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Sample records for ethynylene oligomer monolayers

  1. Cationic phenylene ethynylene polymers and oligomers exhibit efficient antiviral activity.

    PubMed

    Wang, Ying; Canady, Taylor D; Zhou, Zhijun; Tang, Yanli; Price, Dominique N; Bear, David G; Chi, Eva Y; Schanze, Kirk S; Whitten, David G

    2011-07-01

    The antiviral activities of poly(phenylene ethynylene) (PPE)-based cationic conjugated polyelectrolytes (CPE) and oligo-phenylene ethynylenes (OPE) were investigated using two model viruses, the T4 and MS2 bacteriophages. Under UV/visible light irradiation, significant antiviral activity was observed for all of the CPEs and OPEs; without irradiation, most of these compounds exhibited high inactivation activity against the MS2 phage and moderate inactivation ability against the T4 phage. Transmission electron microscopy (TEM) and SDS polyacrylamide gel electrophoresis (SDS-PAGE) reveal that the CPEs and OPEs exert their antiviral activity by partial disassembly of the phage particle structure in the dark and photochemical damage of the phage capsid protein under UV/visible light irradiation.

  2. Effect of polymer chain length on membrane perturbation activity of cationic phenylene ethynylene oligomers and polymers.

    PubMed

    Wang, Ying; Jones, Emmalee M; Tang, Yanli; Ji, Eunkyung; Lopez, Gabriel P; Chi, Eva Y; Schanze, Kirk S; Whitten, David G

    2011-09-06

    The interactions of poly(phenylene ethynylene)- (PPE-) based cationic conjugated polyelectrolytes (CPEs) and oligo(phenylene ethynylene)s (OPEs) with different model lipid membrane systems were investigated to gain insight into the relationship between molecular structure and membrane perturbation ability. The CPE and OPE compounds exhibit broad-spectrum antimicrobial activity, and cell walls and membranes are believed to be their main targets. To better understand how the size, in terms of the number of repeat units, of the CPEs and OPEs affects their membrane disruption activities, a series of PPE-based CPEs and OPEs were synthesized and studied. A number of photophysical techniques were used to investigate the interactions of CPEs and OPEs with model membranes, including unilamellar vesicles and lipid monolayers at the air/water interface. CPE- or OPE-induced dye leakage from vesicles reveals that the CPEs and OPEs selectively perturb model bacterial membranes and that their membrane perturbation abilities are highly dependent on molecular size. Consistent with dye-leakage assay results, the CPEs and OPEs also exhibit chain-length-dependent ability to insert into 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) monolayers. Our results suggest that, for PPE-based CPE and OPE antimicrobials, chain length can be tuned to optimize their membrane perturbation ability.

  3. Effect of Side Chains on Molecular Conformation of Anthracene-Ethynylene-Phenylene-Vinylene Oligomers: A Comparative Density Functional Study With and Without Dispersion Interaction.

    PubMed

    Dong, Chuanding; Hoppe, Harald; Beenken, Wichard J D

    2016-06-02

    Using density functional calculations with and without dispersion interaction, we studied the effects of linear octyl and branched 2-ethylhexyl side chains on the oligomer conformation of the conjugated copolymer poly(p-anthracene-ethynylene)-alt-poly(p-phenylene-vinylene). With dispersion included, the branched side chains can cause significant bending of the oligomer backbone, while without dispersion they induce mainly torsional disorder. The oligomers with mainly linear side chains keep good planarity when optimized with and without dispersion. Despite their dramatically different conformations, the calculated absorption spectra of the oligomers with various side chain combinations are very similar, indicating that the conformation of the copolymer is not the main reason for the experimentally observed different spectra of ordered and disordered phases.

  4. Membrane perturbation activity of cationic phenylene ethynylene oligomers and polymers: selectivity against model bacterial and mammalian membranes.

    PubMed

    Wang, Ying; Tang, Yanli; Zhou, Zhijun; Ji, Eunkyung; Lopez, Gabriel P; Chi, Eva Y; Schanze, Kirk S; Whitten, David G

    2010-08-03

    Poly(phenylene ethyneylene) (PPE)-based cationic conjugated polyelectrolytes (CPEs) and cationic phenylene ethynylene oligomers (OPEs) exhibit broad-spectrum antimicrobial activity, and their main target is believed to be the cell membrane. To understand better how these antimicrobial molecules interact with membranes, a series of PPE-based CPEs and OPEs with different side chains were studied. Large unilamellar vesicles with lipid compositions mimicking those of mammalian or bacterial membranes were used as model membranes. Among the CPEs and OPEs tested, the anionic CPE, PPE-SO(3)(2-) and the smallest cationic OPE-1 are inactive against all vesicles. Other cationic CPEs and OPEs show significant membrane perturbation ability against bacterial membrane mimics but are inactive against a mammalian cell membrane mimic with the exception of PPE-DABCO and two end-only-functionalized OPEs, which also disrupted a mammalian cell membrane mimic. The results suggest that the phospholipid composition of vesicles dominates the interaction of CPE and OPE with lipid membranes.

  5. HAMLET forms annular oligomers when deposited with phospholipid monolayers.

    PubMed

    Baumann, Anne; Gjerde, Anja Underhaug; Ying, Ming; Svanborg, Catharina; Holmsen, Holm; Glomm, Wilhelm R; Martinez, Aurora; Halskau, Oyvind

    2012-04-20

    Recently, the anticancer activity of human α-lactalbumin made lethal to tumor cells (HAMLET) has been linked to its increased membrane affinity in vitro, at neutral pH, and ability to cause leakage relative to the inactive native bovine α-lactalbumin (BLA) protein. In this study, atomic force microscopy resolved membrane distortions and annular oligomers (AOs) produced by HAMLET when deposited at neutral pH on mica together with a negatively charged lipid monolayer. BLA, BAMLET (HAMLET's bovine counterpart) and membrane-binding Peptide C, corresponding to BLA residues 75-100, also form AO-like structures under these conditions but at higher subphase concentrations than HAMLET. The N-terminal Peptide A, which binds to membranes at acidic but not at neutral pH, did not form AOs. This suggests a correlation between the capacity of the proteins/peptides to integrate into the membrane at neutral pH-as observed by liposome content leakage and circular dichroism experiments-and the formation of AOs, albeit at higher concentrations. Formation of AOs, which might be important to HAMLET's tumor toxic action, appears related to the increased tendency of the protein to populate intermediately folded states compared to the native protein, the formation of which is promoted by, but not uniquely dependent on, the oleic acid molecules associated with HAMLET.

  6. Crystalline self-assembly into monolayers of folded oligomers at the air-water interface

    PubMed

    Lederer; Godt; Howes; Kjaer; Als-Nielsen; Lahav; Wegner; Leiserowitz; Weissbuch

    2000-06-16

    Insertion of the 1,3-bis(ethynylene)benzene unit as a rigid spacer into a linear alkyl chain, thus separating the two resulting stems by 9 A. induces chain folding at the air-water interface. These folded molecules self-assemble into crystalline monolayers at this interface, with the plane of the folding unit almost perpendicular to the water surface, as determined by synchrotron grazing-incidence X-ray diffraction. Three distinct molecular shapes, of the types U, inverted U, and M, were obtained in the two-dimensional crystalline state, depending upon the number of spacer units, and the number and position of the hydrophilic groups in the molecule. The molecules form ribbons with a higher crystal coherence in the direction of stacking between the molecular ribbons, and a lower coherence along the ribbon direction. A similar molecule, but with a spacer unit that imposes a 5 A separation between alkyl chains, yields the conventional herringbone arrangement.

  7. Quantum-chemical investigation of the structure and electronic absorption spectra of symmetric triphenylamine oligomers conjugated to vinylene, imine, azine, and ethynylene groups

    NASA Astrophysics Data System (ADS)

    Stromylo, E. V.; Baryshnikov, G. V.; Minaev, B. F.; Grigoras, M.

    2015-05-01

    Based on the density functional theory (DFT) and using the B3LYP and BMK hybrid exchange-correlation functionals, we have studied the structure and electronic-spectral properties of some triphenylamine oligomers that contain various π-electron spacers of end groups and that are of interest as electro- and photoactive materials. Good agreement between calculation results and experimental data on absorption spectra in the visible and UV ranges has been obtained. The nature of visible spectral bands has been elucidated based on interrelations with structural changes of oligomer molecules.

  8. Depolymerisation optimisation of cranberry procyanidins and transport of resultant oligomers on monolayers of human intestinal epithelial Caco-2 cells.

    PubMed

    Ou, Keqin; Gu, Liwei

    2015-01-15

    Procyanidins in cranberries are predominantly polymers (>85%). The objective of this study was to optimise the depolymerisation of polymers and to investigate the absorption of resultant oligomers on Caco-2 cell monolayers. Depolymerisation conditions were optimised using response surface methodology. Depolymerisation, with or without added epicatechin, yielded 644 μg and 202 μg of oligomers (monomer through tetramers) per mg of partially purified polymers (PP), respectively. Oligomers (yielded from both methods) were transported through Caco-2 cell monolayer despite absorption rates being low. With the aid of response surface methodology, the optimum depolymerisation conditions were determined to be 60°C, 0.1M HCl in methanol and 3h without added epicatechin. The predicted maximum yield was 364 μg oligomers per mg of PP. The optimum depolymerisation condition with added epicatechin shared the same temperature, acid concentration and reaction time, in addition to an epicatechin/PP mass ratio of 2.19. Its predicted maximum oligomer yield was 1,089 μg/mg. The predicted yields were verified by experimental data.

  9. Surface-enhanced Raman spectroscopy for detection of toxic amyloid β oligomers adsorbed on self-assembled monolayers

    NASA Astrophysics Data System (ADS)

    Voiciuk, Vladislava; Valincius, Gintaras; Budvytytė, Rima; Matijoška, Algirdas; Matulaitienė, Ieva; Niaura, Gediminas

    Surface-enhanced Raman spectroscopy (SERS) was used to detect different spectral features of small (1-2 nm) and large (5-10 nm) synthetic amyloid Aβ-42 oligomers, exhibiting high and no detectable neurotoxicities, respectively. Adsorption of peptides at self-assembled monolayers (SAM) terminated by methyl and pyridinium groups was employed to differentiate toxic and non-toxic oligomers. Three SAMs were analyzed: hydrophobic heptanethiol (HT) and octadecanethiol (ODT) as well as positively charged N-(6-mercapto)hexylpyridinium (MHP) chloride. SERS study revealed twofold adsorption effect, changes in the monolayer structure and appearance of new bands associated with the adsorbed peptides. A band at 1387 cm-1, observed as a result of the SAM and Aβ-42 interaction, is tentatively assigned to the peptide symmetric stretching vibration of carboxylate groups, and appears to be the most prominent spectral feature distinguishing toxic oligomers from the non-toxic Aβ-42 forms. This band was identified in the spectra of Aβ-42 adsorption on heptanethiol and MHP monolayers, while no clear perturbations were observed in the case of ODT monolayer.

  10. Charge transport in nitro substituted oligo(phenylene-ethynylene) molecules

    NASA Astrophysics Data System (ADS)

    Cabassi, Marco Alberto

    2007-12-01

    This thesis presents research aimed at tackling two issues in the field of molecular electronics. The first issue is the large range of molecular conductance values reported by various research groups for identical molecules. This is addressed by studying the same molecule in dissimilar environments. The second issue is experimental uncertainty---whether the observed effects are inherent to the molecule or due to external causes. This is addressed by performing in-situ spectroscopy of the molecule as part of its electrical characterization. Oligo(phenylene-ethynylene)s are a well studied class of molecules in the field of molecular electronics, and this work focuses on charge transport through nitro substituted oligo(phenylene-ethynylene) molecules. The electrical characterization of these molecules was performed utilizing two testbeds. An electromigrated break-junction testbed was used to probe individual molecules, while a nanowire molecular junction testbed was used to probe self-assembled monolayers of the molecule. Experiments performed on individual molecules revealed a temperature dependent transition in the dominant charge transport mechanism. Above 50K, hopping is the dominant charge transport mechanism, while below 50K direct tunneling is the dominant charge transport mechanism. Experiments performed on self-assembled monolayers did not reveal any temperature dependent transitions. The dominant charge transport mechanism appears to be direct tunneling throughout the temperature range investigated. The results also indicate that molecules embedded in a self-assembled monolayer have significantly lower conductance than individual molecules. This is primarily due to a second charge transport mechanism (hopping) that opens up above 50K that is available only to individual molecules, and secondarily due to better potential screening properties of the self-assembled monolayers. Inelastic electron tunneling spectra obtained for the molecules in a self

  11. Antifungal Properties of Cationic Phenylene Ethynylenes and Their Impact on β-Glucan Exposure

    PubMed Central

    Pappas, Harry C.; Sylejmani, Rina; Graus, Matthew S.; Donabedian, Patrick L.; Whitten, David G.

    2016-01-01

    Candida species are the cause of many bloodstream infections through contamination of indwelling medical devices. These infections account for a 40% mortality rate, posing a significant risk to immunocompromised patients. Traditional treatments against Candida infections include amphotericin B and various azole treatments. Unfortunately, these treatments are associated with high toxicity, and resistant strains have become more prevalent. As a new frontier, light-activated phenylene ethynylenes have shown promising biocidal activity against Gram-positive and -negative bacterial pathogens, as well as the environmental yeast Saccharomyces cerevisiae. In this study, we monitored the viability of Candida species after treatment with a cationic conjugated polymer [poly(p-phenylene ethynylene); PPE] or oligomer [“end-only” oligo(p-phenylene ethynylene); EO-OPE] by flow cytometry in order to explore the antifungal properties of these compounds. The oligomer was found to disrupt Candida albicans yeast membrane integrity independent of light activation, while PPE is able to do so only in the presence of light, allowing for some control as to the manner in which cytotoxic effects are induced. The contrast in killing efficacy between the two compounds is likely related to their size difference and their intrinsic abilities to penetrate the fungal cell wall. Unlike EO-OPE-DABCO (where DABCO is quaternized diazabicyclo[2,2,2]octane), PPE-DABCO displayed a strong propensity to associate with soluble β-glucan, which is expected to inhibit its ability to access and perturb the inner cell membrane of Candida yeast. Furthermore, treatment with PPE-DABCO unmasked Candida albicans β-glucan and increased phagocytosis by Dectin-1-expressing HEK-293 cells. In summary, cationic phenylene ethynylenes show promising biocidal activity against pathogenic Candida yeast cells while also exhibiting immunostimulatory effects. PMID:27161628

  12. Synthesis and chemosensing properties of cinnoline-containing poly(arylene ethynylene)s

    PubMed Central

    Danilkina, Natalia A; Vlasov, Petr S; Vodianik, Semen M; Kruchinin, Andrey A; Vlasov, Yuri G

    2015-01-01

    Summary Novel poly(arylene ethynylene)s comprising a cinnoline core were prepared in high yields via a three-step methodology. A Richter-type cyclization of 2-ethynyl- and 2-(buta-1,3-diynyl)aryltriazenes was used for cinnoline ring formation, followed by a Sonogashira coupling for the introduction of trimethylsilylethynyl moieties and a sila-Sonogashira coupling as the polycondensation technique. The fluorescence of the cinnoline-containing polymers in THF was highly sensitive to quenching by Pd2+ ions. PMID:25977711

  13. Topography and transport properties of oligo(phenylene ethynylene) molecular wires studied by scanning tunneling microscopy

    NASA Technical Reports Server (NTRS)

    Dholakia, Geetha R.; Fan, Wendy; Koehne, Jessica; Han, Jie; Meyyappan, M.

    2003-01-01

    Conjugated phenylene(ethynylene) molecular wires are of interest as potential candidates for molecular electronic devices. Scanning tunneling microscopic study of the topography and current-voltage (I-V) characteristics of self-assembled monolayers of two types of molecular wires are presented here. The study shows that the topography and I-Vs, for small scan voltages, of the two wires are quite similar and that the electronic and structural changes introduced by the substitution of an electronegative N atom in the central phenyl ring of these wires does not significantly alter the self-assembly or the transport properties.

  14. Label-free impedimetric sensor for a ribonucleic acid oligomer specific to hepatitis C virus at a self-assembled monolayer-covered electrode.

    PubMed

    Park, Jin-Young; Lee, Yoon-suk; Chang, Byoung-Yong; Kim, Byeang Hyean; Jeon, Sangmin; Park, Su-Moon

    2010-10-01

    A ribonucleic acid (RNA) sensor based on hybridization of its peptide nucleic acid (PNA) molecule with a target RNA oligomer of the internal ribosome entry site sequence specific to the hepatitis C virus (HCV) and the electrochemical impedance detection is described. This RNA is one of the most conservative molecules of the whole HCV RNA genome. The ammonium ion terminated PNA molecule was immobilized via its host-guest interactions with the diaza crown ring of 3-thiophene-acetamide-diaza-18-crown-6 synthesized by a simple two-step method, which forms a well-defined self-assembled monolayer (SAM) on gold. Hybridization events of the probe PNA with the target RNA were monitored by measuring charge-transfer resistances for the Fe(CN)(6)(3-/4-) redox probe using Fourier transform electrochemical impedance spectroscopy. The ratio of the resistances of the SAM-covered electrode measured before and after hybridization increased linearly with log[RNA] in the rat liver lysate with a detection limit of about 23 pM.

  15. Photochemistry of "end-only" oligo-p-phenylene ethynylenes: complexation with sodium dodecyl sulfate reduces solvent accessibility.

    PubMed

    Hill, Eric H; Evans, Deborah G; Whitten, David G

    2013-08-06

    Cationic oligo-p-phenylene ethynylenes are very effective light-activated biocides and biosensors but degrade upon exposure to light. In this study, we explore the photochemistry of a class of "end-only" compounds from this series, which have cationic moieties on the ends of the backbone. Product characterization by mass spectrometry reveals that the photoreactivity of these molecules is higher than that of a previously studied oligomer and that the primary products of photolysis result from the addition of water or oxygen across the triple bond. In addition, a product suggesting the addition of peroxide or other reactive oxygen species across the triple bond was observed. To explore avenues by which the photodegradation of these compounds can be mitigated, the effects of complexation with sodium dodecyl sulfate micelles on their photochemistry was explored. Classical molecular dynamics simulations revealed that compounds that were protected from photolysis by SDS buried their phenylene ethynylene backbones into the interior of the micelle, protecting it from contact with water. This work has revealed a molecular basis for the protection of a novel class of light-activated biocides from irradiation that is consistent with the proposed photochemistry of these compounds. This information can be useful for developing photodegradation-resistant biocidal materials and applications for current compounds and leads to new molecular design.

  16. Formation of a two-dimensionally well-ordered monolayer of a peptide oligomer by a simple spin-coating process.

    PubMed

    Yoon, Jinhwan; Ree, Moonhor; Hwang, Yongtaek; Lee, Seung Woo; Lee, Byeongdu; Kim, Jong-Seong; Kim, Heesoo; Magonov, Sergei N

    2004-02-03

    Oligo(N(6)-carbobenzyloxy-L-lysine) (OCBL) with n = 8 (n is the number-average degree of polymerization) was synthesized by the n-propylamine-catalyzed ring-opening polymerization of N(6)-carbobenzyloxy-L-lysine N-carboxylic anhydride, which was derived from N(6)-carbobenzyloxy-L-lysine. The formation of two-dimensionally well-ordered strip array monolayer films of the OBCL oligopeptide on graphite substrates was first succeeded by a conventional solution spin-coating process. The ordered strip array monolayer structure was characterized in detail by atomic force microscopy, and its assembly mechanism was examined.

  17. Electronic and structural properties of oligophenylene ethynylenes on Au(111) surfaces

    NASA Astrophysics Data System (ADS)

    Miao, Ling; Seminario, Jorge M.

    2007-05-01

    The interaction of oligophenylene ethynylene (OPE) on the (111) surface of a gold slab resembling a self-assembled monolayer (SAM) is investigated using ab initio density functional theory calculations. The authors performed a full optimization including all atoms in the OPE and in the slab to better understand OPE adsorption on the surface. It is found that OPE has two energetically favorable adsorption sites on the Au surface with relatively different molecular geometries: the nontop site adsorption greatly modifies the (111) surface structure; however, the extensive electron interactions enable a delocalized electron density distribution, implying an improved conductivity between OPE and Au, and the top site which is 0.9eV higher in energy than the nontop and features weaker Au-S bonds. Interestingly the on top configuration shows a strong spin imbalance along the molecule and the nontop shows a small spin imbalance on the surface. This feature is of strong interest for the development of resonators for the detection of chemical and biological agents. They have also calculated the frequency spectrum of these SAMs, which yield deformations in the gold surface yielding peak frequency shifts specific to each absorption site.

  18. Solvent effects on optical excitations of poly para phenylene ethynylene studied by QM/MM simulations based on many-body Green's functions theory

    NASA Astrophysics Data System (ADS)

    Bagheri, B.; Karttunen, M.; Baumeier, B.

    2016-10-01

    Electronic excitations in dilute solutions of poly para phenylene ethynylene (poly-PPE) are studied using a QM/MM approach combining many-body Green's functions theory within the GW approximation and the Bethe-Salpeter equation with polarizable force field models. Oligomers up to a length of 7.5 nm (10 repeat units) functionalized with nonyl side chains are solvated in toluene and water, respectively. After equilibration using atomistic molecular dynamics (MD), the system is partitioned into a quantum region (backbone) embedded into a classical (side chains and solvent) environment. Optical absorption properties are calculated solving the coupled QM/MM system self-consistently and special attention is paid to the effects of solvents. The model allows to differentiate the influence of oligomer conformation induced by the solvation from electronic effects related to local electric fields and polarization. It is found that the electronic environment contributions are negligible compared to the conformational dynamics of the conjugated PPE. An analysis of the electron-hole wave function reveals a sensitivity of energy and localization characteristics of the excited states to bends in the global conformation of the oligomer rather than to the relative of phenyl rings along the backbone.

  19. Conformation of ionizable poly Para phenylene ethynylene in dilute solutions

    DOE PAGES

    Wijesinghe, Sidath; Maskey, Sabina; Perahia, Dvora; ...

    2015-11-03

    The conformation of dinonyl poly para phenylene ethynylenes (PPEs) with carboxylate side chains, equilibrated in solvents of different quality is studied using molecular dynamics simulations. PPEs are of interest because of their tunable electro-optical properties, chemical diversity, and functionality which are essential in wide range of applications. The polymer conformation determines the conjugation length and their assembly mode and affects electro-optical properties which are critical in their current and potential uses. The current study investigates the effect of carboxylate fraction on PPEs side chains on the conformation of chains in the dilute limit, in solvents of different quality. The dinonylmore » PPE chains are modeled atomistically, where the solvents are modeled both implicitly and explicitly. Dinonyl PPEs maintained a stretched out conformation up to a carboxylate fraction f of 0.7 in all solvents studied. The nonyl side chains are extended and oriented away from the PPE backbone in toluene and in implicit good solvent whereas in water and implicit poor solvent, the nonyl side chains are collapsed towards the PPE backbone. Thus, rotation around the aromatic ring is fast and no long range correlations are seen within the backbone.« less

  20. Phenylethynyl terminated imide oligomers

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M. (Inventor); Bryant, Robert G. (Inventor); Jensen, Brian J. (Inventor); Havens, Stephen J. (Inventor)

    1995-01-01

    Four phenylethynyl amine compounds - 3 and 4-aminophenoxy-4'-phenylethynylbenzophenone, and 3 and 4-amino-4'-phenylethynylbenzophenone - were readily prepared and were used to endcap imide oligomers. Phenylethynyl-terminated amide acid oligomers and phenylethynyl-terminated imide oligomers with various molecular weights and compositions were prepared and characterized. These oligomers were cured at 300 to 400 C to provide crosslinked polyimides with excellent solvent resistance, high strength and modulus, and good high temperature properties. Adhesive panels, composites, films, and moldings from these phenylethynyl terminated imide oligomers gave excellent mechanical performance.

  1. Assessing the Sporicidal Activity of Oligo-p-phenylene Ethynylenes and Their Role as Bacillus Germinants.

    PubMed

    Pappas, Harry C; Lovchik, Julie A; Whitten, David G

    2015-04-21

    A wide range of oligo-p-phenylene ethynylenes has been shown to exhibit good biocidal activity against both Gram-negative and Gram-positive bacteria. While cell death may occur in the dark, these biocidal compounds are far more effective in the light as a result of their ability to sensitize the production of cell-damaging reactive oxygen species. In these studies, the interactions of a specific cationic oligo-p-phenylene ethynylene with spore-forming Bacillus atrophaeus and Bacillus anthracis Sterne have been investigated. Flow cytometry assays are used to rapidly monitor cell death as well as spore germination. This compound effectively killed Bacillus anthracis Sterne vegetative cells (over 4 log reduction), presumably by severe perturbations of the bacterial cell wall and cytoplasmic membrane, while also acting as an effective spore germinant in the dark. While 2 log reduction of B. anthracis Sterne spores was observed, it is hypothesized that further killing could be achieved through enhanced germination.

  2. Cationic Oligo(thiophene ethynylene) with Broad-Spectrum and High Antibacterial Efficiency under White Light and Specific Biocidal Activity against S. aureus in Dark.

    PubMed

    Zhao, Qi; Li, Junting; Zhang, Xiaoqian; Li, Zhengping; Tang, Yanli

    2016-01-13

    We designed and synthesized a novel oligo(thiophene ethynylene) (OTE) to investigate the antibacterial activities against Gram-positive (Staphylococcus aureus and Staphylococcus epidermidis) and Gram-negative (Ralstonia solanacearum and Escherichia coli) bacteria in vitro by photodynamic therapy (PDT). Notably, OTE presents broad-spectrum and greatly high antibacterial activities after white light irradiation at nanogram per milliliter concentrations. The half inhibitory concentrations (IC50) values obtained for S. aureus, S. epidermidis, E. coli, and R. solanacearum are 8, 13, 24, and 52 ng/mL after illumination for 30 min, respectively, which are lower than that of other PDT agents. Interestingly, OTE shows the specific and very strong dark killing capability against S. aureus at the concentration of 180 ng/mL for 30 min, which is the highest efficiency biocide against S. aureus without the need of irradiation to date. The antibacterial mechanism investigated demonstrated that reactive oxygen species or singlet-oxygen generated by OTE kills bacteria irreversibly upon white light irradiation, and OTE as a v-type oligomer exerts its toxicity directly on destroying bacterial cytoplasmic membrane in the dark. Importantly, the OTE shows no cell cytotoxicity and excellent biocompatibility. The results indicate that it is potential to provide versatile applications in the efficient control of pathogenic organisms and specific application for killing S. aureus.

  3. Electronic spectroscopy and energy transfer in cadmium selenide quantum dots and conjugated oligomers

    NASA Astrophysics Data System (ADS)

    Javier, Artjay

    The electronic excited state kinetics of CdSe quantum dots (QD) are studied through optical spectroscopy, by subjecting the quantum dots to different experimental conditions, as well as coupling them to phenylene-ethynylene oligomers. CdSe QDs feature a quantum-confined exciton state which pursues a variety of pathways once formed, such as band-edge recombination, charge separation by trapping at the dot surface, and electronic energy transfer (EnT). These phenomena are studied using different CdSe sizes, highlighting the effects of quantum confinement and surface energies on exciton decay. The size dependence of the exciton lifetime is studied, and correlation of the radiative lifetime to theoretical expectations are found, as well as evidence that nonradiative relaxation through crystal vibrations follows the Energy Gap Law and Marcus Inverted Region kinetics. A detailed analysis of the lifetime decays using the Maximum Entropy Method (MEM) reveal the presence of distributed, dual excited states, which are assigned to band-edge recombination and charged exciton decay. Complementary time-resolved PL allows for direct measurement of excited state populations, which changes dramatically upon addition of an inorganic capping layer to the QD, reflecting the suppression of surface carrier trapping. A strong excitation power-dependence of the photo-activated photoluminescence (PL) is correlated to the established observation of PL intermittency. Forming a hybrid nanocomposite of CdSe QDs and phenylene-ethynylene oligomers allows a detailed study of EnT between the organic phase and the inorganic phase, as well as complex energy migration kinetics within the organic phase. The size-dependent, and chain length-dependent EnT is found to arise from the spectral overlap dependence between the phases. Finally, CdSe QDs are mixed into phenylene-ethynylene oligomers at dopant-level concentrations to study the photo-induced phase transformations and subsequent electronic energy

  4. Monofunctional hyperbranched ethylene oligomers.

    PubMed

    Wiedemann, Thomas; Voit, Gregor; Tchernook, Alexandra; Roesle, Philipp; Göttker-Schnetmann, Inigo; Mecking, Stefan

    2014-02-05

    The neutral κ(2)N,O-salicylaldiminato Ni(II) complexes [κ(2)N,O-{(2,6-(3',5'-R2C6H3)2C6H3-N═C(H)-(3,5-I2-2-O-C6H2)}]NiCH3(pyridine)] (1a-pyr, R = Me; 1b-pyr, R = Et; 1c-pyr, R = iPr) convert ethylene to hyperbranched low-molecular-weight oligomers (Mn ca. 1000 g mol(-1)) with high productivities. While all three catalysts are capable of generating hyperbranched structures, branching densities decrease significantly with the nature of the remote substituent along Me > Et > iPr and oligomer molecular weights increase. Consequently, only 1a-pyr forms hyperbranched structures over a wide range of reaction conditions (ethylene pressure 5-30 atm and 20-70 °C). An in situ catalyst system achieves similar activities and identical highly branched oligomer microstructures, eliminating the bottleneck given by the preparation and isolation of Ni-Me catalyst precursor species. Selective introduction of one primary carboxylic acid ester functional group per highly branched oligoethylene molecule was achieved by isomerizing ethoxycarbonylation and alternatively cross metathesis with ethyl acrylate followed by hydrogenation. The latter approach results in complete functionalization and no essential loss of branched oligomer material and molecular weight, as the reacting double bonds are close to a chain end. Reduction yielded a monoalcohol-functionalized oligomer. Introduction of one reactive epoxide group per branched oligomer occurs completely and selectively under mild conditions. All reaction steps involved in oligomerization and monofunctionalization are efficient and readily scalable.

  5. Oligo(p-phenylene ethynylene)-BODIPY derivatives: synthesis, energy transfer, and quantum-chemical calculations.

    PubMed

    Yin, Shouchun; Leen, Volker; Jackers, Carine; Beljonne, David; Van Averbeke, Bernard; Van der Auweraer, Mark; Boens, Noël; Dehaen, Wim

    2011-11-18

    The synthesis and energy-transfer properties of a series of oligo(p-phenylene ethynylene)-BODIPY (OPEB) cassettes are reported. A series of oligo(p-phenylene ethynylene)s (OPEs) with different conjugated chain lengths as energy donor subunit in the energy-transfer system were capped at both ends with BODIPY chromophores as energy-acceptor subunits. The effect of the conjugated chain of OPEs on energy transfer in the OPEB cassettes was investigated by UV/Vis and fluorescence spectroscopy and modeling. With increasing number n of phenyl acetylene units (n=1-7), the absorption and emission maxima of OPEn are bathochromically shifted. In the OPEBn analogues, the absorption maximum assigned to the BODIPY moieties is independent of the length of the OPE spacer. However, the relative absorption intensity of the BODIPY band decreases when the number of phenyl acetylene units is increased. The emission spectra of OPEBn are dominated by a band peaking at 613 nm, corresponding to emission of the BODIPY moieties, regardless of whether excitation is at 420 or 550 nm. Furthermore, a very small band is observed with a maximum between 450 and 500 nm, and its intensity relative to that of the BODIPY emission increases with increasing n, that is, the excited state of OPE subunits is efficiently quenched in OPEBn by energy transfer to the BODIPY moieties. Energy transfer (ET) from OPEn to BODIPY in OPEBn is very efficient (all Φ(ET) values are greater than 98 %) and only slightly decreases with increasing length of the OPE units. These results are supported by theoretical studies that show very high energy transfer efficiency (Φ(ET) >75 %) from the OPE spacer to the BODIPY end-groups for chains with up to 15-20 units.

  6. Polarized photoluminescence from poly(p-phenylene-ethynylene) via a block copolymer nanotemplate.

    PubMed

    Breen, Craig A; Deng, Tao; Breiner, Thomas; Thomas, Edwin L; Swager, Timothy M

    2003-08-20

    A new approach based on a conjugated polymer/block copolymer guest/host system for the generation of polarized photoluminescence is reported. Synthetic modification of a poly(p-phenylene-ethynylene) (PPE) conjugated polymer is used for domain-specific incorporation into a cylindrical morphology block copolymer host matrix. Subsequent ordering of the host nanostructure via roll cast processing templates uniaxial alignment of the guest PPE. The ordered films are optically anisotropic displaying both polarized absorption with a dichroic ratio of 3.0 at 440 nm and polarized emission with a polarization ratio of 7.3 at 472 nm.

  7. Phenylethynyl terminated reactive oligomer

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G. (Inventor); Jensen, Brian J. (Inventor); Hergenrother, Paul M. (Inventor)

    1995-01-01

    A composition of matter having the general structure: ##STR1## (wherein X is F, Cl, or NO.sub.2, and Y is CO, SO.sub.2 or C(CF.sub.3).sub.2) is employed to terminate a nucleophilic reagent, resulting in the exclusive production of phenylethynyl terminated reactive oligomers which display unique thermal characteristics. A reactive diluent having the general structure: ##STR2## (wherein R is any aliphatic or aromatic moiety) is employed to decrease the melt viscosity of a phenylethynyl terminated reactive oligomer and to subsequently react therewith to provide a thermosetting material of enhanced density. These materials have features which make them attractive candidates for use as composite matrices and adhesives.

  8. Photovoltaic cells based on sequentially adsorbed multilayers of conjugated poly(p-phenylene ethynylene)s and a water-soluble fullerene derivative.

    PubMed

    Mwaura, Jeremiah K; Pinto, Mauricio R; Witker, David; Ananthakrishnan, Nisha; Schanze, Kirk S; Reynolds, John R

    2005-10-25

    We describe the layer-by-layer (LBL) fabrication of multilayer films and photovoltaic cells using poly(phenylene ethynylene)-based anionic conjugated polyelectrolytes as electron donors and water-soluble cationic fullerene C60 derivatives as acceptors. LBL film deposition was found to be linearly related to the number of bilayers as monitored by UV-vis absorption. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) of the multilayer films revealed an aggregated but relatively uniform morphology devoid of any long-range phase separation. The maximum incident monochromatic photon to current conversion efficiency (IPCE) of the photovoltaic cells was 5.5%, the highest efficiency reported to date for cells fabricated by using the LBL fabrication technique, and since the thin film cells do not provide complete absorption of the incident light, the current generation per photon absorbed may be as much as 10%. The cells exhibited open circuit voltages of 200-250 mV with highest measured short circuit currents up to 0.5 mA/cm2 and fill factors around 30%. The power conversion efficiencies measured at AM 1.5 solar conditions (100 mW/cm2) varied between 0.01 and 0.04%, and similar to the IPCE results, the efficiency is a function of the thickness of the PV active layer.

  9. Non-adiabatic excited state molecular dynamics of phenylene ethynylene dendrimer using a multiconfigurational Ehrenfest approach

    DOE PAGES

    Fernandez-Alberti, Sebastian; Makhov, Dmitry V.; Tretiak, Sergei; ...

    2016-03-10

    Photoinduced dynamics of electronic and vibrational unidirectional energy transfer between meta-linked building blocks in a phenylene ethynylene dendrimer is simulated using a multiconfigurational Ehrenfest in time-dependent diabatic basis (MCE-TDDB) method, a new variant of the MCE approach developed by us for dynamics involving multiple electronic states with numerous abrupt crossings. Excited-state energies, gradients and non-adiabatic coupling terms needed for dynamics simulation are calculated on-the-fly using the Collective Electron Oscillator (CEO) approach. In conclusion, a comparative analysis of our results obtained using MCE-TDDB, the conventional Ehrenfest method and the surface-hopping approach with and without decoherence corrections is presented.

  10. Oligo(p-phenylene ethynylene) with Cyanoacrylate Terminal Groups and Graphene Composite as Fluorescent Chemical Sensor for Cysteine.

    PubMed

    Adachi, Naoya; Yoshinari, Mariko; Suzuki, Eri; Okada, Mari

    2017-04-08

    A chemical sensor for cysteine (Cys) was fabricated based on a fluorescent oligo(p-phenylene ethynylene)s (OPEs) and OPE-graphene oxide (GO) composite. OPE with cyanoacrylate terminal groups were synthesized by a Pd-catalyzed Sonogashira coupling reaction and Knoevenagel condensation for use as a chemical sensor for Cys. The optical properties and Cys sensing capability of the cyanoacrylate modified OPE and OPE-GO composite were investigated. In addition of Cys, the fluorescence of OPE was blue-shifted and decreased (fluorescence turn-off), while the fluorescence of the OPE-GO composite was enhanced (fluorescence turn-on). Thus, OPE with cyanoacrylate terminal groups and OPE-GO composite acts a highly sensitive fluorescent chemical sensor for Cys.

