)

    Guo, Jia; Xu, Yanhong; Jin, Shangbin; Chen, Long; Kaji, Toshihiko; Honsho, Yoshihito; Addicoat, Matthew A.; Kim, Jangbae; Saeki, Akinori; Ihee, Hyotcherl; Seki, Shu; Irle, Stephan; Hiramoto, Masahiro; Gao, Jia; Jiang, Donglin

    2013-11-01

    Covalent organic frameworks are a class of crystalline organic porous materials that can utilize π-π-stacking interactions as a driving force for the crystallization of polygonal sheets to form layered frameworks and ordered pores. However, typical examples are chemically unstable and lack intrasheet π-conjugation, thereby significantly limiting their applications. Here we report a chemically stable, electronically conjugated organic framework with topologically designed wire frameworks and open nanochannels, in which the π conjugation-spans the two-dimensional sheets. Our framework permits inborn periodic ordering of conjugated chains in all three dimensions and exhibits a striking combination of properties: chemical stability, extended π-delocalization, ability to host guest molecules and hole mobility. We show that the π-conjugated organic framework is useful for high on-off ratio photoswitches and photovoltaic cells. Therefore, this strategy may constitute a step towards realizing ordered semiconducting porous materials for innovations based on two-dimensionally extended π systems.

  12. Conformational Assessment of Adnectin and Adnectin-Drug Conjugate by Hydrogen/Deuterium Exchange Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Huang, Richard Y.-C.; O'Neil, Steven R.; Lipovšek, Daša; Chen, Guodong

    2018-05-01

    Higher-order structure (HOS) characterization of therapeutic protein-drug conjugates for comprehensive assessment of conjugation-induced protein conformational changes is an important consideration in the biopharmaceutical industry to ensure proper behavior of protein therapeutics. In this study, conformational dynamics of a small therapeutic protein, adnectin 1, together with its drug conjugate were characterized by hydrogen/deuterium exchange mass spectrometry (HDX-MS) with different spatial resolutions. Top-down HDX allows detailed assessment of the residue-level deuterium content in the payload conjugation region. HDX-MS dataset revealed the ability of peptide-based payload/linker to retain deuterium in HDX experiments. Combined results from intact, top-down, and bottom-up HDX indicated no significant conformational changes of adnectin 1 upon payload conjugation. [Figure not available: see fulltext.

  13. Preparation and characterization of conjugated polyamidoamine-MPEG-methotrexate for potential drug delivery system

    NASA Astrophysics Data System (ADS)

    Mohd Sabri, Siti Noorzidah bt; Abu, Norhidayah; Mastor, Azreena; Hisham, Siti Farhana; Noorsal, Kartini

    2012-07-01

    Star polymers have unique characteristics due to their well-defined size and tailor ability which makes these polymers attractive candidates as carriers in drug delivery system applications. This work focuses on attaching a drug to the star polymer (polyamidoamine). The conjugation of polyamidoamine (PAMAM, generation 4) with methotrexate (MTX) (model drug) was studied in which monomethyl polyethylene glycol (MPEG) was used as a linker to reduce the toxicity of dendrimer. Conjugation starts with attaching the drug to the linker and followed by further conjugation with the polyamidoamine (PAMAM) dendrimer. The conjugation of PAMAM-PEG-MTX was confirmed through UV-Vis, FTIR, 1H NMR and DSC. The loading capacities and release profile of this conjugate were determined using 1H NMR and UV spectrometer.

  14. Methods of multi-conjugate adaptive optics for astronomy

    NASA Astrophysics Data System (ADS)

    Flicker, Ralf

    2003-07-01

    This work analyses several aspects of multi-conjugate adaptive optics (MCAO) for astronomy. The research ranges from fundamental and technical studies for present-day MCAO projects, to feasibility studies of high-order MCAO instruments for the extremely large telescopes (ELTs) of the future. The first part is an introductory exposition on atmospheric turbulence, adaptive optics (AO) and MCAO, establishing the framework within which the research was carried out The second part (papers I VI) commences with a fundamental design parameter study of MCAO systems, based upon a first-order performance estimation Monte Carlo simulation. It is investigated how the number and geometry of deformable mirrors and reference beacons, and the choice of wavefront reconstruction algorithm, affect system performance. Multi-conjugation introduces the possibility of optically canceling scintillation in part, at the expense of additional optics, by applying the phase correction in a certain sequence. The effects of scintillation when this sequence is not observed are investigated. As a link in characterizing anisoplanatism in conventional AO systems, images made with the AO instrument Hokupa'a on the Gemini-North Telescope were analysed with respect to the anisoplanatism signal. By model-fitting of simulated data, conclusions could be drawn about the vertical distribution of turbulence above the observatory site (Mauna Kea), and the significance to future AO and MCAO instruments with conjugated deformable mirrors is addressed. The problem of tilt anisoplanatism with MCAO systems relying on artificial reference beacons—laser guide stars (LGSs)—is analysed, and analytical models for predicting the effects of tilt anisoplanatism are devised. A method is presented for real-time retrieval of the tilt anisoplanatism point spread function (PSF), using control loop data. An independent PSF estimation of high accuracy is thus obtained which enables accurate PSF photometry and deconvolution

  15. Hydride affinities of cumulated, isolated, and conjugated dienes in acetonitrile.

    PubMed

    Zhu, Xiao-Qing; Liang, Hao; Zhu, Yan; Cheng, Jin-Pei

    2008-11-07

    The hydride affinities (defined as the enthalpy changes in this work) of 15 polarized dienes [five phenyl sulfone substituted allenes (1a), the corresponding five isolated dienes (1b), and the corresponding five conjugated dienes (1c)] in acetonitrile solution were determined by titration calorimetry for the first time. The results display that the hydride affinity scales of the 15 dienes in acetonitrile range from -71.6 to -73.9 kcal/mol for 1a, from -46.2 to -49.7 kcal/mol for 1b, and from -45.0 to -46.5 kcal/mol for 1c, which indicates that the hydride-obtaining abilities of the cumulated dienes (1a) are not only much larger than those of the corresponding conjugated dienes (1c) but also much larger than those of the corresponding isolated dienes (1b). The hydrogen affinities of the 15 dienes as well as the hydrogen affinities and the proton affinities of the radical anions of the dienes (1(-*)) in acetonitrile were also evaluated by using relative thermodynamic cycles according to Hess's law. The results show that (i) the hydrogen affinities of the neutral dienes 1 cover a range from -44.5 to -45.6 kcal/mol for 1a, from -20.4 to -21.4 kcal/mol for 1b, and from -17.3 to -18.5 kcal/mol for 1c; (ii) the hydrogen affinities of the radical anions of the dienes (1(-*)) in acetonitrile cover a range from -40.6 to -47.2 kcal/mol for 1a(-*), from -21.6 to -29.6 kcal/mol for 1b(-*), and from -10.0 to -15.4 kcal/mol for 1c(-*); (iii) the proton affinities of the 15 1a(-*) in acetonitrile cover a range from -97.0 to -100.6 kcal/mol for 1a(-*), from -77.8 to -83.4 kcal/mol for 1b(-*), and from -66.2 to -68.9 kcal/mol for 1c(-*). The main reasons for the great difference between the cumulated dienes and the corresponding isolated and conjugated dienes in the hydride affinity, hydrogen affinity, and proton affinity have been examined. It is evident that these experimental results should be quite valuable to facilitate the elucidation of the origins of the especially high

  16. Theoretical and computational studies of excitons in conjugated polymers

    NASA Astrophysics Data System (ADS)

    Barford, William; Bursill, Robert J.; Smith, Richard W.

    2002-09-01

    We present a theoretical and computational analysis of excitons in conjugated polymers. We use a tight-binding model of π-conjugated electrons, with 1/r interactions for large r. In both the weak-coupling limit (defined by W>>U) and the strong-coupling limit (defined by W<conjugated polymers. We make the following conclusions. (1) In the weak-coupling limit the bound states are Mott-Wannier excitons, i.e., conduction-band electrons bound to valence-band holes. Singlet and triplet excitons whose relative wave functions are odd under a reflection of the relative coordinate are degenerate. Thus, the 2 1A+g and 1 3A-g states are degenerate in this limit. (2) In the strong-coupling limit the bound states are Mott-Hubbard excitons, i.e., particles in the upper Hubbard band bound to holes in the lower Hubbard band. These bound states occur in doublets of even and odd parity excitons. Triplet excitons are magnons bound to the singlet excitons, and hence are degenerate with their singlet counterparts. (3) In the intermediate-coupling regime Mott-Wannier excitons are the more appropriate description for large dimerization, while for the undimerized chain Mott-Hubbard excitons are the correct description. For dimerizations relevant to polyacetylene and polydiacetylene both Mott-Hubbard and Mott-Wannier excitons are present. (4) For all coupling strengths an infinite number of bound states exist for 1/r interactions for an infinite polymer. As a result of the discreteness of the lattice and the restrictions on the exciton wave functions in one dimension, the progression of states does not follow

  17. Process development of a FGF21 protein-antibody conjugate.

    PubMed

    Dirksen, Anouk; Davis, Keith A; Collins, Joe T; Bhattacharya, Keshab; Finneman, Jari I; Pepin, Erin L; Ryczek, Jeffrey S; Brown, Paul W; Wellborn, William B; Mangalathillam, Ratish; Evans, Brad P; Pozzo, Mark J; Finn, Rory F

    2017-09-26

    A scalable, viable process was developed for the Fibroblast Growth Factor 21 (FGF21) protein-antibody conjugate, CVX-343, an extended half-life therapeutic for the treatment of metabolic disease. CVX-343 utilizes the CovX antibody scaffold technology platform that was specifically developed for peptide and protein half-life extension. CVX-343 is representative of a growing number of complex novel peptide- and protein-based bioconjugate molecules currently being explored as therapeutic candidates. The complexity of these bioconjugates, assembled using well-established chemistries, can lead to very difficult production schemes requiring multiple starting materials and a combination of diverse technologies. Key improvements had to be made to the original CVX-343 Phase 1 manufacturing process in preparation for Phase 3 and commercial manufacturing. A strategy of minimizing FGF21 A129C dimerization and stabilizing the FGF21 A129C Drug Substance Intermediate (DSI), linker, and activated FGF21 intermediate was pursued. The use of tris(2-carboxyethyl)phosphine (TCEP) to prevent FGF21 A129C dimerization through disulfide formation was eliminated. FGF21 A129C dimerization and linker hydrolysis were minimized by formulating and activating FGF21 A129C at acidic instead of neutral pH. An activation use test was utilized to guide FGF21 A129C pooling in order to minimize misfolds, dimers, and misfolded dimers in the FGF21 A129C DSI. After final optimization of reaction conditions, a process was established that reduced the consumption of FGF21 A129C by 36% (from 4.7 to 3.0 equivalents) and the consumption of linker by 55% (from 1.4 to 0.95 equivalents for a smaller required amount of FGF21 A129C ). The overall process time was reduced from ∼5 to ∼3 days. The product distribution improved from containing ∼60% to ∼75% desired bifunctionalized (+2 FGF21) FGF21-antibody conjugate in the crude conjugation mixture and from ∼80% to ∼85% in the final CVX-343 Drug Substance

  18. Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel

    PubMed Central

    2013-01-01

    Background Poly lactic-co-glycolic acid (PLGA) based nanoparticles are considered to be a promising drug carrier in tumor targeting but suffer from the high level of opsonization by reticuloendothelial system due to their hydrophobic structure. As a result surface modification of these nanoparticles has been widely studied as an essential step in their development. Among various surface modifications, human serum albumin (HSA) possesses advantages including small size, hydrophilic surface and accumulation in leaky vasculature of tumors through passive targeting and a probable active transport into tumor tissues. Methods PLGA nanoparticles of docetaxel were prepared by emulsification evaporation method and were surface conjugated with human serum albumin. Fourier transform infrared spectrum was used to confirm the conjugation reaction where nuclear magnetic resonance was utilized for conjugation ratio determination. In addition, transmission electron microscopy showed two different contrast media in conjugated nanoparticles. Furthermore, cytotoxicity of free docetaxel, unconjugated and conjugated PLGA nanoparticles was studied in HepG2 cells. Results Size, zeta potential and drug loading of PLGA nanoparticles were about 199 nm, −11.07 mV, and 4%, respectively where size, zeta potential and drug loading of conjugated nanoparticles were found to be 204 nm, −5.6 mV and 3.6% respectively. Conjugated nanoparticles represented a three-phasic release pattern with a 20% burst effect for docetaxel on the first day. Cytotoxicity experiment showed that the IC50 of HSA conjugated PLGA nanoparticles (5.4 μg) was significantly lower than both free docetaxel (20.2 μg) and unconjugated PLGA nanoparticles (6.2 μg). Conclusion In conclusion surface modification of PLGA nanoparticles through HSA conjugation results in more cytotoxicity against tumor cell lines compared with free docetaxel and unconjugated PLGA nanoparticles. Albumin conjugated PLGA nanoparticles may