  11. Vibrational spectroscopy and excited state molecular dynamics of phenylene ethynylene polymers

    NASA Astrophysics Data System (ADS)

    Galindo Cruz, Johan Fabian

    Energy transfer is a vital process because of its critical role in photosynthesis as well as in the development of new technological devices such as biosensors, photovoltaics and light emitting devices. Dendrimeric polymers are one of the most explored light-harvesting molecules. The characterization of the excited states of this group of molecules as well as the study of their energy transfer mechanism is an important step to gain further insight into this process and its application. For this purpose, we have studied a family of two- and three- ring linear poly(phenylene ethynylene) dendrimers which are either meta or ortho substituted. These dendrimers are able to mimic energy transfer that occurs in photosynthetic systems. We have performed IR spectroscopy calculations using linear response theory and analyzed the propagation of the ground state normal modes in the excited state. We identified a band at 2150 cm-1 that is characteristic of S1 in the meta- substituted molecule, for which S1 and S2 have transition densities localized over different regions of the molecule, while the ortho- substituted case, the states are spread over the entire molecule. We find that the coupling between vibrations associated to C≡C triple bonds plays an important role in the nonadiabatic electronic energy transfer. These results are a guide to the experimental characterization of specific electronic excited state vibrations of these molecules. Next, we proceed to study the larger 2G1m-Eper, a Poly(Phenylene Ethynylene) based molecule. We have used Nonadiabatic Excited State Molecular Dynamics to study the energy transfer mechanism after an excitation at 400 nm. We have found that the initial excitation is delocalized between the two monodendrons, evolving to an intermediate state located in one of them. From this state, the system transitions to S1, localized in the perylene trap, and photon emission can take place to return to the ground state. These results are in good

  12. Perforated monolayers

    SciTech Connect

    Regen, S.L.

    1992-01-01

    Our research over this past grant period has focused on (1) developing methods for making in situ permeation measurements at the air-water interface, (2) defining the structural and conformational behavior of selected calix(4)arenes, (3) defining the metal complexation properties of certain upper-rim functionalized calix(4)arenes, and (4) synthesizing a broad series of polymerizable calixarenes, to be used for constructing perforated monolayers and multilayers.

  13. Conformation of ionizable poly Para phenylene ethynylene in dilute solutions

    SciTech Connect

    Wijesinghe, Sidath; Maskey, Sabina; Perahia, Dvora; Grest, Gary S.

    2015-11-03

    The conformation of dinonyl poly para phenylene ethynylenes (PPEs) with carboxylate side chains, equilibrated in solvents of different quality is studied using molecular dynamics simulations. PPEs are of interest because of their tunable electro-optical properties, chemical diversity, and functionality which are essential in wide range of applications. The polymer conformation determines the conjugation length and their assembly mode and affects electro-optical properties which are critical in their current and potential uses. The current study investigates the effect of carboxylate fraction on PPEs side chains on the conformation of chains in the dilute limit, in solvents of different quality. The dinonyl PPE chains are modeled atomistically, where the solvents are modeled both implicitly and explicitly. Dinonyl PPEs maintained a stretched out conformation up to a carboxylate fraction f of 0.7 in all solvents studied. The nonyl side chains are extended and oriented away from the PPE backbone in toluene and in implicit good solvent whereas in water and implicit poor solvent, the nonyl side chains are collapsed towards the PPE backbone. Thus, rotation around the aromatic ring is fast and no long range correlations are seen within the backbone.

  14. Interaction of anionic phenylene ethynylene polymers with lipids: from membrane embedding to liposome fusion.

    PubMed

    Karam, Pierre; Hariri, Amani A; Calver, Christina F; Zhao, Xiaoyong; Schanze, Kirk S; Cosa, Gonzalo

    2014-09-09

    Here we report spectroscopic studies on the interaction of negatively charged, amphiphilic polyphenylene ethynylene (PPE) polymers with liposomes prepared either from negative, positive or zwitterionic lipids. Emission spectra of PPEs of 7 and 49 average repeat units bearing carboxylate terminated side chains showed that the polymer embeds within positively charged lipids where it exists as free chains. No interaction was observed between PPEs and negatively charged lipids. Here the polymer remained aggregated giving rise to broad emission spectra characteristic of the aggregate species. In zwitterionic lipids, we observed that the majority of the polymer remained aggregated yet a small fraction readily embedded within the membrane. Titration experiments revealed that saturation of zwitterionic lipids with polymer typically occurred at a polymer repeat unit to lipid mole ratio close to 0.05. No further membrane embedding was observed above that point. For liposomes prepared from positively charged lipids, saturation was observed at a PPE repeat unit to lipid mole ratio of ∼0.1 and liposome precipitation was observed above this point. FRET studies showed that precipitation was preceded by lipid mixing and liposome fusion induced by the PPEs. This behavior was prominent for the longer polymer and negligible for the shorter polymer at a repeat unit to lipid mole ratio of 0.05. We postulate that fusion is the consequence of membrane destabilization whereby the longer polymer gives rise to more extensive membrane deformation than the shorter polymer.

  15. DFT study of the effect of fluorine atoms on the crystal structure and semiconducting properties of poly(arylene-ethynylene) derivatives

    NASA Astrophysics Data System (ADS)

    Moral, Mónica; García, Gregorio; Garzón, Andrés; Granadino-Roldán, José M.; Fernández-Gómez, Manuel

    2016-04-01

    The effect of fluorine substitution on the molecular structure, crystal packing, and n-type semiconducting properties of a set of poly(arylene-ethynylene) polymers based on alternating thiadiazole and phenyl units linked through ethynylene groups has been studied by means of Density Functional Theory. As a result, an enlargement in the interplanar distance between cofacial polymer chains, as well as a decrease of the electronic coupling and electron mobility is predicted. On the other hand, fluorination could facilitate electron injection into the material. A polymer containing both alkoxy pendant chains and fluorine atoms is proposed as a compromise solution between efficiency of electron injection and charge transport within the material.

  16. Perforated monolayers

    SciTech Connect

    Regen, S.L.

    1992-12-01

    Goal of this research program is to create ultrathin organic membranes that possess uniform and adjustable pores ( < 7[angstrom] diameter). Such membranes are expected to possess high permeation selectivity (permselectivity) and high permeability, and to provide the basis for energy-efficient methods of molecular separation. Work carried out has demonstrated feasibility of using perforated monolayer''-based composites as molecular sieve membranes. Specifically, composite membranes derived from Langmuir-Blodgett multilayers of the calix[6]arene-based surfactant shown below plus poly[l-(trimethylsilyl)-l-propyne] (PTMSP) were found to exhibit sieving behavior towards He, N[sub 2] and SF[sub 6]. Results of derivative studies that have also been completed are also described in this report.

  17. Targeting Cancer with Antisense Oligomers

    SciTech Connect

    Hnatowich, DJ

    2008-10-28

    With financial assistance from the Department of Energy, we have shown definitively that radiolabeled antisense DNAs and other oligomers will accumulate in target cancer cells in vitro and in vivo by an antisense mechanism. We have also shown that the number of mRNA targets for our antisense oligomers in the cancer cell types that we have investigated so far is sufficient to provide and antisense image and/or radiotherapy of cancer in mice. These studies have been reported in about 10 publications. However our observation over the past several years has shown that radiolabeled antisense oligomers administered intravenously in their native and naked form will accumulate and be retained in target xenografts by an antisense mechanism but will also accumulate at high levels in normal organs such as liver, spleen and kidneys. We have investigated unsuccessfully several commercially available vectors. Thus the use of radiolabeled antisense oligomers for the imaging of cancer must await novel approaches to delivery. This laboratory has therefore pursued two new paths, optical imaging of tumor and Auger radiotherapy. We are developing a novel method of optical imaging tumor using antisense oligomers with a fluorophore is administered while hybridized with a shorter complementary oligomer with an inhibitor. In culture and in tumored mice that the duplex remains intact and thus nonfluorescent until it encounters its target mRNA at which time it dissociates and the antisense oligomer binds along with its fluorophore to the target. Simultaneous with the above, we have also observed, as have others, that antisense oligomers migrate rapidly and quantitatively to the nucleus upon crossing cell membranes. The Auger electron radiotherapy path results from this observation since the nuclear migration properties could be used effectively to bring and to retain in the nucleus an Auger emitting radionuclide such as 111In or 125I bound to the antisense oligomer. Since the object becomes

  18. Self-assembly of conjugated oligomers and polymers at the interface: structure and properties.

    PubMed

    Xu, Lirong; Yang, Liu; Lei, Shengbin

    2012-08-07

    In this review, we give a brief account on the recent scanning tunneling microscopy investigation of interfacial structures and properties of π-conjugated semiconducting oligomers and polymers, either at the solid-air (including solid-vacuum) or at the solid-liquid interface. The structural aspects of the self-assembly of both oligomers and polymers are highlighted. Conjugated oligomers can form well ordered supramolecular assemblies either at the air-solid or liquid-solid interface, thanks to the relatively high mobility and structural uniformity in comparison with polymers. The backbone structure, substitution of side chains and functional groups can affect the assembling behavior significantly, which offers the opportunity to tune the supramolecular structure of these conjugated oligomers at the interface. For conjugated polymers, the large molecular weight limits the mobility on the surface and the distribution in size also prevents the formation of long range ordered supramolecular assembly. The submolecular resolution obtained on the assembling monolayers enables a detailed investigation of the chain folding at the interface, both the structural details and the effect on electronic properties. Besides the ability in studying the assembling structures at the interfaces, STM also provides a reasonable way to evaluate the distribution of the molecular weight of conjugated polymers by statistic of the contour length of the adsorbed polymer chains. Both conjugated oligomers and polymers can form composite assemblies with other materials. The ordered assembly of oligomers can act as a template to controllably disperse other molecules such as coronene or fullerene. These investigations open a new avenue to fine tune the assembling structure at the interface and in turn the properties of the composite materials. To summarize scanning tunneling microscopy has demonstrated its surprising ability in the investigation of the assembling structures and properties of

  19. Counterion condensation on heparin oligomers.

    PubMed

    Minsky, Burcu Baykal; Atmuri, Anand; Kaltashov, Igor A; Dubin, Paul L

    2013-04-08

    The electropherogram of native heparin shows a broad distribution of mobilities μ, which truncates abruptly at a notably high μ = 4.7 × 10(-4) cm(2) V(-1) s(-1). This highly skewed mobility distribution is also found for the 20-saccharide chain, which shows from mass spectrometry a more uniform (symmetrical) with respect to sulfation level. Since a partially degraded heparin exhibits oligomer peaks with μ> 5 × 10(-4) cm(2) V(-1) s(-1) (appearing to escape the limitation of the mobility value for native heparin), we examined the electrophoretic behavior of chain-length monodisperse heparin oligomers. Their mobilities varied inversely with the logarithm of the contour length, L, for L from 3 to 10 nm and reached an asymptotic limit for L > 20 nm. The generality of this effect was indicated by similar behavior for oligomers of poly(styrene sulfonate). A recent theory of polyelectrolyte end effects (Manning, G. S. Macromolecules2008, 41, 6217-6227), in which chain termini exhibit reduced counterion condensation was found to quantitatively account for these results. A qualitative explanation for the anomalously high value of μ of native heparin, 10-20% higher than those seen for synthetic polyelectrolytes of higher linear charge density, is suggested on the basis of similar junction effects (Manning, G. S. Macromolecules2008, 41, 6217-6227), which reduce counterion condensation at the interfaces of regions of high and low sulfation. We suggest that these effects should be considered in models for the biofunctionality of the regulated high and low sulfation (NS/NA) domains of heparan sulfate.

  20. Explaining the Cyclic Voltammetry of a Poly(1,4-phenylene-ethynylene)-alt-poly(1,4-phenylene-vinylene) Copolymer upon Oxidation by using Spectroscopic Techniques.

    PubMed

    Enengl, Christina; Enengl, Sandra; Bouguerra, Nassima; Havlicek, Marek; Neugebauer, Helmut; Egbe, Daniel A M

    2017-01-04

    Poly(1,4-phenylene-ethynylene)-alt-poly(1,4-phenylene-vinylene) (PPE-PPV) copolymers have attracted quite a lot of attention in the last few years for electronic device applications owing to their enhanced fluorescence. In this work, we focus on one particular PPE-PPV copolymer with dissymmetrically substituted 1,4-phenylene-ethynylene and symmetrically substituted 1,4-phenylene-vinylene building units. Six successively performed cyclic voltammograms are presented, measured during the oxidation reactions. As the oxidation onset of the electrochemical reaction shifts to lower potentials in each cycle, this behavior is elucidated by using spectroscopic techniques ranging from UV/Vis/near-IR to mid-IR including spin-resonance techniques. Hence, these findings help to explain some of the copolymer's most advantageous properties in terms of possible oxidation products.

  1. Synthetic Antimicrobial Oligomers Induce a Composition-Dependent Topological Transition in Membranes

    SciTech Connect

    Yang, L.; Gordon, V.D.; Mishra, A.; Som, A.; Purdy, K.R.; Davis, M.A.; Tew, G.N.; Wong, G.C.L.

    2009-06-04

    Antimicrobial peptides (AMPs) are cationic amphiphiles that comprise a key component of innate immunity. Synthetic analogues of AMPs, such as the family of phenylene ethynylene antimicrobial oligomers (AMOs), recently demonstrated broad-spectrum antimicrobial activity, but the underlying molecular mechanism is unknown. Homologues in this family can be inactive, specifically active against bacteria, or nonspecifically active against bacteria and eukaryotic cells. Using synchrotron small-angle X-ray scattering (SAXS), we show that observed antibacterial activity correlates with an AMO-induced topological transition of small unilamellar vesicles into an inverted hexagonal phase, in which hexagonal arrays of 3.4-nm water channels defined by lipid tubes are formed. Polarized and fluorescence microscopy show that AMO-treated giant unilamellar vesicles remain intact, instead of reconstructing into a bulk 3D phase, but are selectively permeable to encapsulated macromolecules that are smaller than 3.4 nm. Moreover, AMOs with different activity profiles require different minimum threshold concentrations of phosphoethanolamine (PE) lipids to reconstruct the membrane. Using ternary membrane vesicles composed of DOPG:DOPE:DOPC with a charge density fixed at typical bacterial values, we find that the inactive AMO cannot generate the inverted hexagonal phase even when DOPE completely replaces DOPC. The specifically active AMO requires a threshold ratio of DOPE:DOPC = 4:1, and the nonspecifically active AMO requires a drastically lower threshold ratio of DOPE:DOPC = 1.5:1. Since most gram-negative bacterial membranes have more PE lipids than do eukaryotic membranes, our results imply that there is a relationship between negative-curvature lipids such as PE and antimicrobial hydrophobicity that contributes to selective antimicrobial activity.

  2. Application of a Human Intestinal Epithelial Cell Monolayer to the Prediction of Oral Drug Absorption in Humans as a Superior Alternative to the Caco-2 Cell Monolayer.

    PubMed

    Takenaka, Toru; Harada, Naomoto; Kuze, Jiro; Chiba, Masato; Iwao, Takahiro; Matsunaga, Tamihide

    2016-02-01

    A human small intestinal epithelial cell (HIEC) monolayer was recently established in our laboratories as a novel system to evaluate the Papp (apparent permeability coefficient) of compounds during their absorption in humans. An effusion-based analysis using polyethylene glycol oligomers with molecular weights ranging from 194-898 indicated that HIEC and Caco-2 cell monolayers both had paracellular pores with 2 distinct radiuses (∼ 5 and 9-14 Å), whereas the porosity of large pores was 11-fold higher in the HIEC monolayer (44 × 10(-8)) than in the Caco-2 cells (4 × 10(-8)). A comparison between the fraction-absorbed (Fa) values observed in humans and those predicted from Papp values in both monolayers indicated that the HIEC monolayer had markedly higher precision to predict Fa values with root mean square error of 9.40 than the Caco-2 cells (root mean square error = 16.90) for 10 paracellularly absorbed compounds. Furthermore, the accuracy of the HIEC monolayer to classify the absorption of 23 test drugs with diverse absorption properties, including different pathways in the presence or absence of susceptibility to efflux transporters, was higher than that of the Caco-2 cell monolayer. In conclusion, the HIEC monolayer exhibited advantages over Caco-2 cells in the ranking and prediction of absorption of compounds in humans.

  3. Synthesis and electrical characterization of oligo(phenylene ethynylene) molecular wires coordinated to transition metal complexes.

    PubMed

    Ng, Zhaoyue; Loh, Kian Ping; Li, Liqian; Ho, Peter; Bai, Ping; Yip, John H K

    2009-08-25

    Organometallic wires are interesting alternatives to conventional molecular wires based on a pure organic system because of the presence of d orbitals in the transition metal complex. However, synthetic problems, such as decreased stability of the compounds when labile metal complexes are present, often impede their isolation in a pure state and preclude a rapid development of such hybrid molecular wires. In this work, we show that preassembled self-assembled monolayers (SAM) based on pyridine-terminated 1-((4-acetylthiophenyl)ethynyl)-4-((4-pyridyl)ethynyl)benzene can act as a template for the architectural build up of a second layer of transition metal complexes to form an array of organometallic molecular wires on gold. Ru(II)(terpy)(bipy)(2+) (terpy = 2,2':6',2''-terpyridine and bipy = 2,2'-bipyridine) or cyclometalated Pt(II)(pbipy) (pbipy = 6-phenyl-2,2'-bipyridine) were axially coordinated onto the organic SAM via its terminal pyridinium moieties. Current-voltage studies show that the electronic coupling between the transition metal and organic wire produces a molecular wire that exhibits higher conductance than the original organic chain. The presence of the transition metal complexes in the hybrid molecular wire introduces distinctive negative differential resistance (NDR) effects.

  4. Pathogenesis of Abeta oligomers in synaptic failure.

    PubMed

    Sivanesan, Senthilkumar; Tan, Aaron; Rajadas, Jayakumar

    2013-03-01

    The soluble Abeta oligomers in brain are highly correlated with memory related synaptic dysfunctions in Alzheimer's disease (AD). However, more recent studies implicate the involvement of Abeta dimers and trimers in memory related AD pathology. Apparently, Abeta oligomers can bind with cellular prion protein at the membrane receptors, forming annular amyloid pores and membrane ion channels to induce aberrant spine cytoskeletal changes. Hence synapse targeting of Abeta oligomers involves activation of many receptors such as N-Methyl-D-aspartate (NMDA), alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), nicotinic acetylcholine (nAChRs), p75 neurotrophin (p75NTR) following aberrant clustering of metabotropic glutamate receptors (mGluR5) leading to neuronal loss and LTP failure. In particular, NMDA and AMPA receptor activation by soluble amyloid oligomers involves calcium mediated mitochondrial dysfunction, decreased Ca((2+))/calmodulin-dependent protein kinase II (CaMKII) levels at the synapses accompanying dramatic loss of synaptic proteins such as postsynaptic density-95 (PSD-95), dynamin-1 and synaptophysin. This kind of receptor-Abeta oligomer interaction might eventually affect the neuronal membrane integrity by altering dielectric barrier, various synaptic proteins, spine morphology and density and P/Q calcium currents that might provoke a cascade of events leading to neuronal loss and memory failure. In this review, we try to explain in detail the various possible mechanisms that connect Abeta oligomers with synapse damage and memory failure.

  5. Length Dependence of Tunneling Current Through Single Phenylene Oligomers Measured by Scanning Tunneling Microscopy at Low Temperature

    NASA Astrophysics Data System (ADS)

    Wakamatsu, Satoshi; Fujii, Shintaro; Akiba, Uichi; Fujihira, Masamichi

    2006-04-01

    The length dependence of tunneling current through single phenylene oligomers, i.e., benzenemethanethiol, 4-biphenylmethanethiol and [1,1':4',1''-terphenyl]-4-methanethiol, was determined experimentally by scanning tunneling microscopy (STM). The single phenylene oligomers were isolated in a self-assembled monolayer (SAM) matrix of a disulfide with two spherical bicyclo[2.2.2]octane moieties on Au(111). The STM measurement was conducted at a low temperature to prevent the thermal motions of the isolated molecules that occur at room temperature. The isolated single molecules inserted in the SAM matrix were observed as protrusions in an STM topography using a constant-current mode owing to their higher tunneling ability. The decay constant, β, of the tunneling current through single phenylene oligomers was estimated from the STM heights of the protrusions corresponding to the single phenylene oligomers using a bilayer tunnel junction model. The value of β for tunneling current through single phenylene oligomers was 5.5 ± 0.2 nm-1. In a constant-height mode, we measured the conductance of the isolated single molecules. We estimated an averaged single-molecular conductance of the isolated molecules of a biphenyl derivative to be ca. 2 nS. Here, one side of each isolated molecule was bound via an Au-S bond and the other phenyl end was physically in contact with an Au STM tip.

  6. Diamondoid monolayers as electron emitters

    DOEpatents

    Yang, Wanli; Fabbri, Jason D.; Melosh, Nicholas A.; Hussain, Zahid; Shen, Zhi-Xun

    2013-10-29

    Provided are electron emitters based upon diamondoid monolayers, preferably self-assembled higher diamondoid monolayers. High intensity electron emission has been demonstrated employing such diamondoid monolayers, particularly when the monolayers are comprised of higher diamondoids. The application of such diamondoid monolayers can alter the band structure of substrates, as well as emit monochromatic electrons, and the high intensity electron emissions can also greatly improve the efficiency of field-effect electron emitters as applied to industrial and commercial applications.

  7. Diamondoid monolayers as electron emitters

    DOEpatents

    Yang, Wanli [El Cerrito, CA; Fabbri, Jason D [San Francisco, CA; Melosh, Nicholas A [Menlo Park, CA; Hussain, Zahid [Orinda, CA; Shen, Zhi-Xun [Stanford, CA

    2012-04-10

    Provided are electron emitters based upon diamondoid monolayers, preferably self-assembled higher diamondoid monolayers. High intensity electron emission has been demonstrated employing such diamondoid monolayers, particularly when the monolayers are comprised of higher diamondoids. The application of such diamondoid monolayers can alter the band structure of substrates, as well as emit monochromatic electrons, and the high intensity electron emissions can also greatly improve the efficiency of field-effect electron emitters as applied to industrial and commercial applications.

  8. Lactic acid oligomers (OLAs) as prodrug moieties.

    PubMed

    Kruse, J; Lachmann, B; Lauer, R; Eppacher, S; Noe, C R

    2013-02-01

    In this paper we propose the use of lactic acid oligomers (OLAs) as prodrug moieties. Two synthetic approaches are presented, on the one hand a non selective oligomerisation of lactic acid and on the other hand a block synthesis to tetramers of lactic acid. Dimers of lactic acid were investigated with respect to their plasma stability and their adsorption to albumine. Ibuprofen was chosen as the first drug for OLAylation. The ester 19 of LA(1)-ibuprofen was evaluated with respect to the degradation to human plasma and the adsorption to albumine. All results indicate that lactic acid oligomers are promising prodrug moieties.

  9. The effect of polar end of long-chain fluorocarbon oligomers in promoting the superamphiphobic property over multi-scale rough Al alloy surfaces

    NASA Astrophysics Data System (ADS)

    Saifaldeen, Zubayda S.; Khedir, Khedir R.; Camci, Merve T.; Ucar, Ahmet; Suzer, Sefik; Karabacak, Tansel

    2016-08-01

    Rough structures with re-entrant property and their subsequent surface energy reduction with long-chain fluorocarbon oligomers are both critical in developing superamphiphobic (SAP, i.e. both super hydrophobic and superoleophobic) surfaces. However, morphology of the low-surface energy layer on a rough re-entrant substrate can strongly depend on the fluorocarbon oligomers used. In this study, the effect of polar end of different kinds of long-chain fluorocarbon oligomers in promoting a self-assembled monolayer with close packed molecules and robust adhesion on multi-scale rough Al alloy surfaces was investigated. Hierarchical Al alloy surfaces with microgrooves and nanograss structures were developed by a simple combination of one-directional mechanical sanding and post treatment in boiling de-ionized water (DIW). Three types of long-chain fluorocarbon oligomers of 1H, 1H, 2H, 2H-perfluorodecyltriethoxysilane (PFDTS), 1H, 1H, 2H, 2H-perfluorodecyltrichlorosilane (PFDCS), and perfluorooctanoic acid (PFOA) were chemically vaporized onto these rough Al alloy surfaces. The PFDCS exhibited the lowest surface free energy of less than 10 mN/m. The contact angle and sliding angle measurements for water, ethylene glycol, and peanut oil verified the SAP property of hierarchical rough Al alloy surfaces treated with alkylsilane oligomers (PFDTS, PFDCS). However, the hierarchical surfaces treated with fluorocarbon oligomer with polar acidic tail (PFOA) showed highly amphiphobic properties but could not reach the threshold for SAP. Chemical stability of the hierarchical Al alloy surfaces treated with the fluorocarbon oligomers was tested under the harsh conditions of ultra-sonication in acetone and annealing at high temperature after different treatment times. Contact angle measurements revealed the robustness of the alkylsilane oligomers and deterioration of the PFOA coating particularly for low surface tension liquids. The robust adhesion and close-packing of the alkylsilane

  10. Designing Surface-Confined Coordination Oligomers

    SciTech Connect

    Altman, M.; Rachamim, M; Ichiki, T; Iron, M; Evmenenko, G; Dutta, P; van der Boom, M

    2010-01-01

    HOMO-LUMO engineering of coordination-based oligomers covalently bound to silicon or glass has been achieved by the use of a partially fluorinated chromophore (see graphic). The experimental and computationally derived physical chemical properties of these assemblies are compared to their non-fluorinated analogues.

  11. Glucosamine oligomers: 1. Preparation and characterization.

    PubMed

    Domard, A; Cartier, N

    1989-10-01

    Hydrolysis of chitosan in hot concentrated HCl led to chito-oligosaccharides [beta-(1----4) linked 2-amino-2-deoxy-D-glucose]. The time dependence of the distribution was studied. A convenient choice of the conditions for steric exclusion chromatography of these hydrolysates allowed the separation of the first 15 oligomers and of fractions up to DP = 40.

  12. Scalable Fabrication of Quasi-Three-Dimensional Chiral Plasmonic Oligomers Based on Stepwise Colloid Sphere Lithography Technology

    NASA Astrophysics Data System (ADS)

    Xie, Shiwei; Yang, Jinzhe; Xiao, Xiao; Hou, Yidong; Du, Jinglei; Pang, Lin; Li, Xie; Gao, Fuhua

    2015-10-01

    We report a simple and scalable method for the fabrication of spiral-type chiral plasmonic oligomers based on the stepwise colloid sphere lithography technology. Through carefully adjusting the azimuthal angle Φ of polystyrene (PS) sphere array monolayer and the deposition thickness k n , the chiral plasmonic oligomers composed of four achiral particles can be successfully fabricated on a desired substrate. And their chiral sign, i.e., left-hand or right-hand, is dependent on the anticlockwise or clockwise deposition sequence of the achiral particles. The measured results show a large chiroptical resonance in the visible region, and this resonance can be easily adjusted by using different sizes of PS spheres. Our in-depth theoretical and experimental researches further reveal that the obtained chiral plasmonic oligomers are indeed a kind of quasi-three-dimensional chiral nanostructures, which own a three-dimensional geometrical morphology, but with nonreciprocity chiroptical effect. The ease and scalability (>1 cm2) of the fabrication method make chiral plasmonic oligomers promising candidates for many applications, such as chiral biosensor and catalysis.

  13. Capping of Aβ42 Oligomers by Small Molecule Inhibitors

    PubMed Central

    2015-01-01

    Aβ42 peptides associate into soluble oligomers and protofibrils in the process of forming the amyloid fibrils associated with Alzheimer’s disease. The oligomers have been reported to be more toxic to neurons than fibrils, and have been targeted by a wide range of small molecule and peptide inhibitors. With single touch atomic force microscopy (AFM), we show that monomeric Aβ42 forms two distinct types of oligomers, low molecular weight (MW) oligomers with heights of 1–2 nm and high MW oligomers with heights of 3–5 nm. In both cases, the oligomers are disc-shaped with diameters of ∼10–15 nm. The similar diameters suggest that the low MW species stack to form the high MW oligomers. The ability of Aβ42 inhibitors to interact with these oligomers is probed using atomic force microscopy and NMR spectroscopy. We show that curcumin and resveratrol bind to the N-terminus (residues 5–20) of Aβ42 monomers and cap the height of the oligomers that are formed at 1–2 nm. A second class of inhibitors, which includes sulindac sulfide and indomethacin, exhibit very weak interactions across the Aβ42 sequence and do not block the formation of the high MW oligomers. The correlation between N-terminal interactions and capping of the height of the Aβ oligomers provides insights into the mechanism of inhibition and the pathway of Aβ aggregation. PMID:25422864

  14. Molecular target of synthetic antimicrobial oligomer in bacterial membranes

    NASA Astrophysics Data System (ADS)

    Yang, Lihua; Gordon, Vernita; Som, Abhigyan; Cronan, John; Tew, Gregory; Wong, Gerard

    2008-03-01

    Antimicrobial peptides comprises a key component of innate immunity for a wide range of multicellular organisms. It has been shown that natural antimicrobial peptides and their synthetic analogs have demonstrated broad-spectrum antimicrobial activity via permeating bacterial membranes selectively. Synthetic antimicrobials with tunable structure and toxicological profiles are ideal for investigations of selectivity mechanisms. We investigate interactions and self-assembly using a prototypical family of antimicrobials based on phenylene ethynylene. Results from synchrotron small angle x-ray scattering (SAXS) results and in vitro microbicidal assays on genetically modified `knock-out' bacteria will be presented.

  15. Monte Carlo Simulation of Endlinking Oligomers

    NASA Technical Reports Server (NTRS)

    Hinkley, Jeffrey A.; Young, Jennifer A.

    1998-01-01

    This report describes initial efforts to model the endlinking reaction of phenylethynyl-terminated oligomers. Several different molecular weights were simulated using the Bond Fluctuation Monte Carlo technique on a 20 x 20 x 20 unit lattice with periodic boundary conditions. After a monodisperse "melt" was equilibrated, chain ends were linked whenever they came within the allowed bond distance. Ends remained reactive throughout, so that multiple links were permitted. Even under these very liberal crosslinking assumptions, geometrical factors limited the degree of crosslinking. Average crosslink functionalities were 2.3 to 2.6; surprisingly, they did not depend strongly on the chain length. These results agreed well with the degrees of crosslinking inferred from experiment in a cured phenylethynyl-terminated polyimide oligomer.

  16. Cure Chemistry of Phenylethynyl Terminated Oligomers

    NASA Technical Reports Server (NTRS)

    Wood, Karen H.; Orwoll, Robert A.; Young, Philip R.; Jensen, Brian J.; McNair, Harold M.

    1997-01-01

    The ability to process high performance polymers into quality, void-free composites has been significantly advanced using oligomers terminated with reactive groups which cure or crosslink at elevated temperature without the evolution of volatile byproducts. Several matrix resin systems of considerable interest to the aerospace community utilize phenylethynyl-terminated imide (PETI) technology to achieve this advantage. The present paper addresses the cure chemistry of PETI oligomers. The thermal cure of a low molecular weight model compound was studied using a variety of analytical techniques including differential scanning calorimetry, Fourier transform infrared spectroscopy, and liquid chromatography-mass spectroscopy. The studies indicate an extremely complex cure process. Many stable products were isolated and this paper reports current work on identification of those products. The intent of this research is to provide fundamental insight into the molecular structure of the cured PETI engineering materials so that performance and durability can be more fully assessed.

  17. Oligomer functionalized nanotubes and composites formed therewith

    DOEpatents

    Zettl, Alexander K; Sainsbury, Toby; Frechet, Jean M.J.

    2014-03-18

    Disclosed herein is a sequential functionalization methodology for the covalent modification of nanotubes with between one and four repeat units of a polymer. Covalent attachment of oligomer units to the surface of nanotubes results in oligomer units forming an organic sheath around the nanotubes, polymer-functionalized-nanotubes (P-NTs). P-NTs possess chemical functionality identical to that of the functionalizing polymer, and thus provide nanoscale scaffolds which may be readily dispersed within a monomer solution and participate in the polymerization reaction to form a polymer-nanotube/polymer composite. Formation of polymer in the presence of P-NTs leads to a uniform dispersion of nanotubes within the polymer matrix, in contrast to aggregated masses of nanotubes in the case of pristine-NTs. The covalent attachment of oligomeric units to the surface of nanotubes represents the formation of a functional nanoscale building block which can be readily dispersed and integrated within the polymer to form a novel composite material.

  18. Interaction of arginine oligomer with model membrane

    SciTech Connect

    Yi, Dandan . E-mail: yi_dandan@yahoo.com.cn; Guoming, Li; Gao, Li; Wei, Liang

    2007-08-10

    Short oligomers of arginine (R8) have been shown to cross readily a variety of biological barriers. A hypothesis was put forward that inverted micelles form in biological membranes in the presence of arginine oligomer peptides, facilitating their transfer through the membranes. In order to define the role of peptide-lipid interaction in this mechanism, we prepared liposomes as the model membrane to study the ability of R8 inducing calcein release from liposomes, the fusion of liposomes, R8 binding to liposomes and membrane disturbing activity of the bound R8. The results show that R8 binding to liposome membrane depends on lipid compositions, negative surface charge density and interior water phase pH values of liposomes. R8 has no activity to induce the leakage of calcein from liposomes or improve liposome fusion. R8 does not permeabilize through the membrane spontaneously. These peptides delivering drugs through membranes may depend on receptors and energy.

  19. Ethynyl terminated ester oligomers and polymers therefrom

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M. (Inventor); hesives and composite matrices. (Inventor)

    1987-01-01

    A new class of ethynyl-terminated oligomers and the process for preparing same are disclosed. Upon the application of heat, with or without a catalyst, the ethynyl groups react to provide crosslinking and chain extension to increase the polymer use temperature and improve the polymer solvent resistance. These improved polyesters are potentially useful in packaging, magnetic tapes, capacitors, industrial belting, protective coatings, structural adhesives and composite matrices.

  20. New Acetylene-Terminated Quinoxaline Oligomers

    DTIC Science & Technology

    1982-03-01

    diketone . In this work, we tried other bases, but potassium t-butoxide and lithium t- butoxide gave unsatisfactory results. Synthesis of acetone adduct...the most expensive ingredient. We have previously been able to improve the synthesis of the bisglyoxals needed for these adhesives,2 and are now...general method of synthesis which have been developed is to first condense the quinoxallne oligomer with glyoxal end groups. 2 r ),-CO--CO-Ar--CO--C&O--j

  1. Structural studies on HCN oligomers. [catalysts for prebiotic processes

    NASA Technical Reports Server (NTRS)

    Ferris, J. P.; Edelson, E. H.; Auyeung, J. M.; Joshi, P. C.

    1981-01-01

    NMR spectral studies on the HCN oligomers suggest the presence of carboxamide and urea groupings. The release of CO2, H2O, HCN, CH3CN, HCONH2 and pyridine on pyrolysis is consistent with the presence of these groupings as well as carboxylic acid groups. No basic primary amine groupings could be detected with fluorescamine. Hydrazinolysis of the HCN oligomers releases 10% of the amino acids normally released by acid hydrolysis. The oligomers give a positive biuret test but this is not due to the presence of peptide bonds. There is no conclusive evidence for the presence of peptide bonds in the HCN oligomers. No diglycine was detected on partial hydrolysis of the HCN oligomers at pH 8.5 suggesting that HCN oligomers were not a source of prebiotic peptides.

  2. DNA sequence similarity recognition by hybridization to short oligomers

    DOEpatents

    Milosavljevic, Aleksandar

    1999-01-01

    Methods are disclosed for the comparison of nucleic acid sequences. Data is generated by hybridizing sets of oligomers with target nucleic acids. The data thus generated is manipulated simultaneously with respect to both (i) matching between oligomers and (ii) matching between oligomers and putative reference sequences available in databases. Using data compression methods to manipulate this mutual information, sequences for the target can be constructed.

  3. Amyloid β-protein oligomers and Alzheimer’s disease

    PubMed Central

    2013-01-01

    The oligomer cascade hypothesis, which states that oligomers are the initiating pathologic agents in Alzheimer’s disease, has all but supplanted the amyloid cascade hypothesis, which suggested that fibers were the key etiologic agents in Alzheimer’s disease. We review here the results of in vivo, in vitro and in silico studies of amyloid β-protein oligomers, and discuss important caveats that should be considered in the evaluation of these results. This article is divided into four sections that mirror the main approaches used in the field to better understand oligomers: (1) attempts to locate and examine oligomers in vivo in situ; that is, without removing these species from their environment; (2) studies involving oligomers extracted from human or animal tissues and the subsequent characterization of their properties ex vivo; (3) studies of oligomers that have been produced synthetically and studied using a reductionist approach in relatively simple in vitro biophysical systems; and (4) computational studies of oligomers in silico. These multiple orthogonal approaches have revealed much about the molecular and cell biology of amyloid β-protein. However, as informative as these approaches have been, the amyloid β-protein oligomer system remains enigmatic. PMID:24289820

  4. Polyetherurethane oligomers with aldehyde groups as additives for lubricating oils

    SciTech Connect

    Nikolaev, V.N.; Abramov, E.G.; Tenyushev, A.I.

    1995-01-01

    Polyetherurethane oligomers with aldehyde groups, which we synthesized from polyoxypropylene diols (molecular weight 500, 1000, 1500, 2000, or 3000) with toluene diisocyanate and salicylaldehyde, are of interest as additives for lubricating oils. The effects of these oligomers on the service properties and physicochemical characteristics of lubricating oils were investigated by methods prreviously described. As the lube base stocks we used castor oil, a polyoxypropylene diol and a polyethoxysiloxane. The oligomers are readily soluble in organic solvents and in the lube base stocks, and their solutions are stable during storage and use. We found that the optimal concentration of oligomers is 5%, providing the best lubricating properties, in particular the best antiwear properties.

  5. Macrocyclic 2,7-Anthrylene Oligomers.

    PubMed

    Yamamoto, Yuta; Wakamatsu, Kan; Iwanaga, Tetsuo; Sato, Hiroyasu; Toyota, Shinji

    2016-05-06

    A macrocyclic compound consisting of six 2,7-anthrylene units was successfully synthesized by Ni-mediated coupling of the corresponding dibromo precursor as a novel π-conjugated compound. This compound was sufficiently stable and soluble in organic solvents due to the presence of mesityl groups. X-ray analysis showed that the molecule had a nonplanar and hexagonal wheel-shaped framework of approximately S6 symmetry. The dynamic process between two S6 structures was observed by using the dynamic NMR technique, the barrier being 58 kJ mol(-1) . The spectroscopic properties of the hexamer were compared with those of analogous linear oligomers.

  6. Anharmonic Vibrational Dynamics of DNA Oligomers

    NASA Astrophysics Data System (ADS)

    Kühn, O.; Došlić, N.; Krishnan, G. M.; Fidder, H.; Heyne, K.

    Combining two-color infared pump-probe spectroscopy and anharmonic force field calculations we characterize the anharmonic coupling patterns between fingerprint modes and the hydrogen-bonded symmetric vNH2 stretching vibration in adenine-thymine dA20-dT20 DNA oligomers. Specifically, it is shown that the anharmonic coupling between the δNH2 bending and the vC4=O4 stretching vibration, both absorbing around 1665 cm-1, can be used to assign the vNH2 fundamental transition at 3215 cm-1 despite the broad background absorption of water.

  7. Failure processes in embedded monolayer graphene under axial compression.

    PubMed

    Androulidakis, Charalampos; Koukaras, Emmanuel N; Frank, Otakar; Tsoukleri, Georgia; Sfyris, Dimitris; Parthenios, John; Pugno, Nicola; Papagelis, Konstantinos; Novoselov, Kostya S; Galiotis, Costas

    2014-06-12

    Exfoliated monolayer graphene flakes were embedded in a polymer matrix and loaded under axial compression. By monitoring the shifts of the 2D Raman phonons of rectangular flakes of various sizes under load, the critical strain to failure was determined. Prior to loading care was taken for the examined area of the flake to be free of residual stresses. The critical strain values for first failure were found to be independent of flake size at a mean value of -0.60% corresponding to a yield stress up to -6 GPa. By combining Euler mechanics with a Winkler approach, we show that unlike buckling in air, the presence of the polymer constraint results in graphene buckling at a fixed value of strain with an estimated wrinkle wavelength of the order of 1-2 nm. These results were compared with DFT computations performed on analogue coronene/PMMA oligomers and a reasonable agreement was obtained.

  8. Failure Processes in Embedded Monolayer Graphene under Axial Compression

    PubMed Central

    Androulidakis, Charalampos; Koukaras, Emmanuel N.; Frank, Otakar; Tsoukleri, Georgia; Sfyris, Dimitris; Parthenios, John; Pugno, Nicola; Papagelis, Konstantinos; Novoselov, Kostya S.; Galiotis, Costas

    2014-01-01

    Exfoliated monolayer graphene flakes were embedded in a polymer matrix and loaded under axial compression. By monitoring the shifts of the 2D Raman phonons of rectangular flakes of various sizes under load, the critical strain to failure was determined. Prior to loading care was taken for the examined area of the flake to be free of residual stresses. The critical strain values for first failure were found to be independent of flake size at a mean value of –0.60% corresponding to a yield stress up to -6 GPa. By combining Euler mechanics with a Winkler approach, we show that unlike buckling in air, the presence of the polymer constraint results in graphene buckling at a fixed value of strain with an estimated wrinkle wavelength of the order of 1–2 nm. These results were compared with DFT computations performed on analogue coronene/PMMA oligomers and a reasonable agreement was obtained. PMID:24920340

  9. Cooperative Switching in Nanofibers of Azobenzene Oligomers

    NASA Astrophysics Data System (ADS)

    Weber, Christopher; Liebig, Tobias; Gensler, Manuel; Zykov, Anton; Pithan, Linus; Rabe, Jürgen P.; Hecht, Stefan; Bléger, David; Kowarik, Stefan

    2016-05-01

    Next-generation molecular devices and machines demand the integration of molecular switches into hierarchical assemblies to amplify the response of the system from the molecular level to the meso- or macro-scale. Here, we demonstrate that multi-azobenzene oligomers can assemble to form robust supramolecular nanofibers in which they can be switched repeatedly between the E- and Z-configuration. While in isolated oligomers the azobenzene units undergo reversible photoisomerization independently, in the nanofibers they are coupled via intermolecular interactions and switch cooperatively as evidenced by unusual thermal and kinetic behavior. We find that the photoisomerization rate from the Z-isomer to the E-isomer depends on the fraction of Z-azobenzene in the nanofibers, and is increased by more than a factor of 4 in Z-rich fibers when compared to E-rich fibers. This demonstrates the great potential of coupling individual photochromic units for increasing their quantum efficiency in the solid state with potential relevance for actuation and sensing.

  10. Computing highly specific and mismatch tolerant oligomers efficiently.

    PubMed

    Yamada, Tomoyuki; Morishita, Shinichi

    2003-01-01

    The sequencing of the genomes of a variety of species and the growing databases containing expressed sequence tags (ESTs) and complementary DNAs (cDNAs) facilitate the design of highly specific oligomers for use as genomic markers, PCR primers, or DNA oligo microarrays. The first step in evaluating the specificity of short oligomers of about twenty units in length is to determine the frequencies at which the oligomers occur. However, for oligomers longer than about fifty units this is not efficient, as they usually have a frequency of only 1. A more suitable procedure is to consider the mismatch tolerance of an oligomer, that is, the minimum number of mismatches that allows a given oligomer to match a sub-sequence other than the target sequence anywhere in the genome or the EST database. However, calculating the exact value of mismatch tolerance is computationally costly and impractical. Therefore, we studied the problem of checking whether an oligomer meets the constraint that its mismatch tolerance is no less than a given threshold. Here, we present an efficient dynamic programming algorithm solution that utilizes suffix and height arrays. We demonstrated the effectiveness of this algorithm by efficiently computing a dense list of oligo-markers applicable to the human genome. Experimental results show that the algorithm runs faster than well-known Abrahamson's algorithm by orders of magnitude and is able to enumerate 63% to approximately 79% of qualified oligomers.

  11. Computing highly specific and noise-tolerant oligomers efficiently.

    PubMed

    Yamada, Tomoyuki; Morishita, Shinichi

    2004-03-01

    The sequencing of the genomes of a variety of species and the growing databases containing expressed sequence tags (ESTs) and complementary DNAs (cDNAs) facilitate the design of highly specific oligomers for use as genomic markers, PCR primers, or DNA oligo microarrays. The first step in evaluating the specificity of short oligomers of about 20 units in length is to determine the frequencies at which the oligomers occur. However, for oligomers longer than about fifty units this is not efficient, as they usually have a frequency of only 1. A more suitable procedure is to consider the mismatch tolerance of an oligomer, that is, the minimum number of mismatches that allows a given oligomer to match a substring other than the target sequence anywhere in the genome or the EST database. However, calculating the exact value of mismatch tolerance is computationally costly and impractical. Therefore, we studied the problem of checking whether an oligomer meets the constraint that its mismatch tolerance is no less than a given threshold. Here, we present an efficient dynamic programming algorithm solution that utilizes suffix and height arrays. We demonstrated the effectiveness of this algorithm by efficiently computing a dense list of numerous oligo-markers applicable to the human genome. Experimental results show that the algorithm runs faster than well-known Abrahamson's algorithm by orders of magnitude and is able to enumerate 65% approximately 76% of qualified oligomers.

  12. Origin and diversification of a metabolic cycle in oligomer world.

    PubMed

    Nishio, Tomoaki; Narikiyo, Osamu

    2013-02-01

    Based on the oligomer-world hypothesis we propose an abstract model where the molecular recognition among oligomers is described in the shape space. The origin of life in the oligomer world is regarded as the establishment of a metabolic cycle in a primitive cell. The cycle is sustained by the molecular recognition. If an original cell acquires the ability of the replication of oligomers, the relationship among oligomers changes due to the poor fidelity of the replication. This change leads to the diversification of metabolic cycles. The selection among diverse cycles is the basis of the evolution. The evolvability is one of the essential characters of life. We demonstrate the origin and diversification of the metabolic cycle by the computer simulation of our model. Such a simulation is expected to be the simplified demonstration of what actually occurred in the primordial soup. Our model describes an analog era preceding the digital era based on the genetic code.

  13. Non-aqueous dispersion coatings based on crystalline oligomers

    SciTech Connect

    Jones, F.N.

    1993-12-31

    Amorphous oligomers and polymers are generally used in coatings; crystalline ones are avoided because of the difficulty of achieving homogeneous, defect-free films. However, dispersions of crystalline oligomers offer potential advantages of stability, useful application rheology, and excellent film properties. The authors describe non-aqueous dispersions of mixtures of crystalline and amorphous oligomers. An example is a dispersion of mixtures of crystalline (at ambient temperature) hydroxyl-functional oligomer of terephthalic acid and 1,6-hexanediol mixed with an amorphous hydroxyl-functional oligomer of terephthalic acid and glycidyl neodecanote. Microscopy, WAXD and DSC indicate that the dispersion particles are crystalline and have a diameter of 5 to 20 {mu}m. The dispersions are stable and are thixotropic. Coatings formulated with melamine and polyisocyanate resin crosslinkers form glossy, transparent film with excellent mechanical properties.

  14. Atomic View of a Toxic Amyloid Small Oligomer

    SciTech Connect

    Laganowsky, Arthur; Liu, Cong; Sawaya, Michael R.; Whitelegge, Julian P.; Park, Jiyong; Zhao, Minglei; Pensalfini, Anna; Soriaga, Angela B.; Landau, Meytal; Teng, Poh K.; Cascio, Duilio; Glabe, Charles; Eisenberg, David

    2012-04-30

    Amyloid diseases, including Alzheimer's, Parkinson's, and the prion conditions, are each associated with a particular protein in fibrillar form. These amyloid fibrils were long suspected to be the disease agents, but evidence suggests that smaller, often transient and polymorphic oligomers are the toxic entities. Here, we identify a segment of the amyloid-forming protein {alpha}{beta} crystallin, which forms an oligomeric complex exhibiting properties of other amyloid oligomers: {beta}-sheet-rich structure, cytotoxicity, and recognition by an oligomer-specific antibody. The x-ray-derived atomic structure of the oligomer reveals a cylindrical barrel, formed from six antiparallel protein strands, that we term a cylindrin. The cylindrin structure is compatible with a sequence segment from the {beta}-amyloid protein of Alzheimer's disease. Cylindrins offer models for the hitherto elusive structures of amyloid oligomers.

  15. Glucosamine oligomers: 4. Solid state-crystallization and sustained dissolution.

    PubMed

    Domard, A; Cartier, N

    1992-04-01

    When glucosamine oligomers are stored in the solid state they undergo a process of crystallization. The extent to which this occurs depends on whether the samples are isolated in the -NH3+ or -NH2 form, on the storage time, and on the degree of polymerization of the isolated oligomer. The allomorph obtained by this process seems to correspond to the so-called 'tendon-chitosan'. Dissolution of such aged oligomer samples gives rise to a process of dissociation of the associated chains in the crystal, leading to the establishment of a pseudo-equilibrium between single and associated oligomer chains and hence the simultaneous presence of the 'monomeric', 'dimeric', 'trimeric', etc., forms of the oligomer. The phenomenon cannot be attributed to a process of aggregation in solution. The effects of various parameters on this behaviour have been investigated.

  16. Continuity of Monolayer-Bilayer Junctions for Localization of Lipid Raft Microdomains in Model Membranes

    PubMed Central

    Ryu, Yong-Sang; Wittenberg, Nathan J.; Suh, Jeng-Hun; Lee, Sang-Wook; Sohn, Youngjoo; Oh, Sang-Hyun; Parikh, Atul N.; Lee, Sin-Doo

    2016-01-01

    We show that the selective localization of cholesterol-rich domains and associated ganglioside receptors prefer to occur in the monolayer across continuous monolayer-bilayer junctions (MBJs) in supported lipid membranes. For the MBJs, glass substrates were patterned with poly(dimethylsiloxane) (PDMS) oligomers by thermally-assisted contact printing, leaving behind 3 nm-thick PDMS patterns. The hydrophobicity of the transferred PDMS patterns was precisely tuned by the stamping temperature. Lipid monolayers were formed on the PDMS patterned surface while lipid bilayers were on the bare glass surface. Due to the continuity of the lipid membranes over the MBJs, essentially free diffusion of lipids was allowed between the monolayer on the PDMS surface and the upper leaflet of the bilayer on the glass substrate. The preferential localization of sphingomyelin, ganglioside GM1 and cholesterol in the monolayer region enabled to develop raft microdomains through coarsening of nanorafts. Our methodology provides a simple and effective scheme of non-disruptive manipulation of the chemical landscape associated with lipid phase separations, which leads to more sophisticated applications in biosensors and as cell culture substrates. PMID:27230411

  17. Continuity of monolayer-bilayer junctions for localization of lipid raft microdomains in model membranes

    SciTech Connect

    Ryu, Yong -Sang; Wittenberg, Nathan J.; Suh, Jeng -Hun; Lee, Sang -Wook; Sohn, Youngjoo; Oh, Sang -Hyun; Parikh, Atul N.; Lee, Sin -Doo

    2016-05-27

    We show that the selective localization of cholesterol-rich domains and associated ganglioside receptors prefer to occur in the monolayer across continuous monolayer-bilayer junctions (MBJs) in supported lipid membranes. For the MBJs, glass substrates were patterned with poly(dimethylsiloxane) (PDMS) oligomers by thermally-assisted contact printing, leaving behind 3 nm-thick PDMS patterns. The hydrophobicity of the transferred PDMS patterns was precisely tuned by the stamping temperature. Lipid monolayers were formed on the PDMS patterned surface while lipid bilayers were on the bare glass surface. Due to the continuity of the lipid membranes over the MBJs, essentially free diffusion of lipids was allowed between the monolayer on the PDMS surface and the upper leaflet of the bilayer on the glass substrate. The preferential localization of sphingomyelin, ganglioside GM1 and cholesterol in the monolayer region enabled to develop raft microdomains through coarsening of nanorafts. Furthermore, our methodology provides a simple and effective scheme of non-disruptive manipulation of the chemical landscape associated with lipid phase separations, which leads to more sophisticated applications in biosensors and as cell culture substrates.

  18. Continuity of monolayer-bilayer junctions for localization of lipid raft microdomains in model membranes

    DOE PAGES

    Ryu, Yong -Sang; Wittenberg, Nathan J.; Suh, Jeng -Hun; ...

    2016-05-27

    We show that the selective localization of cholesterol-rich domains and associated ganglioside receptors prefer to occur in the monolayer across continuous monolayer-bilayer junctions (MBJs) in supported lipid membranes. For the MBJs, glass substrates were patterned with poly(dimethylsiloxane) (PDMS) oligomers by thermally-assisted contact printing, leaving behind 3 nm-thick PDMS patterns. The hydrophobicity of the transferred PDMS patterns was precisely tuned by the stamping temperature. Lipid monolayers were formed on the PDMS patterned surface while lipid bilayers were on the bare glass surface. Due to the continuity of the lipid membranes over the MBJs, essentially free diffusion of lipids was allowed betweenmore » the monolayer on the PDMS surface and the upper leaflet of the bilayer on the glass substrate. The preferential localization of sphingomyelin, ganglioside GM1 and cholesterol in the monolayer region enabled to develop raft microdomains through coarsening of nanorafts. Furthermore, our methodology provides a simple and effective scheme of non-disruptive manipulation of the chemical landscape associated with lipid phase separations, which leads to more sophisticated applications in biosensors and as cell culture substrates.« less

  19. Rhodium-coordinated poly(arylene-ethynylene)-alt-poly(arylene-vinylene) copolymer acting as photocatalyst for visible-light-powered NAD⁺/NADH reduction.

    PubMed

    Oppelt, Kerstin T; Gasiorowski, Jacek; Egbe, Daniel Ayuk Mbi; Kollender, Jan Philipp; Himmelsbach, Markus; Hassel, Achim Walter; Sariciftci, Niyazi Serdar; Knör, Günther

    2014-09-10

    A 2,2'-bipyridyl-containing poly(arylene-ethynylene)-alt-poly(arylene-vinylene) polymer, acting as a light-harvesting ligand system, was synthesized and coupled to an organometallic rhodium complex designed for photocatalytic NAD(+)/NADH reduction. The material, which absorbs over a wide spectral range, was characterized by using various analytical techniques, confirming its chemical structure and properties. The dielectric function of the material was determined from spectroscopic ellipsometry measurements. Photocatalytic reduction of nucleotide redox cofactors under visible light irradiation (390-650 nm) was performed and is discussed in detail. The new metal-containing polymer can be used to cover large surface areas (e.g. glass beads) and, due to this immobilization step, can be easily separated from the reaction solution after photolysis. Because of its high stability, the polymer-based catalyst system can be repeatedly used under different reaction conditions for (photo)chemical reduction of NAD(+). With this concept, enzymatic, photo-biocatalytic systems for solar energy conversion can be facilitated, and the precious metal catalyst can be recycled.

  20. Full-Color Emission and Temperature Dependence of the Luminescence in Poly-P -Phenylene Ethynylene-ZnS:Mn2+ Composite Particles

    SciTech Connect

    Chen, Wei; Joly, Alan G.; Malm, Jan-Olle; Bovin, Jan-Olov; Wang, Shaopeng

    2003-07-10

    Synthesis of a nanocomposite material composed of anionic poly (phenylene ethynylene) (aPPE) polymer particles and ZnS:Mn2+ nanoparticles is described and its luminescence properties investigated. aPPE particles have two emissions, one in the blue (460 nm), which are assigned to the 0-0 transition and an excimer, respectively. ZnS:Mn2+ nanoparticle have an emission at 596 nm which is due to the 4T1-6A1 transition of Mn2+ and an emission at 706 nm which is ascribed to a defect-related luminescence. The blue, green, yellow, and red emissions make the composite a potential material for full-color displays. More interesting, the relative intensities of the different emissions may be varied by changing the excitation energy. Photoluminescence excitation and emission spectra as well as observations on luminescence lifetimes indicate that there is negligible energy transfer from the polymer particles to the ZnS:Mn2+ nanoparticle. Temperature studies reveal that the ZnS:Mn2+ particles in the nanocomposite have a significantly reduced thermal quenching energy relative to bare ZnS: > n2+ nanoparticles. In addition, between room temperature and 90 C, the luminescence of the ZnS:Mn2+ nanoparticles at 596 nm increases in intensity with increasing temperature. This surprising phenomenon is attributed to thermoluminescence and thermal curing of the particle surface upon heating.

  1. Soluble Aβ oligomer production and toxicity

    PubMed Central

    Larson, Megan E.; Lesné, Sylvain E.

    2011-01-01

    For nearly 100 years following the first description of this neurological disorder by Dr. Alois Alzheimer, amyloid plaques and neurofibrillary tangles have been hypothesized to cause neuronal loss. With evidence that the extent of insoluble, deposited amyloid poorly correlated with cognitive impairment, research efforts focused on soluble forms of Aβ, also referred as Aβ oligomers. Following a decade of studies, soluble oligomeric forms of Aβ are now believed to induce the deleterious cascade(s) involved in the pathophysiology of Alzheimer’s disease. In this review, we will discuss our current understanding about endogenous oligomeric Aβ production, their relative toxicity in vivo and in vitro, and explore the potential future directions needed for the field. PMID:22121920

  2. Structural and functional properties of prefibrillar α-synuclein oligomers.

    PubMed

    Pieri, Laura; Madiona, Karine; Melki, Ronald

    2016-04-14

    The deposition of fibrillar alpha-synuclein (α-syn) within inclusions (Lewy bodies and Lewy neurites) in neurons and glial cells is a hallmark of synucleinopathies. α-syn populates a variety of assemblies ranging from prefibrillar oligomeric species to fibrils whose specific contribution to neurodegeneration is still unclear. Here, we compare the specific structural and biological properties of distinct soluble prefibrillar α-syn oligomers formed either spontaneously or in the presence of dopamine and glutaraldehyde. We show that both on-fibrillar assembly pathway and distinct dopamine-mediated and glutaraldehyde-cross-linked α-syn oligomers are only slightly effective in perturbing cell membrane integrity and inducing cytotoxicity, while mature fibrils exhibit the highest toxicity. In contrast to low-molecular weight and unstable oligomers, large stable α-syn oligomers seed the aggregation of soluble α-syn within reporter cells although to a lesser extent than mature α-syn fibrils. These oligomers appear elongated in shape. Our findings suggest that α-syn oligomers represent a continuum of species ranging from unstable low molecular weight particles to mature fibrils via stable elongated oligomers composed of more than 15 α-syn monomers that possess seeding capacity.

  3. Toxic species in amyloid disorders: Oligomers or mature fibrils

    PubMed Central

    Verma, Meenakshi; Vats, Abhishek; Taneja, Vibha

    2015-01-01

    Protein aggregation is the hallmark of several neurodegenerative disorders. These protein aggregation (fibrillization) disorders are also known as amyloid disorders. The mechanism of protein aggregation involves conformation switch of the native protein, oligomer formation leading to protofibrils and finally mature fibrils. Mature fibrils have long been considered as the cause of disease pathogenesis; however, recent evidences suggest oligomeric intermediates formed during fibrillization to be toxic. In this review, we have tried to address the ongoing debate for these toxic amyloid species. We did an extensive literature search and collated information from Pubmed (http://www.ncbi.nlm.nih.gov) and Google search using various permutations and combinations of the following keywords: Neurodegeneration, amyloid disorders, protein aggregation, fibrils, oligomers, toxicity, Alzheimer's Disease, Parkinson's Disease. We describe different instances showing the toxicity of mature fibrils as well as oligomers in Alzheimer's Disease and Parkinson's Disease. Distinct structural framework and morphology of amyloid oligomers suggests difference in toxic effect between oligomers and fibrils. We highlight the difference in structure and proposed toxicity pathways for fibrils and oligomers. We also highlight the evidences indicating that intermediary oligomeric species can act as potential diagnostic biomarker. Since the formation of these toxic species follow a common structural switch among various amyloid disorders, the protein aggregation events can be targeted for developing broad-range therapeutics. The therapeutic trials based on the understanding of different protein conformers (monomers, oligomers, protofibrils and fibrils) in amyloid cascade are also described. PMID:26019408

  4. A Generic Method for Design of Oligomer-Specific Antibodies

    PubMed Central

    Brännström, Kristoffer; Lindhagen-Persson, Malin; Gharibyan, Anna L.; Iakovleva, Irina; Vestling, Monika; Sellin, Mikael E.; Brännström, Thomas; Morozova-Roche, Ludmilla; Forsgren, Lars; Olofsson, Anders

    2014-01-01

    Antibodies that preferentially and specifically target pathological oligomeric protein and peptide assemblies, as opposed to their monomeric and amyloid counterparts, provide therapeutic and diagnostic opportunities for protein misfolding diseases. Unfortunately, the molecular properties associated with oligomer-specific antibodies are not well understood, and this limits targeted design and development. We present here a generic method that enables the design and optimisation of oligomer-specific antibodies. The method takes a two-step approach where discrimination between oligomers and fibrils is first accomplished through identification of cryptic epitopes exclusively buried within the structure of the fibrillar form. The second step discriminates between monomers and oligomers based on differences in avidity. We show here that a simple divalent mode of interaction, as within e.g. the IgG isotype, can increase the binding strength of the antibody up to 1500 times compared to its monovalent counterpart. We expose how the ability to bind oligomers is affected by the monovalent affinity and the turnover rate of the binding and, importantly, also how oligomer specificity is only valid within a specific concentration range. We provide an example of the method by creating and characterising a spectrum of different monoclonal antibodies against both the Aβ peptide and α-synuclein that are associated with Alzheimer's and Parkinson's diseases, respectively. The approach is however generic, does not require identification of oligomer-specific architectures, and is, in essence, applicable to all polypeptides that form oligomeric and fibrillar assemblies. PMID:24618582

  5. Structural and functional properties of prefibrillar α-synuclein oligomers

    PubMed Central

    Pieri, Laura; Madiona, Karine; Melki, Ronald

    2016-01-01

    The deposition of fibrillar alpha-synuclein (α-syn) within inclusions (Lewy bodies and Lewy neurites) in neurons and glial cells is a hallmark of synucleinopathies. α-syn populates a variety of assemblies ranging from prefibrillar oligomeric species to fibrils whose specific contribution to neurodegeneration is still unclear. Here, we compare the specific structural and biological properties of distinct soluble prefibrillar α-syn oligomers formed either spontaneously or in the presence of dopamine and glutaraldehyde. We show that both on-fibrillar assembly pathway and distinct dopamine-mediated and glutaraldehyde-cross-linked α-syn oligomers are only slightly effective in perturbing cell membrane integrity and inducing cytotoxicity, while mature fibrils exhibit the highest toxicity. In contrast to low-molecular weight and unstable oligomers, large stable α-syn oligomers seed the aggregation of soluble α-syn within reporter cells although to a lesser extent than mature α-syn fibrils. These oligomers appear elongated in shape. Our findings suggest that α-syn oligomers represent a continuum of species ranging from unstable low molecular weight particles to mature fibrils via stable elongated oligomers composed of more than 15 α-syn monomers that possess seeding capacity. PMID:27075649

  6. Elucidating molecular mass and shape of a neurotoxic Aβ oligomer.

    PubMed

    Sebollela, Adriano; Mustata, Gina-Mirela; Luo, Kevin; Velasco, Pauline T; Viola, Kirsten L; Cline, Erika N; Shekhawat, Gajendra S; Wilcox, Kyle C; Dravid, Vinayak P; Klein, William L

    2014-12-17

    Alzheimer's disease (AD), the most prevalent type of dementia, has been associated with the accumulation of amyloid β oligomers (AβOs) in the central nervous system. AβOs vary widely in size, ranging from dimers to larger than 100 kDa. Evidence indicates that not all oligomers are toxic, and there is yet no consensus on the size of the actual toxic oligomer. Here we used NU4, a conformation-dependent anti-AβO monoclonal antibody, to investigate size and shape of a toxic AβO assembly. By using size-exclusion chromatography and immuno-based detection, we isolated an AβO-NU4 complex amenable for biochemical and morphological studies. The apparent molecular mass of the NU4-targeted oligomer was 80 kDa. Atomic force microscopy imaging of the AβO-NU4 complex showed a size distribution centered at 5.37 nm, an increment of 1.5 nm compared to the size of AβOs (3.85 nm). This increment was compatible with the size of NU4 (1.3 nm), suggesting a 1:1 oligomer to NU4 ratio. NU4-reactive oligomers extracted from AD human brain concentrated in a molecular mass range similar to that found for in vitro prepared oligomers, supporting the relevance of the species herein studied. These results represent an important step toward understanding the connection between AβO size and toxicity.

  7. Force modulated conductance of artificial coiled-coil protein monolayers.

    PubMed

    Atanassov, Alexander; Hendler, Ziv; Berkovich, Inbal; Ashkenasy, Gonen; Ashkenasy, Nurit

    2013-01-01

    Studies of charge transport through proteins bridged between two electrodes have been the subject of intense research in recent years. However, the complex structure of proteins makes it difficult to elucidate transport mechanisms, and the use of simple peptide oligomers may be an over simplified model of the proteins. To bridge this structural gap, we present here studies of charge transport through artificial parallel coiled-coil proteins conducted in dry environment. Protein monolayers uniaxially oriented at an angle of ∼ 30° with respect to the surface normal were prepared. Current voltage measurements, obtained using conductive-probe atomic force microscopy, revealed the mechano-electronic behavior of the protein films. It was found that the low voltage conductance of the protein monolayer increases linearly with applied force, mainly due to increase in the tip contact area. Negligible compression of the films for loads below 26 nN allowed estimating a tunneling attenuation factor, β(0) , of 0.5-0.6 Å(-1) , which is akin to charge transfer by tunneling mechanism, despite the comparably large charge transport distance. These studies show that mechano-electronic behavior of proteins can shed light on their complex charge transport mechanisms, and on how these mechanisms depend on the detailed structure of the proteins. Such studies may provide insightful information on charge transfer in biological systems.

  8. Pramipexole prevents neurotoxicity induced by oligomers of beta-amyloid.

    PubMed

    Uberti, Daniela; Bianchi, Irene; Olivari, Luca; Ferrari-Toninelli, Giulia; Canonico, PierLuigi; Memo, Maurizio

    2007-08-27

    Here we demonstrate that pramipexole, an antiparkinsonian dopamine receptor agonist drug, exerts neuroprotective effects against beta-amyloid neurotoxicity. Using a specific protocol to test individually oligomers, fibrils, or unaggregated amyloid beta-peptide, we found pramipexole able to protect cells against oligomers and fibrils. Unaggregated amyloid beta-peptide was found unable to cause cell death. Fibrils and oligomers were also found to produce elevated amount of free radicals, and this effect was prevented by pramipexole. We propose pramipexole may become in the future a coadjuvant in the treatment of neuropathologies, besides Parkinson's disease, where amyloid beta-peptide-mediated oxidative injury exerts a relevant role.

  9. Phenomenological Modeling for Langmuir Monolayers

    NASA Astrophysics Data System (ADS)

    Baptiste, Dimitri; Kelly, David; Safford, Twymun; Prayaga, Chandra; Varney, Christopher N.; Wade, Aaron

    Experimentally, Langmuir monolayers have applications in molecular optical, electronic, and sensor devices. Traditionally, Langmuir monolayers are described by a rigid rod model where the rods interact via a Leonard-Jones potential. Here, we propose effective phenomenological models and utilize Monte Carlo simulations to analyze the phase behavior and compare with experimental isotherms. Research reported in this abstract was supported by UWF NIH MARC U-STAR 1T34GM110517-01.

  10. Oligomer formation in the radiation-induced polymerization of styrene

    NASA Astrophysics Data System (ADS)

    Harayma, Hiroshi; Al-Sheikhly, Mohamad; Silverman, Joseph

    2003-12-01

    Analyses of the oligomers formed in radiation-induced polymerization of purified styrene were performed. The principal dimeric products were cis- and trans-diphenyl-cyclobutane with a relatively small amount of 1-phenyltetralin; the trimeric products were the optical isomers of 1-phenyl-4-[1'-phenylethyl-(1')]-tetralin in gamma-ray and 60 MeV proton irradiation. Oligomer formation increased with increasing dose, but more gradually than the linear formation of high polymer with dose. The yield was 0.25-3.1 μmol/J at low doses and decreased to an asymptotic value of 0.15 at higher doses. It appears that oligomers act as chain transfer agents during the polymerization reaction which would account for the observed decrease in molecular weight of the high polymer with increase in dose. Although the thermal and radiation-induced polymerization of styrene have different initiation steps, the oligomers produced by both reactions are similar in composition.

  11. Biomimetic peptoid oligomers as dual-action antifreeze agents

    PubMed Central

    Huang, Mia L.; Ehre, David; Jiang, Qi; Hu, Chunhua; Kirshenbaum, Kent; Ward, Michael D.

    2012-01-01

    The ability of natural peptides and proteins to influence the formation of inorganic crystalline materials has prompted the design of synthetic compounds for the regulation of crystal growth, including the freezing of water and growth of ice crystals. Despite their versatility and ease of structural modification, peptidomimetic oligomers have not yet been explored extensively as crystallization modulators. This report describes a library of synthetic N-substituted glycine peptoid oligomers that possess “dual-action” antifreeze activity as exemplified by ice crystal growth inhibition concomitant with melting temperature reduction. We investigated the structural features responsible for these phenomena and observed that peptoid antifreeze activities depend both on oligomer backbone structure and side chain chemical composition. These studies reveal the capability of peptoids to act as ice crystallization regulators, enabling the discovery of a unique and diverse family of synthetic oligomers with potential as antifreeze agents in food production and biomedicine. PMID:23169638

  12. Ultrafast electron transfer in all-carbon-based SWCNT-C60 donor-acceptor nanoensembles connected by poly(phenylene-ethynylene) spacers

    NASA Astrophysics Data System (ADS)

    Barrejón, Myriam; Gobeze, Habtom B.; Gómez-Escalonilla, María J.; Fierro, José Luis G.; Zhang, Minfang; Yudasaka, Masako; Iijima, Sumio; D'Souza, Francis; Langa, Fernando

    2016-08-01

    Building all-carbon based functional materials for light energy harvesting applications could be a solution to tackle and reduce environmental carbon output. However, development of such all-carbon based donor-acceptor hybrids and demonstration of photoinduced charge separation in such nanohybrids is a challenge since in these hybrids part of the carbon material should act as an electron donating or accepting photosensitizer while the second part should fulfil the role of an electron acceptor or donor. In the present work, we have successfully addressed this issue by synthesizing covalently linked all-carbon-based donor-acceptor nanoensembles using single-walled carbon nanotubes (SWCNTs) as the donor and C60 as the acceptor. The donor-acceptor entities in the nanoensembles were connected by phenylene-ethynylene spacer units to achieve better electronic communication and to vary the distance between the components. These novel SWCNT-C60 nanoensembles have been characterized by a number of techniques, including TGA, FT-IR, Raman, AFM, absorbance and electrochemical methods. The moderate number of fullerene addends present on the side-walls of the nanotubes largely preserved the electronic structure of the nanotubes. The thermodynamic feasibility of charge separation in these nanoensembles was established using spectral and electrochemical data. Finally, occurrence of ultrafast electron transfer from the excited nanotubes in these donor-acceptor nanohybrids has been established by femtosecond transient absorption studies, signifying their utility in building light energy harvesting devices.Building all-carbon based functional materials for light energy harvesting applications could be a solution to tackle and reduce environmental carbon output. However, development of such all-carbon based donor-acceptor hybrids and demonstration of photoinduced charge separation in such nanohybrids is a challenge since in these hybrids part of the carbon material should act as an

  13. Subdiffusion of proteins and oligomers on membranes

    NASA Astrophysics Data System (ADS)

    Lepzelter, David; Zaman, Muhammad

    2012-11-01

    Diffusion of proteins on lipid membranes plays a central role in cell signaling processes. From a mathematical perspective, most membrane diffusion processes are explained by the Saffman-Delbrück theory. However, recent studies have suggested a major limitation in the theoretical framework, the lack of complexity in the modeled lipid membrane. Lipid domains (sometimes termed membrane rafts) are known to slow protein diffusion, but there have been no quantitative theoretical examinations of how much diffusion is slowed in a general case. We provide an overall theoretical framework for confined-domain ("corralled") diffusion. Further, there have been multiple apparent contradictions of the basic conclusions of Saffman and Delbrück, each involving cases in which a single protein or an oligomer has multiple transmembrane regions passing through a lipid phase barrier. We present a set of corrections to the Saffman-Delbrück theory to account for these experimental observations. Our corrections are able to provide a quantitative explanation of numerous cellular signaling processes that have been considered beyond the scope of the Saffman-Delbrück theory, and may be extendable to other forms of subdiffusion.

  14. Monolayer coated aerogels and method of making

    DOEpatents

    Zemanian, Thomas Samuel; Fryxell, Glen; Ustyugov, Oleksiy A.

    2006-03-28

    Aerogels having a monolayer coating are described. The aerogel and a monolayer forming precursor are provided in a supercritical fluid, whereupon the aerogel and the monolayer forming precursor are reacted in said supercritical fluid to form a covalent bond between the aerogel and the monolayer forming precursor. Suitable aerogels are ceramic oxides such as silica, alumina, aluminosilicate, and combinations thereof. Suitable monolayer forming precursors include alkyl silanes, chlorosilanes, boranes, chloroboranes, germanes, and combinations thereof. The method may also include providing a surface preparation agent such as water, or hydroetching an aerogel to enhance the coating of the monolayer.

  15. Synthesis and Photophysical and Electroluminescent Properties of Poly(1,4-phenylene–ethynylene)-alt-poly(1,4-phenylene–vinylene)s with Various Dissymmetric Substitution of Alkoxy Side Chains

    PubMed Central

    2016-01-01

    The synthesis and characterization of a set of conjugated polymers, poly(1,4-phenylene–ethynylene)-alt-poly(1,4-phenylene–vinylene)s (PPE–PPVs), with a dissymmetrical configuration (partial or total) of alkoxy side chains is reported. Five new polymers bearing octyloxy and/or octadecyloxy side chains at the phenylene–ethynylene and phenylene–vinylene segments, respectively, were obtained. Two symmetrical substituted polymers were used for comparison. Polymers with weight-average molecular weight, Mw, up to 430 000 g/mol and degree of polymerization between 17 and 322 were obtained by a Horner–Wadsworth–Emmons olefination polycondensation reaction of the respective luminophoric dialdehydes and bisphosphonates. As expected, identical conjugated backbones in all polymers results in very similar photophysical response in dilute solution, with high fluorescence quantum yields between 50% and 80%. In contrast, the thin film properties are dependent on the combinatorial effects of side chain configuration, molecular weight, and film thickness parameters, which are the basis of the resulting comparison and discussion. PMID:26877550

  16. Functional Diversity of Isoamylase Oligomers: The ISA1 Homo-Oligomer Is Essential for Amylopectin Biosynthesis in Rice Endosperm1[W][OA

    PubMed Central

    Utsumi, Yoshinori; Utsumi, Chikako; Sawada, Takayuki; Fujita, Naoko; Nakamura, Yasunori

    2011-01-01

    Rice (Oryza sativa) endosperm has two isoamylase (ISA) oligomers, ISA1 homo-oligomer and ISA1-ISA2 hetero-oligomer. To examine their contribution to starch synthesis, expression of the ISA1 or ISA2 gene was differently regulated in various transgenic plants. Although suppression of ISA2 gene expression caused the endosperm to have only the homo-oligomer, no significant effects were detected on the starch phenotypes. In contrast, ISA2 overexpression led to endosperm having only the hetero-oligomer, and starch synthesis in the endosperm was drastically impaired, both quantitatively and qualitatively, because the starch was devoid of typical starch features, such as thermal and x-ray diffraction properties, and water-soluble highly branched maltodextrins were accumulated. In the ISA2 overexpressed line, about 60% to 70% of the ISA1-ISA2 hetero-oligomer was bound to starch, while the ISA homo- and hetero-oligomers from the wild type were mostly present in the soluble form at the early milking stage of the endosperm. Detailed analysis of the relative amounts of homo- and hetero-oligomers in various lines also led us to the conclusion that the ISA1 homo-oligomer is essential, but not the ISA1-ISA2 oligomer, for starch production in rice endosperm. The relative amounts of ISA1 and ISA2 proteins were shown to determine the ratio of both oligomers and the stoichiometry of both ISAs in the hetero-oligomer. It was noted when compared with the homo-oligomer that all the hetero-oligomers from rice endosperm and leaf and potato (Solanum tuberosum) tuber were much more stable at 40°C. This study provides substantial data on the structural and functional diversity of ISA oligomers between plant tissues and species. PMID:21436381

  17. Electromelting of confined monolayer ice.

    PubMed

    Qiu, Hu; Guo, Wanlin

    2013-05-10

    In sharp contrast to the prevailing view that electric fields promote water freezing, here we show by molecular dynamics simulations that monolayer ice confined between two parallel plates can melt into liquid water under a perpendicularly applied electric field. The melting temperature of the monolayer ice decreases with the increasing strength of the external field due to the field-induced disruption of the water-wall interaction induced well-ordered network of the hydrogen bond. This electromelting process should add an important new ingredient to the physics of water.