  19. Synthesis and evaluation of the antioxidative potential of minoxidil-polyamine conjugates.

    PubMed

    Hadjipavlou-Litina, Dimitra; Magoulas, George E; Bariamis, Stavros E; Tsimali, Zinovia; Avgoustakis, Konstantinos; Kontogiorgis, Christos A; Athanassopoulos, Constantinos M; Papaioannou, Dionissios

    2013-07-01

    A series of conjugates (MNX-CO-PA) of minoxidil (MNX) with the polyamines (PAs) putrescine (PUT), spermidine (SPD) and spermine (SPM) as well as dopamine were produced through activation of MNX with N,N'-carbonyldiimidazole, followed by reaction with dopamine or selectively protected PAs and acid-mediated deprotection. These conjugates together with conjugates of the general type MNX-PA or PA-MNX-PA, readily produced using literature protocols, were tested as antioxidants. The most potent inhibitors of lipid peroxidation were the conjugates MNX-SPM (2, 94%), SPM-MNX-SPM (4, 94%) and MNX-N(4)-SPD (7, 91%) and MNX (91%). The most powerful lipoxygenase (LOX) inhibitors were MNX (IC50 = 20 μM) and the conjugates MNX-N(8)-SPD (9, IC50 = 22.1 μM), MNX-CO-dopamine (11, IC50 = 28 μM) and MNX-N(1)-SPD (8, IC50 = 30 μM). The most interesting conjugates 2, MNX-CO-PUT (5), 8 and 11 as well as MNX were generally found to exhibit weaker (22-36.5%) or no (conjugate 8) anti-inflammatory activity than indomethacin (47%) with the exception of MNX which showed almost equal potency (49%) to indomethacin. The cytocompatibility of conjugates and MNX at the highest concentration of 100 μM showed a survival percentage of 87-107%, with the exception of conjugates with SPM (compound 2) and MNX-CO-SPM (6), which showed considerable cytotoxicity (survival percentage 8-14%). Molecular docking studies were carried on conjugate 9 and the parent compound MNX and were found to be in accordance with our experimental biological results. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  20. Differences between the endocytosis of horseradish peroxidase and its conjugate with wheat germ agglutinin by cultured fibroblasts.

    PubMed

    Stieber, A; Gonatas, J O; Gonatas, N K

    1984-04-01

    A covalent conjugate of wheat germ agglutinin (WGA) with horseradish peroxidase (HRP) was used for a morphologic study of its adsorptive endocytosis by cultured human fibroblasts. Initial binding at 4 degrees C of the conjugate was observed over the entire plasma membrane, including "coated" and smooth pits. Endocytosis of HRP and the WGA-HRP conjugate was observed in lysosomes, but only the conjugate was seen in a cisterna of the Golgi apparatus (GERL), and in adjacent coated vesicles.

  1. Improved Conjugate Gradient Bundle Adjustment of Dunhuang Wall Painting Images

    NASA Astrophysics Data System (ADS)

    Hu, K.; Huang, X.; You, H.

    2017-09-01

    Bundle adjustment with additional parameters is identified as a critical step for precise orthoimage generation and 3D reconstruction of Dunhuang wall paintings. Due to the introduction of self-calibration parameters and quasi-planar constraints, the structure of coefficient matrix of the reduced normal equation is banded-bordered, making the solving process of bundle adjustment complex. In this paper, Conjugate Gradient Bundle Adjustment (CGBA) method is deduced by calculus of variations. A preconditioning method based on improved incomplete Cholesky factorization is adopt to reduce the condition number of coefficient matrix, as well as to accelerate the iteration rate of CGBA. Both theoretical analysis and experimental results comparison with conventional method indicate that, the proposed method can effectively conquer the ill-conditioned problem of normal equation and improve the calculation efficiency of bundle adjustment with additional parameters considerably, while maintaining the actual accuracy.

  2. Polyglycerol-opioid conjugate produces analgesia devoid of side effects.

    PubMed

    González-Rodríguez, Sara; Quadir, Mohiuddin A; Gupta, Shilpi; Walker, Karolina A; Zhang, Xuejiao; Spahn, Viola; Labuz, Dominika; Rodriguez-Gaztelumendi, Antonio; Schmelz, Martin; Joseph, Jan; Parr, Maria K; Machelska, Halina; Haag, Rainer; Stein, Christoph

    2017-07-04

    Novel painkillers are urgently needed. The activation of opioid receptors in peripheral inflamed tissue can reduce pain without central adverse effects such as sedation, apnoea, or addiction. Here, we use an unprecedented strategy and report the synthesis and analgesic efficacy of the standard opioid morphine covalently attached to hyperbranched polyglycerol (PG-M) by a cleavable linker. With its high-molecular weight and hydrophilicity, this conjugate is designed to selectively release morphine in injured tissue and to prevent blood-brain barrier permeation. In contrast to conventional morphine, intravenous PG-M exclusively activated peripheral opioid receptors to produce analgesia in inflamed rat paws without major side effects such as sedation or constipation. Concentrations of morphine in the brain, blood, paw tissue, and in vitro confirmed the selective release of morphine in the inflamed milieu. Thus, PG-M may serve as prototype of a peripherally restricted opioid formulation designed to forego central and intestinal side effects.

  3. Stabilization of penicillinase-hapten conjugate for enzyme immunoassay.

    PubMed

    Omidfar, K; Rasaee, Mohammad J; Zaraee, Ali B; Amir, M Pour; Rahbarizadeh, F

    2002-01-01

    The influence of various additives, such as organic solvents, polyhydric alcohols, salts, polymers, and cross-linker, on the stability and storage ability of penicillinase-morphine conjugate was studied in liquid and solid (freeze dried) states. The results of these experiments showed that using low concentrations of CaCl2 (0.1-0.2%) could stabilize enzyme activity in both states for more than seven months. The immunoreactivity of antigen toward the antibody did not change significantly. However, a cross-linker such as glutaraldehyde and various additives such as dimethylsulfoxide, glycerol, polyethylene glycol, gelatin, dextran, ammonium sulfate, lactose, and sucrose did not have any effect on stability. In addition, it was found that the presence of lactose and sucrose in the lyophilization procedure gives a significant amount of protection to the enzyme, which could last for a period of seven months and preserve almost 95% of the enzyme activity, as well as immunoreactivity of the tracer molecule.

  4. Silica passivated conjugated polymer nanoparticles for biological imaging applications

    NASA Astrophysics Data System (ADS)

    Bourke, Struan; Urbano, Laura; Olona, Antoni; Valderrama, Ferran; Dailey, Lea Ann; Green, Mark A.

    2017-02-01

    Colorectal and prostate cancers are major causes of cancer-related death, with early detection key to increased survival. However, as symptoms occur during advanced stages and current diagnostic methods have limitations, there is a need for new fluorescent probes that remain bright, are biocompatible and can be targeted. Conjugated polymer nanoparticles have shown great promise in biological imaging due to their unique optical properties. We have synthesised small, bright, photo-stable CN-PPV, nanoparticles encapsulated with poloxamer polymer and a thin silica shell. By incubating the CN-PPV silica shelled cross-linked (SSCL) nanoparticles in mammalian (HeLa) cells; we were able to show that cellular uptake occurred. Uptake was also shown by incubating the nanoparticles in RWPE-1, WPE1-NB26 and WPE1- NA22 prostate cancer cell lines. Finally, HEK cells were used to show the particles had limited cytotoxicity.

  5. Cationic lipid-conjugated hydrocortisone as selective antitumor agent.

    PubMed

    Rathore, Bhowmira; Chandra Sekhar Jaggarapu, Madhan Mohan; Ganguly, Anirban; Reddy Rachamalla, Hari Krishna; Banerjee, Rajkumar

    2016-01-27

    Hydrocortisone, the endogenously expressed steroidal, hormonal ligand for glucocorticoid receptor (GR), is body's natural anti-inflammatory and xenobiotic metabolizing agent. It has both palliative as well as adverse effects in different cancer patients. Herein, we show that conjugation product of C16-carbon chain-associated cationic lipid and hydrocortisone (namely, HYC16) induces selective toxicity in cancer (e.g. melanoma, breast cancer and lung adenocarcinoma) cells with least toxicity in normal cells, through induction of apoptosis and cell cycle arrest at G2/M phase. Further, significant tumor growth inhibition was observed in syngeneic melanoma tumor model with considerable induction of apoptosis in tumor-associated cells. In contrast to hydrocortisone, significantly higher anti-angiogenic behavior of HYC16 helped in effective tumor shrinkage. This is the first demonstration to convert natural hormone hydrocortisone into a selective bioactive entity possessing anti-tumor effect. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. Heterocyclic Drug-polymer Conjugates for Cancer Targeted Drug Delivery.

    PubMed

    Kaur, Harmeet; Desai, Sapna D; Kumar, Virender; Rathi, Pooja; Singh, Jasbir

    2016-01-01

    New polymer therapeutics like polymer-drug conjugates (PDCs) are developing day by day. Heterocyclic drugs with excellent cytotoxic properties are available, but lack of their specificity makes them available to the normal cells also, which is the main cause of their toxicity. Drugs in the form of PDCs make delivery possible to the specific sites. Most of the PDCs are designed with the aim to either target and/or to get activated in specific cancer microenvironments. Therefore, the most exploited targets for cancer drug delivery are; cancer cell enzymes, heat shock protein 90 (HSP90), multi-drug resistance (MDR) proteins, angiogenesis, apoptosis and cell membrane receptors (e.g., folates, transferrin, etc.). In this review, we will summarize PDCs of heterocyclic drugs, like doxorubicin (DOX), daunorubicin, paclitaxel (PTX), docetaxel (DTX), cisplatin, camptothecin (CPT), geldanamycin (GDM), etc., and some of their analogs for efficient delivery of drugs to cancer cells.

  7. Peptide and protein nanoparticle conjugates: versatile platforms for biomedical applications.

    PubMed

    Spicer, Christopher D; Jumeaux, Coline; Gupta, Bakul; Stevens, Molly M

    2018-05-21

    Peptide- and protein-nanoparticle conjugates have emerged as powerful tools for biomedical applications, enabling the treatment, diagnosis, and prevention of disease. In this review, we focus on the key roles played by peptides and proteins in improving, controlling, and defining the performance of nanotechnologies. Within this framework, we provide a comprehensive overview of the key sequences and structures utilised to provide biological and physical stability to nano-constructs, direct particles to their target and influence their cellular and tissue distribution, induce and control biological responses, and form polypeptide self-assembled nanoparticles. In doing so, we highlight the great advances made by the field, as well as the challenges still faced in achieving the clinical translation of peptide- and protein-functionalised nano-drug delivery vehicles, imaging species, and active therapeutics.

  8. Sustained gastrointestinal activity of dendronized polymer-enzyme conjugates

    NASA Astrophysics Data System (ADS)

    Fuhrmann, Gregor; Grotzky, Andrea; Lukić, Ružica; Matoori, Simon; Luciani, Paola; Yu, Hao; Zhang, Baozhong; Walde, Peter; Schlüter, A. Dieter; Gauthier, Marc A.; Leroux, Jean-Christophe

    2013-07-01

    Methods to stabilize and retain enzyme activity in the gastrointestinal tract are investigated rarely because of the difficulty of protecting proteins from an environment that has evolved to promote their digestion. Preventing the degradation of enzymes under these conditions, however, is critical for the development of new protein-based oral therapies. Here we show that covalent conjugation to polymers can stabilize orally administered therapeutic enzymes at different locations in the gastrointestinal tract. Architecturally and functionally diverse polymers are used to protect enzymes sterically from inactivation and to promote interactions with mucin on the stomach wall. Using this approach the in vivo activity of enzymes can be sustained for several hours in the stomach and/or in the small intestine. These findings provide new insight and a firm basis for the development of new therapeutic and imaging strategies based on orally administered proteins using a simple and accessible technology.

  9. Low dose ionizing radiation detection using conjugated polymers

    SciTech Connect

    Silva, E.A.B.; Borin, J.F.; Nicolucci, P.

    2005-03-28

    In this work, the effect of gamma radiation on the optical properties of poly[2-methoxy-5-(2{sup '}-ethylhexyloxy)-p-phenylenevinylene] (MEH-PPV) is studied. The samples were irradiated at room temperature with different doses from 0 Gy to 152 Gy using a {sup 60}Co gamma ray source. For thin films, significant changes in the UV-visible spectra were only observed at high doses (>1 kGy). In solution, shifts in absorption peaks are observed at low doses (<10 Gy), linearly dependent on dose. The shifts are explained by conjugation reduction, and possible causes are discussed. Our results indicate that MEH-PPV solution can be used as a dosimeter adequatemore » for medical applications.« less

  10. Cationic Conjugated Polymers-Induced Quorum Sensing of Bacteria Cells.

    PubMed

    Zhang, Pengbo; Lu, Huan; Chen, Hui; Zhang, Jiangyan; Liu, Libing; Lv, Fengting; Wang, Shu

    2016-03-15

    Bacteria quorum sensing (QS) has attracted significant interest for understanding cell-cell communication and regulating biological functions. In this work, we demonstrate that water-soluble cationic conjugated polymers (PFP-G2) can interact with bacteria to form aggregates through electrostatic interactions. With bacteria coated in the aggregate, PFP-G2 can induce the bacteria QS system and prolong the time duration of QS signal molecules (autoinducer-2 (AI-2)) production. The prolonged AI-2 can bind with specific protein and continuously regulate downstream gene expression. Consequently, the bacteria show a higher survival rate against antibiotics, resulting in decreased antimicrobial susceptibility. Also, AI-2 induced by PFP-G2 can stimulate 55.54 ± 12.03% more biofilm in E. coli. This method can be used to understand cell-cell communication and regulate biological functions, such as the production of signaling molecules, antibiotics, other microbial metabolites, and even virulence.

  11. pH dependent conjugation of Ibuprofen to PEGylated nanoparticles

    NASA Astrophysics Data System (ADS)

    Bharti, Shivani; Jain, Shikshita; Kaur, Gurvir; Gupta, Shikha; Tripathi, S. K.

    2018-04-01

    In this paper, Ibuprofen, a water insoluble drug was covalently attached to PEGylated nanoparticles. Firstly, Surface functionalization of water dispersed core/shell nanoparticles had been done using hydrophilic polymer PEG-diamine. Therefore, PEGylated nanoparticles contain NH2 groups over the surface of nanoparticles and can be used for the further attachment of biomolecules. Ibuprofen was covalently loaded on the PEGylated core/shell nanoparticles using carbodiimide reaction. The synthesis had been carried out under two different pH environments, as the solubility of Ibuprofen is pH dependent. The resultant samples were characterized using UV-Vis absorption and FT-IR spectroscopy. The results strongly suggest the successful chemical conjugation of Ibuprofen to PEGylated nanoparticles in aqueous media and they could be further used for drug delivery applications.

  12. Delocalization Drives Free Charge Generation in Conjugated Polymer Films

    DOE PAGES

    Pace, Natalie A.; Reid, Obadiah G.; Rumbles, Garry

    2018-02-19

    We demonstrate that the product of photoinduced electron transfer between a conjugated polymer host and a dilute molecular sensitizer is controlled by the structural state of the polymer. Ordered semicrystalline solids exhibit free charge generation, while disordered polymers in the melt phase do not. We use photoluminescence (PL) and time-resolved microwave conductivity (TRMC) measurements to sweep through polymer melt transitions in situ. Free charge generation measured by TRMC turns off upon melting, whereas PL quenching of the molecular sensitizers remains constant, implying unchanged electron transfer efficiency. The key difference is the intermolecular order of the polymer host in the solidmore » state compared to the melt. We propose that this order-disorder transition modulates the localization length of the initial charge-transfer state, which controls the probability of free charge formation.« less

  13. Preconditioned conjugate residual methods for the solution of spectral equations

    NASA Technical Reports Server (NTRS)

    Wong, Y. S.; Zang, T. A.; Hussaini, M. Y.

    1986-01-01

    Conjugate residual methods for the solution of spectral equations are described. An inexact finite-difference operator is introduced as a preconditioner in the iterative procedures. Application of these techniques is limited to problems for which the symmetric part of the coefficient matrix is positive definite. Although the spectral equation is a very ill-conditioned and full matrix problem, the computational effort of the present iterative methods for solving such a system is comparable to that for the sparse matrix equations obtained from the application of either finite-difference or finite-element methods to the same problems. Numerical experiments are shown for a self-adjoint elliptic partial differential equation with Dirichlet boundary conditions, and comparison with other solution procedures for spectral equations is presented.

  14. Aerodynamic shape optimization using preconditioned conjugate gradient methods

    NASA Technical Reports Server (NTRS)

    Burgreen, Greg W.; Baysal, Oktay

    1993-01-01

    In an effort to further improve upon the latest advancements made in aerodynamic shape optimization procedures, a systematic study is performed to examine several current solution methodologies as applied to various aspects of the optimization procedure. It is demonstrated that preconditioned conjugate gradient-like methodologies dramatically decrease the computational efforts required for such procedures. The design problem investigated is the shape optimization of the upper and lower surfaces of an initially symmetric (NACA-012) airfoil in inviscid transonic flow and at zero degree angle-of-attack. The complete surface shape is represented using a Bezier-Bernstein polynomial. The present optimization method then automatically obtains supercritical airfoil shapes over a variety of freestream Mach numbers. Furthermore, the best optimization strategy examined resulted in a factor of 8 decrease in computational time as well as a factor of 4 decrease in memory over the most efficient strategies in current use.

  15. Conjugated Polymer Zwitterions: Efficient Interlayer Materials in Organic Electronics.

    PubMed

    Liu, Yao; Duzhko, Volodimyr V; Page, Zachariah A; Emrick, Todd; Russell, Thomas P

    2016-11-15

    Conjugated polymer zwitterions (CPZs) are neutral, hydrophilic, polymer semiconductors. The pendent zwitterions, viewed as side chain dipoles, impart solubility in polar solvents for solution processing, and open opportunities as interfacial components of optoelectronic devices, for example, between metal electrodes and organic semiconductor active layers. Such interlayers are crucial for defining the performance of organic electronic devices, e.g., field-effect transistors (OFETs), light-emitting diodes (OLEDs), and photovoltaics (OPVs), all of which consist of multilayer structures. The interlayers reduce the Schottky barrier height and thus improve charge injection in OFETs and OLEDs. In OPVs, the interlayers serve to increase the built-in electric potential difference (V bi ) across the active layer, ensuring efficient extraction of photogenerated charge carriers. In general, polar and even charged electronically active polymers have gained recognition for their ability to modify metal/semiconductor interfaces to the benefit of organic electronics. While conjugated polyelectrolytes (CPEs) as interlayer materials are well-documented, open questions remain about the role of mobile counterions in CPE-containing devices. CPZs possess the processing advantages of CPEs, but as neutral molecules lack any potential complications associated with counterions. The electronic implications of CPZs on metal electrodes stem from the orientation of the zwitterion dipole moment in close proximity to the metal surface, and the resultant surface-induced polarization. This generates an interfacial dipole (Δ) at the CPZ/metal interface, altering the work function of the electrode, as confirmed by ultraviolet photoelectron spectroscopy (UPS), and improving device performance. An ideal cathode interlayer would reduce electrode work function, have orthogonal processability to the active layer, exhibit good film forming properties (i.e., wettability/uniformity), prevent exciton

  16. Phase transition in conjugated oligomers suspended in chloroform

    NASA Astrophysics Data System (ADS)

    Dwivedi, Shikha; Kumar, Anupam; Yadav, S. N. S.; Mishra, Pankaj

    2015-08-01

    Density functional theory (DFT) has been used to investigate the isotropic-nematic (I-N) phase transition in a system of high aspect ratio conjugated oligomers suspended in chloroform. The interaction between the oligomers is modeled using Gay-Berne potential in which effect of solvent is implicit. Percus-Yevick integral equation theory has been used to evaluate the pair correlation functions of the fluid phase at several temperatures and densities. These pair correlation function has been used in the DFT to evaluate the I-N freezing parameters. Highly oriented nematic is found to stabilize at low density. The results obtained are in qualitative agreement with the simulation and are verifiable.

  17. Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites

    PubMed Central

    Jarrad, Angie M.; Karoli, Tomislav; Debnath, Anjan; Tay, Chin Yen; Huang, Johnny X.; Kaeslin, Geraldine; Elliott, Alysha G.; Miyamoto, Yukiko; Ramu, Soumya; Kavanagh, Angela M.; Zuegg, Johannes; Eckmann, Lars; Blaskovich, Mark A.T.; Cooper, Matthew A.

    2015-01-01

    Metronidazole has been used clinically for over 50 years as an antiparasitic and broad-spectrum antibacterial agent effective against anaerobic bacteria. However resistance to metronidazole in parasites and bacteria has been reported, and improved second-generation metronidazole analogues are needed. The copper catalysed Huigsen azide-alkyne 1,3-dipolar cycloaddition offers a way to efficiently assemble new libraries of metronidazole analogues. Several new metronidazole-triazole conjugates (Mtz-triazoles) have been identified with excellent broad spectrum antimicrobial and antiparasitic activity targeting Clostridium difficile, Entamoeba histolytica and Giardia lamblia. Cross resistance to metronidazole was observed against stable metronidazole resistant C. difficile and G. lamblia strains. However for the most potent Mtz-triazoles, the activity remained in a therapeutically relevant window. PMID:26117821

  18. Elastic Organic Crystals of a Fluorescent π-Conjugated Molecule.

    PubMed

    Hayashi, Shotaro; Koizumi, Toshio

    2016-02-18

    An elastic organic crystal of a π-conjugated molecule has been fabricated. A large fluorescent single crystal of 1,4-bis[2-(4-methylthienyl)]-2,3,5,6-tetrafluorobenzene (over 1 cm long) exhibited a fibril lamella morphology based on slip-stacked molecular wires, and it was found to be a remarkably elastic crystalline material. The straight crystal was capable of bending more than 180° under applied stress and then quickly reverted to its original shape upon relaxation. In addition, the fluorescence quantum yield of the crystal was about twice that of the compound in THF solution. Mechanical bending-relaxation resulted in reversible change of the morphology and fluorescence. This research offers a more general approach to flexible crystals as a promising new family of organic semiconducting materials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Monolignol ferulate conjugates are naturally incorporated into plant lignins

    PubMed Central

    Karlen, Steven D.; Zhang, Chengcheng; Peck, Matthew L.; Smith, Rebecca A.; Padmakshan, Dharshana; Helmich, Kate E.; Free, Heather C. A.; Lee, Seonghee; Smith, Bronwen G.; Lu, Fachuang; Sedbrook, John C.; Sibout, Richard; Grabber, John H.; Runge, Troy M.; Mysore, Kirankumar S.; Harris, Philip J.; Bartley, Laura E.; Ralph, John

    2016-01-01

    Angiosperms represent most of the terrestrial plants and are the primary research focus for the conversion of biomass to liquid fuels and coproducts. Lignin limits our access to fibers and represents a large fraction of the chemical energy stored in plant cell walls. Recently, the incorporation of monolignol ferulates into lignin polymers was accomplished via the engineering of an exotic transferase into commercially relevant poplar. We report that various angiosperm species might have convergently evolved to natively produce lignins that incorporate monolignol ferulate conjugates. We show that this activity may be accomplished by a BAHD feruloyl–coenzyme A monolignol transferase, OsFMT1 (AT5), in rice and its orthologs in other monocots. PMID:27757415