  18. Imide Oligomers Endcapped with Phenylethynl Phthalic Anhydrides and Polymers Therefrom

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M. (Inventor); Smith, Joseph G., Jr. (Inventor)

    1998-01-01

    Controlled molecular weight phenylethynyl terminated imide oligomers (PETIs) have been prepared by the cyclodehydration of precursor phenylethynyl terminated amic acid oligomers. Amino terminated amic acid oligomers are prepared from the reaction of dianhydride(s) with an excess of diamine(s) and subsequently endcapped with phenylethynyl phthalic anhydride(s) (PEPA). The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N.N-dimethylacetamide under nitrogen at room temperature. The amic acid oligomers are subsequently cyclodehydrated either thermally or cheznicauy to the corresponding imide oligomers. Direct preparation of PETIs from the reaction of dianhydxide(s) with an excess of diamine(s) and endcapped with phenylethynyl phthalic anhydride(s) has been performed in m-cresol. Phenylethynyl phthalic anhydrides are synthesized by the palladium catalyzed reaction of phenylacetylene with bromo substituted phthalic anhydrides in triethylamine. These new materials exhibit excellent properties and are potentially useful as adhesives, coatings, films, moldings and composite matrices.

  19. Imide oligomers endcapped with phenylethynyl phthalic anhydrides and polymers therefrom

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M. (Inventor); Smith, Jr., Joseph G. (Inventor)

    1996-01-01

    Controlled molecular weight phenylethynyl terminated imide oligomers (PETIs) have been prepared by the cyclodehydration of precursor phenylethynyl terminated amic acid oligomers. Amino terminated amic acid oligomers are prepared from the reaction of dianhydride(s) with an excess of diamine(s) and subsequently endcapped with phenylethynyl phthalic anhydride(s) (PEPA). The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide under nitrogen at room temperature. The amic acid oligomers are subsequently cyclodehydrated either thermally or chemically to the corresponding imide oligomers. Direct preparation of PETIs from the reaction of dianhydride(s) with an excess of diamine(s) and endcapped with phenylethynyl phthalic anhydride(s) has been performed in m-cresol. Phenylethynyl phthalic anhydrides are synthesized by the palladium catalyzed reaction of phenylacetylene with bromo substituted phthalic anhydrides in triethylamine. These new materials exhibit excellent properties and are potentially useful as adhesives, coatings, films, moldings and composite matrices.

  20. ortho-Phenylene oligomers with terminal push-pull substitution.

    PubMed

    He, Jian; Mathew, Sanyo M; Cornett, Sarah D; Grundy, Stephan C; Hartley, C Scott

    2012-05-07

    ortho-Phenylenes are an emerging class of helical oligomers and polymers. We have synthesized a series of push-pull-substituted o-phenylene oligomers (dimethylamino/nitro) up to the octamer. Conformational analysis of the hexamer using a combination of low-temperature NMR spectroscopy and ab initio predictions of (1)H NMR chemical shifts indicates that, like other o-phenylenes, they exist as compact helices in solution. However, the substituents are found to have a significant effect on their conformational behavior: the nitro-functionalized terminus is 3-fold more likely to twist out of the helix. Protonation of the dimethylamino group favors the helical conformer. UV/vis spectroscopy indicates that the direct charge-transfer interaction between the push-pull substituents attenuates quickly compared to other conjugated systems, with no significant charge-transfer band for oligomers longer than the trimer. On protonation of the dimethylamino group, significant bathochromic shifts with increasing oligomer length are observed: the effective conjugation length is 9 repeat units, more than twice that of the parent oligomer. This behavior may be rationalized through examination of the frontier molecular orbitals of these compounds, which exhibit greater delocalization after protonation, as shown by DFT calculations.

  1. Preparation and applications of a variety of fluoroalkyl end-capped oligomer/hydroxyapatite composites.

    PubMed

    Takashima, Hiroki; Iwaki, Ken-Ichi; Furukuwa, Rika; Takishita, Katsuhisa; Sawada, Hideo

    2008-04-15

    A variety of fluoroalkyl end-capped oligomers were applied to the preparation of fluorinated oligomer/hydroxyapatite (HAp) composites (particle size: 38-356 nm), which exhibit a good dispersibility in water and traditional organic solvents. These fluoroalkyl end-capped oligomer/HAp composites were easily prepared by the reactions of disodium hydrogen phosphate and calcium chloride in the presence of self-assembled molecular aggregates formed by fluoroalkyl end-capped oligomers in aqueous solutions. In these fluorinated HAp composites thus obtained, fluoroalkyl end-capped acrylic acid oligomers and 2-methacryloyloxyethanesulfonic acid oligomer/HAp nanocomposites afforded transparent colorless solutions toward water; however, fluoroalkyl end-capped N,N-dimethylacrylamide oligomer and acryloylmorpholine oligomer were found to afford transparent colorless solutions with trace amounts of white-colored HAp precipitants under similar conditions. HAp could be encapsulated more effectively into fluorinated 2-methacryloyloxyethanesulfonic acid oligomeric aggregate cores to afford colloidal stable fluorinated oligomer/HAp composites, compared to that of fluorinated acrylic acid oligomers. These fluorinated oligomer/HAp composites were applied to the surface modification of glass and PVA to exhibit a good oleophobicity imparted by fluorine. HAp formation was newly observed on the modified polyethylene terephthalate film surface treated with fluorinated 2-methacryloyloxyethanesulfonic acid oligomers and acrylic acid oligomer/HAp composites by soaking these films into the simulated body fluid.

  2. Single Particle Characterization of Aβ Oligomers in Solution

    PubMed Central

    Yusko, Erik C.; Prangkio, Panchika; Sept, David; Rollings, Ryan C.; Li, Jiali; Mayer, Michael

    2012-01-01

    Determining the pathological role of amyloids in amyloid-associated diseases will require a method for determining the dynamic distributions in size and shape of amyloid oligomers with high resolution. Here, we explored the potential of resistive-pulse sensing through lipid bilayer-coated nanopores to measure the size of individual amyloid-β oligomers directly in solution and without chemical modification. This method classified individual amyloid-β aggregates as spherical oligomers, protofibrils, or mature fibers and made it possible to account for the large heterogeneity of amyloid-β aggregate sizes. The approach revealed the distribution of protofibrillar lengths as well as the average cross-sectional area of protofibrils and fibers. PMID:22686709

  3. Proportion effect in diblock co-oligomer molecular diodes

    NASA Astrophysics Data System (ADS)

    Hu, G. C.; Zhang, G. P.; Li, Y.; Ren, J. F.; Wang, C. K.

    2014-10-01

    Based on ab-initio theory and nonequilibrium Green's function method, the effect of proportion on the rectification in pyrimidinyl-phenyl diblock co-oligomer diodes is investigated in two regimes. For a short co-oligomer diode, it is found that the 1:1 proportion of the two moieties favors the largest rectification ratio. For a long co-oligomer diode, an interesting proportion-dependent variation of the rectifying direction is observed. Furthermore, the optimal proportion for the largest rectification ratio is not 1:1 any longer. A deep understanding can be achieved by analyzing the bias-dependent transmission spectra combined with the evolution of the molecular orbitals.

  4. Aggregation of inorganic nanoparticles mediated by biomimetic oligomers.

    PubMed

    Tigger-Zaborov, Hagar; Maayan, Galia

    2015-09-14

    Assemblies of nanoparticles (NPs) have been broadly used for the construction of materials with unique spectroscopic and chiral properties for applications in various scientific disciplines such as sensing, bio-nanotechnology and medicine. Mediating the aggregation of NPs by synthetic biomimetic oligomers, namely, DNA, PNA, peptides and peptide mimics, rather than by small organic molecules has been shown to produce interesting supramolecular structures and enable the combination of the biocompatibility of the mediators and the spectroscopic properties of the NPs. Yet, the key to using this powerful approach for designing new functional materials is to understand the NPs aggregation patterns induced by biopolymers and biomimetic oligomers. Herein we describe the important developments in this field, from early studies to recent work with an emphasis on synthetic methods and tools for controlled assembly of metal NPs by biomimetic polymers and oligomers.

  5. Direct detection of alpha synuclein oligomers in vivo

    PubMed Central

    2013-01-01

    Background Rat models of Parkinson’s disease are widely used to elucidate the mechanisms underlying disease etiology or to investigate therapeutic approaches. Models were developed using toxins such as MPTP or 6-OHDA to specifically target dopaminergic neurons resulting in acute neuronal loss in the substantia nigra or by using viral vectors to induce the specific and gradual expression of alpha synuclein in the substantia nigra. The detection of alpha- synuclein oligomers, the presumed toxic species, in these models and others has been possible using only indirect biochemical approaches to date. Here we coinjected AAVs encoding alpha-synuclein fused to the N- or C-terminal half of VenusYFP in rat substantia nigra pars compacta and describe for the first time a novel viral vector rodent model with the unique ability to directly detect and track alpha synuclein oligomers ex vivo and in vivo. Results Viral coinjection resulted in widespread VenusYFP signal within the nigrostriatal pathway, including cell bodies in the substantia nigra and synaptic accumulation in striatal terminals, suggestive of in vivo alpha-synuclein oligomers formation. Transduced rats showed alpha-synuclein induced dopaminergic neuron loss in the substantia nigra, the appearance of dystrophic neurites, and gliosis in the striatum. Moreover, we have applied in vivo imaging techniques in the living mouse to directly image alpha-synuclein oligomers in the cortex. Conclusion We have developed a unique animal model that provides a tool for the Parkinson’s disease research community with which to directly detect alpha- synuclein oligomers in vivo and screen therapeutic approaches targeting alpha-synuclein oligomers. PMID:24252244

  6. Dynamic assessment of Amyloid oligomers - cell membrane interaction by advanced impedance spectroscopy

    NASA Astrophysics Data System (ADS)

    Gheorghiu, M.; David, S.; Polonschii, C.; Bratu, D.; Gheorghiu, E.

    2013-04-01

    The amyloid β (Aβ) peptides are believed to be pivotal in Alzheimer's disease (AD) pathogenesis and onset of vascular dysfunction. Recent studies indicate that Aβ1-42 treatment influences the expression of tight junction protein complexes, stress fibre formation, disruption and aggregation of actin filaments and cellular gap formation. Aiming for functional characterization of model cells upon Aβ1-42 treatment, we deployed an advanced Electric Cell-substrate Impedance Sensing for monitoring cell evolution. A precision Impedance Analyzer with a multiplexing module developed in house was used for recording individual electrode sets in the 40 Hz - 100 KHz frequency range. In a step forward from the classical ECIS assays, we report on a novel data analysis algorithm that enables access to cellular and paracellular electrical parameters and cell surface interaction with fully developed cell monolayers. The evolution of the impedance at selected frequencies provides evidence for a dual effect of Aβ42 exposure, at both paracellular permeability and cell adherence level, with intricate dynamics that open up new perspectives on Aβ1-42 oligomers - cell membrane interaction. Validation of electrical impedance assays of the amyloid fibrils effect on cell membrane structure is achieved by both AFM analysis and Surface Plasmon Resonance studies. The capabilities of this noninvasive, real time platform for cell analysis in a wider applicative context are outlined.

  7. Memantine rescues transient cognitive impairment caused by high-molecular-weight aβ oligomers but not the persistent impairment induced by low-molecular-weight oligomers.

    PubMed

    Figueiredo, Cláudia P; Clarke, Julia R; Ledo, José Henrique; Ribeiro, Felipe C; Costa, Carine V; Melo, Helen M; Mota-Sales, Axa P; Saraiva, Leonardo M; Klein, William L; Sebollela, Adriano; De Felice, Fernanda G; Ferreira, Sergio T

    2013-06-05

    Brain accumulation of soluble amyloid-β oligomers (AβOs) has been implicated in synapse failure and cognitive impairment in Alzheimer's disease (AD). However, whether and how oligomers of different sizes induce synapse dysfunction is a matter of controversy. Here, we report that low-molecular-weight (LMW) and high-molecular-weight (HMW) Aβ oligomers differentially impact synapses and memory. A single intracerebroventricular injection of LMW AβOs (10 pmol) induced rapid and persistent cognitive impairment in mice. On the other hand, memory deficit induced by HMW AβOs (10 pmol) was found to be reversible. While memory impairment in LMW oligomer-injected mice was associated with decreased hippocampal synaptophysin and GluN2B immunoreactivities, synaptic pathology was not detected in the hippocampi of HMW oligomer-injected mice. On the other hand, HMW oligomers, but not LMW oligomers, induced oxidative stress in hippocampal neurons. Memantine rescued both neuronal oxidative stress and the transient memory impairment caused by HMW oligomers, but did not prevent the persistent cognitive deficit induced by LMW oligomers. Results establish that different Aβ oligomer assemblies act in an orchestrated manner, inducing different pathologies and leading to synapse dysfunction. Furthermore, results suggest a mechanistic explanation for the limited efficacy of memantine in preventing memory loss in AD.

  8. Oligomer Molecules for Efficient Organic Photovoltaics.

    PubMed

    Lin, Yuze; Zhan, Xiaowei

    2016-02-16

    Solar cells, a renewable, clean energy technology that efficiently converts sunlight into electricity, are a promising long-term solution for energy and environmental problems caused by a mass of production and the use of fossil fuels. Solution-processed organic solar cells (OSCs) have attracted much attention in the past few years because of several advantages, including easy fabrication, low cost, lightweight, and flexibility. Now, OSCs exhibit power conversion efficiencies (PCEs) of over 10%. In the early stage of OSCs, vapor-deposited organic dye materials were first used in bilayer heterojunction devices in the 1980s, and then, solution-processed polymers were introduced in bulk heterojunction (BHJ) devices. Relative to polymers, vapor-deposited small molecules offer potential advantages, such as a defined molecular structure, definite molecular weight, easy purification, mass-scale production, and good batch-to-batch reproducibility. However, the limited solubility and high crystallinity of vapor-deposited small molecules are unfavorable for use in solution-processed BHJ OSCs. Conversely, polymers have good solution-processing and film-forming properties and are easily processed into flexible devices, whereas their polydispersity of molecular weights and difficulty in purification results in batch to batch variation, which may hamper performance reproducibility and commercialization. Oligomer molecules (OMs) are monodisperse big molecules with intermediate molecular weights (generally in the thousands), and their sizes are between those of small molecules (generally with molecular weights <1000) and polymers (generally with molecular weights >10000). OMs not only overcome shortcomings of both vapor-deposited small molecules and solution-processed polymers, but also combine their advantages, such as defined molecular structure, definite molecular weight, easy purification, mass-scale production, good batch-to-batch reproducibility, good solution processability

  9. Electronic coherence dynamics in trans-polyacetylene oligomers.

    PubMed

    Franco, Ignacio; Brumer, Paul

    2012-04-14

    Electronic coherence dynamics in trans-polyacetylene oligomers are considered by explicitly computing the time dependent molecular polarization from the coupled dynamics of electronic and vibrational degrees of freedom in a mean-field mixed quantum-classical approximation. The oligomers are described by the Su-Schrieffer-Heeger Hamiltonian and the effect of decoherence is incorporated by propagating an ensemble of quantum-classical trajectories with initial conditions obtained by sampling the Wigner distribution of the nuclear degrees of freedom. The electronic coherence of superpositions between the ground and excited and between pairs of excited states is examined for chains of different length, and the dynamics is discussed in terms of the nuclear overlap function that appears in the off-diagonal elements of the electronic reduced density matrix. For long oligomers the loss of coherence occurs in tens of femtoseconds. This time scale is determined by the decay of population into other electronic states through vibronic interactions, and is relatively insensitive to the type and class of superposition considered. By contrast, for smaller oligomers the decoherence time scale depends strongly on the initially selected superposition, with superpositions that can decay as fast as 50 fs and as slow as 250 fs. The long-lived superpositions are such that little population is transferred to other electronic states and for which the vibronic dynamics is relatively harmonic.

  10. Low-Temperature, Dry Transfer-Printing of a Patterned Graphene Monolayer

    NASA Astrophysics Data System (ADS)

    Cha, Sugkyun; Cha, Minjeong; Lee, Seojun; Kang, Jin Hyoun; Kim, Changsoon

    2015-12-01

    Graphene has recently attracted much interest as a material for flexible, transparent electrodes or active layers in electronic and photonic devices. However, realization of such graphene-based devices is limited due to difficulties in obtaining patterned graphene monolayers on top of materials that are degraded when exposed to a high-temperature or wet process. We demonstrate a low-temperature, dry process capable of transfer-printing a patterned graphene monolayer grown on Cu foil onto a target substrate using an elastomeric stamp. A challenge in realizing this is to obtain a high-quality graphene layer on a hydrophobic stamp made of poly(dimethylsiloxane), which is overcome by introducing two crucial modifications to the conventional wet-transfer method - the use of a support layer composed of Au and the decrease in surface tension of the liquid bath. Using this technique, patterns of a graphene monolayer were transfer-printed on poly(3,4-ethylenedioxythiophene):polystyrene sulfonate and MoO3, both of which are easily degraded when exposed to an aqueous or aggressive patterning process. We discuss the range of application of this technique, which is currently limited by oligomer contaminants, and possible means to expand it by eliminating the contamination problem.

  11. Low-Temperature, Dry Transfer-Printing of a Patterned Graphene Monolayer

    PubMed Central

    Cha, Sugkyun; Cha, Minjeong; Lee, Seojun; Kang, Jin Hyoun; Kim, Changsoon

    2015-01-01

    Graphene has recently attracted much interest as a material for flexible, transparent electrodes or active layers in electronic and photonic devices. However, realization of such graphene-based devices is limited due to difficulties in obtaining patterned graphene monolayers on top of materials that are degraded when exposed to a high-temperature or wet process. We demonstrate a low-temperature, dry process capable of transfer-printing a patterned graphene monolayer grown on Cu foil onto a target substrate using an elastomeric stamp. A challenge in realizing this is to obtain a high-quality graphene layer on a hydrophobic stamp made of poly(dimethylsiloxane), which is overcome by introducing two crucial modifications to the conventional wet-transfer method – the use of a support layer composed of Au and the decrease in surface tension of the liquid bath. Using this technique, patterns of a graphene monolayer were transfer-printed on poly(3,4-ethylenedioxythiophene):polystyrene sulfonate and MoO3, both of which are easily degraded when exposed to an aqueous or aggressive patterning process. We discuss the range of application of this technique, which is currently limited by oligomer contaminants, and possible means to expand it by eliminating the contamination problem. PMID:26648526

  12. Unique Properties of the Rabbit Prion Protein Oligomer

    PubMed Central

    Yu, Ziyao; Huang, Pei; Yu, Yuanhui; Zheng, Zhen; Huang, Zicheng; Guo, Chenyun; Lin, Donghai

    2016-01-01

    Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative disorders infecting both humans and animals. Recent works have demonstrated that the soluble prion protein oligomer (PrPO), the intermediate of the conformational transformation from the host-derived cellular form (PrPC) to the disease-associated Scrapie form (PrPSc), exerts the major neurotoxicity in vitro and in vivo. Rabbits show strong resistance to TSEs, the underlying mechanism is unclear to date. It is expected that the relative TSEs-resistance of rabbits is closely associated with the unique properties of rabbit prion protein oligomer which remain to be addressed in detail. In the present work, we prepared rabbit prion protein oligomer (recRaPrPO) and human prion protein oligomer (recHuPrPO) under varied conditions, analyzed the effects of pH, NaCl concentration and incubation temperature on the oligomerization, and compared the properties of recRaPrPO and recHuPrPO. We found that several factors facilitated the formation of prion protein oligomers, including low pH, high NaCl concentration, high incubation temperature and low conformational stability of monomeric prion protein. RecRaPrPO was formed more slowly than recHuPrPO at physiological-like conditions (< 57°C, < 150 mM NaCl). Furthermore, recRaPrPO possessed higher susceptibility to proteinase K and lower cytotoxicity in vitro than recHuPrPO. These unique properties of recRaPrPO might substantially contribute to the TSEs-resistance of rabbits. Our work sheds light on the oligomerization of prion proteins and is of benefit to mechanistic understanding of TSEs-resistance of rabbits. PMID:27529173

  13. Imide Oligomers Containing Pendent and Terminal Phenylethynyl Groups-2

    NASA Technical Reports Server (NTRS)

    Connell, J. W.; Smith, J. G., Jr.; Hergenrother, P. M.

    1998-01-01

    As part of a program to develop high-performance/high-temperature structural resins for aeronautical applications, imide oligomers containing pendent and terminal phenylethynyl groups were prepared, characterized and the cured resins evaluated as composite matrices. The oligomers were prepared at a calculated number-average molecular weight of 5000 g/mol and contained 15-20 mol% pendent phenylethynyl groups. In previous work, an oligomer containing pendent and terminal phenylethynyl groups exhibited a high glass transition temperature (approximately 313 C), and laminates therefrom exhibited high compressive properties, but processability, fracture toughness, microcrack resistance and damage tolerance were less than desired. In an attempt to improve these deficiencies, modifications in the oligomeric backbone involving the incorporation of 1,3-bis(3-aminophenoxy)benzene were investigated as a means of improving processability and toughness without detracting from the high glass transition temperature and high compressive properties. The amide acid oligomeric solutions were prepared in N-methyl-2-pyrrolidinone and were subsequently processed into imide powder, thin films, adhesive tape and carbon fiber prepreg. Neat resin plaques were fabricated from imide powder by compression moulding. The maximum processing pressure was 1.4 MPa and the cure temperature ranged from 350 to 371 C for 1 h for the mouldings, adhesives, films and composites. The properties of the 1,3-bis(3-aniinophenoxy)benzene modified cured imide oligomers containing pendent and terminal phenylethynyl groups are compared with those of previously prepared oligomers containing pendent and terminal phenylethynyl groups of similar composition and molecular weight.

  14. Modeling Stimuli-Responsive Nanoparticle Monolayer

    NASA Astrophysics Data System (ADS)

    Yong, Xin

    2015-03-01

    Using dissipative particle dynamics (DPD), we model a monolayer formed at the water-oil interface, which comprises stimuli-responsive nanoparticles. The solid core of the nanoparticle encompasses beads arranged in an fcc lattice structure and its surface is uniformly grafted with stimuli-responsive polymer chains. The surface-active nanoparticles adsorb to the interface from the suspension to minimize total energy of the system and create a monolayer covering the interface. We investigate the monolayer formation by characterizing the detailed adsorption kinetics. We explore the microstructure of the monolayer at different surface coverage, including the particle crowding and ordering, and elucidate the response of monolayer to external stimuli. The collective behavior of the particles within the monolayer is demonstrated quantitatively by vector-vector autocorrelation functions. This study provides a fundamental understanding of the interfacial behavior of stimuli-responsive nanoparticles.

  15. Surface Coverage and Structure of Mixed DNA/Alkylthiol Monolayers on Gold: Characterization by XPS, NEXAFS, and Fluorescence Intensity Measurements

    PubMed Central

    Lee, Chi-Ying; Gong, Ping; Harbers, Gregory M.; Grainger, David W.; Castner, David G.; Gamble, Lara J.

    2006-01-01

    Self-assembly of thiol-terminated single-stranded DNA (HS-ssDNA) on gold has served as an important model system for DNA immobilization at surfaces. Here, we report a detailed study of the surface composition and structure of mixed self-assembled DNA monolayers containing a short alkylthiol surface diluent [11-mercapto-1-undecanol (MCU)] on gold supports. These mixed DNA monolayers were studied with X-ray photoelectron spectroscopy (XPS), near-edge X-ray absorption fine structure spectroscopy (NEXAFS), and fluorescence intensity measurements. XPS results on sequentially adsorbed DNA/MCU monolayers on gold indicated that adsorbed MCU molecules first incorporate into the HS-ssDNA monolayer and, upon longer MCU exposures, displace adsorbed HS-ssDNA molecules from the surface. Thus, HS-ssDNA surface coverage steadily decreased with MCU exposure time. Polarization-dependent NEXAFS and fluorescence results both show changes in signals consistent with changes in DNA orientation after only 30 min of MCU exposure. NEXAFS polarization dependence (followed by monitoring the N 1s → π* transition) of the mixed DNA monolayers indicated that the DNA nucleotide base ring structures are oriented more parallel to the gold surface compared to DNA bases in pure HS-ssDNA monolayers. This indicates that HS-ssDNA oligomers reorient toward a more-upright position upon MCU incorporation. Fluorescence intensity results using end-labeled DNA probes on gold show little observable fluorescence on pure HS-ssDNA monolayers, likely due to substrate quenching effects between the fluorophore and the gold. MCU diluent incorporation into HS-ssDNA monolayers initially increases DNA fluorescence signal by densifying the chemisorbed monolayer, prompting an upright orientation of the DNA, and moving the terminal fluorophore away from the substrate. Immobilized DNA probe density and DNA target hybridization in these mixed DNA monolayers, as well as effects of MCU diluent on DNA hybridization in complex

  16. Surface Coverage and Structure of Mixed DNA/Alkylthiol Monolayers on Gold: Characterization by XPS, NEXAFS, and Fluorescence Intensity Measurements

    SciTech Connect

    Lee,C.; Gong, P.; Harbers, G.; Grainger, D.; Castner, D.; Gamble, L.

    2006-01-01

    Self-assembly of thiol-terminated single-stranded DNA (HS-ssDNA) on gold has served as an important model system for DNA immobilization at surfaces. Here, we report a detailed study of the surface composition and structure of mixed self-assembled DNA monolayers containing a short alkylthiol surface diluent [11-mercapto-1-undecanol (MCU)] on gold supports. These mixed DNA monolayers were studied with X-ray photoelectron spectroscopy (XPS), near-edge X-ray absorption fine structure spectroscopy (NEXAFS), and fluorescence intensity measurements. XPS results on sequentially adsorbed DNA/MCU monolayers on gold indicated that adsorbed MCU molecules first incorporate into the HS-ssDNA monolayer and, upon longer MCU exposures, displace adsorbed HS-ssDNA molecules from the surface. Thus, HS-ssDNA surface coverage steadily decreased with MCU exposure time. Polarization-dependent NEXAFS and fluorescence results both show changes in signals consistent with changes in DNA orientation after only 30 min of MCU exposure. NEXAFS polarization dependence (followed by monitoring the N 1s{yields}{pi}* transition) of the mixed DNA monolayers indicated that the DNA nucleotide base ring structures are oriented more parallel to the gold surface compared to DNA bases in pure HS-ssDNA monolayers. This indicates that HS-ssDNA oligomers reorient toward a more-upright position upon MCU incorporation. Fluorescence intensity results using end-labeled DNA probes on gold show little observable fluorescence on pure HS-ssDNA monolayers, likely due to substrate quenching effects between the fluorophore and the gold. MCU diluent incorporation into HS-ssDNA monolayers initially increases DNA fluorescence signal by densifying the chemisorbed monolayer, prompting an upright orientation of the DNA, and moving the terminal fluorophore away from the substrate. Immobilized DNA probe density and DNA target hybridization in these mixed DNA monolayers, as well as effects of MCU diluent on DNA hybridization in

  17. Capping of aβ42 oligomers by small molecule inhibitors.

    PubMed

    Fu, Ziao; Aucoin, Darryl; Ahmed, Mahiuddin; Ziliox, Martine; Van Nostrand, William E; Smith, Steven O

    2014-12-23

    Aβ42 peptides associate into soluble oligomers and protofibrils in the process of forming the amyloid fibrils associated with Alzheimer's disease. The oligomers have been reported to be more toxic to neurons than fibrils, and have been targeted by a wide range of small molecule and peptide inhibitors. With single touch atomic force microscopy (AFM), we show that monomeric Aβ42 forms two distinct types of oligomers, low molecular weight (MW) oligomers with heights of 1-2 nm and high MW oligomers with heights of 3-5 nm. In both cases, the oligomers are disc-shaped with diameters of ~10-15 nm. The similar diameters suggest that the low MW species stack to form the high MW oligomers. The ability of Aβ42 inhibitors to interact with these oligomers is probed using atomic force microscopy and NMR spectroscopy. We show that curcumin and resveratrol bind to the N-terminus (residues 5-20) of Aβ42 monomers and cap the height of the oligomers that are formed at 1-2 nm. A second class of inhibitors, which includes sulindac sulfide and indomethacin, exhibit very weak interactions across the Aβ42 sequence and do not block the formation of the high MW oligomers. The correlation between N-terminal interactions and capping of the height of the Aβ oligomers provides insights into the mechanism of inhibition and the pathway of Aβ aggregation.

  18. Structure and shear response of lipid monolayers

    SciTech Connect

    Dutta, P.; Ketterson, J.B.

    1990-02-01

    Organic monolayers and multilayers are both scientifically fascinating and technologically promising; they are, however, both complex systems and relatively inaccessible to experimental probes. In this Progress Report, we describe our X-ray diffraction studies, which have given us substantial new information about the structures and phase transitions in monolayers on the surface of water; our use of these monolayers as a unique probe of the dynamics of wetting and spreading; and our studies of monolayer mechanical properties using a simple but effective technique available to anyone using the Wilhelmy method to measure surface tension.

  19. Equilibrating Nanoparticle Monolayers Using Wetting Films

    SciTech Connect

    Pontoni, D.; Alvine, K; Checco, A; Gang, O; Ocko, B; Pershan, P

    2009-01-01

    Monolayers of bimodal gold nanoparticles on silicon are investigated by a combination of microscopy (dry monolayers) and x-ray diffraction (dry and wet monolayers). In the presence of an excess of small particles, the nanoscale packing structure closely resembles the small-particle-rich scenario of the structural crossover transition that has been predicted and also observed with micron-scale hard-sphere colloids. Structural morphology is monitored in situ during monolayer dissolution and reassembly within the thin liquid wetting film. This approach allows investigation of size and solvent effects on nanoparticles in quasi-two-dimensional confinement.

  20. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity.

    PubMed

    Izzo, Nicholas J; Xu, Jinbin; Zeng, Chenbo; Kirk, Molly J; Mozzoni, Kelsie; Silky, Colleen; Rehak, Courtney; Yurko, Raymond; Look, Gary; Rishton, Gilbert; Safferstein, Hank; Cruchaga, Carlos; Goate, Alison; Cahill, Michael A; Arancio, Ottavio; Mach, Robert H; Craven, Rolf; Head, Elizabeth; LeVine, Harry; Spires-Jones, Tara L; Catalano, Susan M

    2014-01-01

    Amyloid beta (Abeta) 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD). We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic effects on synapses in vitro and cognitive deficits in vivo. Knockdown of sigma-2/PGRMC1 (progesterone receptor membrane component 1) protein expression in vitro using siRNA results in a highly correlated reduction in binding of exogenous Abeta oligomers to neurons of more than 90%. Expression of sigma-2/PGRMC1 is upregulated in vitro by treatment with Abeta oligomers, and is dysregulated in Alzheimer's disease patients' brain compared to age-matched, normal individuals. Specific, high affinity small molecule receptor antagonists and antibodies raised against specific regions on this receptor can displace synthetic Abeta oligomer binding to synaptic puncta in vitro and displace endogenous human AD patient oligomers from brain tissue sections in a dose-dependent manner. These receptor antagonists prevent and reverse the effects of Abeta oligomers on membrane trafficking and synapse loss in vitro and cognitive deficits in AD mouse models. These findings suggest sigma-2/PGRMC1 receptors mediate saturable oligomer binding to synaptic puncta on neurons and that brain penetrant, small molecules can displace endogenous and synthetic oligomers and improve cognitive deficits in AD models. We propose that sigma-2/PGRMC1 is a key mediator of the pathological effects of

  1. Dewetting of a solid monolayer.

    PubMed

    Pierre-Louis, O; Chame, Anna; Saito, Yukio

    2007-09-28

    We report on the dewetting of a monolayer on a solid substrate, where mass transport occurs via surface diffusion. For a wide range of parameters, a labyrinthine pattern of bilayer islands is formed. An irreversible regime and a thermodynamic regime are identified. In both regimes, the velocity of a dewetting front, the wavelength of the bilayer island pattern, and the rate of nucleation of dewetted zones are obtained. We also point out the existence of a scaling behavior, which is analyzed by means of a geometrical model.

  2. Anticoagulant flavonoid oligomers from the rhizomes of Alpinia platychilus.

    PubMed

    Shen, Chuan-Pu; Luo, Jian-Guang; Yang, Ming-Hua; Kong, Ling-Yi

    2015-10-01

    Two pairs of enantiomers of flavonoid oligomers (1a and 1b, 2a and 2b) along with one known chalcone (3) were isolated from the rhizomes of Alpinia platychilus. Their structures were elucidated on the basis of spectroscopic data (MS and 1D/2D NMR). The absolute configurations of the flavonoid oligomers were established by their ECD spectra. Separation of the enantiomeric mixtures (1a and 1b, 2a and 2b) was achieved on a chiral column using hexane:isopropyl alcohol:ethanol (7:2:1) as eluents. The anticoagulant assay showed that 2a, 2b and 3 exhibited potent activities to prolong the prothrombin times (PT) and the thrombin times (TT).

  3. 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.

  4. Synthesis of long prebiotic oligomers on mineral surfaces.

    PubMed

    Ferris, J P; Hill, A R; Liu, R; Orgel, L E

    1996-05-02

    Most theories of the origin of biological organization assume that polymers with lengths in the range of 30-60 monomers are needed to make a genetic system viable. But it has not proved possible to synthesize plausibly prebiotic polymers this long by condensation in aqueous solution, because hydrolysis competes with polymerization. The potential of mineral surfaces to facilitate prebiotic polymerization was pointed out long ago. Here we describe a system that models prebiotic polymerization by the oligomerization of activated monomers--both nucleotides and amino acids. We find that whereas the reactions in solution produce only short oligomers (the longest typically being a 10-mer), the presence of mineral surfaces (montmorillonite for nucleotides, illite and hydroxylapatite for amino acids) induces the formation of oligomers up to 55 monomers long. These are formed by successive 'feedings' with the monomers; polymerization takes place on the mineral surfaces in a manner akin to solid-phase synthesis of biopolymers.

  5. Synthesis of long Prebiotic Oligomers on Mineral Surfaces

    NASA Technical Reports Server (NTRS)

    Ferris, James P.; Hill, Aubrey R., Jr.; Liu, Rihe; Orgel, Leslie E.

    1996-01-01

    Most theories of the origin of biological organization assume that polymers with lengths in the range of 30-60 monomers are needed to make a genetic system viable. But it has not proved possible to synthesize plausibly prebiotic polymers this long by condensation in aqueous solution, because hydrolysis competes with polymerization. The potential of mineral surfaces to facilitate prebiotic polymerization was pointed out long ago. Here we describe a system that models prebiotic polymerization by the oligomerization of activated monomers -both nucleotides and amino acids. We find that whereas the reactions in solution produce only short oligomers (the longest typically being a 10-mer), the presence of mineral surfaces (montmorillonite for nucleotides, illite and hydroxylapatite for amino adds) induces the formation of oligomers up to 55 monomers long. These are formed by successive "feedings" with the monomers; polymerization takes place on the mineral surfaces in a manner akin to solid-phase synthesis of biopolymers.

  6. Phase behavior of a lattice hydrophobic oligomer in explicit water.

    PubMed

    Romero-Vargas Castrillón, Santiago; Matysiak, Silvina; Stillinger, Frank H; Rossky, Peter J; Debenedetti, Pablo G

    2012-08-09

    We investigate the thermodynamics of hydrophobic oligomer collapse using a water-explicit, three-dimensional lattice model. The model captures several aspects of protein thermodynamics, including the emergence of cold- and thermal-unfolding, as well as unfolding at high solvent density (a phenomenon akin to pressure-induced denaturation). We show that over a range of conditions spanning a ≈14% increase in solvent density, the oligomer transforms into a compact, strongly water-penetrated conformation at low temperature. This contrasts with thermal unfolding at high temperature, where the system "denatures" into an extended random coil conformation. We report a phase diagram for hydrophobic collapse that correctly captures qualitative aspects of cold and thermal unfolding at low to intermediate solvent densities.

  7. Production of random DNA oligomers for scalable DNA computing.

    PubMed

    Wang, Sixue S L; Johnson, John J X; Hughes, Bradley S T; Karabay, Dundar A O; Bader, Karson D W; Austin, Allen; Austin, Alan; Habib, Aisha; Hatef, Husnia; Joshi, Megha; Nguyen, Lawrence; Mills, Allen P

    2009-01-01

    While remarkably complex networks of connected DNA molecules can form from a relatively small number of distinct oligomer strands, a large computational space created by DNA reactions would ultimately require the use of many distinct DNA strands. The automatic synthesis of this many distinct strands is economically prohibitive. We present here a new approach to producing distinct DNA oligomers based on the polymerase chain reaction (PCR) amplification of a few random template sequences. As an example, we designed a DNA template sequence consisting of a 50-mer random DNA segment flanked by two 20-mer invariant primer sequences. Amplification of a dilute sample containing about 30 different template molecules allows us to obtain around 10(11) copies of these molecules and their complements. We demonstrate the use of these amplicons to implement some of the vector operations that will be required in a DNA implementation of an analog neural network.