  20. Monolayers and multilayers of conjugated polymers as nanosized electronic components.

    PubMed

    Zotti, Gianni; Vercelli, Barbara; Berlin, Anna

    2008-09-01

    Conjugated polymers (CPs) are interesting materials for preparing devices based on nanoscopic molecular architectures because they exhibit electrical, electronic, magnetic, and optical properties similar to those of metals or semiconductors while maintaining the flexibility and ease of processing of polymers. The production of well-defined mono- and multilayers of CPs on electrodes with nanometer-scale, one-dimensional resolution remains, however, an important challenge. In this Account, we describe the preparation and conductive properties of nanometer-sized CP molecular structures formed on electrode surfaces--namely, self-assembled monolayer (SAM), brush-type, and self-assembled multilayer CPs--and in combination with gold nanoparticles (AuNPs). We have electrochemically polymerized SAMs of carboxyalkyl-functionalized terthiophenes aligned either perpendicular or parallel to the electrode surface. Anodic coupling of various pyrrole- and thiophene-based monomers in solution with the oligothiophene-based SAMs produced brush-like films. Microcontact printing of these SAMs produced patterns that, after heterocoupling, exhibited large height enhancements, as measured using atomic force microscopy (AFM). We have employed layer-by-layer self-assembly of water-soluble polythiophene-based polyelectrolytes to form self-assembled multilayers. The combination of isostructural polycationic and polyanionic polythiophenes produced layers of chains aligned parallel to the substrate plane. These stable, robust, and dense layers formed with high regularity on the preformed monolayers, with minimal interchain penetration. Infrared reflection/adsorption spectroscopy and X-ray diffraction analyses revealed unprecedented degrees of order. Deposition of soluble polypyrroles produced molecular layers that, when analyzed using a gold-coated AFM tip, formed gold-polymer-gold junctions that were either ohmic or rectifying, depending of the layer sequence. We also describe the electronic

  1. Delocalization Drives Free Charge Generation in Conjugated Polymer Films

    SciTech Connect

    Pace, Natalie A.; Reid, Obadiah G.; Rumbles, Garry

    We demonstrate that the product of photoinduced electron transfer between a conjugated polymer host and a dilute molecular sensitizer is controlled by the structural state of the polymer. Ordered semicrystalline solids exhibit free charge generation, while disordered polymers in the melt phase do not. We use photoluminescence (PL) and time-resolved microwave conductivity (TRMC) measurements to sweep through polymer melt transitions in situ. Free charge generation measured by TRMC turns off upon melting, whereas PL quenching of the molecular sensitizers remains constant, implying unchanged electron transfer efficiency. The key difference is the intermolecular order of the polymer host in the solidmore » state compared to the melt. We propose that this order-disorder transition modulates the localization length of the initial charge-transfer state, which controls the probability of free charge formation.« less

  2. Conference report: hot topics in antibody-drug conjugate development.

    PubMed

    Thudium, Karen; Bilic, Sanela

    2013-12-01

    American Association of Pharmaceutical Scientists National Biotechnology Conference Sheraton San Diego Hotel and Marina, San Diego, CA, USA, 19-23 May 2013 The National Biotechnology Conference, is a premier meeting for biotechnology professionals covering a broad range of hot topics in the biotechnology industry. Attracting participants from academia, industry and regulatory, this meeting features sessions that aim to address emerging subjects of interest and allows for open exchange between scientists. The 2013 conference featured leading researchers in the fields of antibody-drug conjugates (ADCs) and immunogenicity. Herein, we present a summary of the ADC hot topics, including bioanalytical and PK considerations, quantitative evaluation of the impact of immunogenicity and ADME to understand ADC drug-drug interactions, and clinical considerations for ADC development. This article aims to summarize the recommendations that were made by the speakers during various sessions throughout the conference.

  3. Navigating conjugated polymer actuated neural probes in a brain phantom

    NASA Astrophysics Data System (ADS)

    Daneshvar, Eugene D.; Kipke, Daryl; Smela, Elisabeth

    2012-04-01

    Neural probe insertion methods have a direct impact on the longevity of the device in the brain. Initial tissue and vascular damage caused by the probe entering the brain triggers a chronic tissue response that is known to attenuate neural recordings and ultimately encapsulate the probes. Smaller devices have been found to evoke reduced inflammatory response. One way to record from undamaged neural networks may be to position the electrode sites away from the probe. To investigate this approach, we are developing probes with controllably movable electrode projections, which would move outside of the zone that is damaged by the insertion of the larger probe. The objective of this study was to test the capability of conjugated polymer bilayer actuators to actuate neural electrode projections from a probe shank into a transparent brain phantom. Parylene neural probe devices, having five electrode projections with actuating segments and with varying widths (50 - 250 μm) and lengths (200 - 1000 μm) were fabricated. The electroactive polymer polypyrrole (PPy) was used to bend or flatten the projections. The devices were inserted into the brain phantom using an electronic microdrive while simultaneously activating the actuators. Deflections were quantified based on video images. The electrode projections were successfully controlled to either remain flat or to actuate out-of-plane and into the brain phantom during insertion. The projection width had a significant effect on their ability to deflect within the phantom, with thinner probes deflecting but not the wider ones. Thus, small integrated conjugated polymer actuators may enable multiple neuro-experiments and applications not possible before.

  4. Governing equations for electro-conjugate fluid flow

    NASA Astrophysics Data System (ADS)

    Hosoda, K.; Takemura, K.; Fukagata, K.; Yokota, S.; Edamura, K.

    2013-12-01

    An electro-conjugation fluid (ECF) is a kind of dielectric liquid, which generates a powerful flow when high DC voltage is applied with tiny electrodes. This study deals with the derivation of the governing equations for electro-conjugate fluid flow based on the Korteweg-Helmholtz (KH) equation which represents the force in dielectric liquid subjected to high DC voltage. The governing equations consist of the Gauss's law, charge conservation with charge recombination, the KH equation, the continuity equation and the incompressible Navier-Stokes equations. The KH equation consists of coulomb force, dielectric constant gradient force and electrostriction force. The governing equation gives the distribution of electric field, charge density and flow velocity. In this study, direct numerical simulation (DNS) is used in order to get these distribution at arbitrary time. Successive over-relaxation (SOR) method is used in analyzing Gauss's law and constrained interpolation pseudo-particle (CIP) method is used in analyzing charge conservation with charge recombination. The third order Runge-Kutta method and conservative second-order-accurate finite difference method is used in analyzing the Navier-Stokes equations with the KH equation. This study also deals with the measurement of ECF ow generated with a symmetrical pole electrodes pair which are made of 0.3 mm diameter piano wire. Working fluid is FF-1EHA2 which is an ECF family. The flow is observed from the both electrodes, i.e., the flow collides in between the electrodes. The governing equation successfully calculates mean flow velocity in between the collector pole electrode and the colliding region by the numerical simulation.

  5. An overview of NSPCG: A nonsymmetric preconditioned conjugate gradient package

    NASA Astrophysics Data System (ADS)

    Oppe, Thomas C.; Joubert, Wayne D.; Kincaid, David R.

    1989-05-01

    The most recent research-oriented software package developed as part of the ITPACK Project is called "NSPCG" since it contains many nonsymmetric preconditioned conjugate gradient procedures. It is designed to solve large sparse systems of linear algebraic equations by a variety of different iterative methods. One of the main purposes for the development of the package is to provide a common modular structure for research on iterative methods for nonsymmetric matrices. Another purpose for the development of the package is to investigate the suitability of several iterative methods for vector computers. Since the vectorizability of an iterative method depends greatly on the matrix structure, NSPCG allows great flexibility in the operator representation. The coefficient matrix can be passed in one of several different matrix data storage schemes. These sparse data formats allow matrices with a wide range of structures from highly structured ones such as those with all nonzeros along a relatively small number of diagonals to completely unstructured sparse matrices. Alternatively, the package allows the user to call the accelerators directly with user-supplied routines for performing certain matrix operations. In this case, one can use the data format from an application program and not be required to copy the matrix into one of the package formats. This is particularly advantageous when memory space is limited. Some of the basic preconditioners that are available are point methods such as Jacobi, Incomplete LU Decomposition and Symmetric Successive Overrelaxation as well as block and multicolor preconditioners. The user can select from a large collection of accelerators such as Conjugate Gradient (CG), Chebyshev (SI, for semi-iterative), Generalized Minimal Residual (GMRES), Biconjugate Gradient Squared (BCGS) and many others. The package is modular so that almost any accelerator can be used with almost any preconditioner.

  6. Total variation superiorized conjugate gradient method for image reconstruction

    NASA Astrophysics Data System (ADS)

    Zibetti, Marcelo V. W.; Lin, Chuan; Herman, Gabor T.

    2018-03-01

    The conjugate gradient (CG) method is commonly used for the relatively-rapid solution of least squares problems. In image reconstruction, the problem can be ill-posed and also contaminated by noise; due to this, approaches such as regularization should be utilized. Total variation (TV) is a useful regularization penalty, frequently utilized in image reconstruction for generating images with sharp edges. When a non-quadratic norm is selected for regularization, as is the case for TV, then it is no longer possible to use CG. Non-linear CG is an alternative, but it does not share the efficiency that CG shows with least squares and methods such as fast iterative shrinkage-thresholding algorithms (FISTA) are preferred for problems with TV norm. A different approach to including prior information is superiorization. In this paper it is shown that the conjugate gradient method can be superiorized. Five different CG variants are proposed, including preconditioned CG. The CG methods superiorized by the total variation norm are presented and their performance in image reconstruction is demonstrated. It is illustrated that some of the proposed variants of the superiorized CG method can produce reconstructions of superior quality to those produced by FISTA and in less computational time, due to the speed of the original CG for least squares problems. In the Appendix we examine the behavior of one of the superiorized CG methods (we call it S-CG); one of its input parameters is a positive number ɛ. It is proved that, for any given ɛ that is greater than the half-squared-residual for the least squares solution, S-CG terminates in a finite number of steps with an output for which the half-squared-residual is less than or equal to ɛ. Importantly, it is also the case that the output will have a lower value of TV than what would be provided by unsuperiorized CG for the same value ɛ of the half-squared residual.

  7. Understanding Interfacial Alignment in Solution Coated Conjugated Polymer Thin Films

    SciTech Connect

    Qu, Ge; Zhao, Xikang; Newbloom, Gregory M.

    Domain alignment in conjugated polymer thin films can significantly enhance charge carrier mobility. However, the alignment mechanism during meniscus-guided solution coating remains unclear. Furthermore, interfacial alignment has been rarely studied despite its direct relevance and critical importance to charge transport. In this study, we uncover a significantly higher degree of alignment at the top interface of solution coated thin films, using a donor–acceptor conjugated polymer, poly(diketopyrrolopyrrole-co-thiopheneco- thieno[3,2- b]thiophene-co-thiophene) (DPP2T-TT), as the model system. At the molecular level, we observe in-plane π–π stacking anisotropy of up to 4.8 near the top interface with the polymer backbone aligned parallel to the coatingmore » direction. The bulk of the film is only weakly aligned with the backbone oriented transverse to coating. At the mesoscale, we observe a well-defined fibril-like morphology at the top interface with the fibril long axis pointing toward the coating direction. Significantly smaller fibrils with poor orientational order are found on the bottom interface, weakly aligned orthogonal to the fibrils on the top interface. The high degree of alignment at the top interface leads to a charge transport anisotropy of up to 5.4 compared to an anisotropy close to 1 on the bottom interface. We attribute the formation of distinct interfacial morphology to the skin-layer formation associated with high Peclet number, which promotes crystallization on the top interface while suppressing it in the bulk. As a result, we further infer that the interfacial fibril alignment is driven by the extensional flow on the top interface arisen from increasing solvent evaporation rate closer to the meniscus front.« less

  8. Understanding Interfacial Alignment in Solution Coated Conjugated Polymer Thin Films

    DOE PAGES

    Qu, Ge; Zhao, Xikang; Newbloom, Gregory M.; ...

    2017-08-01

    Domain alignment in conjugated polymer thin films can significantly enhance charge carrier mobility. However, the alignment mechanism during meniscus-guided solution coating remains unclear. Furthermore, interfacial alignment has been rarely studied despite its direct relevance and critical importance to charge transport. In this study, we uncover a significantly higher degree of alignment at the top interface of solution coated thin films, using a donor–acceptor conjugated polymer, poly(diketopyrrolopyrrole-co-thiopheneco- thieno[3,2- b]thiophene-co-thiophene) (DPP2T-TT), as the model system. At the molecular level, we observe in-plane π–π stacking anisotropy of up to 4.8 near the top interface with the polymer backbone aligned parallel to the coatingmore » direction. The bulk of the film is only weakly aligned with the backbone oriented transverse to coating. At the mesoscale, we observe a well-defined fibril-like morphology at the top interface with the fibril long axis pointing toward the coating direction. Significantly smaller fibrils with poor orientational order are found on the bottom interface, weakly aligned orthogonal to the fibrils on the top interface. The high degree of alignment at the top interface leads to a charge transport anisotropy of up to 5.4 compared to an anisotropy close to 1 on the bottom interface. We attribute the formation of distinct interfacial morphology to the skin-layer formation associated with high Peclet number, which promotes crystallization on the top interface while suppressing it in the bulk. As a result, we further infer that the interfacial fibril alignment is driven by the extensional flow on the top interface arisen from increasing solvent evaporation rate closer to the meniscus front.« less

  9. Controlling Androgen receptor nuclear localization by dendrimer conjugates

    NASA Astrophysics Data System (ADS)

    Wang, Haoyu

    Androgen Receptor (AR) antagonists, such as bicalutamide and flutamide have been used widely in the treatment of prostate cancer. Although initial treatment is effective, prostate cancer cells often acquire antiandrogen resistance with prolonged treatment. AR over-expression and AR mutations contribute to the development of antiandrogen resistant cancer. Second generation antiandrogens such as enzalutamide are more effective and show reduced AR nuclear localization. In this study, derivatives of PAN52, a small molecule antiandrogen previously developed in our lab, were conjugated to the surface of generation 4 and generation 6 PAMAM dendrimers to obtain antiandrogen PAMAM dendrimer conjugates (APDC). APDCs readily enter cells and associate with AR in the cytoplasm. Due to their large size and positive charge, they can not enter the nucleus, thus retaining AR in the cytoplasm. In addition, APDCs are effective in decreasing AR mediated transcription and cell proliferation. APDC is the first AR antagonists that inhibit DHT-induced nuclear localization of AR. By inhibiting AR nuclear localization, APDC represents a new class of antiandrogens that offer an alternative approach to addressing antiandrogen-resistant prostate cancer. Lysine post-translational modification of AR Nuclear Localization Sequence (NLS) has great impact on AR cellular localization. It is of interest to understand which modifications modulate AR translocation into the nucleus. In this study, we prepared dendrimer-based acetyltransferase mimetic (DATM), DATM is able to catalytically acetylate AR in CWR22Rv1 cells, which will be a useful tool for studying AR modification effect on AR cellular localization. Derivatives of DATM, which transfer other chemical groups to AR, can be prepared similarly, and with more dendrimer based AR modification tools prepared in future, we will be able to understand and control AR cellular localization through AR modification.

  10. Product development studies of amino acid conjugate of Aceclofenac.

    PubMed

    Singh, Ajay Pal; Ramadan, Wafa Mossa; Dahiya, Rajiv; Sarpal, A S; Pathak, Kamla

    2009-04-01

    The prodrugs designed by classical approach increase lipophilicity of the drug, which decreases the water solubility thus decreasing the concentration gradient, which controls drug absorption. To overcome the limitations of traditional prodrug approach, water soluble prodrugs can be designed by adding selected amino acid to the drug moiety that are the substrates for the enzyme located at the intestinal brush border thus overcoming pharmaceutical problem without compromising bioavailability. ACaa (Amino acid conjugate of Aceclofenac) was synthesized by conjugation with l-phenylalanine by conventional coupling method using N, N-dicyclohexylcarbodiimide and ACaa was characterized by melting point, TLC, photomicrograph, UV, FT-IR, FT-NMR, MS-FAB, XRD and DSC. As a part of product development study ACaa was subjected to studies like In-vivo in albino rats and in-vitro like ACaa reversion to AC (Aceclofenac) in aqueous buffers of pH 1.21, 2.38. 3.10, 6.22 and 7.41, at a constant concentration (0.05M), ionic strength (micro = 0.5) and at a temperature of 37 degrees C +/- 0.5 degrees C, ACaa showed negligible reversion (2.15 %) up to 24 hrs study at acidic pH thus suggesting stability in acidic environment of stomach, the rate of reversion increased as pH of medium increased. pH- partition profile, pH- solubility profile and micromeritic studies were also carried out in comparison to pure drug. The solubility and lipophilicity of ACaa exhibited higher values at all pH range when compared to AC. The micromeritic properties also evaluated in terms of particle shape and size, IQCS and kurtosis. Resulting IQCS value approached zero thus suggesting reducing in the degree of skewness.

  11. Lattice Boltzmann formulation for conjugate heat transfer in heterogeneous media.

    PubMed

    Karani, Hamid; Huber, Christian

    2015-02-01

    In this paper, we propose an approach for studying conjugate heat transfer using the lattice Boltzmann method (LBM). The approach is based on reformulating the lattice Boltzmann equation for solving the conservative form of the energy equation. This leads to the appearance of a source term, which introduces the jump conditions at the interface between two phases or components with different thermal properties. The proposed source term formulation conserves conductive and advective heat flux simultaneously, which makes it suitable for modeling conjugate heat transfer in general multiphase or multicomponent systems. The simple implementation of the source term approach avoids any correction of distribution functions neighboring the interface and provides an algorithm that is independent from the topology of the interface. Moreover, our approach is independent of the choice of lattice discretization and can be easily applied to different advection-diffusion LBM solvers. The model is tested against several benchmark problems including steady-state convection-diffusion within two fluid layers with parallel and normal interfaces with respect to the flow direction, unsteady conduction in a three-layer stratified domain, and steady conduction in a two-layer annulus. The LBM results are in excellent agreement with analytical solution. Error analysis shows that our model is first-order accurate in space, but an extension to a second-order scheme is straightforward. We apply our LBM model to heat transfer in a two-component heterogeneous medium with a random microstructure. This example highlights that the method we propose is independent of the topology of interfaces between the different phases and, as such, is ideally suited for complex natural heterogeneous media. We further validate the present LBM formulation with a study of natural convection in a porous enclosure. The results confirm the reliability of the model in simulating complex coupled fluid and thermal dynamics

  12. Polyhedral meshing in numerical analysis of conjugate heat transfer

    NASA Astrophysics Data System (ADS)

    Sosnowski, Marcin; Krzywanski, Jaroslaw; Grabowska, Karolina; Gnatowska, Renata

    2018-06-01

    Computational methods have been widely applied in conjugate heat transfer analysis. The very first and crucial step in such research is the meshing process which consists in dividing the analysed geometry into numerous small control volumes (cells). In Computational Fluid Dynamics (CFD) applications it is desirable to use the hexahedral cells as the resulting mesh is characterized by low numerical diffusion. Unfortunately generating such mesh can be a very time-consuming task and in case of complicated geometry - it may not be possible to generate cells of good quality. Therefore tetrahedral cells have been implemented into commercial pre-processors. Their advantage is the ease of its generation even in case of very complex geometry. On the other hand tetrahedrons cannot be stretched excessively without decreasing the mesh quality factor, so significantly larger number of cells has to be used in comparison to hexahedral mesh in order to achieve a reasonable accuracy. Moreover the numerical diffusion of tetrahedral elements is significantly higher. Therefore the polyhedral cells are proposed within the paper in order to combine the advantages of hexahedrons (low numerical diffusion resulting in accurate solution) and tetrahedrons (rapid semi-automatic generation) as well as to overcome the disadvantages of both the above mentioned mesh types. The major benefit of polyhedral mesh is that each individual cell has many neighbours, so gradients can be well approximated. Polyhedrons are also less sensitive to stretching than tetrahedrons which results in better mesh quality leading to improved numerical stability of the model. In addition, numerical diffusion is reduced due to mass exchange over numerous faces. This leads to a more accurate solution achieved with a lower cell count. Therefore detailed comparison of numerical modelling results concerning conjugate heat transfer using tetrahedral and polyhedral meshes is presented in the paper.

  13. Iron oxide-based conjugates for cancer theragnostics

    NASA Astrophysics Data System (ADS)

    Phuc Nguyen, Xuan; Tran, Dai Lam; Thu Ha, Phuong; Pham, Hong Nam; Trang Mai, Thu; Linh Pham, Hoai; Le, Van Hong; Do, Hung Manh; Bich Hoa Phan, Thi; Giang Pham, Thi Ha; Nguyen, Dac Tu; Nhung Hoang, Thi My; Lam, Khanh; Quy Nguyen, Thi

    2012-09-01

    In this paper we first summarize our recent research on fabrication and structure characterization of conjugates of Fe3O4 nanoparticles (MNPs) encapsulated by several organic materials such as oleic acid (OL), starch (ST), dextran (D), chitosan (CS), O-carboxymethyl chitosan (OCMCS) and the copolymer of poly(styrene-co-acrylic acid (St-co-AA)). The ferrofluids stability and toxicity were also considered. The magnetic inductive heating (MIH) curves were measured using a set up with an alternating (ac) magnetic field of strength of 40-100 Oe and frequency of 180-240 kHz. We then present new results dealing with attempting to apply the MNP/copolymer ferrofluid for treatment of Sarcoma 180 tumor. In vitro as well as ex vivo MIH experiments were carried out as preparation steps in order to estimate the proper conditions for the in vivo MIH experiment. As for the latter, we have successfully carried out the treatment of solid tumor of size around 6 × 6 mm inoculated on Swiss mice with use of a dose of 0.3-0.4 mg ml-1 ferrofluid injected subcutaneously into the tumor and field-irradiated for 30 min. Two groups of treated mice recovered in three weeks from MIH treatment three times during the first week. We finally show that curcumin loaded MNP-based conjugates showed themselves to be a potential agent for application as a bimodal contrast enhancer of magnetic resonance imaging (MRI) and fluorescence imaging. Additionally, in vitro and ex vivo studies by these two techniques evidenced that macrophage is capable of uptake and tends to carry the MNPs into a tumor.

  14. Conjugal properties of the Sinorhizobium meliloti plasmid mobilome.

    PubMed

    Pistorio, Mariano; Giusti, María A; Del Papa, María F; Draghi, Walter O; Lozano, Mauricio J; Tejerizo, Gonzalo Torres; Lagares, Antonio

    2008-09-01

    The biology and biochemistry of plasmid transfer in soil bacteria is currently under active investigation because of its central role in prokaryote adaptation and evolution. In this work, we examined the conjugal properties of the cryptic plasmids present in a collection of the N(2)-fixing legume-symbiont Sinorhizobium meliloti. The study was performed on 65 S. meliloti isolates recovered from 25 humic soils of Argentina, which were grouped into 22 plasmid-profile types [i.e. plasmid operational taxonomic units (OTUs)]. The cumulative Shannon index calculated for the observed plasmid profiles showed a clear saturation plateau, thus indicating an adequate representation of the S. meliloti plasmid-profile types in the isolates studied. The results show that isolates of nearly 14% of the plasmid OTUs hosted transmissible plasmids and that isolates of 29% of the plasmid OTUs were able to retransfer the previously characterized mobilizable-cryptic plasmid pSmeLPU88b to a third recipient strain. It is noteworthy that isolates belonging to 14% of the plasmid OTUs proved to be refractory to the entrance of the model plasmid pSmeLPU88b, suggesting either the presence of surface exclusion phenomena or the occurrence of restriction incompatibility with the incoming replicon. Incompatibility for replication between resident plasmids and plasmid pSmeLPU88b was observed in c. 20% of the OTUs. The results reported here reveal a widespread compatibility among the conjugal functions of the cryptic plasmids in S. meliloti, and this fact, together with the observed high proportion of existing donor genotypes, points to the extrachromosomal compartment of the species as being an extremely active plasmid mobilome.