  8. Multifunctional self-assembled monolayers

    SciTech Connect

    Zawodzinski, T.; Bar, G.; Rubin, S.; Uribe, F.; Ferrais, J.

    1996-06-01

    This is the final report of at three year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The specific goals of this research project were threefold: to develop multifunctional self-assembled monolayers, to understand the role of monolayer structure on the functioning of such systems, and to apply this knowledge to the development of electrochemical enzyme sensors. An array of molecules that can be used to attach electrochemically active biomolecules to gold surfaces has been synthesized. Several members of a class of electroactive compounds have been characterized and the factors controlling surface modification are beginning to be characterized. Enzymes have been attached to self-assembled molecules arranged on the gold surface, a critical step toward the ultimate goal of this project. Several alternative enzyme attachment strategies to achieve robust enzyme- modified surfaces have been explored. Several means of juxtaposing enzymes and mediators, electroactive compounds through which the enzyme can exchange electrons with the electrode surface, have also been investigated. Finally, the development of sensitive biosensors based on films loaded with nanoscale-supported gold particles that have surface modified with the self-assembled enzyme and mediator have been explored.

  9. Changes of adiponectin oligomer composition by moderate weight reduction.

    PubMed

    Bobbert, Thomas; Rochlitz, Helmut; Wegewitz, Uta; Akpulat, Suzan; Mai, Knut; Weickert, Martin O; Möhlig, Matthias; Pfeiffer, Andreas F H; Spranger, Joachim

    2005-09-01

    Adiponectin affects lipid metabolism and insulin sensitivity. However, adiponectin circulates in three different oligomers that may also have distinct biological functions. We aimed to analyze the role of these oligomers in obesity and lipid metabolism after weight reduction. A total of 17 obese volunteers (15 women and 2 men) participated in a weight reduction program. Individuals were characterized before and after 6 months of a balanced diet. Adiponectin was determined by enzyme-linked immunosorbent assay, and oligomers were detected by nondenaturating Western blot. BMI decreased (35.1 +/- 1.2 to 32.8 +/- 1.1 kg/m(2), P < 0.001), which was associated with an improved metabolite profile. Total adiponectin increased from 5.3 +/- 0.5 to 6.1 +/- 0.6 microg/ml (P = 0.076). High (HMW) and medium molecular weight (MMW) adiponectin oligomers significantly increased during weight reduction (HMW: 0.37 +/- 0.07 to 0.4 +/- 0.08 microg/ml, P = 0.042; MMW: 2.3 +/- 0.2 to 2.9 +/- 0.3 microg/ml, P = 0.007), while low molecular weight (LMW) did not significantly change. Body weight inversely correlated with HMW (r = -0.695, P = 0.002) and positively with LMW (r = 0.579, P = 0.015). Interestingly, HDL cholesterol and HMW were strongly correlated (r = 0.665, P = 0.007). Indeed, HMW and free fatty acids before weight reduction predicted approximately 60% of HDL changes during intervention. In conclusion, weight reduction results in a relative increase of HMW/MMW adiponectin and a reduction of LMW adiponectin. Total adiponectin and especially HMW adiponectin are related to circulating HDL cholesterol.

  10. Ethynyl-terminated ester oligomers and polymers therefrom

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M. (Inventor); Havens, Stephen J. (Inventor)

    1986-01-01

    A class of ethynyl terminated oligomers and the process for preparing the same are disclosed. Upon the application of heat, with or without a catalyst, the ethynyl groups react to provide crosslinking and chain extension to increase the polymer use temperature and improve the polymer solvent resistance. These polyesters are potentially useful in packaging, magnetic tapes, capacitors, industrial belting, protective coatings, structural adhesives and composite matrices.

  11. Using hyperbranched oligomer functionalized glass fillers to reduce shrinkage stress

    PubMed Central

    Ye, Sheng; Azarnoush, Setareh; Smith, Ian R.; Cramer, Neil B.; Stansbury, Jeffrey W.; Bowman, Christopher N

    2012-01-01

    Objective Fillers are widely utilized to enhance the mechanical properties of polymer resins. However, polymerization stress has the potential to increase due to the higher elastic modulus achieved upon filler addition. Here, we demonstrate a hyperbranched oligomer functionalized glass filler UV curable resin composite which is able to reduce the shrinkage stress without sacrificing mechanical properties. Methods A 16-functional alkene-terminated hyperbranched oligomer is synthesized by thiol-acrylate and thiol-yne reactions and the product structure is analyzed by 1H-NMR, mass spectroscopy, and gel permeation chromatography. Surface functionalization of the glass filler is measured by thermogravimetric analysis. Reaction kinetics, mechanical properties and shrinkage stress are studied via Fourier transform infrared spectroscopy, dynamic mechanical analysis and a tensometer, respectively. Results Silica nanoparticles are functionalized with a flexible 16-functional alkene-terminated hyperbranched oligomer which is synthesized by multistage thiol-ene/yne reactions. 93% of the particle surface was covered by this oligomer and an interfacial layer ranging from 0.7 – 4.5 nm thickness is generated. A composite system with these functionalized silica nanoparticles incorporated into the thiol-yne-methacrylate resin demonstrates 30% reduction of shrinkage stress (from 0.9 MPa to 0.6 MPa) without sacrificing the modulus (3100 ± 300 MPa) or glass transition temperature (62 ± 3 °C). Moreover, the shrinkage stress of the composite system builds up at much later stages of the polymerization as compared to the control system. Significance Due to the capability of reducing shrinkage stress without sacrificing mechanical properties, this composite system will be a great candidate for dental composite applications. PMID:22717296

  12. Characterization of reducible peptide oligomers as carriers for gene delivery.

    PubMed

    Kiselev, Anton; Egorova, Anna; Laukkanen, Antti; Baranov, Vladislav; Urtti, Arto

    2013-01-30

    The stability of DNA-polyplexes and intracellular DNA release are important features of gene delivery systems. To study these features, we have evaluated reducible cysteine-flanked linear lysine and arginine-rich peptides, modified with histidine residues. The reducible disulfide bonds in cysteine flanked peptides and histidine residues should augment DNA release from the peptide-DNA complexes upon disintegration of the reducible bonds. Template polymerization and oxidative polycondensation were applied to obtain peptide oligomers used for DNA-polyplex preparation. The peptides and DNA-peptide complexes were investigated with physical, chemical and transfection measurements. Physicochemical and transfection properties of DNA-polyplexes depended on the amino acid sequence of the peptidic polymers and type of the polymerization. MALDI-TOF analysis of oxidatively polycondensed products revealed several forms of peptide oligomers corresponding to 5-8 amino acid monomers. DNA-peptide particles based on template-polymerized complexes were more resistant to relaxation by negatively charged heparan sulfate than polyplexes formed with oxidatively condensed peptides. Complexes of DNA with the polycations prepared by oxidative polycondensation exhibited a 100-1000-fold higher level of gene expression compared to DNA/template-polymerized peptide complexes. The most efficient transgene expression was shown with arginine-rich polyplexes. Transfection efficacy of the arginine-rich polyplexes was even 10-fold better than that of DNA/PEI complexes. On average, polyplexes based on cysteine-flanked peptide oligomers showed lower cytotoxicity than non-reducible high molecular weight polylysine/DNA particles. We conclude that reducible peptide oligomers provide efficient DNA transfection and have the potential as vehicles for gene delivery.

  13. Synthesis of soybean oil-based thiol oligomers.

    PubMed

    Wu, Jennifer F; Fernando, Shashi; Weerasinghe, Dimuthu; Chen, Zhigang; Webster, Dean C

    2011-08-22

    Industrial grade soybean oil (SBO) and thiols were reacted to generate thiol-functionalized oligomers via a thermal, free radical initiated thiol-ene reaction between the SBO double bond moieties and the thiol functional groups. The effect of the reaction conditions, including thiol concentration, catalyst loading level, reaction time, and atmosphere, on the molecular weight and the conversion to the resultant soy-thiols were examined in a combinatorial high-throughput fashion using parallel synthesis, combinatorial FTIR, and rapid gel permeation chromatography (GPC). High thiol functionality and concentration, high thermal free radical catalyst concentration, long reaction time, and the use of a nitrogen reaction atmosphere were found to favor fast consumption of the SBO, and produced high molecular weight products. The thiol conversion during the reaction was inversely affected by a high thiol concentration, but was favored by a long reaction time and an air reaction atmosphere. These experimental observations were explained by the initial low affinity of the SBO and thiol, and the improved affinity between the generated soy-thiol oligomers and unreacted SBO during the reaction. The synthesized soy-thiol oligomers can be used for renewable thiol-ene UV curable materials and high molecular solids and thiourethane thermal cure materials.

  14. Molecular modeling of crystalline alkylthiophene oligomers and polymers.

    PubMed

    Moreno, Margherita; Casalegno, Mosè; Raos, Guido; Meille, Stefano V; Po, Riccardo

    2010-02-04

    We present the results of a thorough molecular modeling study of several alkylthiophene-based oligomers and polymers. In particular, we consider two polymers whose limit-ordered crystal structures have been recently reported by our group, on the basis of powder X-ray data analysis: poly(3-(S)-2-methylbutylthiophene) (P3MBT) and form I' of poly(3-butylthiophene) (P3BT). We first describe the development of a series general purpose force fields for the simulation of these and related systems. The force fields incorporate the results of ab initio calculations of the bond torsion energies of selected oligomers and differ in the set of atomic charges used to represent the electrostatic interactions. We then present the results of an extensive validation of these force fields, by means of molecular mechanics (MM) energy minimizations and molecular dynamics (MD) simulations of the crystal structures of these oligomers and polymers. While our "best" force field does not outperform the others on each of the investigated systems, it provides a balanced description of their overall structure and energetics. Finally, our MM minimizations and MD simulations confirm that the reported crystal structures of P3MBT and P3BT are stable and correspond to well-defined energetic minima. The room-temperature MD simulations reveal a certain degree of side-chain disorder, even in our virtually defect-free polymer crystal models.

  15. Deuteration-induced scission of C{sub 58} oligomers

    SciTech Connect

    Loeffler, Daniel; Jester, Stefan-S.; Weis, Patrick; Boettcher, Artur; Kappes, Manfred M.

    2006-12-14

    The reaction of solid C{sub 58} films with atomic deuterium to yield deuterofullerenes, C{sub 58}D{sub x}, has been investigated by thermal desorption spectroscopy coupled with mass spectrometric detection, ultraviolet photoionization spectroscopy (21.2 eV), and atomic force microscopy (AFM). The average composition of the deuterofullerenes created depends on deuterium dose, beam flux, and surface temperature. Low deuterium exposures at room temperature yield predominantly C{sub 58}D{sub 6-8} cages. Saturation exposures at room temperature yield mass spectra peaked at C{sub 58}D{sub 26}. After saturation exposures at elevated surface temperatures ({approx}500 K), the (subsequently) desorbed material reveals a comparatively narrow mass spectral distribution centered at C{sub 58}D{sub 30}. Deuteration is associated with cleavage of covalent cage-cage bonds in the starting C{sub 58} oligomer material, as evidenced by a considerable lowering of the sublimation energies of C{sub 58}D{sub x} compared to desorption of C{sub 58} desorbed from pure oligomer films. Correspondingly, AFM images reveal a D-induced, thermally activated transition from dendritic C{sub 58} oligomer islands into smooth-rimmed islands composed of deuterated cages. Deuterated films exhibit a significantly lower work function than bare C{sub 58} films. Progressing deuteration also gradually raises the surface ionization potential.

  16. α-Synuclein oligomers and clinical implications for Parkinson disease.

    PubMed

    Kalia, Lorraine V; Kalia, Suneil K; McLean, Pamela J; Lozano, Andres M; Lang, Anthony E

    2013-02-01

    Protein aggregation within the central nervous system has been recognized as a defining feature of neurodegenerative diseases since the early 20th century. Since that time, there has been a growing list of neurodegenerative disorders, including Parkinson disease, which are characterized by inclusions of specific pathogenic proteins. This has led to the long-held dogma that these characteristic protein inclusions, which are composed of large insoluble fibrillar protein aggregates and visible by light microscopy, are responsible for cell death in these diseases. However, the correlation between protein inclusion formation and cytotoxicity is inconsistent, suggesting that another form of the pathogenic proteins may be contributing to neurodegeneration. There is emerging evidence implicating soluble oligomers, smaller protein aggregates not detectable by conventional microscopy, as potential culprits in the pathogenesis of neurodegenerative diseases. The protein α-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites. However, α-synuclein also forms oligomeric species, with certain conformations being toxic to cells. The mechanisms by which these α-synuclein oligomers cause cell death are being actively investigated, as they may provide new strategies for diagnosis and treatment of Parkinson disease and related disorders. Here we review the possible role of α-synuclein oligomers in cell death in Parkinson disease and discuss the potential clinical implications.

  17. Oligomers, organosulfates, and nitroxy organosulfates identified in rainwater

    NASA Astrophysics Data System (ADS)

    Altieri, K. E.; Turpin, B. J.; Seitzinger, S. P.

    2008-12-01

    Wet deposition is an important removal mechanism for atmospheric organic matter, and a potentially important input for receiving ecosystems, yet less than 50 percent of rainwater organic matter is considered chemically characterized. Precipitation samples collected in New Jersey, USA, were analyzed by negative ion ultra-high resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). We document the presence of 552 unique compounds in the rainwater over a mass range of 50-500 Da, in four compound classes (i.e., CHO, CHOS, CHON, and CHONS). The presence of oligomers, organosulfates, nitroxy organosulfates, organic acids, and linear alkylbenzene sulfonates is reported. Some compounds detected have distinct primary sources; however, the composition of the bulk of this material suggests it is formed in the atmosphere and composed of known contributors to secondary organic aerosol. For example, eight oligomer series known to form through aqueous photooxidation of methylglyoxal and organosulfate compounds known to form from 4 precursors in smog chamber experiments were identified in the rainwater samples. The oligomers, organosulfates, and nitroxy organosulfates detected in the rainwater could all contribute to the HULIS fraction of atmospheric organic matter.

  18. Size-dependent neurotoxicity of β-amyloid oligomers

    PubMed Central

    Cizas, Paulius; Budvytyte, Rima; Morkuniene, Ramune; Moldovan, Radu; Broccio, Matteo; Lösche, Mathias; Niaura, Gediminas; Valincius, Gintaras; Borutaite, Vilmante

    2010-01-01

    The link between the size of soluble amyloid β (Aβ) oligomers and their toxicity to rat cerebellar granule cells (CGC) was investigated. Variation in conditions during in vitro oligomerization of Aβ1-42 resulted in peptide assemblies with different particle size as measured by atomic force microscopy and confirmed by the dynamic light scattering and fluorescence correlation spectroscopy. Small oligomers of Aβ1-42 with a mean particle z-height of 1-2 nm exhibited propensity to bind to the phospholipid vesicles and they were the most toxic species that induced rapid neuronal necrosis at submicromolar concentrations whereas the bigger aggregates (z-height above 4-5 nm) did not bind vesicles and did not cause detectable neuronal death. Similar neurotoxic pattern was also observed in primary cultures of cortex neurons whereas Aβ1–42 oligomers, monomers and fibrils were non-toxic to glial cells in CGC cultures or macrophage J774 cells. However, both oligomeric forms of Aβ1-42 induced reduction of neuronal cell densities in the CGC cultures. PMID:20153288

  19. Size-dependent neurotoxicity of beta-amyloid oligomers.

    PubMed

    Cizas, Paulius; Budvytyte, Rima; Morkuniene, Ramune; Moldovan, Radu; Broccio, Matteo; Lösche, Mathias; Niaura, Gediminas; Valincius, Gintaras; Borutaite, Vilmante

    2010-04-15

    The link between the size of soluble amyloid beta (Abeta) oligomers and their toxicity to rat cerebellar granule cells (CGC) was investigated. Variation in conditions during in vitro oligomerization of Abeta(1-42) resulted in peptide assemblies with different particle size as measured by atomic force microscopy and confirmed by dynamic light scattering and fluorescence correlation spectroscopy. Small oligomers of Abeta(1-42) with a mean particle z-height of 1-2 nm exhibited propensity to bind to phospholipid vesicles and they were the most toxic species that induced rapid neuronal necrosis at submicromolar concentrations whereas the bigger aggregates (z-height above 4-5 nm) did not bind vesicles and did not cause detectable neuronal death. A similar neurotoxic pattern was also observed in primary cultures of cortex neurons whereas Abeta(1-42) oligomers, monomers and fibrils were non-toxic to glial cells in CGC cultures or macrophage J774 cells. However, both oligomeric forms of Abeta(1-42) induced reduction of neuronal cell densities in the CGC cultures.

  20. The Viscoelastic Behavior of Polymer/Oligomer Blends

    NASA Astrophysics Data System (ADS)

    Zheng, Wei; McKenna, Gregory; Simon, Sindee

    2009-03-01

    The dynamics in athermal blends of poly(α-methyl styrene) (PaMS) and its short chain oligomer are investigated using rheometry and differential scanning calorimetry (DSC). Master curves for the dynamic shear responses, G' and G", are successfully constructed for both the pure materials and the blends, indicating the validity of the time-temperature superposition principle. The temperature dependence of the shift factor follows the WLF (Williams-Landel-Ferry) behavior over the temperature range studied, and for the blends, the dependence is dominated by the high mobility oligomer. The discrete relaxation spectra of the materials are calculated and are found to be broader for the blends than for the pure materials. A similar domination of the dynamics by the oligomer is observed in DSC enthalpy recovery studies and in the broadened glass transition from DSC. The ability to predict the dynamic responses of the blends from the responses of the neat materials is examined, and whether this prediction needs to incorporate the self-concentration idea as described in Colmenero's model will be discussed.

  1. Optimized Ultrasonic Irradiation Finds Out Ultrastable Aβ1-40 Oligomers.

    PubMed

    Nakajima, Kichitaro; So, Masatomo; Takahashi, Kazuma; Tagawa, Yoh-Ichi; Hirao, Masahiko; Goto, Yuji; Ogi, Hirotsugu

    2017-03-16

    Oligomer species of amyloid β (Aβ) peptides are intensively investigated because of their relevance to Alzheimer's disease (AD), and a stable oligomer will be a cause of AD. In this article, we investigate the structural stability of two representative Aβ1-40 oligomers, which are with and without the β-sheet structure, denoted by β and non-β oligomers, respectively, using optimized ultrasonic irradiation (OUI). Recent studies reveal that OUI significantly accelerates the fibril formation in Aβ1-40 monomers; it is capable of transforming any unstable oligomers into fibrils (the dead-end products) in a short time. First, we find that β oligomers can be produced under high-speed stirring agitation; their β-sheet structures are evaluated by the circular-dichroism spectrum measurement, by the immunoassay using the fibril-specific OC antibody, and by the seeding experiment, showing identical characteristics to those formed in previous reports. Second, we form non-β oligomers in a high-concentration NaCl solution and confirm that they include no β-sheet structure, and they are recognized by the oligomer-specific A11 antibody. Furthermore, we confirm the neurotoxicity of the two types of oligomers using the neural tissue derived from mouse embryonic stem cells. We apply the OUI agitation to the β and non-β oligomers. The non-β oligomers are transformed into the fibrils, indicating that they are intermediate species in the fibrillation pathway. However, the β oligomers are surprisingly unaffected by OUI, indicating their high thermodynamic stability. We conclude that the β oligomers should be the independent dead-end products of another pathway, different from the fibrillation pathway.

  2. Stilling Waves with Ordered Molecular Monolayers

    ERIC Educational Resources Information Center

    Vitz, Ed

    2008-01-01

    A demonstration of the damping effect of an oil monolayer on water waves is described. The history of this remarkable demonstration--with a 2000 (or more) year span--and a brief explanation in terms of the properties of water and the monolayer are presented. If a layer of olive oil, one molecule thick (about one-ten millionth of a centimeter), is…

  3. Nonlinear light scattering by a dipole monolayer

    NASA Astrophysics Data System (ADS)

    Averbukh, B. B.; Averbukh, I. B.

    2013-08-01

    Scattering of a strong p-polarized monochromatic field by a dipole monolayer is considered. It is shown that a triplet should be observed at incident angles (between the wave vector of the incident wave and the normal to the monolayer surface) not too close to π/2 in the spectrum of the scattered radiation. For grazing incidence of a strong field on the monolayer, waves with frequencies of the strong field and the high-frequency component of the triplet scatter forward and backward. In this case, radiation with frequency of the low-frequency component of the triplet propagates in the form of two inhomogeneous waves along the monolayer on both sides of it, exponentially decaying with distance from the monolayer.

  4. Synthesis and Optoelectronic Characterization of Some Star-Shaped Oligomers with Benzene and Triphenylamine Cores

    PubMed Central

    Ivan, Teofilia; Vacareanu, Loredana; Grigoras, Mircea

    2012-01-01

    Six star-shaped oligomers containing triphenylamine (D1–D3) and benzene unit (D4–D6) as cores have been synthesized by Wittig condensation or Heck coupling reaction using aromatic aldehydes and triphenylphosphonium salts or aromatic halogenated compounds with vinyl triphenylamine. All oligomers have well-defined molecular structure and high purity. Characterization of the oligomers was made by FT-IR, 1H-NMR spectroscopy, UV-Vis, and fluorescence spectroscopy. The electrochemical behavior was studied by cyclic voltammetry (CV). The cyclic voltammograms have revealed that oligomers undergo quasireversible or irreversible redox processes. The irreversible process is associated with electrochemical polymerization of oligomers by dimerization of unsubstituted triphenylamine groups. Thermal characterization was accomplished by TGA and DSC methods and evidenced that all oligomers were stable materials until 250°C and have formed stable molecular glasses after first heating scan. PMID:24052859

  5. Radiative decay of excitons in model aggregates of {pi}-conjugated oligomers

    SciTech Connect

    Manas, E.S.; Spano, F.C.

    1998-07-01

    Spontaneous emission from exciton states in an aggregate of {pi}-conjugated oligomers is studied theoretically. Each oligomer is taken as a ring of N carbon atoms and is treated using a PPP Hamiltonian. Coulombic interactions between rings are treated to first order. The radiative decay rate {gamma} from an exciton state in an aggregate of M aligned oligomers is superradiant, being M times faster than the decay rate of an isolated oligomer exciton. Inter-oligomer interactions have little effect on the exciton size and energy when the oligomer size N is large compared to the interoligomer spacing. However, when N is small, both the exciton size and energy are strongly affected by these interactions, leading to a markedly different N dependence for {gamma}.

  6. Coulomb excitations of monolayer germanene

    NASA Astrophysics Data System (ADS)

    Shih, Po-Hsin; Chiu, Yu-Huang; Wu, Jhao-Ying; Shyu, Feng-Lin; Lin, Ming-Fa

    2017-01-01

    The feature-rich electronic excitations of monolayer germanene lie in the significant spin-orbit coupling and the buckled structure. The collective and single-particle excitations are diversified by the magnitude and direction of transferred momentum, the Fermi energy and the gate voltage. There are four kinds of plasmon modes, according to the unique frequency- and momentum-dependent phase diagrams. They behave as two-dimensional acoustic modes at long wavelength. However, for the larger momenta, they might change into another kind of undamped plasmons, become the seriously suppressed modes in the heavy intraband e–h excitations, keep the same undamped plasmons, or decline and then vanish in the strong interband e–h excitations. Germanene, silicene and graphene are quite different from one another in the main features of the diverse plasmon modes.

  7. Coulomb excitations of monolayer germanene

    PubMed Central

    Shih, Po-Hsin; Chiu, Yu-Huang; Wu, Jhao-Ying; Shyu, Feng-Lin; Lin, Ming-Fa

    2017-01-01

    The feature-rich electronic excitations of monolayer germanene lie in the significant spin-orbit coupling and the buckled structure. The collective and single-particle excitations are diversified by the magnitude and direction of transferred momentum, the Fermi energy and the gate voltage. There are four kinds of plasmon modes, according to the unique frequency- and momentum-dependent phase diagrams. They behave as two-dimensional acoustic modes at long wavelength. However, for the larger momenta, they might change into another kind of undamped plasmons, become the seriously suppressed modes in the heavy intraband e–h excitations, keep the same undamped plasmons, or decline and then vanish in the strong interband e–h excitations. Germanene, silicene and graphene are quite different from one another in the main features of the diverse plasmon modes. PMID:28091555

  8. Thermoelectric transport in monolayer phosphorene

    NASA Astrophysics Data System (ADS)

    Zare, Moslem; Rameshti, Babak Zare; Ghamsari, Farnood G.; Asgari, Reza

    2017-01-01

    We apply the generalized Boltzmann theory to describe thermoelectric transport properties of monolayer phosphorene in the presence of short- and long-range charged impurity interactions. First, we propose a low-energy Hamiltonian to explore the accurate electronic band structure of phosphorene in comparison with those results obtained by density-functional simulations. We explain the effect of the coupling between the conduction and valence bands on the thermoelectric properties. We show that the electric conductivity of phosphorene is highly anisotropic, while the Seebeck coefficient and figure of merit, without being influenced via either the presence or absence of the coupling term, are nearly isotropic. Furthermore, we demonstrate that the conductivity for the n type of doping is more influenced by the coupling term than that of the p type. Along with thermopower sign change, profound thermoelectric effects can be achieved.

  9. Highly doped silicon nanowires by monolayer doping.

    PubMed

    Veerbeek, Janneke; Ye, Liang; Vijselaar, Wouter; Kudernac, Tibor; van der Wiel, Wilfred G; Huskens, Jurriaan

    2017-02-23

    Controlling the doping concentration of silicon nanostructures is challenging. Here, we investigated three different monolayer doping techniques to obtain silicon nanowires with a high doping dose. These routes were based on conventional monolayer doping, starting from covalently bound dopant-containing molecules, or on monolayer contact doping, in which a source substrate coated with a monolayer of a carborane silane was the dopant source. As a third route, both techniques were combined to retain the benefits of conformal monolayer formation and the use of an external capping layer. These routes were used for doping fragile porous nanowires fabricated by metal-assisted chemical etching. Differences in porosity were used to tune the total doping dose inside the nanowires, as measured by X-ray photoelectron spectroscopy and secondary ion mass spectrometry measurements. The higher the porosity, the higher was the surface available for dopant-containing molecules, which in turn led to a higher doping dose. Slightly porous nanowires could be doped via all three routes, which resulted in highly doped nanowires with (projected areal) doping doses of 10(14)-10(15) boron atoms per cm(2) compared to 10(12) atoms per cm(2) for a non-porous planar sample. Highly porous nanowires were not compatible with the conventional monolayer doping technique, but monolayer contact doping and the combined route resulted for these highly porous nanowires in tremendously high doping doses up to 10(17) boron atoms per cm(2).

  10. Direct Correlation Between Ligand-Induced α-Synuclein Oligomers and Amyloid-like Fibril Growth

    PubMed Central

    Nors Perdersen, Martin; Foderà, Vito; Horvath, Istvan; van Maarschalkerweerd, Andreas; Nørgaard Toft, Katrine; Weise, Christoph; Almqvist, Fredrik; Wolf-Watz, Magnus; Wittung-Stafshede, Pernilla; Vestergaard, Bente

    2015-01-01

    Aggregation of proteins into amyloid deposits is the hallmark of several neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. The suggestion that intermediate oligomeric species may be cytotoxic has led to intensified investigations of pre-fibrillar oligomers, which are complicated by their transient nature and low population. Here we investigate alpha-synuclein oligomers, enriched by a 2-pyridone molecule (FN075), and the conversion of oligomers into fibrils. As probed by leakage assays, the FN075 induced oligomers potently disrupt vesicles in vitro, suggesting a potential link to disease related degenerative activity. Fibrils formed in the presence and absence of FN075 are indistinguishable on microscopic and macroscopic levels. Using small angle X-ray scattering, we reveal that FN075 induced oligomers are similar, but not identical, to oligomers previously observed during alpha-synuclein fibrillation. Since the levels of FN075 induced oligomers correlate with the amounts of fibrils among different FN075:protein ratios, the oligomers appear to be on-pathway and modeling supports an ‘oligomer stacking model’ for alpha-synuclein fibril elongation. PMID:26020724

  11. Quantitative analysis of co-oligomer formation by amyloid-beta peptide isoforms

    NASA Astrophysics Data System (ADS)

    Iljina, Marija; Garcia, Gonzalo A.; Dear, Alexander J.; Flint, Jennie; Narayan, Priyanka; Michaels, Thomas C. T.; Dobson, Christopher M.; Frenkel, Daan; Knowles, Tuomas P. J.; Klenerman, David

    2016-06-01

    Multiple isoforms of aggregation-prone proteins are present under physiological conditions and have the propensity to assemble into co-oligomers with different properties from self-oligomers, but this process has not been quantitatively studied to date. We have investigated the amyloid-β (Aβ) peptide, associated with Alzheimer’s disease, and the aggregation of its two major isoforms, Aβ40 and Aβ42, using a statistical mechanical modelling approach in combination with in vitro single-molecule fluorescence measurements. We find that at low concentrations of Aβ, corresponding to its physiological abundance, there is little free energy penalty in forming co-oligomers, suggesting that the formation of both self-oligomers and co-oligomers is possible under these conditions. Our model is used to predict the oligomer concentration and size at physiological concentrations of Aβ and suggests the mechanisms by which the ratio of Aβ42 to Aβ40 can affect cell toxicity. An increased ratio of Aβ42 to Aβ40 raises the fraction of oligomers containing Aβ42, which can increase the hydrophobicity of the oligomers and thus promote deleterious binding to the cell membrane and increase neuronal damage. Our results suggest that co-oligomers are a common form of aggregate when Aβ isoforms are present in solution and may potentially play a significant role in Alzheimer’s disease.

  12. Low-resolution structure of a vesicle disrupting α-synuclein oligomer that accumulates during fibrillation

    PubMed Central

    Giehm, Lise; Svergun, Dmitri I.; Otzen, Daniel E.; Vestergaard, Bente

    2011-01-01

    One of the major hallmarks of Parkinson disease is aggregation of the protein α-synuclein (αSN). Aggregate cytotoxicity has been linked to an oligomeric species formed at early stages in the aggregation process. Here we follow the fibrillation process of αSN in solution over time using small angle X-ray scattering and resolve four major coexisting species in the fibrillation process, namely monomer, dimer, fibril and an oligomer. By ab initio modeling to fit the data, we obtain a low-resolution structure of a symmetrical and slender αSN fibril in solution, consisting of a repeating unit with a maximal distance of 900 Å and a diameter of ∼180 Å. The same approach shows the oligomer to be shaped like a wreath, with a central channel and with dimensions corresponding to the width of the fibril. The structure, accumulation and decay of this oligomer is consistent with an on-pathway role for the oligomer in the fibrillation process. We propose an oligomer-driven αSN fibril formation mechanism, where the fibril is built from the oligomers. The wreath-shaped structure of the oligomer highlights its potential cytotoxicity by simple membrane permeabilization. This is confirmed by the ability of the purified oligomer to disrupt liposomes. Our results provide the first structural description in solution of a potentially cytotoxic oligomer, which accumulates during the fibrillation of αSN. PMID:21300904

  13. Electrochemical Deposition Of Thiolate Monolayers On Metals

    NASA Technical Reports Server (NTRS)

    Porter, Marc D.; Weissharr, Duane E.

    1995-01-01

    Electrochemical method devised for coating metal (usually, gold) surfaces with adherent thiolate monolayers. Affords greater control over location and amount of material deposited and makes it easier to control chemical composition of deposits. One important potential use for this method lies in fabrication of chemically selective thin-film resonators for microwave oscillators used to detect pollutants: monolayer formulated to bind selectively pollutant chemical species of interest, causing increase in mass of monolayer and corresponding decrease in frequency of resonance. Another important potential use lies in selective chemical derivatization for purposes of improving adhesion, lubrication, protection against corrosion, electrocatalysis, and electroanalysis.

  14. Monolayer coated gold nanoparticles for delivery applications

    PubMed Central

    Rana, Subinoy; Bajaj, Avinash; Mout, Rubul; Rotello, Vincent M.

    2011-01-01

    Gold nanoparticles (AuNPs) provide attractive vehicles for delivery of drugs, genetic materials, proteins, and small molecules. AuNPs feature low core toxicity coupled with the ability to parametrically control particle size and surface properties. In this review, we focus on engineering of the AuNP surface monolayer, highlighting recent advances in tuning monolayer structures for efficient delivery of drugs and biomolecules. This review covers two broad categories of particle functionalization, organic monolayers and biomolecule coatings, and discusses their applications in drug, DNA/RNA, protein and small molecule delivery. PMID:21925556

  15. Electrorheology of aniline-oligomer suspensions under oscillatory shear

    NASA Astrophysics Data System (ADS)

    Mrlik, M.; Pavlinek, V.; Almajdalawi, S.; Saha, P.; Bober, P.; Stejskal, J.

    2013-02-01

    Preparation of the aniline oligomers by the oxidation of aniline with p-benzoquinone in the solutions of methanesulfonic acid (MSA) and the rheology of their suspensions in silicone oil are presented in this study. This synthesis provides particles of flake-like morphology and various conductivities depending on the molar concentration of MSA. Further, the electrorheological (ER) performance of the particles suspended in the silicone oil was measured as well as dielectric properties of suspensions. Finally, the effect of the temperature on the ER activity was investigated.

  16. Aromatic small molecules remodel toxic soluble oligomers of amyloid beta through three independent pathways.

    PubMed

    Ladiwala, Ali Reza A; Dordick, Jonathan S; Tessier, Peter M

    2011-02-04

    In protein conformational disorders ranging from Alzheimer to Parkinson disease, proteins of unrelated sequence misfold into a similar array of aggregated conformers ranging from small oligomers to large amyloid fibrils. Substantial evidence suggests that small, prefibrillar oligomers are the most toxic species, yet to what extent they can be selectively targeted and remodeled into non-toxic conformers using small molecules is poorly understood. We have evaluated the conformational specificity and remodeling pathways of a diverse panel of aromatic small molecules against mature soluble oligomers of the Aβ42 peptide associated with Alzheimer disease. We find that small molecule antagonists can be grouped into three classes, which we herein define as Class I, II, and III molecules, based on the distinct pathways they utilize to remodel soluble oligomers into multiple conformers with reduced toxicity. Class I molecules remodel soluble oligomers into large, off-pathway aggregates that are non-toxic. Moreover, Class IA molecules also remodel amyloid fibrils into the same off-pathway structures, whereas Class IB molecules fail to remodel fibrils but accelerate aggregation of freshly disaggregated Aβ. In contrast, a Class II molecule converts soluble Aβ oligomers into fibrils, but is inactive against disaggregated and fibrillar Aβ. Class III molecules disassemble soluble oligomers (as well as fibrils) into low molecular weight species that are non-toxic. Strikingly, Aβ non-toxic oligomers (which are morphologically indistinguishable from toxic soluble oligomers) are significantly more resistant to being remodeled than Aβ soluble oligomers or amyloid fibrils. Our findings reveal that relatively subtle differences in small molecule structure encipher surprisingly large differences in the pathways they employ to remodel Aβ soluble oligomers and related aggregated conformers.

  17. Multicellular density fluctuations in epithelial monolayers

    NASA Astrophysics Data System (ADS)

    Zehnder, Steven M.; Wiatt, Marina K.; Uruena, Juan M.; Dunn, Alison C.; Sawyer, W. Gregory; Angelini, Thomas E.

    2015-09-01

    Changes in cell size often accompany multicellular motion in tissue, and cell number density is known to strongly influence collective migration in monolayers. Density fluctuations in other forms of active matter have been explored extensively, but not the potential role of density fluctuations in collective cell migration. Here we investigate collective motion in cell monolayers, focusing on the divergent component of the migration velocity field to probe density fluctuations. We find spatial patterns of diverging and converging cell groups throughout the monolayers, which oscillate in time with a period of approximately 3-4 h. Simultaneous fluorescence measurements of a cytosol dye within the cells show that fluid passes between groups of cells, facilitating these oscillations in cell density. Our findings reveal that cell-cell interactions in monolayers may be mediated by intercellular fluid flow.

  18. Accurate Molecular Dimensions from Stearic Acid Monolayers.

    ERIC Educational Resources Information Center

    Lane, Charles A.; And Others

    1984-01-01

    Discusses modifications in the fatty acid monolayer experiment to reduce the inaccurate moleculary data students usually obtain. Copies of the experimental procedure used and a Pascal computer program to work up the data are available from the authors. (JN)

  19. Method to synthesize metal chalcogenide monolayer nanomaterials

    SciTech Connect

    Hernandez-Sanchez, Bernadette A.; Boyle, Timothy J.

    2016-12-13

    Metal chalcogenide monolayer nanomaterials can be synthesized from metal alkoxide precursors by solution precipitation or solvothermal processing. The synthesis routes are more scalable, less complex and easier to implement than other synthesis routes.

  20. C60 fullerene promotes lung monolayer collapse

    PubMed Central

    Barnoud, Jonathan; Urbini, Laura; Monticelli, Luca

    2015-01-01

    Airborne nanometre-sized pollutants are responsible for various respiratory diseases. Such pollutants can reach the gas-exchange surface in the alveoli, which is lined with a monolayer of lung surfactant. The relationship between physiological effects of pollutants and molecular-level interactions is largely unknown. Here, we determine the effects of carbon nanoparticles on the properties of a model of lung monolayer using molecular simulations. We simulate phase-separated lipid monolayers in the presence of a model pollutant nanoparticle, C60 fullerene. In the absence of nanoparticles, the monolayers collapse only at very low surface tensions (around 0 mN m−1). In the presence of nanoparticles, instead, monolayer collapse is observed at significantly higher surface tensions (up to ca 10 mN m−1). Collapse at higher tensions is related to lower mechanical rigidity of the monolayer. It is possible that similar mechanisms operate on lung surfactant in vivo, which suggests that health effects of airborne carbon nanoparticles may be mediated by alterations of the mechanical properties of lung surfactant. PMID:25589571

  1. Extended monolayer of cyano-ended oligo(para-phenylenes) at the air/HOPG interface investigated by high-resolution AFM

    NASA Astrophysics Data System (ADS)

    Hourani, W.; Lamare, S.; Makoudi, Y.; Palmino, F.; Cherioux, F.

    2016-10-01

    The formation of functional networks on surfaces is one of the main challenges in the field of nanotechnologies. In this paper, we shall propose a very simple process which can be used to achieve the formation of extended monolayer of functional oligo(para-phenylenes) molecules at the air/graphite interface. By developing a convergent strategy, we successfully achieved the synthesis of oligo(para-phenylenes) molecules with a tuneable length. The photophysical properties of these new oligomers were characterized by UV-vis absorption and fluorescence spectroscopy. Deposition of these molecules by a simple spin-coating process on a highly oriented pyrolytic graphite (HOPG) surface leads to the formation of extended monolayered 2D networks. These networks were characterized by atomic force microscopy experiments under ambient conditions with submolecular resolution thus providing the adsorption model of these molecules on an HOPG surface.

  2. Amyloid oligomer structure characterization from simulations: A general method

    SciTech Connect

    Nguyen, Phuong H.; Li, Mai Suan

    2014-03-07

    Amyloid oligomers and plaques are composed of multiple chemically identical proteins. Therefore, one of the first fundamental problems in the characterization of structures from simulations is the treatment of the degeneracy, i.e., the permutation of the molecules. Second, the intramolecular and intermolecular degrees of freedom of the various molecules must be taken into account. Currently, the well-known dihedral principal component analysis method only considers the intramolecular degrees of freedom, and other methods employing collective variables can only describe intermolecular degrees of freedom at the global level. With this in mind, we propose a general method that identifies all the structures accurately. The basis idea is that the intramolecular and intermolecular states are described in terms of combinations of single-molecule and double-molecule states, respectively, and the overall structures of oligomers are the product basis of the intramolecular and intermolecular states. This way, the degeneracy is automatically avoided. The method is illustrated on the conformational ensemble of the tetramer of the Alzheimer's peptide Aβ{sub 9−40}, resulting from two atomistic molecular dynamics simulations in explicit solvent, each of 200 ns, starting from two distinct structures.

  3. Broadband terahertz dynamics of propylene glycol monomer and oligomers

    NASA Astrophysics Data System (ADS)

    Koda, Shota; Mori, Tatsuya; Kojima, Seiji

    2016-12-01

    We investigated the broadband terahertz spectra (0.1-5.0 THz) of glass-forming liquids, propylene glycol (PG), its oligomers poly (propylene glycol)s (PPGs), and poly (propylene glycol) diglycidyl ether (PPG-de) using broadband terahertz time-domain spectroscopy and low-frequency Raman scattering. The numerical value of the dielectric loss at around 1.5 THz, which is the peak position of broad peaks in all samples, decreased as the molecular weight increased. Furthermore, the peak at around 1.5 THz is insensitive to the molecular weight. For PPGs, the side chain effect of the oligomer was observed in the terahertz region. Based on the experimental and calculation results for the PPGs and PPG-de, whose end groups are epoxy groups, the beginnings of the increases in the observed dielectric loss above 3.5 THz of the PPGs are assigned to the OH bending vibration. The higher value of the dielectric loss in the terahertz region for the PPG-de can be the tail of a broad peak located in the MHz region. The difference between the Raman susceptibility and dielectric loss reflects the difference in the observable molecular dynamics between the infrared and Raman spectroscopies.

  4. Amyloid oligomer structure characterization from simulations: A general method

    NASA Astrophysics Data System (ADS)

    Nguyen, Phuong H.; Li, Mai Suan; Derreumaux, Philippe

    2014-03-01

    Amyloid oligomers and plaques are composed of multiple chemically identical proteins. Therefore, one of the first fundamental problems in the characterization of structures from simulations is the treatment of the degeneracy, i.e., the permutation of the molecules. Second, the intramolecular and intermolecular degrees of freedom of the various molecules must be taken into account. Currently, the well-known dihedral principal component analysis method only considers the intramolecular degrees of freedom, and other methods employing collective variables can only describe intermolecular degrees of freedom at the global level. With this in mind, we propose a general method that identifies all the structures accurately. The basis idea is that the intramolecular and intermolecular states are described in terms of combinations of single-molecule and double-molecule states, respectively, and the overall structures of oligomers are the product basis of the intramolecular and intermolecular states. This way, the degeneracy is automatically avoided. The method is illustrated on the conformational ensemble of the tetramer of the Alzheimer's peptide Aβ9-40, resulting from two atomistic molecular dynamics simulations in explicit solvent, each of 200 ns, starting from two distinct structures.

  5. Lipid raft disruption protects mature neurons against amyloid oligomer toxicity.

    PubMed

    Malchiodi-Albedi, Fiorella; Contrusciere, Valentina; Raggi, Carla; Fecchi, Katia; Rainaldi, Gabriella; Paradisi, Silvia; Matteucci, Andrea; Santini, Maria Teresa; Sargiacomo, Massimo; Frank, Claudio; Gaudiano, Maria Cristina; Diociaiuti, Marco

    2010-04-01

    A specific neuronal vulnerability to amyloid protein toxicity may account for brain susceptibility to protein misfolding diseases. To investigate this issue, we compared the effects induced by oligomers from salmon calcitonin (sCTOs), a neurotoxic amyloid protein, on cells of different histogenesis: mature and immature primary hippocampal neurons, primary astrocytes, MG63 osteoblasts and NIH-3T3 fibroblasts. In mature neurons, sCTOs increased apoptosis and induced neuritic and synaptic damages similar to those caused by amyloid beta oligomers. Immature neurons and the other cell types showed no cytotoxicity. sCTOs caused cytosolic Ca(2+) rise in mature, but not in immature neurons and the other cell types. Comparison of plasma membrane lipid composition showed that mature neurons had the highest content in lipid rafts, suggesting a key role for them in neuronal vulnerability to sCTOs. Consistently, depletion in gangliosides protected against sCTO toxicity. We hypothesize that the high content in lipid rafts makes mature neurons especially vulnerable to amyloid proteins, as compared to other cell types; this may help explain why the brain is a target organ for amyloid-related diseases.

  6. Charge transfer interactions in oligomer coated gold nanoclusters

    NASA Astrophysics Data System (ADS)

    Newmai, M. Boazbou; Kumar, Pandian Senthil

    2016-05-01

    Gold nanoclusters were synthesized by a bottom-up synergistic approach of in-situ oligomerization of the monomer, N-vinyl pyrrolidone (NVP) and simultaneous weak reduction of Au-NVP complexes in the absence of any other external energy sources, thereby making these tiny gold clusters as the most elemental building blocks to construct further novel nano/microstructures with application potentials. It is well-known that metal clusters with less than 2 nm size do not show the usual surface plasmon band, because of the presence of a band-gap at the fermi level. Nevertheless, our present oligomer coated gold clusters show a discrete intense band at around 630 nm, which could very well be attributed to the charge transfer between the oligomer chain and the surface Au atoms. Such kind of sacrificial plasmon induced charge transfer interaction, observed for the very first time to the best of our knowledge, were also strongly corroborated through the enhancement / shifting of specific vibrational / rotational peaks as observed from the FTIR and Raman measurements as a function of the metal oxidation states, thus representing a new prototype for an efficient solar energy conversion probe.

  7. Amyloid oligomer structure characterization from simulations: a general method.

    PubMed

    Nguyen, Phuong H; Li, Mai Suan; Derreumaux, Philippe

    2014-03-07

    Amyloid oligomers and plaques are composed of multiple chemically identical proteins. Therefore, one of the first fundamental problems in the characterization of structures from simulations is the treatment of the degeneracy, i.e., the permutation of the molecules. Second, the intramolecular and intermolecular degrees of freedom of the various molecules must be taken into account. Currently, the well-known dihedral principal component analysis method only considers the intramolecular degrees of freedom, and other methods employing collective variables can only describe intermolecular degrees of freedom at the global level. With this in mind, we propose a general method that identifies all the structures accurately. The basis idea is that the intramolecular and intermolecular states are described in terms of combinations of single-molecule and double-molecule states, respectively, and the overall structures of oligomers are the product basis of the intramolecular and intermolecular states. This way, the degeneracy is automatically avoided. The method is illustrated on the conformational ensemble of the tetramer of the Alzheimer's peptide Aβ9-40, resulting from two atomistic molecular dynamics simulations in explicit solvent, each of 200 ns, starting from two distinct structures.

  8. Sedimentation studies on human amylin fail to detect low-molecular-weight oligomers.

    PubMed

    Vaiana, Sara M; Ghirlando, Rodolfo; Yau, Wai-Ming; Eaton, William A; Hofrichter, James

    2008-04-01

    Sedimentation velocity experiments show that only monomers coexist with amyloid fibrils of human islet amyloid-polypeptide. No oligomers containing <100 monomers could be detected, suggesting that the putative toxic oligomers are much larger than those found for the Alzheimer's peptide, Abeta(1-42).

  9. Heat Resistant Characteristics of Major Royal Jelly Protein 1 (MRJP1) Oligomer.

    PubMed

    Moriyama, Takanori; Ito, Aimi; Omote, Sumire; Miura, Yuri; Tsumoto, Hiroki

    2015-01-01

    Soluble royal jelly protein is a candidate factor responsible for mammiferous cell proliferation. Major royal jelly protein 1 (MRJP1), which consists of oligomeric and monomeric forms, is an abundant proliferative protein in royal jelly. We previously reported that MRJP1 oligomer has biochemical heat resistance. Therefore, in the present study, we investigated the effects of several heat treatments (56, 65 and 96°C) on the proliferative activity of MRJP1 oligomer. Heat resistance studies showed that the oligomer molecular forms were slightly maintained until 56℃, but the molecular forms were converted to macromolecular heat-aggregated MRJP1 oligomer at 65℃ and 96℃. But, the growth activity of MRJP1 oligomer treated with 96°C was slightly attenuated when compared to unheated MRJP1 oligomer. On the other hand, the cell proliferation activity was preserved until 96℃ by the cell culture analysis of Jurkat cells. In contrast, those of IEC-6 cells were not preserved even at 56°C. The present observations suggest that the bioactive heat-resistance properties were different by the origin of the cells. The cell proliferation analysis showed that MRJP1 oligomer, but not MRJP2 and MRJP3, significantly increased cell numbers, suggesting that MRJP1 oligomer is the predominant proliferation factor for mammiferous cells.

  10. Seeding induced by alpha-synuclein oligomers provides evidence for spreading of alpha-synuclein pathology.

    PubMed

    Danzer, Karin M; Krebs, Simon K; Wolff, Michael; Birk, Gerald; Hengerer, Bastian

    2009-10-01

    Lewy bodies, alpha-synuclein (alpha-syn) immunopositive intracellular deposits, are the pathological hallmark of Parkinson's disease (PD). Interestingly, Lewybody-like structures have been identified in fetal tissue grafts about one decade after transplantation into the striatum of PD patients. One possible explanation for the accelerated deposition of alpha-syn in the graft is that the aggregation of alpha-syn from the host tissue to the graft is spread by a prion disease-like mechanism. We discuss here an in vitro model which might recapitulate some aspects of disease propagation in PD. We found here that in vitro-generated alpha-syn oligomers induce transmembrane seeding of alpha-syn aggregation in a dose- and time-dependent manner. This effect was observed in primary neuronal cultures as well as in neuronal cell lines. The seeding oligomers were characterized by a distinctive lithium dodecyl sulfate-stable oligomer pattern and could be generated in a dynamic process out of pore-forming oligomers. We propose that alpha-syn oligomers form as a dynamic mixture of oligomer types with different properties and that alpha-syn oligomers can be converted into different types depending on the brain milieu conditions. Our data indicate that extracellular alpha-syn oligomers can induce intracellular alpha-syn aggregation, therefore we hypothesize that a similar mechanism might lead to alpha-syn pathology propagation.

  11. Amyloid-beta oligomers increase the localization of prion protein at the cell surface.

    PubMed

    Caetano, Fabiana A; Beraldo, Flavio H; Hajj, Glaucia N M; Guimaraes, Andre L; Jürgensen, Sofia; Wasilewska-Sampaio, Ana Paula; Hirata, Pedro H F; Souza, Ivana; Machado, Cleiton F; Wong, Daisy Y-L; De Felice, Fernanda G; Ferreira, Sergio T; Prado, Vania F; Rylett, R Jane; Martins, Vilma R; Prado, Marco A M

    2011-05-01

    In Alzheimer's disease, the amyloid-β peptide (Aβ) interacts with distinct proteins at the cell surface to interfere with synaptic communication. Recent data have implicated the prion protein (PrP(C)) as a putative receptor for Aβ. We show here that Aβ oligomers signal in cells in a PrP(C)-dependent manner, as might be expected if Aβ oligomers use PrP(C) as a receptor. Immunofluorescence, flow cytometry and cell surface protein biotinylation experiments indicated that treatment with Aβ oligomers, but not monomers, increased the localization of PrP(C) at the cell surface in cell lines. These results were reproduced in hippocampal neuronal cultures by labeling cell surface PrP(C). In order to understand possible mechanisms involved with this effect of Aβ oligomers, we used live cell confocal and total internal reflection microscopy in cell lines. Aβ oligomers inhibited the constitutive endocytosis of PrP(C), but we also found that after Aβ oligomer-treatment PrP(C) formed more clusters at the cell surface, suggesting the possibility of multiple effects of Aβ oligomers. Our experiments show for the first time that Aβ oligomers signal in a PrP(C)-dependent way and that they can affect PrP(C) trafficking, increasing its localization at the cell surface.

  12. Wnt-5a occludes Aβ oligomer-induced depression of glutamatergic transmission in hippocampal neurons

    PubMed Central

    2010-01-01

    Background Soluble amyloid-β (Aβ;) oligomers have been recognized to be early and key intermediates in Alzheimer's disease (AD)-related synaptic dysfunction. Aβ oligomers block hippocampal long-term potentiation (LTP) and impair rodent spatial memory. Wnt signaling plays an important role in neural development, including synaptic differentiation. Results We report here that the Wnt signaling activation prevents the synaptic damage triggered by Aβ oligomers. Electrophysiological analysis of Schaffer collaterals-CA1 glutamatergic synaptic transmission in hippocampal slices indicates that Wnt-5a increases the amplitude of field excitatory postsynaptic potentials (fEPSP) and both AMPA and NMDA components of the excitatory postsynaptic currents (EPSCs), without modifying the paired pulse facilitation (PPF). Conversely, in the presence of Aβ oligomers the fEPSP and EPSCs amplitude decreased without modification of the PPF, while the postsynaptic scaffold protein (PSD-95) decreased as well. Co-perfusion of hippocampal slices with Wnt-5a and Aβ oligomers occludes against the synaptic depression of EPSCs as well as the reduction of PSD-95 clusters induced by Aβ oligomers in neuronal cultures. Taken together these results indicate that Wnt-5a and Aβ oligomers inversely modulate postsynaptic components. Conclusion These results indicate that post-synaptic damage induced by Aβ oligomers in hippocampal neurons is prevented by non-canonical Wnt pathway activation. PMID:20205789

  13. Theory of microphase separation in homopolymer oligomer mixtures

    NASA Astrophysics Data System (ADS)

    Olemskoi, Alexander; Savelyev, Alexey

    2005-11-01

    This work starts with the review of theoretical methods proposed, during past decades, for description of phase behavior in different polymer systems, involving variety of linear polymers (regular and polydisperse block (co)polymers, random polymers) and the polymer systems with non-covalent bonds of different strength. Microphase separation (MS) into different ordered mesophases is known to be the principal property of such systems. It is shown that most of the theoretical approaches proposed for description of the MS are based on the simple random phase approximation (RPA). It turns out, however, that mean field RPA method applied to description of the systems with non-covalent bonds does not provide the whole picture of MS. We show that the problem here arises when one treats both Flory-Huggins non-associated interactions and non-covalent bonds (hydrogen, ionic) within the unified RPA scheme, which is obviously rough for description of the latter type of interactions. Such a theory was developed in a few recent papers for the systems involving weak hydrogen bonds between homopolymer chains and the low molecular weight oligomers (surfactants). However, it leaves some experimental data unaccounted. The purpose of this review is to consider more detailed theory which is able to explain not only all the experimental data for the above systems but also to take into account the strength variation of non-bonding interactions. In particular, we consider the strong ionic interactions, weak hydrogen bonding, and the interactions of intermediate strength between polymer chain and short oligomers within our unifying theory. To develop such a description in a self-consistent way we propose to use a general field theory of stochastic systems. The mesoscopic (lamellar) structure of the periodically alternating layers of stretched homopolymer chains surrounded by perpendicularly oriented oligomeric tails is studied for the systems with both strong (ionic) and weak (hydrogen

  14. Alzheimer's Therapeutics Targeting Amyloid Beta 1–42 Oligomers I: Abeta 42 Oligomer Binding to Specific Neuronal Receptors Is Displaced by Drug Candidates That Improve Cognitive Deficits

    PubMed Central

    Izzo, Nicholas J.; Staniszewski, Agnes; To, Lillian; Fa, Mauro; Teich, Andrew F.; Saeed, Faisal; Wostein, Harrison; Walko, Thomas; Vaswani, Anisha; Wardius, Meghan; Syed, Zanobia; Ravenscroft, Jessica; Mozzoni, Kelsie; Silky, Colleen; Rehak, Courtney; Yurko, Raymond; Finn, Patricia; Look, Gary; Rishton, Gilbert; Safferstein, Hank; Miller, Miles; Johanson, Conrad; Stopa, Edward; Windisch, Manfred; Hutter-Paier, Birgit; Shamloo, Mehrdad; Arancio, Ottavio; LeVine, Harry; Catalano, Susan M.

    2014-01-01

    Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta) 1–42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD). Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce deficits in membrane trafficking in neuronal cultures with an EC50 that corresponds to its binding affinity. The therapeutic lead compounds we have found are pharmacological antagonists of Abeta oligomers, reducing the binding of Abeta oligomers to neurons in vitro, preventing spine loss in neurons and preventing and treating oligomer-induced deficits in membrane trafficking. These molecules are highly brain penetrant and prevent and restore cognitive deficits in mouse models of Alzheimer's disease. Counter-screening these compounds against a broad panel of potential CNS targets revealed they are highly potent and specific ligands of the sigma-2/PGRMC1 receptor. Brain concentrations of the compounds corresponding to greater than 80% receptor occupancy at the sigma-2/PGRMC1 receptor restore cognitive function in transgenic hAPP Swe/Ldn mice. These studies demonstrate that synthetic and human-derived Abeta oligomers act as pharmacologically-behaved ligands at neuronal receptors - i.e. they exhibit saturable binding to a target, they exert a functional effect related to their binding and their displacement by small molecule antagonists blocks their functional effect. The first-in-class small molecule receptor antagonists described here restore memory to normal in multiple AD

  15. Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers I: Abeta 42 oligomer binding to specific neuronal receptors is displaced by drug candidates that improve cognitive deficits.

    PubMed

    Izzo, Nicholas J; Staniszewski, Agnes; To, Lillian; Fa, Mauro; Teich, Andrew F; Saeed, Faisal; Wostein, Harrison; Walko, Thomas; Vaswani, Anisha; Wardius, Meghan; Syed, Zanobia; Ravenscroft, Jessica; Mozzoni, Kelsie; Silky, Colleen; Rehak, Courtney; Yurko, Raymond; Finn, Patricia; Look, Gary; Rishton, Gilbert; Safferstein, Hank; Miller, Miles; Johanson, Conrad; Stopa, Edward; Windisch, Manfred; Hutter-Paier, Birgit; Shamloo, Mehrdad; Arancio, Ottavio; LeVine, Harry; Catalano, Susan M

    2014-01-01

    Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta) 1-42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD). Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce deficits in membrane trafficking in neuronal cultures with an EC50 that corresponds to its binding affinity. The therapeutic lead compounds we have found are pharmacological antagonists of Abeta oligomers, reducing the binding of Abeta oligomers to neurons in vitro, preventing spine loss in neurons and preventing and treating oligomer-induced deficits in membrane trafficking. These molecules are highly brain penetrant and prevent and restore cognitive deficits in mouse models of Alzheimer's disease. Counter-screening these compounds against a broad panel of potential CNS targets revealed they are highly potent and specific ligands of the sigma-2/PGRMC1 receptor. Brain concentrations of the compounds corresponding to greater than 80% receptor occupancy at the sigma-2/PGRMC1 receptor restore cognitive function in transgenic hAPP Swe/Ldn mice. These studies demonstrate that synthetic and human-derived Abeta oligomers act as pharmacologically-behaved ligands at neuronal receptors--i.e. they exhibit saturable binding to a target, they exert a functional effect related to their binding and their displacement by small molecule antagonists blocks their functional effect. The first-in-class small molecule receptor antagonists described here restore memory to normal in multiple AD models

  16. X-ray Crystallographic Structure of Oligomers Formed by a Toxic β-Hairpin Derived from α-Synuclein: Trimers and Higher-Order Oligomers.

    PubMed

    Salveson, Patrick J; Spencer, Ryan K; Nowick, James S

    2016-04-06

    Oligomeric assemblies of the protein α-synuclein are thought to cause neurodegeneration in Parkinson's disease and related synucleinopathies. Characterization of α-synuclein oligomers at high resolution is an outstanding challenge in the field of structural biology. The absence of high-resolution structures of oligomers formed by α-synuclein impedes understanding the synucleinopathies at the molecular level. This paper reports the X-ray crystallographic structure of oligomers formed by a peptide derived from residues 36-55 of α-synuclein. The peptide 1a adopts a β-hairpin structure, which assembles in a hierarchical fashion. Three β-hairpins assemble to form a triangular trimer. Three copies of the triangular trimer assemble to form a basket-shaped nonamer. Two nonamers pack to form an octadecamer. Molecular modeling suggests that full-length α-synuclein may also be able to assemble in this fashion. Circular dichroism spectroscopy demonstrates that peptide 1a interacts with anionic lipid bilayer membranes, like oligomers of full-length α-synuclein. LDH and MTT assays demonstrate that peptide 1a is toxic toward SH-SY5Y cells. Comparison of peptide 1a to homologues suggests that this toxicity results from nonspecific interactions with the cell membrane. The oligomers formed by peptide 1a are fundamentally different than the proposed models of the fibrils formed by α-synuclein and suggest that α-Syn36-55, rather than the NAC, may nucleate oligomer formation.

  17. An investigation into the effect of amphiphilic siloxane oligomers on dermal fibroblasts.

    PubMed

    Farrugia, Brooke L; Keddie, Daniel J; George, Graeme A; Lynam, Emily C; Brook, Michael A; Upton, Zee; Dargaville, Tim R

    2012-07-01

    This study investigates the effect of well-defined poly(dimethylsiloxane)-poly(ethylene glycol) (PDMS-PEG) ABA linear block co-oligomers on the proliferation of human dermal fibroblasts. The co-oligomers assessed ranged in molecular weight (MW) from 1335 to 5208 Da and hydrophilic-lipophilic balance (HLB) from 5.9 to 16.6 by varying the number of both PDMS and PEG units. In general, it was found that co-oligomers of low MW or intermediate hydrophilicity significantly reduced fibroblast proliferation. A linear relationship between down-regulation of fibroblast proliferation, and the ratio HLB/MW was observed at concentrations of 0.1 and 1.0 wt % of the oligomers. This enabled the structures with highest efficiency to be determined. These results suggest the possible use of the PEG-PDMS-PEG block co-oligomers as an alternative to silicone gels for hypertrophic scar remediation.

  18. Direct PIP2 binding mediates stable oligomer formation of the serotonin transporter

    PubMed Central

    Anderluh, Andreas; Hofmaier, Tina; Klotzsch, Enrico; Kudlacek, Oliver; Stockner, Thomas; Sitte, Harald H.; Schütz, Gerhard J.

    2017-01-01

    The human serotonin transporter (hSERT) mediates uptake of serotonin from the synaptic cleft and thereby terminates serotonergic signalling. We have previously found by single-molecule microscopy that SERT forms stable higher-order oligomers of differing stoichiometry at the plasma membrane of living cells. Here, we report that SERT oligomer assembly at the endoplasmic reticulum (ER) membrane follows a dynamic equilibration process, characterized by rapid exchange of subunits between different oligomers, and by a concentration dependence of the degree of oligomerization. After trafficking to the plasma membrane, however, the SERT stoichiometry is fixed. Stabilization of the oligomeric SERT complexes is mediated by the direct binding to phosphoinositide phosphatidylinositol-4,5-biphosphate (PIP2). The observed spatial decoupling of oligomer formation from the site of oligomer operation provides cells with the ability to define protein quaternary structures independent of protein density at the cell surface. PMID:28102201

  19. Star-shaped tetrathiafulvalene oligomers towards the construction of conducting supramolecular assembly

    PubMed Central

    Hasegawa, Masashi

    2015-01-01

    Summary The construction of redox-active supramolecular assemblies based on star-shaped and radially expanded tetrathiafulvalene (TTF) oligomers with divergent and extended conjugation is summarized. Star-shaped TTF oligomers easily self-aggregate with a nanophase separation to produce supramolecular structures, and their TTF units stack face-to-face to form columnar structures using the fastener effect. Based on redox-active self-organizing supramolecular structures, conducting nanoobjects are constructed by doping of TTF oligomers with oxidants after the formation of such nanostructures. Although radical cations derived from TTF oligomers strongly interact in solution to produce a mixed-valence dimer and π-dimer, it seems to be difficult to produce nanoobjects of radical cations different from those of neutral TTF oligomers. In some cases, however, radical cations form nanostructured fibers and rods by controlling the supramolecular assembly, oxidation states, and counter anions employed. PMID:26664579

  20. Alginate gels with a combination of calcium and chitosan oligomer mixtures as crosslinkers.

    PubMed

    Feng, Yiming; Kopplin, Georg; Sato, Kimihiko; Draget, Kurt I; Vårum, Kjell M

    2017-01-20

    Alginates are polysaccharides that are widely used in relation to their ability to form gels. Recently we reported that alginates may also form gels with chitosan oligomers as crosslinkers (Khong, Aarstad, Skjåk-Bræk, Draget, & Vårum, 2013). The purpose of the present study was to characterize alginate gels crosslinked with calcium and chitosan oligomers. Using two different alginates of similar molecular weights but different chemical composition, i.e. guluronic acid content of 46 and 68%, we found that both alginates could form homogeneous gels with calcium and chitosan oligomers separately and without syneresis. Systematic combinations of calcium and chitosan oligomers as crosslinkers were tested, showing that up to 50% of the calcium could be substituted with chitosan oligomers without reduction in gel strength or increased syneresis for the alginate with the lowest guluronic acid content. Furthermore, the kinetics of the combined gels were different from pure calcium alginate gels.

  1. Preparation of Chito-Oligomers by Hydrolysis of Chitosan in the Presence of Zeolite as Adsorbent.

    PubMed

    Ibrahim, Khalid A; El-Eswed, Bassam I; Abu-Sbeih, Khaleel A; Arafat, Tawfeeq A; Al Omari, Mahmoud M H; Darras, Fouad H; Badwan, Adnan A

    2016-07-23

    An increasing interest has recently been shown to use chitin/chitosan oligomers (chito-oligomers) in medicine and food fields because they are not only water-soluble, nontoxic, and biocompatible materials, but they also exhibit numerous biological properties, including antibacterial, antifungal, and antitumor activities, as well as immuno-enhancing effects on animals. Conventional depolymerization methods of chitosan to chito-oligomers are either chemical by acid-hydrolysis under harsh conditions or by enzymatic degradation. In this work, hydrolysis of chitosan to chito-oligomers has been achieved by applying adsorption-separation technique using diluted HCl in the presence of different types of zeolite as adsorbents. The chito-oligomers were retrieved from adsorbents and characterized by differential scanning calorimetry (DSC), liquid chromatography/mass spectroscopy (LC/MS), and ninhydrin test.

  2. The Role of Amyloid-β Oligomers in Toxicity, Propagation, and Immunotherapy

    PubMed Central

    Sengupta, Urmi; Nilson, Ashley N.; Kayed, Rakez

    2016-01-01

    The incidence of Alzheimer's disease (AD) is growing every day and finding an effective treatment is becoming more vital. Amyloid-β (Aβ) has been the focus of research for several decades. The recent shift in the Aβ cascade hypothesis from all Aβ to small soluble oligomeric intermediates is directing the search for therapeutics towards the toxic mediators of the disease. Targeting the most toxic oligomers may prove to be an effective treatment by preventing their spread. Specific targeting of oligomers has been shown to protect cognition in rodent models. Additionally, the heterogeneity of research on Aβ oligomers may seem contradictory until size and conformation are taken into account. In this review, we will discuss Aβ oligomers and their toxicity in relation to size and conformation as well as their influence on inflammation and the potential of Aβ oligomer immunotherapy. PMID:27211547

  3. Preparation of Chito-Oligomers by Hydrolysis of Chitosan in the Presence of Zeolite as Adsorbent

    PubMed Central

    Ibrahim, Khalid A.; El-Eswed, Bassam I.; Abu-Sbeih, Khaleel A.; Arafat, Tawfeeq A.; Al Omari, Mahmoud M. H.; Darras, Fouad H.; Badwan, Adnan A.

    2016-01-01

    An increasing interest has recently been shown to use chitin/chitosan oligomers (chito-oligomers) in medicine and food fields because they are not only water-soluble, nontoxic, and biocompatible materials, but they also exhibit numerous biological properties, including antibacterial, antifungal, and antitumor activities, as well as immuno-enhancing effects on animals. Conventional depolymerization methods of chitosan to chito-oligomers are either chemical by acid-hydrolysis under harsh conditions or by enzymatic degradation. In this work, hydrolysis of chitosan to chito-oligomers has been achieved by applying adsorption-separation technique using diluted HCl in the presence of different types of zeolite as adsorbents. The chito-oligomers were retrieved from adsorbents and characterized by differential scanning calorimetry (DSC), liquid chromatography/mass spectroscopy (LC/MS), and ninhydrin test. PMID:27455287

  4. Structural Characteristics of the Alpha-Synuclein Oligomers Stabilized By the Flavonoid Baicalein

    SciTech Connect

    Hong, D.-P.; Fink, A.L.; Uversky, V.N.

    2009-05-18

    The flavonoid baicalein inhibits fibrillation of alpha-synuclein, which is a major component of Lewy bodies in Parkinson's disease. It has been known that baicalein induces the formation of alpha-synuclein oligomers and consequently prevents their fibrillation. In order to evaluate the structural properties of baicalein-stabilized oligomers, we purified oligomer species by HPLC and examined their stability and structure by CD, Fourier transform infrared spectroscopy, size exclusion chromatography HPLC, small-angle X-ray scattering, and atomic force microscopy. Baicalein-stabilized oligomers are beta-sheet-enriched according to CD and Fourier transform infrared spectroscopy analyses. They did not form fibrils even after very prolonged incubation. From small-angle X-ray scattering data and atomic force microscopy images, the oligomers were characterized as quite compact globular species. Oligomers were extremely stable, with a GdmCl C(m)=3.3 M. This high stability explains the previously observed inhibition properties of baicalein against alpha-synuclein fibrillation. These baicalein-stabilized oligomers, added to the solution of aggregating alpha-synuclein, were able to noticeably inhibit its fibrillation. After prolonged coincubation, short fibrils were formed, suggesting an effective interaction of oligomers with monomeric alpha-synuclein. Membrane permeability tests suggested that the baicalein-stabilized oligomers had a mild effect on the integrity of the membrane surface. This effect was rather similar to that of the monomeric protein, suggesting that targeted stabilization of certain alpha-synuclein oligomers might offer a potential strategy for the development of novel Parkinson's disease therapies.

  5. One-Step Synthesis of Precursor Oligomers for Organic Photovoltaics: A Comparative Study between Polymers and Small Molecules.

    PubMed

    Li, Wei; Wang, Daojuan; Wang, Suhao; Ma, Wei; Hedström, Svante; James, David Ian; Xu, Xiaofeng; Persson, Petter; Fabiano, Simone; Berggren, Magnus; Inganäs, Olle; Huang, Fei; Wang, Ergang

    2015-12-16

    Two series of oligomers TQ and rhodanine end-capped TQ-DR were synthesized using a facile one-step method. Their optical, electrical, and thermal properties and photovoltaic performances were systematically investigated and compared. The TQ series of oligomers were found to be amorphous, whereas the TQ-DR series are semicrystalline. For the TQ oligomers, the results obtained in solar cells show that as the chain length of the oligomers increases, an increase in power conversion efficiency (PCE) is obtained. However, when introducing 3-ethylrhodanine into the TQ oligomers as end groups, the PCE of the TQ-DR series of oligomers decreases as the chain length increases. Moreover, the TQ-DR series of oligomers give much higher performances compared to the original amorphous TQ series of oligomers owing to the improved extinction coefficient (ε) and crystallinity afforded by the rhodanine. In particular, the highly crystalline oligomer TQ5-DR, which has the shortest conjugation length shows a high hole mobility of 0.034 cm(2) V(-1) s(-1) and a high PCE of 3.14%, which is the highest efficiency out of all of the six oligomers. The structure-property correlations for all of the oligomers and the TQ1 polymer demonstrate that structural control of enhanced intermolecular interactions and crystallinity is a key for small molecules/oligomers to achieve high mobilities, which is an essential requirement for use in OPVs.

  6. Brain amyloid-β oligomers in ageing and Alzheimer's disease.

    PubMed

    Lesné, Sylvain E; Sherman, Mathew A; Grant, Marianne; Kuskowski, Michael; Schneider, Julie A; Bennett, David A; Ashe, Karen H

    2013-05-01

    Alzheimer's disease begins about two decades before the onset of symptoms or neuron death, and is believed to be caused by pathogenic amyloid-β aggregates that initiate a cascade of molecular events culminating in widespread neurodegeneration. The microtubule binding protein tau may mediate the effects of amyloid-β in this cascade. Amyloid plaques comprised of insoluble, fibrillar amyloid-β aggregates are the most characteristic feature of Alzheimer's disease. However, the correspondence between the distribution of plaques and the pattern of neurodegeneration is tenuous. This discrepancy has stimulated the investigation of other amyloid-β aggregates, including soluble amyloid-β oligomers. Different soluble amyloid-β oligomers have been studied in several mouse models, but not systematically in humans. Here, we measured three amyloid-β oligomers previously described in mouse models-amyloid-β trimers, Aβ*56 and amyloid-β dimers-in brain tissue from 75 cognitively intact individuals, ranging from young children to the elderly, and 58 impaired subjects with mild cognitive impairment or probable Alzheimer's disease. As in mouse models, where amyloid-β trimers appear to be the fundamental amyloid-β assembly unit of Aβ*56 and are present in young mice prior to memory decline, amyloid-β trimers in humans were present in children and adolescents; their levels rose gradually with age and were significantly above baseline in subjects in their 70s. Aβ*56 levels were negligible in children and young adults, rose significantly above baseline in subjects in their 40s and increased steadily thereafter. Amyloid-β dimers were undetectable until subjects were in their 60s; their levels then increased sharply and correlated with plaque load. Remarkably, in cognitively intact individuals we found strong positive correlations between Aβ*56 and two pathological forms of soluble tau (tau-CP13 and tau-Alz50), and negative correlations between Aβ*56 and two postsynaptic

  7. Phase-Specific Diffusivity of DPPG Monolayers

    NASA Astrophysics Data System (ADS)

    Dewitt, Joel; Thapa, Prem; Flanders, Bret

    2004-03-01

    The primary role of lung surfactant is to reduce the alveolar surface tension during exhalation in a reversible manner. Failure to do so results in respiratory distress syndrome. Model lung surfactants provide simplified systems for studying the mechanisms that underlie this essential role of alveolar surfactant. Dipalmitoyl-phosphatidylglycerol (DPPG) monolayers exhibit reversible folding when compressed to a critical surface tension. This process may exemplify how the compression-expansion cycle attains reversibility and, thus, requires penetrating study. The buckling theory for reversible collapse provides a promising though untested description of this process, but poor knowledge of domain boundary widths in DPPG monolayers impedes the evaluation of this theory as a model for the observed behavior. In turn, the measurement of the domain boundary widths requires knowledge of the phase-specific viscosities of the monolayer. In this study, multi-particle tracking has been used to determine the phase-specific diffusion coefficients of polystyrene spheres embedded in DPPG monolayers. By invoking a Stokes-Einstein relationship that is appropriate for spheres diffusing in a viscous surfactant, the phase specific viscosities of the monolayers have been estimated. The rationale for this work is that this knowledge will promote the quantitative evaluation of buckling as a model for reversible folding and, thus, promote growth in understanding of the folding mechanism in model lung surfactants.