  15. Dual peptide conjugation strategy for improved cellular uptake and mitochondria targeting.

    PubMed

    Lin, Ran; Zhang, Pengcheng; Cheetham, Andrew G; Walston, Jeremy; Abadir, Peter; Cui, Honggang

    2015-01-21

    Mitochondria are critical regulators of cellular function and survival. Delivery of therapeutic and diagnostic agents into mitochondria is a challenging task in modern pharmacology because the molecule to be delivered needs to first overcome the cell membrane barrier and then be able to actively target the intracellular organelle. Current strategy of conjugating either a cell penetrating peptide (CPP) or a subcellular targeting sequence to the molecule of interest only has limited success. We report here a dual peptide conjugation strategy to achieve effective delivery of a non-membrane-penetrating dye 5-carboxyfluorescein (5-FAM) into mitochondria through the incorporation of both a mitochondrial targeting sequence (MTS) and a CPP into one conjugated molecule. Notably, circular dichroism studies reveal that the combined use of α-helix and PPII-like secondary structures has an unexpected, synergistic contribution to the internalization of the conjugate. Our results suggest that although the use of positively charged MTS peptide allows for improved targeting of mitochondria, with MTS alone it showed poor cellular uptake. With further covalent linkage of the MTS-5-FAM conjugate to a CPP sequence (R8), the dually conjugated molecule was found to show both improved cellular uptake and effective mitochondria targeting. We believe these results offer important insight into the rational design of peptide conjugates for intracellular delivery.

  16. Anticancer activity of drug conjugates in head and neck cancer cells.

    PubMed

    Majumdar, Debatosh; Rahman, Mohammad Aminur; Chen, Zhuo Georgia; Shin, Dong M

    2016-06-01

    Sexually transmitted oral cancer/head and neck cancer is increasing rapidly. Human papilloma virus (HPV) is playing a role in the pathogenesis of a subset of squamous cell carcinoma of head and neck (SCCHN). Paclitaxel is a widely used anticancer drug for breast, ovarian, testicular, cervical, non-small cell lung, head and neck cancer. However, it is water insoluble and orally inactive. We report the synthesis of water soluble nanosize conjugates of paclitaxel, branched PEG, and EGFR-targeting peptide by employing native chemical ligation. We performed a native chemical ligation between the N-hydroxy succinimide (NHS) ester of paclitaxel succinate and cysteine at pH 6.5 to give the cysteine-conjugated paclitaxel derivative. The thiol functionality of cysteine was activated and subsequently conjugated to multiarm thiol-PEG to obtain the paclitaxel branched PEG conjugate. Finally, we conjugated an EGFR-targeting peptide to obtain conjugates of paclitaxel, branched PEG, and EGFR-targeting peptide. These conjugates show anticancer activity against squamous cell carcinoma of head and neck cells (SCCHN, Tu212).

  17. Dog bites man or man bites dog? The enigma of the amino acid conjugations

    PubMed Central

    Beyoğlu, Diren; Smith, Robert L.; Idle, Jeffrey R.

    2012-01-01

    The proposition posed is that the value of amino acid conjugation to the organism is not, as in the traditional view, to use amino acids for the detoxication of aromatic acids. Rather, the converse is more likely, to use aromatic acids that originate from the diet and gut microbiota to assist in the regulation of body stores of amino acids, such as glycine, glutamate, and, in certain invertebrates, arginine, that are key neurotransmitters in the CNS. As such, the amino acid conjugations are not so much detoxication reactions, rather they are homeostatic and neuroregulatory processes. Experimental data have been culled in support of this hypothesis from a broad range of scientific and clinical literature. Such data include the low detoxication value of amino acid conjugations and the Janus nature of certain amino acids that are both neurotransmitters and apparent conjugating agents. Amino acid scavenging mechanisms in blood deplete brain amino acids. Amino acids glutamate and glycine when trafficked from brain are metabolized to conjugates of aromatic acids in hepatic mitochondria and then irreversibly excreted into urine. This process is used clinically to deplete excess nitrogen in cases of urea cycle enzymopathies through excretion of glycine or glutamine as their aromatic acid conjugates. Untoward effects of high-dose phenylacetic acid surround CNS toxicity. There appears to be a relationship between extent of glycine scavenging by benzoic acid and psychomotor function. Glycine and glutamine scavenging by conjugation with aromatic acids may have important psychosomatic consequences that link diet to health, wellbeing, and disease. PMID:22227274

  18. Peptide- and saccharide-conjugated dendrimers for targeted drug delivery: a concise review

    PubMed Central

    Liu, Jie; Gray, Warren D.; Davis, Michael E.; Luo, Ying

    2012-01-01

    Dendrimers comprise a category of branched materials with diverse functions that can be constructed with defined architectural and chemical structures. When decorated with bioactive ligands made of peptides and saccharides through peripheral chemical groups, dendrimer conjugates are turned into nanomaterials possessing attractive binding properties with the cognate receptors. At the cellular level, bioactive dendrimer conjugates can interact with cells with avidity and selectivity, and this function has particularly stimulated interests in investigating the targeting potential of dendrimer materials for the design of drug delivery systems. In addition, bioactive dendrimer conjugates have so far been studied for their versatile capabilities to enhance stability, solubility and absorption of various types of therapeutics. This review presents a brief discussion on three aspects of the recent studies to use peptide- and saccharide-conjugated dendrimers for drug delivery: (i) synthesis methods, (ii) cell- and tissue-targeting properties and (iii) applications of conjugated dendrimers in drug delivery nanodevices. With more studies to elucidate the structure–function relationship of ligand–dendrimer conjugates in transporting drugs, the conjugated dendrimers hold promise to facilitate targeted delivery and improve drug efficacy for discovery and development of modern pharmaceutics. PMID:23741608

  19. Conjugated ionomers for photovoltaic applications: electric field driven charge separation in organic photovoltaics. Final Technical report

    SciTech Connect

    Lonergan, Mark

    Final technical report for Conjugated ionomers for photovoltaic applications, electric field driven charge separation in organic photovoltaics. The central goal of the work we completed was been to understand the photochemical and photovoltaic properties of ionically functionalized conjugated polymers (conjugated ionomers or polyelectrolytes) and energy conversion systems based on them. We primarily studied two classes of conjugated polymer interfaces that we developed based either upon undoped conjugated polymers with an asymmetry in ionic composition (the ionic junction) or doped conjugated polymers with an asymmetry in doping type (the p-n junction). The materials used for these studies have primarily been themore » polyacetylene ionomers. We completed a detailed study of p-n junctions with systematically varying dopant density, photochemical creation of doped junctions, and experimental and theoretical work on charge transport and injection in polyacetylene ionomers. We have also completed related work on the use of conjugated ionomers as interlayers that improve the efficiency or organic photovoltaic systems and studied several important aspects of the chemistry of ionically functionalized semiconductors, including mechanisms of so-called "anion-doping", the formation of charge transfer complexes with oxygen, and the synthesis of new polyfluorene polyelectrolytes. We also worked worked with the Haley group at the University of Oregon on new indenofluorene-based organic acceptors.« less

  20. Immunochemical Parameters of Some Commercial Conjugates for the Fluorescent Treponemal Antibody-Absorption Test

    PubMed Central

    Hunter, E. F.; Smith, J. F.; Lewis, J. S.; McGrew, B. E.; Schmale, J. D.

    1972-01-01

    Fluorescein-labeled anti-human globulins were examined to determine the need for standardization of conjugates used in the fluorescent treponemal antibody-absorption (FTA-ABS) test. Twenty-one of 33 conjugates submitted by commercial manufacturers to the Reagents Control Activity, Venereal Disease Research Laboratory, for evaluation in the FTA-ABS test were available for study. Conjugates, after evaluation in FTA-ABS performance tests, were examined by immunoelectrophoresis, by titration against immunoglobulins G and M (IgG, IgM) with FTA-ABS techniques, and by the biuret protein and fluorescein diacetate methods for determining fluorescein to protein (F/P) ratios. The conjugates were predominately anti-IgG globulin with anti-light-chain activity. Differences were noted in the ability of some conjugates to detect IgM antibody. The F/P ratios of those conjugates that could be determined varied from 2.6 to 17.8 μg of fluorescein per mg of protein. The need to identify and standardize both the immunologic capabilities and the optimum F/P ratio for FTA-ABS test conjugates is presented. PMID:4564403

  1. Preparation, characterization, and immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugates

    PubMed Central

    1980-01-01

    A method is presented for covalently bonding Haemophilus influenzae type b capsular polysaccharide (HIB Ps) to several proteins. The method is efficient and relies upon the use of adipic dihydrazide as a spacer between the capsular polysaccharide and the carrier protein. In contrast to the poor immunogenicity of the purified HIB Ps in mice and rabbits, the HIB Ps-protein conjugates induced serum anti-type b antibodies having bactericidal activity at levels shown to be protective in humans when low doses were injected subcutaneously in a saline solution. The antibody response in mice was related to the dose of the conjugates, increased with the number of injections, and could be primed by the previous injection of the carrier protein. The HIB Ps- protein conjugates were immunogenic in three different mouse strains. The importance of the carrier molecule for the enhanced immunogenicity of the HIB Ps-protein conjugates was shown by the failure of HIB Ps hybrids prepared with either the homologous polysaccharide or pneumococcus type 3 polysaccharide to induce antibodie in mice. Rabbits injected with the HIB Ps-protein conjugates emulsified in Freund's adjuvant produced high levels of serum anti-type b antibodies which induced a bactericidal effect upon H. influenzae type b organisms. It is proposed that the HIB Ps component of the polysaccharide protein conjugates has been converted to a thymic-dependent immunogen. This method may be used to prepare protein-polysaccharide conjugates with HIB Ps and other polysaccharides to be considered for human use. PMID:6967514

  2. Improved Synthesis and In Vitro Evaluation of an Aptamer Ribosomal Toxin Conjugate

    PubMed Central

    Kelly, Linsley; Kratschmer, Christina; Maier, Keith E.; Yan, Amy C.

    2016-01-01

    Delivery of toxins, such as the ricin A chain, Pseudomonas exotoxin, and gelonin, using antibodies has had some success in inducing specific toxicity in cancer treatments. However, these antibody-toxin conjugates, called immunotoxins, can be bulky, difficult to express, and may induce an immune response upon in vivo administration. We previously reported delivery of a recombinant variant of gelonin (rGel) by the full-length prostate-specific membrane antigen (PSMA) binding aptamer, A9, to potentially circumvent some of these problems. Here, we report a streamlined approach to generating aptamer-rGel conjugates utilizing a chemically synthesized minimized form of the A9 aptamer. Unlike the full-length A9 aptamer, this minimized variant can be chemically synthesized with a 5′ terminal thiol. This facilitates the large scale synthesis and generation of aptamer toxin conjugates linked by a reducible disulfide linkage. Using this approach, we generated aptamer-toxin conjugates and evaluated their binding specificity and toxicity. On PSMA(+) LNCaP prostate cancer cells, the A9.min-rGel conjugate demonstrated an IC50 of ∼60 nM. Additionally, we performed a stability analysis of this conjugate in mouse serum where the conjugate displayed a t1/2 of ∼4 h, paving the way for future in vivo experiments. PMID:27228412

  3. cRGD Peptide-Conjugated Pyropheophorbide-a Photosensitizers for Tumor Targeting in Photodynamic Therapy.

    PubMed

    Li, Wenjing; Tan, Sihai; Xing, Yutong; Liu, Qian; Li, Shuang; Chen, Qingle; Yu, Min; Wang, Fengwei; Hong, Zhangyong

    2018-04-02

    Pyropheophorbide-a (Pyro) is a highly promising photosensitizer for tumor photodynamic therapy (PDT), although its very limited tumor-accumulation ability seriously restricts its clinical applications. A higher accumulation of photosensitizers is very important for the treatment of deeply seated and larger tumors. The conjugation of Pyro with tumor-homing peptide ligands could be a very useful strategy to optimize the physical properties of Pyro. Herein, we reported our studies on the conjugation of Pyro with a cyclic cRGDfK (cRGD) peptide, an integrin binding sequence, to develop highly tumor-specific photosensitizers for PDT application. To further reduce the nonspecific uptake and, thus, reduce the background distribution of the conjugates in normal tissues, we opted to add a highly hydrophilic polyethylene glycol (PEG) chain and an extra strongly hydrophilic carboxylic acid group as the linker to avoid the direct connection of the strongly hydrophobic Pyro macrocycle and cRGD ligand. We reported here the synthesis and characterization of these conjugates, and the influence of the hydrophilic modification on the biological function of the conjugates was carefully studied. The tumor-accumulation ability and photodynamic-induced cell-killing ability of these conjugates were evaluated through both in vitro cell-based experiment and in vivo distribution and tumor therapy experiments with tumor-bearing mice. Thus, the synthesized conjugate significantly improved the tumor enrichment and tumor selectivity of Pyro, as well as abolished the xenograft tumors in the murine model through a one-time PDT treatment.