  8. Nanoparticle interaction with model lung surfactant monolayers

    PubMed Central

    Harishchandra, Rakesh Kumar; Saleem, Mohammed; Galla, Hans-Joachim

    2010-01-01

    One of the most important functions of the lung surfactant monolayer is to form the first line of defence against inhaled aerosols such as nanoparticles (NPs), which remains largely unexplored. We report here, for the first time, the interaction of polyorganosiloxane NPs (AmorSil20: 22 nm in diameter) with lipid monolayers characteristic of alveolar surfactant. To enable a better understanding, the current knowledge about an established model surface film that mimics the surface properties of the lung is reviewed and major results originating from our group are summarized. The pure lipid components dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol have been used to study the biophysical behaviour of their monolayer films spread at the air–water interface in the presence of NPs. Film balance measurements combined with video-enhanced fluorescence microscopy have been used to investigate the formation of domain structures and the changes in the surface pattern induced by NPs. We are able to show that NPs are incorporated into lipid monolayers with a clear preference for defect structures at the fluid–crystalline interface leading to a considerable monolayer expansion and fluidization. NPs remain at the air–water interface probably by coating themselves with lipids in a self-assembly process, thereby exhibiting hydrophobic surface properties. We also show that the domain structure in lipid layers containing surfactant protein C, which is potentially responsible for the proper functioning of surfactant material, is considerably affected by NPs. PMID:19846443

  9. Formation of RNA oligomers on montmorillonite: site of catalysis

    NASA Technical Reports Server (NTRS)

    Ertem, G.; Ferris, J. P.

    1998-01-01

    Certain montmorillonites catalyze the self condensation of the 5'-phosphorimidazolide of nucleosides in pH 8 aqueous electrolyte solutions at ambient temperatures leading to formation of RNA oligomers. In order to establish the nature of the sites on montmorillonite responsible for this catalytic activity, oligomerization reactions were run with montmorillonites which had been selectively modified (I) at the edges by (a) fluoride treatment, (b) silylation, (c) metaphosphate treatment of the anion exchange sites (II) in the interlayer by (a) saturation with quaternary alkylammonium ions of increasing size, (b) aluminum polyoxo cations. High pressure liquid chromatography, HPLC, analysis of condensation products for their chain lengths and yields indicated that modification at the edges did not affect the catalytic activity to a significant extent, while blocking the interlayer strongly inhibited product formation.

  10. A Kinetic Model for Cell Damage Caused by Oligomer Formation.

    PubMed

    Hong, Liu; Huang, Ya-Jing; Yong, Wen-An

    2015-10-06

    It is well known that the formation of amyloid fiber may cause invertible damage to cells, although the underlying mechanism has not been fully understood. In this article, a microscopic model considering the detailed processes of amyloid formation and cell damage is constructed based on four simple assumptions, one of which is that cell damage is raised by oligomers rather than mature fibrils. By taking the maximum entropy principle, this microscopic model in the form of infinite mass-action equations together with two reaction-convection partial differential equations (PDEs) has been greatly coarse-grained into a macroscopic system consisting of only five ordinary differential equations (ODEs). With this simple model, the effects of primary nucleation, elongation, fragmentation, and protein and seeds concentration on amyloid formation and cell damage have been extensively explored and compared with experiments. We hope that our results will provide new insights into the quantitative linkage between amyloid formation and cell damage.

  11. VCD Studies on Chiral Characters of Metal Complex Oligomers

    PubMed Central

    Sato, Hisako; Yamagishi, Akihiko

    2013-01-01

    The present article reviews the results on the application of vibrational circular dichroism (VCD) spectroscopy to the study of stereochemical properties of chiral metal complexes in solution. The chiral characters reflecting on the vibrational properties of metal complexes are revealed by measurements of a series of β-diketonato complexes with the help of theoretical calculation. Attention is paid to the effects of electronic properties of a central metal ion on vibrational energy levels or low-lying electronic states. The investigation is further extended to the oligomers of β-diketonato complex units. The induction of chiral structures is confirmed by the VCD spectra when chiral inert moieties are connected with labile metal ions. These results have demonstrated how VCD spectroscopy is efficient in revealing the static and dynamic properties of mononuclear and multinuclear chiral metal complexes, which are difficult to clarify by means of other spectroscopes. PMID:23296273

  12. VCD studies on chiral characters of metal complex oligomers.

    PubMed

    Sato, Hisako; Yamagishi, Akihiko

    2013-01-07

    The present article reviews the results on the application of vibrational circular dichroism (VCD) spectroscopy to the study of stereochemical properties of chiral metal complexes in solution. The chiral characters reflecting on the vibrational properties of metal complexes are revealed by measurements of a series of β-diketonato complexes with the help of theoretical calculation. Attention is paid to the effects of electronic properties of a central metal ion on vibrational energy levels or low-lying electronic states. The investigation is further extended to the oligomers of β-diketonato complex units. The induction of chiral structures is confirmed by the VCD spectra when chiral inert moieties are connected with labile metal ions. These results have demonstrated how VCD spectroscopy is efficient in revealing the static and dynamic properties of mononuclear and multinuclear chiral metal complexes, which are difficult to clarify by means of other spectroscopes.

  13. EGFP oligomers as natural fluorescence and hydrodynamic standards

    PubMed Central

    Vámosi, György; Mücke, Norbert; Müller, Gabriele; Krieger, Jan Wolfgang; Curth, Ute; Langowski, Jörg; Tóth, Katalin

    2016-01-01

    EGFP oligomers are convenient standards for experiments on fluorescent protein-tagged biomolecules. In this study, we characterized their hydrodynamic and fluorescence properties. Diffusion coefficients D of EGFP1–4 were determined by analytical ultracentrifugation with fluorescence detection and by fluorescence correlation spectroscopy (FCS), yielding 83.4…48.2 μm2/s and 97.3…54.8 μm2/s from monomer to tetramer. A “barrels standing in a row” model agreed best with the sedimentation data. Oligomerization red-shifted EGFP emission spectra without any shift in absorption. Fluorescence anisotropy decreased, indicating homoFRET between the subunits. Fluorescence lifetime decreased only slightly (4%) indicating insignificant quenching by FRET to subunits in non-emitting states. FCS-measured D, particle number and molecular brightness depended on dark states and light-induced processes in distinct subunits, resulting in a dependence on illumination power different for monomers and oligomers. Since subunits may be in “on” (bright) or “off” (dark) states, FCS-determined apparent brightness is not proportional to that of the monomer. From its dependence on the number of subunits, the probability of the “on” state for a subunit was determined to be 96% at pH 8 and 77% at pH 6.38, i.e., protonation increases the dark state. These fluorescence properties of EGFP oligomeric standards can assist interpreting results from oligomerized EGFP fusion proteins of biological interest. PMID:27622431

  14. Fluorene- and benzofluorene-cored oligomers as low threshold and high gain amplifying media

    SciTech Connect

    Kazlauskas, Karolis Kreiza, Gediminas; Bobrovas, Olegas; Adomėnienė, Ona; Adomėnas, Povilas; Juršėnas, Saulius; Jankauskas, Vygintas

    2015-07-27

    Deliberate control of intermolecular interactions in fluorene- and benzofluorene-cored oligomers was attempted via introduction of different-length alkyl moieties to attain high emission amplification and low amplified spontaneous emission (ASE) threshold at high oligomer concentrations. Containing fluorenyl peripheral groups decorated with different-length alkyl moieties, the oligomers were found to express weak concentration quenching of emission, yet excellent carrier drift mobilities (close to 10{sup −2} cm{sup 2}/V/s) in the amorphous films. Owing to the larger radiative decay rates (>1.0 × 10{sup 9 }s{sup −1}) and smaller concentration quenching, fluorene-cored oligomers exhibited down to one order of magnitude lower ASE thresholds at higher concentrations as compared to those of benzofluorene counterparts. The lowest threshold (300 W/cm{sup 2}) obtained for the fluorene-cored oligomers at the concentration of 50 wt % in polymer matrix is among the lowest reported for solution-processed amorphous films in ambient conditions, what makes the oligomers promising for lasing application. Great potential in emission amplification was confirmed by high maximum net gain (77 cm{sup −1}) revealed for these compounds. Although the photostability of the oligomers was affected by photo-oxidation, it was found to be comparable to that of various organic lasing materials including some commercial laser dyes evaluated under similar excitation conditions.

  15. Giant piezoelectricity of monolayer group IV monochalcogenides

    NASA Astrophysics Data System (ADS)

    Fei, Ruixiang; Li, Wenbin; Li, Ju; Yang, Li

    We predict enormous, anisotropic piezoelectric effects in intrinsic monolayer group IV monochalcogenides (MX, M =Sn or Ge, X =Se or S), including SnSe, SnS, GeSe, and GeS. Using first-principle simulations based on the modern theory of polarization, we find that their piezoelectric coefficients are about one to two orders of magnitude larger than those of other 2D materials, such as MoS2 and GaSe, and bulk quartz and AlN which are widely used in industry. This enhancement is a result of the unique ``puckered'' C2v symmetry and electronic structure of monolayer group IV monochalcogenides. Given the achieved experimental advances in the fabrication of monolayers, their flexible character, and ability to withstand enormous strain, these 2D structures with giant piezoelectric effects may be promising for a broad range of applications such as nano-sized sensors, piezotronics, and energy harvesting in portable electronic devices.

  16. Edge plasmons in monolayer black phosphorus

    NASA Astrophysics Data System (ADS)

    Bao, Zhi-Wei; Wu, Hong-Wei; Zhou, Yu

    2016-12-01

    In this paper, we numerically investigate the edge plasmons in monolayer black phosphorus. It is found that the complex effective indexes of these modes depend on the molecular configuration of the edge. We have calculated the ratio of the real over the imaginary part of the mode effective index, and the results indicate that such edge modes indeed possess outstanding propagation performances in the mid-infrared. In the case of black phosphorus nanoribbon, it seems that only the anti-symmetric modes have low losses, and may be of use in applications. Compared with those at the edge of monolayer black phosphorus, the propagation performances can be further enhanced due to the mode coupling between the two edges. In the end, the effects of substrates are discussed. Our study shows that monolayer black phosphorus may be regarded as a promising candidate for plasmonic applications in the mid-infrared.

  17. Magneto photoluminescence measurements of tungsten disulphide monolayers

    NASA Astrophysics Data System (ADS)

    Kuhnert, Jan; Rahimi-Iman, Arash; Heimbrodt, Wolfram

    2017-03-01

    Layered transition-metal dichalcogenides have attracted great interest in the last few years. Thinned down to the monolayer limit they change from an indirect band structure to a direct band gap in the visible region. Due to the monolayer thickness the inversion symmetry of the crystal is broken and spin and valley are coupled to each other. The degeneracy between the two equivalent valleys, K and K‧, respectively, can be lifted by applying an external magnetic field. Here, we present photoluminescence measurements of CVD-grown tungsten disulphide (WS2) monolayers at temperatures of 2 K. By applying magnetic fields up to 7 T in Faraday geometry, a splitting of the photoluminescence peaks can be observed. The magnetic field dependence of the A-exciton, the trion and three bound exciton states is discussed and the corresponding g-factors are determined.

  18. High-resolution atomic force microscopy of soluble Abeta42 oligomers.

    PubMed

    Mastrangelo, Iris A; Ahmed, Mahiuddin; Sato, Takeshi; Liu, Wei; Wang, Chengpu; Hough, Paul; Smith, Steven O

    2006-04-21

    Soluble oligomers and protofibrils are widely thought to be the toxic forms of the Abeta42 peptide associated with Alzheimer's disease. We have investigated the structure and formation of these assemblies using a new approach in atomic force microscopy (AFM) that yields high-resolution images of hydrated proteins and allows the structure of the smallest molecular weight (MW) oligomers to be observed and characterized. AFM images of monomers, dimers and other low MW oligomers at early incubation times (< 1h) are consistent with a hairpin structure for the monomeric Abeta42 peptide. The low MW oligomers are relatively compact and have significant order. The most constant dimension of these oligomers is their height (approximately 1-3 nm) above the mica surface; their lateral dimensions (width and length) vary between 5 nm and 10nm. Flat nascent protofibrils with lengths of over 40 nm are observed at short incubation times (< or = 3h); their lateral dimensions of 6-8 nm are consistent with a mass-per-length of 9 kDa/nm previously predicted for the elementary fibril subunit. High MW oligomers with lateral dimensions of 15-25 nm and heights ranging from 2-8 nm are common at high concentrations of Abeta. We show that an inhibitor designed to block the sheet-to-sheet packing in Abeta fibrils is able to cap the heights of these oligomers at approximately 4 nm. The observation of fine structure in the high MW oligomers suggests that they are able to nucleate fibril formation. AFM images obtained as a function of incubation time reveal a sequence of assembly from monomers to soluble oligomers and protofibrils.

  19. Stiffness of lipid monolayers with phase coexistence.

    PubMed

    Caruso, Benjamín; Mangiarotti, Agustín; Wilke, Natalia

    2013-08-27

    The surface dilational modulus--or compressibility modulus--has been previously studied for monolayers composed of pure materials, where a jump in this modulus was related with the onset of percolation as a result of the establishment of a connected structure at the molecular level. In this work, we focused on monolayers composed of two components of low lateral miscibility. Our aim was to investigate the compressibility of mixed monolayers at pressures and compositions in the two-phase region of the phase diagram, in order to analyze the effect of the mechanical properties of each phase on the stiffness of the composite. In nine different systems with distinct molecular dipoles and charges, the stiffness of each phase and the texture at the plane of the monolayer were studied. In this way, we were able to analyze the general compressibility of two-phase lipid monolayers, regardless of the properties of their constituent parts. The results are discussed in the light of the following two hypotheses: first, the stiffness of the composite could be dominated by the stiffness of each phase as a weighted sum according to the percentage of each phase area, regardless of the distribution of the phases in the plane of the monolayer. Alternatively, the stiffness of the composite could be dominated by the mechanical properties of the continuous phase. Our results were better explained by this latter proposal, as in all the analyzed mixtures it was found that the mechanical properties of the percolating phase were the determining factors. The value of the compression modulus was closer to the value of the connected phase than to that of the dispersed phase, indicating that the bidimensional composites displayed mechanical properties that were related to the properties of each phases in a rather complex manner.

  20. Active Tensile Modulus of an Epithelial Monolayer

    NASA Astrophysics Data System (ADS)

    Vincent, Romaric; Bazellières, Elsa; Pérez-González, Carlos; Uroz, Marina; Serra-Picamal, Xavier; Trepat, Xavier

    2015-12-01

    A general trait of cell monolayers is their ability to exert contractile stresses on their surroundings. The scaling laws that link such contractile stresses with the size and geometry of constituent cells remain largely unknown. In this Letter, we show that the active tension of an epithelial monolayer scales linearly with the size of the constituent cells, a surprisingly simple relationship. The slope of this relationship defines an active tensile modulus, which depends on the concentration of myosin and spans more than 2 orders of magnitude across cell types and molecular perturbations.

  1. Monochromatic electron photoemission from diamondoid monolayers

    SciTech Connect

    Yang, Wanli; Yang, Wanli L.; Fabbri, J.D.; Willey, T.M.; Lee, J.R.I.; Dahl, J.E.; Carlson, R.M.K.; Schreiner, P.R.; Fokin, A.A.; Tkachenko, B.A.; Fokina, N.A.; Meevasana, W.; Mannella, N.; Tanaka, K.; Zhou, X.J.; van Buuren, T.; Kelly, M.A.; Hussain, Z.; Melosh, N.A.; Shen, Z.-X.

    2007-02-27

    We found monochromatic electron photoemission from large-area self-assembled monolayers of a functionalized diamondoid, [121]tetramantane-6-thiol. Photoelectron spectra of the diamondoid monolayers exhibited a peak at the low-kinetic energy threshold; up to 68percent of all emitted electrons were emitted within this single energy peak. The intensity of the emission peak is indicative of diamondoids being negative electron affinity materials. With an energy distribution width of less than 0.5 electron volts, this source of monochromatic electrons may find application in technologies such as electron microscopy, electron beam lithography, and field-emission flatpanel displays.

  2. Monochromatic Electron Photoemission from DiamondoidMonolayers

    SciTech Connect

    Yang, W.L.

    2010-04-15

    We found monochromatic electron photoemission from large-area self-assembled monolayers of a functionalized diamondoid, [121]tetramantane-6-thiol. Photoelectron spectra of the diamondoid monolayers exhibited a peak at the low-kinetic energy threshold; up to 68% of all emitted electrons were emitted within this single energy peak. The intensity of the emission peak is indicative of diamondoids being negative electron affinity materials. With an energy distribution width of less than 0.5 electron volts, this source of monochromatic electrons may find application in technologies such as electron microscopy, electron beam lithography, and field-emission flat-panel displays.

  3. Low temperature photoresponse of monolayer tungsten disulphide

    SciTech Connect

    Cao, Bingchen; Shen, Xiaonan; Shang, Jingzhi; Cong, Chunxiao; Yang, Weihuang; Eginligil, Mustafa E-mail: meginligil@ntu.edu.sg; Yu, Ting E-mail: meginligil@ntu.edu.sg

    2014-11-01

    High photoresponse can be achieved in monolayers of transition metal dichalcogenides. However, the response times are inconveniently limited by defects. Here, we report low temperature photoresponse of monolayer tungsten disulphide prepared by exfoliation and chemical vapour deposition (CVD) method. The exfoliated device exhibits n-type behaviour; while the CVD device exhibits intrinsic behaviour. In off state, the CVD device has four times larger ratio of photoresponse for laser on/off and photoresponse decay–rise times are 0.1 s (limited by our setup), while the exfoliated device has few seconds. These findings are discussed in terms of charge trapping and localization.

  4. Thermal Reaction of Cinnamate Oligomers and Their Effect on the Orientational Stability of Liquid Crystals

    NASA Astrophysics Data System (ADS)

    Hah, Hyundae; Sung, Shi‑Joon; Park, Jung‑Ki

    2006-08-01

    Cinnamate groups are well-known for a dimerization reaction upon exposure to ultraviolet irradiation and a thermal reaction after being heated. In this study, to verify the thermal reaction of the cinnamate group in detail, we investigated the thermal crosslinking of cinnamate oligomers. The thermal reaction of cinnamate oligomers of low molecular weight is induced more readily by thermal energy compared with that of cinnamate polymers. This reaction is attributed to a radical reaction involving the carbon-carbon double bond in the cinnamate group. The orientation of the liquid crystal depended on the length of the spacers in the cinnamate oligomers.

  5. Studies on Oligomer Metal Complexes Derived from Bisamic Acid of Pyromellitic Dianhydride and 4-Bromoaniline

    PubMed Central

    Patel, Yogesh S.

    2014-01-01

    Novel oligomer metal complexes (2a–f) of the ligand 2,5-bis((4-bromophenyl)carbamoyl) terephthalic acid (1) were prepared using transition metal salts and characterized by various spectroscopic techniques. The geometry of oligomer metal complexes was carried out by electronic spectral analysis and magnetic measurement studies. Polymeric properties have also been carried out. Ligand was synthesized using pyromellitic dianhydride and 4-bromoaniline. It was duly characterized. All novel synthesized compounds 1 and 2a–f were evaluated for their antibacterial and antifungal activity. The results showed significantly higher antibacterial and antifungal activity of oligomer metal complexes compared to the ligand. PMID:27379295

  6. Studies on Oligomer Metal Complexes Derived from Bisamic Acid of Pyromellitic Dianhydride and 4-Bromoaniline.

    PubMed

    Patel, Yogesh S

    2014-01-01

    Novel oligomer metal complexes (2a-f) of the ligand 2,5-bis((4-bromophenyl)carbamoyl) terephthalic acid (1) were prepared using transition metal salts and characterized by various spectroscopic techniques. The geometry of oligomer metal complexes was carried out by electronic spectral analysis and magnetic measurement studies. Polymeric properties have also been carried out. Ligand was synthesized using pyromellitic dianhydride and 4-bromoaniline. It was duly characterized. All novel synthesized compounds 1 and 2a-f were evaluated for their antibacterial and antifungal activity. The results showed significantly higher antibacterial and antifungal activity of oligomer metal complexes compared to the ligand.

  7. Common structure and toxic function of amyloid oligomers implies a common mechanism of pathogenesis.

    PubMed

    Glabe, Charles G; Kayed, Rakez

    2006-01-24

    Recent findings indicate that soluble amyloid oligomers may represent the primary pathologic species in degenerative diseases. These amyloid oligomers share common structural features and the ability to permeabilize membranes, suggesting that they also share a common primary mechanism of pathogenesis. Membrane permeabilization by amyloid oligomers may initiate a common group of downstream pathologic processes, including intracellular calcium dyshomeostasis, production of reactive oxygen species, altered signaling pathways, and mitochondrial dysfunction that represent key effectors of cellular dysfunction and cell death in amyloid-associated degenerative disease, such as sporadic inclusion-body myositis.

  8. Red-emitting π-conjugated oligomers infused single-wall carbon nanotube sheets

    NASA Astrophysics Data System (ADS)

    Fujimori, Toshihiko; Urita, Koki

    2016-04-01

    We demonstrate the one-step thermal fusion and infusion of pyrene molecules inside single-wall carbon nanotubes (SWCNTs). Despite the presence of metallic-SWCNTs, which behave as a quencher due to gapless electronic states, the nanohybrids consisting of pyrene and/or azupyrene oligomers infused SWCNT sheets exhibit red fluorescence by the ultraviolet, blue, and green light excitations. The wavelength-independent light-emitting behavior is explained by (1) infused PAH oligomers inside semiconducting-SWCNTs and (2) the peculiar π-π interaction through mixed π-conjugated state between the π-conjugated oligomers and non-armchair metallic-SWCNTs.

  9. Phenylethynyl Terminated Arylene Ether Oxadiazole and Triazole Oligomers and Their Cured Polymers

    NASA Technical Reports Server (NTRS)

    Thompson, C. M.; Hergenrother, P. M.

    2001-01-01

    Several novel phenylethynyl terminated arylene ether oligomers containing oxadiazole and triazole rings were prepared as part of an effort to develop high performance polymers with an attractive combination of properties (e.g. processability and mechanical performance) for future NASA applications. The oligomers displayed low melt viscosities and good solubilities. Thin films cast from solutions of the oligomers and cured for one hour at 350 C in air gave good tensile properties. Titanium to titanium (6Al-4V) tensile shear specimens were readily fabricated and provided moderate strengths. The chemistry and properties of these new materials are discussed.

  10. Effect of molecular weight of oligomer on ionic diffusion in oligomer electrolytes and its implication for dye-sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Park, Jong Hyuk; Choi, Kyu Jin; Kim, Junkyung; Kang, Yong Soo; Lee, Sang-Soo

    This study measures the diffusion coefficients of I - and I 3 - in oligomer electrolytes as a function of the molecular weight of oligomers and investigates their effect on the performance of dye-sensitized solar cells (DSSCs). The high-diffusion coefficients of ions in an oligomer electrolyte with a lower molecular weight can help to promote the redox mechanism in DSSCs and thereby increase the short-circuit current density. They can also cause a decrease in the open-circuit voltage since a high-diffusion coefficient of I 3 - is capable of reducing the lifetime of electrons in TiO 2 electrodes. To offset these effects, N-methyl-benzimidazole is added to the oligomer electrolytes, thereby improving the open-circuit voltage and fill factor and, consequently, the overall energy-conversion efficiency, which increases to over 5%. A further test involving storage at a high temperature of 75 °C demonstrates that DSSCs employing the oligomer electrolytes show excellent thermal stability over 200 h.

  11. Large Soluble Oligomers of Amyloid β-Protein from Alzheimer Brain Are Far Less Neuroactive Than the Smaller Oligomers to Which They Dissociate.

    PubMed

    Yang, Ting; Li, Shaomin; Xu, Huixin; Walsh, Dominic M; Selkoe, Dennis J

    2017-01-04

    Soluble oligomers of amyloid β-protein (oAβ) isolated from the brains of Alzheimer's disease (AD) patients have been shown experimentally (in the absence of amyloid plaques) to impair hippocampal synaptic plasticity, decrease synapses, induce tau hyperphosphorylation and neuritic dystrophy, activate microglial inflammation, and impair memory in normal adult rodents. Nevertheless, there has been controversy about what types of oligomers actually confer these AD-like phenotypes. Here, we show that the vast majority of soluble Aβ species obtained from brains of humans who died with confirmed AD elute at high molecular weight (HMW) on nondenaturing size-exclusion chromatography. These species have little or no cytotoxic activity in several bioassays. However, incubation of HMW oAβ in mildly alkaline buffer led to their quantitative dissociation into low molecular weight oligomers (∼8-70 kDa), and these were now far more bioactive: they impaired hippocampal LTP, decreased neuronal levels of β2-adrenergic receptors, and activated microglia in wt mice in vivo Thus, most soluble Aβ assemblies in AD cortex are large and inactive but under certain circumstances can dissociate into smaller, highly bioactive species. Insoluble amyloid plaques likely sequester soluble HMW oligomers, limiting their potential to dissociate. We conclude that conditions that destabilize HMW oligomers or retard the sequestration of their smaller, more bioactive components are important drivers of Aβ toxicity. Selectively targeting these small, cytotoxic forms should be therapeutically beneficial.

  12. Coulombic free energy and salt ion association per phosphate of all-atom models of DNA oligomer: dependence on oligomer size.

    PubMed

    Shkel, Irina A; Record, M Thomas

    2012-08-23

    We investigate how the coulombic Gibbs free energy and salt ion association per phosphate charge of DNA oligomers vary with oligomer size (i.e. number of charged residues ∣ZD∣) at 0.15 M univalent salt by non-linear Poisson Boltzmann (NLPB) analysis of all-atom DNA models. Calculations of these quantities ([Formula: see text], [Formula: see text]) are performed for short and long double-stranded (ds) and single-stranded (ss) DNA oligomers, ranging from 4 to 118 phosphates (ds) and from 2 to 59 phosphates (ss). Behaviors of [Formula: see text] and [Formula: see text] as functions of ∣ZD∣ provide a measure of the range of the coulombic end effect and determine the size of an oligomer at which an interior region with the properties (per charge) of the infinite-length polyelectrolyte first appears. This size (10-11 phosphates at each end for ds DNA and 6-9 for ss DNA at 0.15 M salt) is in close agreement with values obtained previously by Monte Carlo and NLPB calculations for cylindrical models of polyions, and by analysis of binding of oligocations to DNA oligomers. Differences in [Formula: see text] and in [Formula: see text] between ss and ds DNA are used to predict effects of oligomeric size and salt concentration on duplex stability in the vicinity of 0.15 M salt. Results of all-atom calculations are compared with results of less structurally detailed models and with experimental data.

  13. Synaptotoxic amyloid-β oligomers: a molecular basis for the cause, diagnosis, and treatment of Alzheimer's disease?

    PubMed

    Klein, William L

    2013-01-01

    The oligomer hypothesis for Alzheimer's disease (AD)was introduced in 1998. It was based on evidence that oligomers could exist free of amyloid fibrils, that fibril-free oligomer solutions rapidly inhibited long term potentiation, and that oligomers ultimately caused a highly selective nerve cell death. Fibrils no longer were the only toxins made by amyloid-β (Aβ), and likely not the most important ones. Oligomers provided a new basis for instigating AD. Since introduction of the hypothesis, more than 1,500 articles on oligomers have been published. Articles for this review were selected for contributions to oligomer theory at three different levels. The first set demonstrated new aspects of oligomer pathobiology in cell models, showing that exposure of neurons to oligomers is sufficient to cause key features of AD neuropathology. The second set confirmed the relationship between oligomers and salient AD neuropathology in animal models, consistent with other in vivo studies that overall have substantiated cell-based discoveries. The third set developed strategies for therapeutic targeting of oligomers, introducing both small molecule and antibody-based approaches. These and related findings from many groups have helped establish oligomers as central to the mechanism of AD pathogenesis. Comprising a ligand-based attack on specific synapses, the action of toxic oligomers gives a molecular basis to account for key features of AD neuropathology and to explain why early disease targets memory. Although there still is no effective treatment for AD, insights over the past five years raise hopes that new approaches targeting Aβ oligomers could finally bring disease-modifying therapeutics.

  14. Compressibility study of quaternary phospholipid blend monolayers.

    PubMed

    Cavalcanti, Leide P; Tho, Ingunn; Konovalov, Oleg; Fossheim, Sigrid; Brandl, Martin

    2011-07-01

    The mechanical properties of liposome membranes are strongly dependent on type and ratio of lipid compounds, which can have important role in drug targeting and release processes when liposome is used as drug carrier. In this work we have used Brewster's angle microscopy to monitor the lateral compression process of lipid monolayers containing as helper lipids either distearoyl phosphatidylethanolamine (DSPE) or dioleoyl phophatidylethanolamine (DOPE) molecules on the Langmuir trough. The compressibility coefficient was determined for lipid blend monolayers containing the helper lipids above, cholesterol, distearoyl phosphatidylcholine (DSPC) and pegylated-DSPE at room temperature. Two variables, the cholesterol fraction and the ratio ρ between the helper lipid (either DSPE or DOPE) and the reference lipid DSPC, were studied by multivariate analysis to evaluate their impact on the compressibility coefficient of the monolayers. The cholesterol level was found to be the most significant variable for DSPE blends while the ratio ρ was the most significant one for DOPE blend monolayers. It was also found that these two variables can exhibit positive interaction and the same compressibility value can be obtained with different blend compositions.

  15. Adsorption of Ions at Uncharged Insoluble Monolayers.

    PubMed

    Peshkova, Tatyana V; Minkov, Ivan L; Tsekov, Roumen; Slavchov, Radomir I

    2016-09-06

    A method is proposed for the experimental determination of the adsorption of inorganic electrolytes at a surface covered with insoluble surfactant monolayer. This task is complicated by the fact that the change of the salt concentration alters both chemical potentials of the electrolyte and the surfactant. Our method resolves the question by combining data for the surface pressure versus area of the monolayer at several salt concentrations with data for the equilibrium spreading pressure of crystals of the surfactant (used to fix a standard state). We applied the method to alcohols spread at the surface of concentrated halide solutions. The measured salt adsorption is positive and has nonmonotonic dependence on the area per surfactant molecule. For the liquid expanded film, depending on the concentration, there is one couple of ions adsorbed per each 3-30 surfactant molecules. We analyzed which ion, the positive or the negative, stands closer to the surface, by measuring the effect of NaCl on the Volta potential of the monolayer. The potentiometric data suggest that Na(+) is specifically adsorbed, while Cl(-) remains in the diffuse layer, i.e., the surface is positively charged. The observed reverse Hofmeister series of the adsorptions of NaF, NaCl, and NaBr suggests the same conclusion holds for all these salts. The force that causes the adsorption of Na(+) seems to be the interaction of the ion with the dipole moment of the monolayer.

  16. Hydrolytic kinetics of biodegradable polyester monolayers

    SciTech Connect

    Lee, W.K.; Gardella, J.A. Jr.

    2000-04-04

    The rate of hydrolysis of Langmuir monolayer films of a series of biodegradable polyesters was investigated at the air/water interface. The present study investigated parameters such as degradation medium, pH, and time. The hydrolysis of polyester monolayers strongly depended on both the degradation medium used to control subphase pH and the concentration of active ions. Under the conditions studied here, polymer monolayers showed faster hydrolysis when they were exposed to a basic subphase rather than that of acidic or neutral subphase. The basic (pH = 10) hydrolysis of [poly(l-lactide)/polycaprolactone](l-PLA/PCL 1/1 by mole) blend was faster than that of each homopolymer at the initial stage. This result is explained by increasing numbers of base attack sites per unit area owing to the very slow hydrolysis of PCL, a dilution effect on the concentration of l-PLA monolayers. Conversely the hydrolytic behavior of l-lactide-co-caprolactone (1/1 by mole) was similar to that of PCL even though the chemical compositions of the blend and the copolymer are very similar to each other. The resistance of the copolymer to hydrolysis might be attributed to the hydrophobicity and the steric hindrance of caprolactone unit in the copolymer.

  17. Adsorption of Ions at Uncharged Insoluble Monolayers

    NASA Astrophysics Data System (ADS)

    Peshkova, T. V.; Minkov, I. L.; Tsekov, R.; Slavchov, R. I.

    2016-08-01

    A method is proposed for the experimental determination of the adsorption of inorganic electrolytes at a surface covered with insoluble surfactant monolayer. This task is complicated by the fact that the change of the salt concentration alters both chemical potentials of the electrolyte and the surfactant. Our method resolves the question by combining data for the surface pressure versus area of the monolayer at several salt concentrations with data for the equilibrium spreading pressure of crystals of the surfactant (used to fix a standard state). We applied the method to alcohols spread at the surface of concentrated halide solutions. The measured salt adsorption is positive and has nonmonotonic dependence on the area per surfactant molecule. For the liquid expanded film, depending on the concentration, there is one couple of ions adsorbed per each 3–30 surfactant molecules. We analyzed which ion, the positive or the negative, stands closer to the surface, by measuring the effect of NaCl on the Volta potential of the monolayer. The potentiometric data suggest that Na+ is specifically adsorbed, while Cl– remains in the diffuse layer, i.e., the surface is positively charged. The observed reverse Hofmeister series of the adsorptions of NaF, NaCl, and NaBr suggests the same conclusion holds for all these salts. The force that causes the adsorption of Na+ seems to be the interaction of the ion with the dipole moment of the monolayer.

  18. Modulation of dipalmitoylphosphatidylcholine monolayers by dimethyl sulfoxide.

    PubMed

    Dabkowska, Aleksandra P; Collins, Louise E; Barlow, David J; Barker, Robert; McLain, Sylvia E; Lawrence, M Jayne; Lorenz, Christian D

    2014-07-29

    The action of the penetration-enhancing agent, dimethyl sulfoxide (DMSO), on phospholipid monolayers was investigated at the air-water interface using a combination of experimental techniques and molecular dynamics simulations. Brewster angle microscopy revealed that DPPC monolayers remained laterally homogeneous at subphase concentrations up to a mole fraction of 0.1 DMSO. Neutron reflectometry of the monolayers in combination with isotopic substitution enabled the determination of solvent profiles as a function of distance perpendicular to the interface for the different DMSO subphase concentrations. These experimental results were compared to those obtained from molecular dynamic (MD) simulations of the corresponding monolayer systems. There was excellent agreement found between the MD-derived reflectivity curves and the measured data for all of the H/D contrast variations investigated. The MD provide a detailed description of the distribution of water and DMSO molecules around the phosphatidylcholine headgroup, and how this distribution changes with increasing DMSO concentrations. Significantly, the measurements and simulations that are reported here support the hypothesis that DMSO acts by dehydrating the phosphatidylcholine headgroup, and as such provide the first direct evidence that it does so primarily by displacing water molecules bound to the choline group.

  19. Calcium sensitive ring-like oligomers formed by synaptotagmin

    PubMed Central

    Wang, Jing; Bello, Oscar; Auclair, Sarah M.; Wang, Jing; Coleman, Jeff; Pincet, Frederic; Krishnakumar, Shyam S.; Sindelar, Charles V.; Rothman, James E.

    2014-01-01

    The synaptic vesicle protein synaptotagmin-1 (SYT) is required to couple calcium influx to the membrane fusion machinery. However, the structural mechanism underlying this process is unclear. Here we report an unexpected circular arrangement (ring) of SYT’s cytosolic domain (C2AB) formed on lipid monolayers in the absence of free calcium ions as revealed by electron microscopy. Rings vary in diameter from 18–43 nm, corresponding to 11–26 molecules of SYT. Continuous stacking of the SYT rings occasionally converts both lipid monolayers and bilayers into protein-coated tubes. Helical reconstruction of the SYT tubes shows that one of the C2 domains (most likely C2B, based on its biochemical properties) interacts with the membrane and is involved in ring formation, and the other C2 domain points radially outward. SYT rings are disrupted rapidly by physiological concentrations of free calcium but not by magnesium. Assuming that calcium-free SYT rings are physiologically relevant, these results suggest a simple and novel mechanism by which SYT regulates neurotransmitter release: The ring acts as a spacer to prevent the completion of the soluble N-ethylmaleimide–sensitive factor activating protein receptor (SNARE) complex assembly, thereby clamping fusion in the absence of calcium. When the ring disassembles in the presence of calcium, fusion proceeds unimpeded. PMID:25201968

  20. Reactive Processing with Difunctional Oligomers to Increase Interfacial Adhesion in Polymer Blends

    NASA Astrophysics Data System (ADS)

    O'Brien, Charles; Rice+, Kevin; Dadmun, Mark

    2000-03-01

    The intoduction of blocky copolymers represents a possible method of compatibilizing two immiscible polymers in a blend. However, copolymers do not diffuse quickly to the interface of a polymer blend system. Therefore, reactive processing is being investigated as a means to form in-situ compatibilizers for polymer blends. A model system composed of poly(bisphenol A-co-epichlorohydrin) blended with poly(ethylene oxide) that is compatibilized with difunctional oligomers that are the same structure as the blend components is currently under investigation. It is expected that the oligomers can undergo an addition copolymerization during processing to create the blocky copolymers at the biphasic interface. Initial tensile measurements show that the addition of the reactive oligomers improves the properties of the blend. Additionally, preliminary results indicate that reactive oligomers may act as plasticizers and continue to polymerize at room temperature after the blend is removed from the melt mixer if insufficiently mixed.

  1. Enhanced Emission of Highly Labeled DNA Oligomers near Silver Metallic Surfaces

    PubMed Central

    Malicka, Joanna; Gryczynski, Ignacy; Lakowicz, Joseph R.

    2009-01-01

    Fluorescein is a widely used fluorescent probe in DNA analysis. One difficulty with fluorescein is its self-quenching due to resonance energy transfer between the residues, which results in decreased intensities with increasing labeling density. We examined the emission spectral properties of DNA oligomers labeled with one or five fluorescein residues. The emission intensity of the more highly labeled oligomer was decreased due to self-quenching. The self-quenching was mostly eliminated when this oligomer was held ~90 Å from the surface of metallic silver particles. The intensities increased 7- and 19-fold for the oligomers with one or five fluoresceins, respectively. The increased intensity did not result in increased photobleaching. These results suggest the use of substrates coated with silver particles for increased sensitivity on DNA arrays or for DNA analysis. PMID:14632044

  2. Microwave assisted synthesis of bithiophene based donor-acceptor-donor oligomers and their optoelectronic performances

    NASA Astrophysics Data System (ADS)

    Bathula, Chinna; Buruga, Kezia; Lee, Sang Kyu; Khazi, Imtiyaz Ahmed M.; Kang, Youngjong

    2017-07-01

    In this article we present the synthesis of two novel bithiophene based symmetrical π conjugated oligomers with donor-acceptor-donor (D-A-D) structures by microwave assisted PdCl2(dppf) catalyzed Suzuki coupling reaction. These molecules contain electron rich bithiophene as a donor, dithienothiadiazole[3,4-c]pyridine and phthalic anhydride units as acceptors. The shorter reaction time, excellent yields and easy product isolation are the advantages of this method. The photophysical prerequisites for electronic application such as strong and broad optical absorption, thermal stability, and compatible energy levels were determined for synthesized oligomers. Optical band gap for the oligomers is found to be 1.72-1.90 eV. The results demonstrated the novel oligomers to be promising candidates in organic optoelectronic applications.