  4. Parametric phase conjugation for the second harmonic of a nonlinear ultrasonic beam

    NASA Astrophysics Data System (ADS)

    Brysev, A. P.; Bunkin, F. V.; Hamilton, M. F.; Klopotov, R. V.; Krutyanskii, L. M.; Yan, K.

    2003-01-01

    The effect of phase conjugation for the second harmonic of a focused ultrasonic beam was investigated experimentally and by numerical simulation. An ultrasonic pulse with the carrier frequency f=3 MHz was emitted into water and focused at a point between the source and the phase conjugating system. The phase conjugation for the second harmonic of the incident wave (2 f=6 MHz) was performed in a magnetostrictive ceramic as a result of the parametric interaction of the incident wave with the pumping magnetic field (the pumping frequency was f p=4 f=12 MHz). The axial and focal distributions of sound pressure in the incident and conjugated beams were measured using a broadband PVDF membrane hydrophone. The corresponding calculations were performed by solving numerically the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation allowing for the nonlinearity, diffraction, and thermoviscous absorption. The results of measurements agreed well with the calculations and showed that the field of a conjugate wave adequately reproduces the field of the second harmonic of the incident wave. A certain advantage of focusing with the phase conjugation for the second harmonic was demonstrated in comparison with the operation at the doubled frequency of the incident wave. The results of this study can serve as a basis for the utilization of the phase conjugation of harmonics in ultrasonic tomography and nondestructive testing.

  5. Effect of guar gum conjugation on functional, antioxidant and antimicrobial activity of egg white lysozyme.

    PubMed

    Hamdani, Afshan Mumtaz; Wani, Idrees Ahmed; Bhat, Naseer Ahmad; Siddiqi, Raushid Ahmad

    2018-02-01

    This study was undertaken to analyze the effect of conjugation of egg-white lysozyme with guar gum. Lysozyme is an antimicrobial polypeptide that can be used for food preservation. Its antibacterial activity is limited to gram positive bacteria. Conjugation with polysaccharides like guar gum may broaden its activity against gram negatives. Conjugate was developed through Maillard reaction. Assays carried out included sugar estimation, SDS-PAGE, GPC, color, FT-IR, DSC, thermal stability, solubility, emulsifying, foaming and antioxidant activity. In addition, antimicrobial activity of the conjugate was determined against two gram positive (Staphyllococcus aureus and Enterococcus) and two gram negative pathogens (E. coli and Salmonella). Results showed higher functional properties of lysozyme-guar gum conjugate. The antioxidant properties increased from 2.02-35.80% (Inhibition of DPPH) and 1.65-4.93AAE/g (reducing power) upon guar gum conjugation. Conjugate significantly inhibited gram negative bacteria and the antibacterial activity also increased significantly against gram positive pathogens. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Direct Conjugation of Emerging Contaminants in Arabidopsis: Indication for an Overlooked Risk in Plants?

    PubMed

    Fu, Qiuguo; Zhang, Jianbo; Borchardt, Dan; Schlenk, Daniel; Gan, Jay

    2017-06-06

    Agricultural use of treated wastewater, biosolids, and animal wastes introduces a multitude of contaminants of emerging concerns (CECs) into the soil-plant system. The potential for food crops to accumulate CECs depends largely on their metabolism in plants, which at present is poorly understood. Here, we evaluated the metabolism of naproxen and ibuprofen, two of the most-used human drugs from the Profen family, in Arabidopsis thaliana cells and the Arabidopsis plant. The complementary use of high-resolution mass spectrometry and 14 C labeling allowed the characterization of both free and conjugated metabolites, as well as nonextractable residues. Naproxen and ibuprofen, in their parent form, were conjugated quickly and directly with glutamic acid and glutamine, and further with peptides, in A. thaliana cells. For example, after 120 h, the metabolites of naproxen accounted for >90% of the extractable chemical mass, while the intact parent itself was negligible. The structures of glutamate and glutamine conjugates were confirmed using synthesized standards and further verified in whole plants. Amino acid conjugates may easily deconjugate, releasing the parent molecule. This finding highlights the possibility that the bioactivity of such CECs may be effectively preserved through direct conjugation, a previously overlooked risk. Many other CECs are also carboxylic acids, such as the profens. Therefore, direct conjugation may be a common route for plant metabolism of these CECs, making it imperative to consider conjugates when assessing their risks.

  7. Androgen Receptor Antagonism By Divalent Ethisterone Conjugates In Castrate-Resistant Prostate Cancer Cells

    PubMed Central

    Levine, Paul M.; Lee, Eugine; Greenfield, Alex; Bonneau, Richard; Logan, Susan K.; Garabedian, Michael J.; Kirshenbaum, Kent

    2013-01-01

    Sustained treatment of prostate cancer with Androgen Receptor (AR) antagonists can evoke drug resistance, leading to castrate-resistant disease. Elevated activity of the AR is often associated with this highly aggressive disease state. Therefore, new therapeutic regimens that target and modulate AR activity could prove beneficial. We previously introduced a versatile chemical platform to generate competitive and non-competitive multivalent peptoid oligomer conjugates that modulate AR activity. In particular, we identified a linear and a cyclic divalent ethisterone conjugate that exhibit potent anti-proliferative properties in LNCaP-abl cells, a model of castrate-resistant prostate cancer. Here, we characterize the mechanism of action of these compounds utilizing confocal microscopy, time-resolved fluorescence resonance energy transfer, chromatin immunoprecipitation, flow cytometry, and microarray analysis. The linear conjugate competitively blocks AR action by inhibiting DNA binding. In addition, the linear conjugate does not promote AR nuclear localization or co-activator binding. In contrast, the cyclic conjugate promotes AR nuclear localization and induces cell-cycle arrest, despite its inability to compete against endogenous ligand for binding to AR in vitro. Genome-wide expression analysis reveals that gene transcripts are differentially affected by treatment with the linear or cyclic conjugate. Although the divalent ethisterone conjugates share extensive chemical similarities, we illustrate that they can antagonize the AR via distinct mechanisms of action, establishing new therapeutic strategies for potential applications in AR pharmacology. PMID:22871957

  8. Phthalocyanine-Peptide Conjugates for Epidermal Growth Factor Receptor Targeting1

    PubMed Central

    Ongarora, Benson G.; Fontenot, Krystal R.; Hu, Xiaoke; Sehgal, Inder; Satyanarayana-Jois, Seetharama D.; Vicente, M. Graça H.

    2012-01-01

    Four phthalocyanine (Pc)-peptide conjugates designed to target the epidermal growth factor receptor (EGFR) were synthesized and evaluated in vitro using four cell lines: human carcinoma A431 and HEp2, human colorectal HT-29, and kidney Vero (negative control) cells. Two peptide ligands for EGFR were investigated: EGFR-L1 and -L2, bearing 6 and 13 amino acid residues, respectively. The peptides and Pc-conjugates were shown to bind to EGFR using both theoretical (Autodock) and experimental (SPR) investigations. The Pc-EGFR-L1 conjugates 5a and 5b efficiently targeted EGFR and were internalized, in part due to their cationic charge, whereas the uncharged Pc-EGFR-L2 conjugates 4b and 6a poorly targeted EGFR maybe due to their low aqueous solubility. All conjugates were non-toxic (IC50 > 100 µM) to HT-29 cells, both in the dark and upon light activation (1 J/cm2). Intravenous (iv) administration of conjugate 5b into nude mice bearing A431 and HT-29 human tumor xenografts resulted in a near-IR fluorescence signal at ca. 700 nm, 24 h after administration. Our studies show that Pc-EGFR-L1 conjugates are promising near-IR fluorescent contrast agents for CRC, and potentially other EGFR over-expressing cancers. PMID:22468711

  9. Naproxen conjugated mPEG-PCL micelles for dual triggered drug delivery.

    PubMed

    Karami, Zahra; Sadighian, Somayeh; Rostamizadeh, Kobra; Parsa, Maliheh; Rezaee, Saeed

    2016-04-01

    A conjugate of the NSAIDs drug, naproxen, with diblock methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) copolymer was synthesized by the reaction of copolymer with naproxen in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. The naproxen conjugated copolymers were characterized with different techniques including (1)HNMR, FTIR, and DSC. The naproxen conjugated mPEG-PCL copolymers were self-assembled into micelles in aqueous solution. The TEM analysis revealed that the micelles had the average size of about 80 nm. The release behavior of conjugated copolymer was investigated in two different media with the pH values of 7.4 and 5.2. In vitro release study showed that the drug release rate was dependant on pH as it was higher at lower pH compared to neutral pH. Another feature of the conjugated micelles was a more sustained release profile compared to the conjugated copolymer. The kinetic of the drug release from naproxen conjugated micelles under different values of pH was also investigated by different kinetic models such as first-order, Makoid-Banakar, Weibull, Logistic, and Gompertz. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Synthesis, characterization, mucoadhesion and biocompatibility of thiolated carboxymethyl dextran-cysteine conjugate.

    PubMed

    Shahnaz, G; Perera, G; Sakloetsakun, D; Rahmat, D; Bernkop-Schnürch, A

    2010-05-21

    This study was aimed at improving the mucoadhesive properties of carboxymethyl dextran by the covalent attachment of cysteine. Mediated by a carbodiimide, l-cysteine was covalently attached to the polymer. The resulting CMD-cysteine conjugate (CMD-(273) conjugate) displayed 273+/-20 micromol thiol groups per gram of polymer (mean+/-S.D.; n=3). Within 2h the viscosity of an aqueous mucus/CMD-(273) conjugate mixture pH 7.4 increased at 37 degrees C by more than 85% compared to a mucus/carboxymethyl dextran mixture indicating enlarged interactions between the mucus and the thiolated polymer. Due to the immobilization of cysteine, the swelling velocity of the polymer was significantly accelerated (p<0.05). In aqueous solutions the CMD-(273) conjugate was capable of forming inter- and/or intramolecular disulfide bonds. Because of this crosslinking process within the polymeric network, the cohesive properties of the conjugate were also improved. Tablets comprising the unmodified polymer disintegrated within 15 min, whereas tablets of the CMD-(273) conjugate remained stable for 160 min (means+/-S.D.; n=3). Results from LDH and MTT assays on Caco-2 cells revealed 4.96+/-0.98% cytotoxicity and 94.1+/-0.9% cell viability for the CMD-(273) conjugate, respectively. Controlled release of model compound from CMD-(273) conjugate tablets was observed over 6h. These findings suggest that CMD-(273) conjugate is a promising novel polymer for drug delivery systems providing improved mucoadhesive and cohesive properties, greater stability and biocompatibility. Copyright 2010 Elsevier B.V. All rights reserved.

  11. A physico-chemical assessment of the thermal stability of pneumococcal conjugate vaccine components

    PubMed Central

    Gao, Fang; Lockyer, Kay; Burkin, Karena; Crane, Dennis T; Bolgiano, Barbara

    2014-01-01

    Physico-chemical analysis of pneumococcal polysaccharide (PS)-protein conjugate vaccine components used for two commercially licensed vaccines was performed to compare the serotype- and carrier protein-specific stabilities of these vaccines. Nineteen different monovalent pneumococcal conjugates from commercial vaccines utilizing CRM197, diphtheria toxoid (DT), Protein D (PD) or tetanus toxoid (TT) as carrier proteins were incubated at temperatures up to 56°C for up to eight weeks or were subjected to freeze-thawing (F/T). Structural stability was evaluated by monitoring their size, integrity and carrier protein conformation. The molecular size of the vaccine components was well maintained for Protein D, TT and DT conjugates at -20°C, 4°C and F/T, and for CRM197 conjugates at 4°C and F/T. It was observed that four of the eight serotypes of Protein D conjugates tended to form high molecular weight complexes at 37°C or above. The other conjugated carrier proteins also appeared to form oligomers or ‘aggregates’ at elevated temperatures, but rarely when frozen and thawed. There was evidence of degradation in some of the conjugates as evidenced by the formation of lower molecular weight materials which correlated with measured free saccharide. In conclusion, pneumococcal-Protein D/TT/DT and most CRM197 bulk conjugate vaccines were stable when stored at 2–8°C, the recommended temperature. In common between the conjugates produced by the two manufacturers, serotypes 1, 5, and 19F were relatively less stable and 6B was the most stable, with types 7F and 23F also showing good stability. PMID:25483488

  12. Synthesis and therapeutic effect of styrene–maleic acid copolymer-conjugated pirarubicin

    PubMed Central

    Tsukigawa, Kenji; Liao, Long; Nakamura, Hideaki; Fang, Jun; Greish, Khaled; Otagiri, Masaki; Maeda, Hiroshi

    2015-01-01

    Previously, we prepared a pirarubicin (THP)-encapsulated micellar drug using styrene–maleic acid copolymer (SMA) as the drug carrier, in which active THP was non-covalently encapsulated. We have now developed covalently conjugated SMA-THP (SMA-THP conjugate) for further investigation toward clinical development, because covalently linked polymer–drug conjugates are known to be more stable in circulation than drug-encapsulated micelles. The SMA-THP conjugate also formed micelles and showed albumin binding capacity in aqueous solution, which suggested that this conjugate behaved as a macromolecule during blood circulation. Consequently, SMA-THP conjugate showed significantly prolonged circulation time compared to free THP and high tumor-targeting efficiency by the enhanced permeability and retention (EPR) effect. As a result, remarkable antitumor effect was achieved against two types of tumors in mice without apparent adverse effects. Significantly, metastatic lung tumor also showed the EPR effect, and this conjugate reduced metastatic tumor in the lung almost completely at 30 mg/kg once i.v. (less than one-fifth of the maximum tolerable dose). Although SMA-THP conjugate per se has little cytotoxicity in vitro (1/100 of free drug THP), tumor-targeted accumulation by the EPR effect ensures sufficient drug concentrations in tumor to produce an antitumor effect, whereas toxicity to normal tissues is much less. These findings suggest the potential of SMA-THP conjugate as a highly favorable candidate for anticancer nanomedicine with good stability and tumor-targeting properties in vivo. PMID:25529761

  13. Synthesis and properties of a biodegradable polymer-drug conjugate: Methotrexate-poly(glycerol adipate).

    PubMed

    Suksiriworapong, Jiraphong; Taresco, Vincenzo; Ivanov, Delyan P; Styliari, Ioanna D; Sakchaisri, Krisada; Junyaprasert, Varaporn Buraphacheep; Garnett, Martin C

    2018-07-01

    Polymer-drug conjugates have been actively developed as potential anticancer drug delivery systems. In this study, we report the first polymer-anticancer drug conjugate with poly(glycerol adipate) (PGA) through the successful conjugation of methotrexate (MTX). MTX-PGA conjugates were controllably and simply fabricated by carbodiimide-mediated coupling reaction with various high molar ratios of MTX. The MTX-PGA conjugate self-assembled into nanoparticles with size dependent on the amount of conjugated MTX and the pH of medium. Change in particle size was attributed to steric hindrance and bulkiness inside the nanoparticle core and dissociation of free functional groups of the drug. The MTX-PGA nanoparticles were physically stable in media with pH range of 5-9 and ionic strength of up to 0.15 M NaCl and further chemically stable against hydrolysis in pH 7.4 medium over 30 days but enzymatically degradable to release unchanged free drug. Although 30%MTX-PGA nanoparticles exhibited only slightly less potency than free MTX in 791T cells in contrast to previously reported human serum albumin-MTX conjugates which had >300 times lower potency than free MTX. However, the MTX nanoparticles showed 7 times higher toxicity to Saos-2 cells than MTX. Together with the enzymic degradation experiments, these results suggest that with a suitable biodegradable polymer a linker moiety is not a necessary component. These easily synthesised PGA drug conjugates lacking a linker moiety could therefore be an effective new pathway for development of polymer drug conjugates. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Glutathione-Conjugates of Deoxynivalenol in Naturally Contaminated Grain Are Primarily Linked via the Epoxide Group

    PubMed Central

    Uhlig, Silvio; Stanic, Ana; Hofgaard, Ingerd S.; Kluger, Bernhard; Schuhmacher, Rainer; Miles, Christopher O.

    2016-01-01

    A glutathione (GSH) adduct of the mycotoxin 4-deoxynivalenol (DON), together with a range of related conjugates, has recently been tentatively identified by LC-MS of DON-treated wheat spikelets. In this study, we prepared samples of DON conjugated at the 10- and 13-positions with GSH, Cys, CysGly, γ-GluCys and N-acetylcysteine (NAC). The mixtures of conjugates were used as standards for LC-HRMS analysis of one of the DON-treated wheat spikelet samples, as well as 19 Norwegian grain samples of spring wheat and 16 grain samples of oats that were naturally-contaminated with DON at concentrations higher than 1 mg/kg. The artificially-contaminated wheat spikelets contained conjugates of GSH, CysGly and Cys coupled at the olefinic 10-position of DON, whereas the naturally-contaminated harvest-ripe grain samples contained GSH, CysGly, Cys, and NAC coupled mainly at the 13-position on the epoxy group. The identities of the conjugates were confirmed by LC-HRMS comparison with authentic standards, oxidation to the sulfoxides with hydrogen peroxide, and examination of product-ion spectra from LC-HRMS/MS analysis. No γ-GluCys adducts of DON were detected in any of the samples. The presence of 15-O-acetyl-DON was demonstrated for the first time in Norwegian grain. The results indicate that a small but significant proportion of DON is metabolized via the GSH-conjugation pathway in plants. To our knowledge, this is the first report of in vivo conjugation of trichothecenes via their epoxy group, which has generally been viewed as unreactive. Because conjugation at the 13-position of DON and other trichothecenes has been shown to be irreversible, this type of conjugate may prove useful as a biomarker of exposure to DON and other 12,13-epoxytrichothecenes. PMID:27845722

  15. Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

    PubMed Central

    2015-01-01

    Summary The conjugate addition reaction has been a useful tool in the formation of carbon–carbon bonds. The utility of this reaction has been demonstrated in the synthesis of many natural products, materials, and pharmacological agents. In the last three decades, there has been a significant increase in the development of asymmetric variants of this reaction. Unfortunately, conjugate addition reactions using α,β-unsaturated amides and lactams remain underdeveloped due to their inherently low reactivity. This review highlights the work that has been done on both diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams. PMID:25977728

  16. Second and third order nonlinear optical properties of conjugated molecules and polymers

    NASA Technical Reports Server (NTRS)

    Perry, Joseph W.; Stiegman, Albert E.; Marder, Seth R.; Coulter, Daniel R.; Beratan, David N.; Brinza, David E.

    1988-01-01

    Second- and third-order nonlinear optical properties of some newly synthesized organic molecules and polymers are reported. Powder second-harmonic-generation efficiencies of up to 200 times urea have been realized for asymmetric donor-acceptor acetylenes. Third harmonic generation chi(3)s have been determined for a series of small conjugated molecules in solution. THG chi(3)s have also been determined for a series of soluble conjugated copolymers prepared using ring-opening metathesis polymerization. The results are discussed in terms of relevant molecular and/or macroscopic structural features of these conjugated organic materials.

  17. Synthesis of polycyclic aromatic hydrocarbon-protein conjugates for preparation and immunoassay of antibodies.

    PubMed

    Glushkov, Andrey N; Kostyanko, Mikhail V; Cherno, Sergey V; Vasilchenko, Ilya L

    2002-04-01

    The method is described dealing with the synthesis of conjugates protein-polycyclic aromatic hydrocarbons (PAHs), highly soluble in water, stable without special stabilizers and containing the minimum quantity of cross-linked products. The reaction of protein with PAH containing an aldehyde group, has been carried out in an alkaline solution, and stabilization of the conjugate has been achieved by reduction with sodium borohydride in the presence of a compound blocking the formation of an insoluble polymeric fraction. The efficiency of synthesized conjugates for the induction and immunoassay of Abs to PAH for benzo[a]pyrene is shown.

  18. Effects of digital phase-conjugate light intensity on time-reversal imaging through animal tissue.

    PubMed

    Toda, Sogo; Kato, Yuji; Kudo, Nobuki; Shimizu, Koichi

    2018-04-01

    For transillumination imaging of animal tissues, we have attempted to suppress the scattering effect in a turbid medium using the time-reversal principle of phase-conjugate light. We constructed a digital phase-conjugate system to enable intensity modulation and phase modulation. Using this system, we clarified the effectiveness of the intensity information for restoration of the original light distribution through a turbid medium. By varying the scattering coefficient of the medium, we clarified the limit of time-reversal ability with intensity information of the phase-conjugate light. Experiment results demonstrated the applicability of the proposed technique to animal tissue.

  19. Development of Efficient Chemistry to Generate Site-Specific Disulfide-Linked Protein- and Peptide-Payload Conjugates: Application to THIOMAB Antibody-Drug Conjugates.

    PubMed

    Sadowsky, Jack D; Pillow, Thomas H; Chen, Jinhua; Fan, Fang; He, Changrong; Wang, Yanli; Yan, Gang; Yao, Hui; Xu, Zijin; Martin, Shanique; Zhang, Donglu; Chu, Phillip; Dela Cruz-Chuh, Josefa; O'Donohue, Aimee; Li, Guangmin; Del Rosario, Geoffrey; He, Jintang; Liu, Luna; Ng, Carl; Su, Dian; Lewis Phillips, Gail D; Kozak, Katherine R; Yu, Shang-Fan; Xu, Keyang; Leipold, Douglas; Wai, John

    2017-08-16

    Conjugation of small molecule payloads to cysteine residues on proteins via a disulfide bond represents an attractive strategy to generate redox-sensitive bioconjugates, which have value as potential diagnostic reagents or therapeutics. Advancement of such "direct-disulfide" bioconjugates to the clinic necessitates chemical methods to form disulfide connections efficiently, without byproducts. The disulfide connection must also be resistant to premature cleavage by thiols prior to arrival at the targeted tissue. We show here that commonly employed methods to generate direct disulfide-linked bioconjugates are inadequate for addressing these challenges. We describe our efforts to optimize direct-disulfide conjugation chemistry, focusing on the generation of conjugates between cytotoxic payloads and cysteine-engineered antibodies (i.e., THIOMAB antibody-drug conjugates, or TDCs). This work culminates in the development of novel, high-yielding conjugation chemistry for creating direct payload disulfide connections to any of several Cys mutation sites in THIOMAB antibodies or to Cys sites in other biomolecules (e.g., human serum albumin and cell-penetrating peptides). We conclude by demonstrating that hindered direct disulfide TDCs with two methyl groups adjacent to the disulfide, which have heretofore not been described for any bioconjugate, are more stable and more efficacious in mouse tumor xenograft studies than less hindered analogs.

  20. Specific Conjugation of the Hinge Region for Homogeneous Preparation of Antibody Fragment-Drug Conjugate: A Case Study for Doxorubicin-PEG-anti-CD20 Fab' Synthesis.

    PubMed

    Zhou, Zhan; Zhang, Jing; Zhang, Yan; Ma, Guanghui; Su, Zhiguo

    2016-01-20

    Conventional preparation strategies for antibody-drug conjugates (ADCs) result in heterogeneous products with various molecular sizes and species. In this study, we developed a homogeneous preparation strategy by site-specific conjugation of the anticancer drug with an antibody fragment. The model drug doxorubicin (DOX) was coupled to the Fab' fragment of anti-CD20 IgG at its permissive sites through a heterotelechelic PEG linker, generating an antibody fragment-drug conjugate (AFDC). Anti-CD20 IgG was digested and reduced specifically with β-mercaptoethylamine to generate the Fab' fragment with two free mercapto groups in its hinge region. Meanwhile, DOX was conjugated with α-succinimidylsuccinate ω-maleimide polyethylene glycol (NHS-PEG-MAL) to form MAL-PEG-DOX, which was subsequently linked to the free mercapto containing Fab' fragment to form a Fab'-PEG-DOX conjugate. The dual site-specific bioconjugation was achieved through the combination of highly selective reduction of IgG and introduction of heterotelechelic PEG linker. The resulting AFDC provides an utterly homogeneous product, with a definite ratio of one fragment to two drugs. Laser confocal microscopy and cell ELISA revealed that the AFDC could accumulate in the antigen-positive Daudi tumor cell. In addition, the Fab'-PEG-DOX retained appreciable targeting ability and improved antitumor activity, demonstrating an excellent therapeutic effect on the lymphoma mice model for better cure rate and significantly reduced side effects.