  3. The Anti-Prion Antibody 15B3 Detects Toxic Amyloid-β Oligomers

    PubMed Central

    Stravalaci, Matteo; Tapella, Laura; Beeg, Marten; Rossi, Alessandro; Joshi, Pooja; Pizzi, Erika; Mazzanti, Michele; Balducci, Claudia; Forloni, Gianluigi; Biasini, Emiliano; Salmona, Mario; Diomede, Luisa; Chiesa, Roberto; Gobbi, Marco

    2016-01-01

    15B3 is a monoclonal IgM antibody that selectively detects pathological aggregates of the prion protein (PrP). We report the unexpected finding that 15B3 also recognizes oligomeric but not monomeric forms of amyloid-β (Aβ)42, an aggregating peptide implicated in the pathogenesis of Alzheimer’s disease (AD). The 15B3 antibody: i) inhibits the binding of synthetic Aβ42 oligomers to recombinant PrP and neuronal membranes; ii) prevents oligomer-induced membrane depolarization; iii) antagonizes the inhibitory effects of oligomers on the physiological pharyngeal contractions of the nematode Caenorhabditis elegans; and iv) counteracts the memory deficits induced by intracerebroventricular injection of Aβ42 oligomers in mice. Thus this antibody binds to pathologically relevant forms of Aβ, and offers a potential research, diagnostic, and therapeutic tool for AD. PMID:27392850

  4. Vesicle permeabilization by purified soluble oligomers of prion protein: a comparative study of the interaction of oligomers and monomers with lipid membranes.

    PubMed

    Chich, J-F; Chapuis, C; Henry, C; Vidic, J; Rezaei, H; Noinville, S

    2010-04-09

    The conversion of normal cellular prion protein (PrP) into its pathological isoform, scrapie PrP, may occur at the cell surface or, more probably, in late endosomes. The early events leading to the structural conversion of PrP appear to be related to the presence of more or less stable soluble oligomers, which might mediate neurotoxicity. In the current study, we investigate the interaction of alpha-rich PrP monomers and beta-rich size-exclusion-chromatography-purified PrP oligomers with lipid membranes. We compare their structural properties when associated with lipid bilayers and study their propensities to permeabilize the membrane at physiological pH. We also study the influence of the N-terminal flexible region (residues 24-103) by comparing full-length PrP(24-234) and N-terminally truncated PrP(104-234) oligomers. We showed that both 12-subunit oligomers cause an immediate and large increase in the permeability of the membrane, whereas equivalent amounts of monomeric forms cause no detectable leakage. Although the two monomeric PrP constructs undergo an alpha-to-beta conformational change when bound to the negatively charged membrane, only the full-length form of monomeric PrP has a weak fusogenic effect. Finally, the oligomers affect the integrity of the membrane differently from the monomers, independently of the presence of the N-terminal flexible domain. As for other forms of amyloidogenesis, a reasonable mechanism for the toxicity arising from PrP fibrillization must be associated with low-molecular-weight oligomeric intermediates, rather than with mature fibrils. Knowledge of the mechanism of action of these soluble oligomers would have a high impact on the development of novel therapeutic targets.

  5. Salt anions promote the conversion of HypF-N into amyloid-like oligomers and modulate the structure of the oligomers and the monomeric precursor state.

    PubMed

    Campioni, Silvia; Mannini, Benedetta; López-Alonso, Jorge P; Shalova, Irina N; Penco, Amanda; Mulvihill, Estefania; Laurents, Douglas V; Relini, Annalisa; Chiti, Fabrizio

    2012-12-07

    An understanding of the solution factors contributing to the rate of aggregation of a protein into amyloid oligomers, to the modulation of the conformational state populated prior to aggregation and to the structure/morphology of the resulting oligomers is one of the goals of present research in this field. We have studied the influence of six different salts on the conversion of the N-terminal domain of Escherichiacoli HypF (HypF-N) into amyloid-like oligomers under conditions of acidic pH. Our results show that salts having different anions (NaCl, NaClO(4), NaI, Na(2)SO(4)) accelerate oligomerization with an efficacy that follows the electroselectivity series of the anions (SO(4)(2-)≥ ClO(4)(-)>I(-)>Cl(-)). By contrast, salts with different cations (NaCl, LiCl, KCl) have similar effects. We also investigated the effect of salts on the structure of the final and initial states of HypF-N aggregation. The electroselectivity series does not apply to the effect of anions on the structure of the oligomers. By contrast, it applies to their effect on the content of secondary structure and on the exposure of hydrophobic clusters of the monomeric precursor state. The results therefore indicate that the binding of anions to the positively charged residues of HypF-N at low pH is the mechanism by which salts modulate the rate of oligomerization and the structure of the monomeric precursor state but not the structure of the resulting oligomers. Overall, the data contribute to rationalize the effect of salts on amyloid-like oligomer formation and to explain the role of charged biological macromolecules in protein aggregation processes.

  6. Bacterial Resistance to Antisense Peptide Phosphorodiamidate Morpholino Oligomers

    PubMed Central

    Puckett, Susan E.; Reese, Kaleb A.; Mitev, Georgi M.; Mullen, Valerie; Johnson, Rudd C.; Pomraning, Kyle R.; Mellbye, Brett L.; Tilley, Lucas D.; Iversen, Patrick L.; Freitag, Michael

    2012-01-01

    Peptide phosphorodiamidate morpholino oligomers (PPMOs) are synthetic DNA mimics that bind cRNA and inhibit bacterial gene expression. The PPMO (RFF)3RXB-AcpP (where R is arginine, F, phenylalanine, X is 6-aminohexanoic acid, B is β-alanine, and AcpP is acyl carrier protein) is complementary to 11 bases of the essential gene acpP (which encodes acyl carrier protein). The MIC of (RFF)3RXB-AcpP was 2.5 μM (14 μg/ml) in Escherichia coli W3110. The rate of spontaneous resistance of E. coli to (RFF)3RXB-AcpP was 4 × 10−7 mutations/cell division. A spontaneous (RFF)3RXB-AcpP-resistant mutant (PR200.1) was isolated. The MIC of (RFF)3RXB-AcpP was 40 μM (224 μg/ml) for PR200.1. The MICs of standard antibiotics for PR200.1 and W3110 were identical. The sequence of acpP was identical in PR200.1 and W3110. PR200.1 was also resistant to other PPMOs conjugated to (RFF)3RXB or peptides with a similar composition or pattern of cationic and nonpolar residues. Genomic sequencing of PR200.1 identified a mutation in sbmA, which encodes an active transport protein. In separate experiments, a (RFF)3RXB-AcpP-resistant isolate (RR3) was selected from a transposome library, and the insertion was mapped to sbmA. Genetic complementation of PR200.1 or RR3 with sbmA restored susceptibility to (RFF)3RXB-AcpP. Deletion of sbmA caused resistance to (RFF)3RXB-AcpP. We conclude that resistance to (RFF)3RXB-AcpP was linked to the peptide and not the phosphorodiamidate morpholino oligomer, dependent on the composition or repeating pattern of amino acids, and caused by mutations in sbmA. The data further suggest that (RFF)3R-XB PPMOs may be transported across the plasma membrane by SbmA. PMID:22985881

  7. Bacterial resistance to antisense peptide phosphorodiamidate morpholino oligomers.

    PubMed

    Puckett, Susan E; Reese, Kaleb A; Mitev, Georgi M; Mullen, Valerie; Johnson, Rudd C; Pomraning, Kyle R; Mellbye, Brett L; Tilley, Lucas D; Iversen, Patrick L; Freitag, Michael; Geller, Bruce L

    2012-12-01

    Peptide phosphorodiamidate morpholino oligomers (PPMOs) are synthetic DNA mimics that bind cRNA and inhibit bacterial gene expression. The PPMO (RFF)(3)RXB-AcpP (where R is arginine, F, phenylalanine, X is 6-aminohexanoic acid, B is β-alanine, and AcpP is acyl carrier protein) is complementary to 11 bases of the essential gene acpP (which encodes acyl carrier protein). The MIC of (RFF)(3)RXB-AcpP was 2.5 μM (14 μg/ml) in Escherichia coli W3110. The rate of spontaneous resistance of E. coli to (RFF)(3)RXB-AcpP was 4 × 10(-7) mutations/cell division. A spontaneous (RFF)(3)RXB-AcpP-resistant mutant (PR200.1) was isolated. The MIC of (RFF)(3)RXB-AcpP was 40 μM (224 μg/ml) for PR200.1. The MICs of standard antibiotics for PR200.1 and W3110 were identical. The sequence of acpP was identical in PR200.1 and W3110. PR200.1 was also resistant to other PPMOs conjugated to (RFF)(3)RXB or peptides with a similar composition or pattern of cationic and nonpolar residues. Genomic sequencing of PR200.1 identified a mutation in sbmA, which encodes an active transport protein. In separate experiments, a (RFF)(3)RXB-AcpP-resistant isolate (RR3) was selected from a transposome library, and the insertion was mapped to sbmA. Genetic complementation of PR200.1 or RR3 with sbmA restored susceptibility to (RFF)(3)RXB-AcpP. Deletion of sbmA caused resistance to (RFF)(3)RXB-AcpP. We conclude that resistance to (RFF)(3)RXB-AcpP was linked to the peptide and not the phosphorodiamidate morpholino oligomer, dependent on the composition or repeating pattern of amino acids, and caused by mutations in sbmA. The data further suggest that (RFF)(3)R-XB PPMOs may be transported across the plasma membrane by SbmA.

  8. Optically and redox-active ferroceneacetylene polymers and oligomers

    PubMed

    Plenio; Hermann; Sehring

    2000-05-15

    The palladium-catalyzed Sonogashira reaction can be used to build optically active, oligomeric 1,2,3-substituted ferrocenes up to the tetramer, as well as polymers, by sequential coupling of optically active (ee > 98 %), planar chiral iodoferroceneacetylenes and ferroceneacetylenes. (SFC)-1-Iodoferrocene-2-carbaldehyde (1) was reduced to the alcohol and methylated to give the corresponding methyl ether, which was Sonogashira-coupled with HC(triple bond)CSiEt3, resulting in (RFc)-1-(C(triple bond)CSiEt3)-2-methoxymethylferrocene (4) (79%, three steps). Orthometalation with tBuLi followed by quenching with 1,2-diodoethane gave (RFc)-1-(C(triple bond)CSiEt3)-2-methoxymethyl-3-iodoferrocene (5). Deprotection of the acetylene with nBu4NF resulted in (RFc)-1-ethynyl-2-methoxymethyl-3-iodoferrocene (6), which was Sonogashira-coupled with itself to produce an optically active polymer. Deprotection of 4 with nBu4NF and Sonogashira coupling of the product with 5 resulted in the dinuclear ferrocene 9. Deprotection of 9 and coupling with 5, followed by deprotection of the resulting acetylene 11, gave the trinuclear ferrocene 12. Another such sequence involving 11 and 5 produced a tetranuclear ferrocene 13. To study the electronic communication in such oligomers in more detail, two symmetrical, closely interrelated, trinuclear ferrocenes 18 and 19 were synthesized. The redox potentials of all the ferrocenes and the ferroceneacetylene polymer were determined by cyclic and square-wave voltammetry. All the metallocenes were investigated by UV/Vis spectroscopy. A linear relationship was found between lambdamax and l/n (n=number of ferrocene units in the oligomer). The polymer displayed two redox waves in the cyclic voltammogram, at 0.65 and 0.795 V. The corresponding mixed-valence oligoferrocene cations were synthesized from four ferroceneacetylenes, and their metal-metal charge transfer bands were examined by UV/Vis-NIR. The resonance exchange integrals Had, calculated on the

  9. Styrene-terminated polysulfone oligomers as matrix material for graphite reinforced composites: An initial study

    NASA Technical Reports Server (NTRS)

    Garcia, Dana; Bowles, Kenneth J.; Vannucci, Raymond D.

    1987-01-01

    Styrene terminated polysulfone oligomers are part of an oligomeric class of compounds with end groups capable of thermal polymerization. These materials can be used as matrices for graphite reinforced composites. The initial evaluation of styrene terminated polysulfone oligomer based composites are summarized in terms of fabrication methods, and mechanical and environmental properties. In addition, a description and evaluation is provided of the NASA/Industry Fellowship Program for Technology Transfer.

  10. Soluble Prion Protein Binds Isolated Low Molecular Weight Amyloid-β Oligomers Causing Cytotoxicity Inhibition.

    PubMed

    Williams, Thomas L; Choi, Jin-Kyu; Surewicz, Krystyna; Surewicz, Witold K

    2015-12-16

    A growing number of observations indicate that soluble amyloid-β (Aβ) oligomers play a major role in Alzheimer's disease. Recent studies strongly suggest that at least some of the neurotoxic effects of these oligomers are mediated by cellular, membrane-anchored prion protein and that Aβ neurotoxicity can be inhibited by soluble recombinant prion protein (rPrP) and its fragments. However, the mechanism by which rPrP interacts with Aβ oligomers and prevents their toxicity is largely unknown, and studies in this regard are hindered by the large structural heterogeneity of Aβ oligomers. To overcome this difficulty, here we used photoinduced cross-linking of unmodified proteins (PICUP) to isolate well-defined oligomers of Aβ42 and characterize these species with regard to their cytotoxicity and interaction with rPrP, as well the mechanism by which rPrP inhibits Aβ42 cytotoxicity. Our data shows that the addition of rPrP to the assembling Aβ42 results in a shift in oligomer size distribution, decreasing the population of toxic tetramers and higher order oligomers and increasing the population of nontoxic (and possibly neuroprotective) monomers. Isolated oligomeric species of Aβ42 are cytotoxic to primary neurons and cause permeation of model lipid bilayers. These toxic effects, which are oligomer size-dependent, can be inhibited by the addition of rPrP, and our data suggest potential mechanisms of this inhibitory action. This insight should help in current efforts to develop PrP-based therapeutics for Alzheimer's disease.

  11. Oligomer formation of the gB glycoprotein of herpes simplex virus type 1.

    PubMed Central

    Highlander, S L; Goins, W F; Person, S; Holland, T C; Levine, M; Glorioso, J C

    1991-01-01

    Oligomer formation of the gB glycoprotein of herpes simplex virus type 1 was studied by sedimentation analysis of radioactively labeled infected cell and virion lysates. Fractions from sucrose gradients were precipitated with a pool of gB-specific monoclonal antibodies and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Pulse-labeled gB from infected cell was synthesized as monomers and converted to oligomers posttranslationally. The oligomers from infected cells and from virions sedimented as dimers, and there was no evidence of higher-molecular-weight forms. To identify amino acid sequences of gB that contribute to oligomer formation, pairs of mutant plasmids were transfected into Vero cells and superinfected with a gB-null mutant virus to stimulate plasmid-specified gene expression. Radioactively labeled lysates were precipitated with antibodies and examined by SDS-PAGE. Polypeptides from cotransfections were precipitated with an antibody that recognized amino acid sequences present in only one of the two polypeptides. A coprecipitated polypeptide lacking the antibody target epitope was presumed to contain the sequences necessary for oligomer formation. Using this technique, two noncontiguous sites for oligomer formation were detected. An upstream site was localized between residues 93 and 282, and a downstream site was localized between residues 596 and 711. Oligomer formation resulted from molecular interactions between two upstream sites, between two downstream sites, and between an upstream and a downstream site. A schematic diagram of a gB oligomer is presented that is consistent with these data. Images PMID:1649330

  12. A HRMS study of oligomer formation through aqueous phase photooxidation of methylvinyl-ketone and methacrolein

    NASA Astrophysics Data System (ADS)

    Salque-moreton, G.; Liu, Y.; Voisin, D.; Siekmann, F.; Renard, P.; Monod, A.; Thissen, R.

    2012-04-01

    Global estimates of secondary organic aerosol (SOA) formation flux show that the current descriptions miss a large fraction of the sources. Aqueous phase photochemistry in cloud droplets and deliquescent aerosol may provide some of this missing flux. Organic reactions in those media, particularly leading to higher molecular weight products thus need better understanding. Here, we investigated the aqueous phase photooxidation of methacrolein (MACR) and methylvinyl-ketone (MVK), which are the two main oxidation products of isoprene, the volatile organic compound (VOC) that is mostly emitted on the global scale. In our experiments, photolysis of H2O2 provided OH radicals whose reaction with MACR or MVK produced oligomers. Firstly, oligomers were analyzed using electrospray ionization coupled with high-resolution linear ion trap Orbitrap™ (Thermo Corp.) mass spectrometer (HRMS). This technique enabled to propose the unambiguous elemental composition of the produced compounds as data were collected for a mass range of m/z 50-2000 amu. The mass of oligomers increased strongly in positive and negative ionization modes when initial concentrations of MACR and MVK were increased from 2 to 20 mM. Typical regular patterns of oligomer formation were observed for both precursors, and extended up to 1400 amu. These patterns were very different from each other for the two precursors although both showed regular mass differences of 70 amu. In addition, we used a Kendrick analysis and identified more than 20 distinct chemical oligomer series produced by photooxidation of both MACR and MVK, some of which reaching more than 1400 amu. The HRMS investigations allowed us to propose a mechanism of production of oligomers. Upon nebulization, both oligomer systems produce SOA with a mass yield of 2-12%. This mass yield increases with reaction time and precursor concentration. Moreover, time evolution of the oligomer systems observed with the Orbitrap will be compared to HR

  13. KCTD Hetero-oligomers Confer Unique Kinetic Properties on Hippocampal GABAB Receptor-Induced K+ Currents.

    PubMed

    Fritzius, Thorsten; Turecek, Rostislav; Seddik, Riad; Kobayashi, Hiroyuki; Tiao, Jim; Rem, Pascal D; Metz, Michaela; Kralikova, Michaela; Bouvier, Michel; Gassmann, Martin; Bettler, Bernhard

    2017-02-01

    GABAB receptors are the G-protein coupled receptors for the main inhibitory neurotransmitter in the brain, GABA. GABAB receptors were shown to associate with homo-oligomers of auxiliary KCTD8, KCTD12, KCTD12b, and KCTD16 subunits (named after their T1 K(+)-channel tetramerization domain) that regulate G-protein signaling of the receptor. Here we provide evidence that GABAB receptors also associate with hetero-oligomers of KCTD subunits. Coimmunoprecipitation experiments indicate that two-thirds of the KCTD16 proteins in the hippocampus of adult mice associate with KCTD12. We show that the KCTD proteins hetero-oligomerize through self-interacting T1 and H1 homology domains. Bioluminescence resonance energy transfer measurements in live cells reveal that KCTD12/KCTD16 hetero-oligomers associate with both the receptor and the G-protein. Electrophysiological experiments demonstrate that KCTD12/KCTD16 hetero-oligomers impart unique kinetic properties on G-protein-activated Kir3 currents. During prolonged receptor activation (one min) KCTD12/KCTD16 hetero-oligomers produce moderately desensitizing fast deactivating K(+) currents, whereas KCTD12 and KCTD16 homo-oligomers produce strongly desensitizing fast deactivating currents and nondesensitizing slowly deactivating currents, respectively. During short activation (2 s) KCTD12/KCTD16 hetero-oligomers produce nondesensitizing slowly deactivating currents. Electrophysiological recordings from hippocampal neurons of KCTD knock-out mice are consistent with these findings and indicate that KCTD12/KCTD16 hetero-oligomers increase the duration of slow IPSCs. In summary, our data demonstrate that simultaneous assembly of distinct KCTDs at the receptor increases the molecular and functional repertoire of native GABAB receptors and modulates physiologically induced K(+) current responses in the hippocampus.

  14. Oligomers of the amyloid-beta protein disrupt working memory: confirmation with two behavioral procedures.

    PubMed

    Poling, Alan; Morgan-Paisley, Kineta; Panos, John J; Kim, Eun-Mee; O'Hare, Eugene; Cleary, James P; Lesné, Sylvain; Ashe, Karen H; Porritt, Matthew; Baker, Lisa E

    2008-11-21

    Converging lines of evidence suggest that oligomers of amyloid-beta play a role in the cognitive impairment characteristic of Alzheimer's disease, but only three studies have provided experimental evidence of such impairment. To provide additional information about the effects of these oligomers on memory, the present study examined the memory of groups of rats exposed to ICV injections of the culture media (CM) of Chinese Hamster Ovary cells that were (7PA2) and were not (CHO-) transfected with a human mutation of amyloid precursor protein that appears to cause early-onset Alzheimer's disease. The 7PA2 CM, which contained concentrations of soluble amyloid-beta oligomers physiologically relevant to those found in human brain, significantly disrupted working memory in rats tested in a radial-arm maze. In contrast, CHO- CM, which did not contain such oligomers, had no effect on memory. The disruptive effects of 7PA2-derived amyloid-beta oligomers, evident 2h after exposure, disappeared within a day. These findings are compared to results from 7PA2 CM tested under a complex procedure thought to measure aspects of executive function. The results confirm the disruptive effects of low-n amyloid-beta oligomers and extend them to a well-established rat model of memory.

  15. Low Molecular Weight Oligomers with Aromatic Backbone as Efficient Nonviral Gene Vectors.

    PubMed

    Luan, Chao-Ran; Liu, Yan-Hong; Zhang, Ji; Yu, Qing-Ying; Huang, Zheng; Wang, Bing; Yu, Xiao-Qi

    2016-05-04

    A series of oligomers were synthesized via ring-opening polymerization. Although the molecular weights of these oligomers are only ∼2.5 kDa, they could efficiently bind and condense DNA into nanoparticles. These oligomers gave comparable transfection efficiency (TE) to PEI 25 kDa, while their TE could even increase with the presence of serum, and up to 65 times higher TE than PEI was obtained. The excellent serum tolerance was also confirmed by TEM, flow cytometry, and BSA adsorption assay. Moreover, structure-activity relationship studies revealed some interesting factors. First, oligomers containing aromatic rings in the backbone showed better DNA binding ability. These materials could bring more DNA cargo into the cells, leading to much better TE. Second, the isomerism of the disubstituted phenyl group on the oligomer backbone has large effect on the transfection. The ortho-disubstituted ones gave at least 1 order of magnitude higher TE than meta- or para-disubstituted oligomers. Gel electrophoresis involving DNase and heparin indicated that the difficulty to release DNA might contribute to the lower TE of the latter. Such clues may help us to design novel nonviral gene vectors with high efficiency and biocompatibility.

  16. Liquid crystalline thermosets from ester, ester-imide, and ester-amide oligomers

    NASA Technical Reports Server (NTRS)

    Dingemans, Theodorous J. (Inventor); Weiser, Erik S. (Inventor); St. Clair, Terry L. (Inventor)

    2005-01-01

    Main chain thermotropic liquid crystal esters, ester-imides, and ester-amides were prepared from AA, BB, and AB type monomeric materials and were end-capped with phenylacetylene, phenylmaleimide, or nadimide reactive end-groups. The resulting reactive end-capped liquid crystal oligomers exhibit a variety of improved and preferred physical properties. The end-capped liquid crystal oligomers are thermotropic and have, preferably, molecular weights in the range of approximately 1000-15,000 grams per mole. The end-capped liquid crystal oligomers have broad liquid crystalline melting ranges and exhibit high melt stability and very low melt viscosities at accessible temperatures. The end-capped liquid crystal oligomers are stable for up to an hour in the melt phase. These properties make the end-capped liquid crystal oligomers highly processable by a variety of melt process shape forming and blending techniques including film extrusion, fiber spinning, reactive injection molding (RIM), resin transfer molding (RTM), resin film injection (RFI), powder molding, pultrusion, injection molding, blow molding, plasma spraying and thermo-forming. Once processed and shaped, the end-capped liquid crystal oligomers were heated to further polymerize and form liquid crystalline thermosets (LCT). The fully cured products are rubbers above their glass transition temperatures. The resulting thermosets display many properties that are superior to their non-end-capped high molecular weight analogs.

  17. Liquid Crystalline Thermosets from Ester, Ester-Imide, and Ester-Amide Oligomers

    NASA Technical Reports Server (NTRS)

    Dingemans, Theodornus J. (Inventor); Weiser, Erik S. (Inventor); SaintClair, Terry L. (Inventor)

    2005-01-01

    Main chain thermotropic liquid crystal esters, ester-imides, and ester-amides were prepared from AA, BB, and AB type monomeric materials and were end-capped with phenylacetylene, phenylmaleimide, or nadimide reactive end-groups. The resulting reactive end-capped liquid crystal oligomers exhibit a variety of improved and preferred physical properties. The end-capped liquid crystal oligomers are thermotropic and have, preferably, molecular weights in the range of approximately 1000-15,OOO grams per mole. The end-capped liquid crystal oligomers have broad liquid crystalline melting ranges and exhibit high melt stability and very low melt viscosities at accessible temperatures. The end-capped liquid crystal oligomers are stable for up to an hour in the melt phase. These properties make the end-capped liquid crystal oligomers highly processable by a variety of melt process shape forming and blending techniques including film extrusion, fiber spinning, reactive injection molding (RIM), resin transfer molding (RTM), resin film injection (RFI), powder molding, pultrusion, injection molding, blow molding, plasma spraying and thermo-forming. Once processed and shaped, the end- capped liquid crystal oligomers were heated to further polymerize and form liquid crystalline thermosets (LCT). The fully cured products are rubbers above their glass transition temperatures. The resulting thermosets display many properties that are superior to their non-end-capped high molecular weight analogs.

  18. π-Conjugated Discrete Oligomers Containing Planar and Nonplanar Aromatic Motifs.

    PubMed

    Li, Ji; Terec, Anamaria; Wang, Yue; Joshi, Hrishikesh; Lu, Yunpeng; Sun, Handong; Stuparu, Mihaiela C

    2017-03-01

    A new family of π-conjugated oligomers featuring a nonplanar polycyclic aromatic hydrocarbon, corannulene, and a planar aromatic unit, thiophene, is synthesized through an iterative metal-catalyzed coupling protocol. The two structural motifs are connected through an acetylene linkage. In the shorter oligomers, a thiophene unit is attached to one or two corannulenes. In the higher analogues, two, three, and four thiophene units are placed in an alternating fashion with three, four, and five corannulene units, respectively. Photophysical studies reveal extended π-effects that initially increase and then attenuate as a function of the oligomer length. Notably, longer oligomers are found to be highly active for nonlinear absorption and emission properties. The oligomer with three corannulene and two thiophene units exhibits a two-photon absorption cross section of 600 GM and two-photon-excited intense green luminescence. This work, therefore, introduces the concept of combining planar and nonplanar aromatic motifs in the design of π-conjugated discrete oligomers, establishes synthetic feasibility of such hybrid materials, reports on their photophysical properties that is anticipated to have significant implications for future research targets, and features the discovery that corannulene derivatives can exhibit excellent nonlinear optical activity when extended through π-bridges.

  19. α-Synuclein Oligomers Induced by Docosahexaenoic Acid Affect Membrane Integrity

    PubMed Central

    Fecchio, Chiara; De Franceschi, Giorgia; Relini, Annalisa; Greggio, Elisa; Dalla Serra, Mauro; Bubacco, Luigi; Polverino de Laureto, Patrizia

    2013-01-01

    A key feature of Parkinson disease is the aggregation of α-synuclein and its intracellular deposition in fibrillar form. Increasing evidence suggests that the pathogenicity of α-synuclein is correlated with the activity of oligomers formed in the early stages of its aggregation process. Oligomers toxicity seems to be associated with both their ability to bind and affect the integrity of lipid membranes. Previously, we demonstrated that α-synuclein forms oligomeric species in the presence of docosahexaenoic acid and that these species are toxic to cells. Here we studied how interaction of these oligomers with membranes results in cell toxicity, using cellular membrane-mimetic and cell model systems. We found that α-synuclein oligomers are able to interact with large and small unilamellar negatively charged vesicles acquiring an increased amount of α-helical structure, which induces small molecules release. We explored the possibility that oligomers effects on membranes could be due to pore formation, to a detergent-like effect or to fibril growth on the membrane. Our biophysical and cellular findings are consistent with a model where α-synuclein oligomers are embedded into the lipid bilayer causing transient alteration of membrane permeability. PMID:24312431

  20. Effect of Zn(2+) ions on the assembly of amylin oligomers: insight into the molecular mechanisms.

    PubMed

    Wineman-Fisher, Vered; Miller, Yifat

    2016-08-03

    Amylin is an endocrine hormone and is a member of the family of amyloid peptides and proteins that emerge as potential scaffolds by self-assembly processes. Zn(2+) ions can bind to amylin peptides to form self-assembled Zn(2+)-amylin oligomers. In the current work the binding sites of Zn(2+) ions in the self-assembled amylin oligomers at various concentrations of zinc have been investigated. Our results yield two conclusions. First, in the absence of Zn(2+) ions polymorphic states (i.e. various classes of amylin oligomers) are obtained, but when Zn(2+) ions bind to amylin peptides to form Zn(2+)-amylin oligomers, the polymorphism is decreased, i.e. Zn(2+) ions bind only to specific classes of amylin. At low concentrations of Zn(2+) ions the polymorphism is smaller than at high concentrations. Second, the structural features of the self-assembled amylin oligomers are not affected by the presence of Zn(2+) ions. This study proposes new molecular mechanisms of the self-assembly of Zn(2+)-amylin oligomers.

  1. Cyclen-based lipidic oligomers as potential gene delivery vehicles.

    PubMed

    Yi, Wen-Jing; Zhang, Qin-Fang; Zhang, Ji; Liu, Qiang; Ren, Laifeng; Chen, Qian-Ming; Guo, Liandi; Yu, Xiao-Qi

    2014-03-01

    A series of cyclen-based linear oligomers bearing hydrophobic long chains (lipopolymers Cy-LC, where Cy and LC represent cyclen-based linear backbone and hydrophobic long chain substituents, respectively) were designed and synthesized. The effects of type and degree of substitution (DS) of hydrophobic long chains on the transfection efficiency were systematically studied. The nitrogen atoms with relatively strong basicity on the cyclen ensure their good DNA binding ability, which was confirmed by gel retardation and ethidium bromide exclusion assays. Lipopolyplexes could be formed as nanoparticles with suitable sizes and zeta potentials for gene transfection. In vitro gene delivery experiments revealed that the linoleic acid (LIN) substituted material Cy-LIN has better transfection efficiency than 25 kDa polyethylenimine in the absence or in the presence of serum. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and hemolysis assays showed low cytotoxicity and good biocompatibility of the lipopolyplexes. Fluorescent labeled DNA was used to study the cellular uptake and intracellular distribution of transfected DNA. Flow cytometry results suggested that a long chain is necessary for efficient cellular uptake, and images from confocal laser scanning microscopy showed that after 4h transfection, most of the fluorescent labeled DNA accumulated in the perinuclear region, which was required for efficient gene expression. Moreover, it was also found that the DS of the hydrophobic moiety can adjust the balance between DNA binding ability and dissociation of polyplexes, significantly affecting the transfection efficiency.

  2. Synthesis and Characterization of Poly (Arylene Ether Benzimidazole) Oligomers

    NASA Technical Reports Server (NTRS)

    Leonard, Michael J.

    1995-01-01

    Several poly(arylene ether benzimidazole) oligomers were prepared by the nucleophilic aromatic substitution reaction of a bisphenol benzimidazole and various alkyl-substituted aromatic bisphenols with an activated aromatic dihalide in N, N-dimethylacetarnide. Moderate to high molecular weight terpolymers were obtained in all cases, as shown by their inherent viscosities, which ranged from 0.50 to 0.87 dL g(sup -1). Glass transition temperatures (T(sub g)s) of polymer powders ranged from 267-280 C. Air-dried unoriented thin film T(sub g)s were markedly lower than those of the powders, whereas T(sub g)s of films dried in a nitrogen atmosphere were identical to those of the corresponding powders. In addition, air-dried films were dark amber and brittle, whereas nitrogen-dried films were yellow and creasable. Nitrogen-dried films showed slightly higher thin-film tensile properties than the air-dried films, as well.

  3. Amyloid beta oligomers induce impairment of neuronal insulin receptors.

    PubMed

    Zhao, Wei-Qin; De Felice, Fernanda G; Fernandez, Sara; Chen, Hui; Lambert, Mary P; Quon, Michael J; Krafft, Grant A; Klein, William L

    2008-01-01

    Recent studies have indicated an association between Alzheimer's disease (AD) and central nervous system (CNS) insulin resistance. However, the cellular mechanisms underlying the link between these two pathologies have not been elucidated. Here we show that signal transduction by neuronal insulin receptors (IR) is strikingly sensitive to disruption by soluble Abeta oligomers (also known as ADDLs). ADDLs are known to accumulate in AD brain and have recently been implicated as primary candidates for initiating deterioration of synapse function, composition, and structure. Using mature cultures of hippocampal neurons, a preferred model for studies of synaptic cell biology, we found that ADDLs caused a rapid and substantial loss of neuronal surface IRs specifically on dendrites bound by ADDLs. Removal of dendritic IRs was associated with increased receptor immunoreactivity in the cell body, indicating redistribution of the receptors. The neuronal response to insulin, measured by evoked IR tyrosine autophosphorylation, was greatly inhibited by ADDLs. Inhibition also was seen with added glutamate or potassium-induced depolarization. The effects on IR function were completely blocked by NMDA receptor antagonists, tetrodotoxin, and calcium chelator BAPTA-AM. Downstream from the IR, ADDLs induced a phosphorylation of Akt at serine473, a modification associated with neurodegenerative and insulin resistance diseases. These results identify novel factors that affect neuronal IR signaling and suggest that insulin resistance in AD brain is a response to ADDLs, which disrupt insulin signaling and may cause a brain-specific form of diabetes as part of an overall pathogenic impact on CNS synapses.

  4. Structure and stability of oligomer/α-cyclodextrin inclusion complexes.

    NASA Astrophysics Data System (ADS)

    Hunt, Marcus; Villar, Silvia; Gomez, Marian; Tonelli, Alan; Balik, Maury

    2007-03-01

    Cyclomaltohexaose (α-cyclodextrin, α-CD) can form inclusion complexes (ICs) with polymer molecules in the columnar crystal in which α-CD molecules stack to form a molecular tube. Complementary water vapor sorption and wide-angle X-ray diffractomery (WAXD) were performed on oligomer/α-CD ICs to probe their structures and stabilities. To discern the effect of guest molecule hydrophobicity on water adsorption isotherms, polyethylene glycol (PEG, MW = 600 g/mol) and hexatriacontane (HTC) guests were used. Sorption isotherms for PEG/α-CD IC are similar to those obtained for pure α-CD and PEG, suggesting the presence of dethreaded PEG in the sample. WAXD collected before and after water vapor sorption of PEG/α-CD IC indicated a partial conversion from columnar to cage crystal structure, the thermodynamically preferred structure for pure α-CD, due to dethreading of PEG. This behavior does not occur for HTC/α-CD IC. Sorption isotherms collected at 20, 30, 40 and 50 C allowed the calculation of differential heats of adsorption and integral entropies of adsorbed water, while solid-state ^13C NMR suggested a dramatic increase in HTC and α-CD mobilities upon complexation.

  5. Unique copper-induced oligomers mediate alpha-synuclein toxicity.

    PubMed

    Wright, Josephine A; Wang, Xiaoyan; Brown, David R

    2009-08-01

    Parkinson's disease and a number of other neurodegenerative diseases have been linked to either genetic mutations in the alpha-synuclein gene or show evidence of aggregates of the alpha-synuclein protein, sometimes in the form of Lewy bodies. There currently is no clear evidence of a distinct neurotoxic species of alpha-synuclein to explain the death of neurons in these diseases. We undertook to assess the toxicity of alpha-synuclein via exogenous application in cell culture. Initially, we showed that only aggregated alpha-synuclein is neurotoxic and requires the presence copper but not iron. Other members of the synuclein family showed no toxicity in any form and inherited point mutations did not alter the effective toxic concentration of alpha-synuclein. Through protein fractionation techniques, we were able to isolate an oligomeric species responsible for the toxicity of alpha-synuclein. This oligomeric species has a unique stellate appearance under EM and again, requires association with copper to induce cell death. The results allow us to suggest that the toxic species of alpha-synuclein in vivo could possibly be these stellate oligomers and not fibrils. Our data provide a link between the recently noted association of copper and alpha-synuclein and a potential role for the combination in causing neurodegeneration.

  6. GeneGenie: optimized oligomer design for directed evolution

    PubMed Central

    Swainston, Neil; Currin, Andrew; Day, Philip J.; Kell, Douglas B.

    2014-01-01

    GeneGenie, a new online tool available at http://www.gene-genie.org, is introduced to support the design and self-assembly of synthetic genes and constructs. GeneGenie allows for the design of oligonucleotide cohorts encoding the gene sequence optimized for expression in any suitable host through an intuitive, easy-to-use web interface. The tool ensures consistent oligomer overlapping melting temperatures, minimizes the likelihood of misannealing, optimizes codon usage for expression in a selected host, allows for specification of forward and reverse cloning sequences (for downstream ligation) and also provides support for mutagenesis or directed evolution studies. Directed evolution studies are enabled through the construction of variant libraries via the optional specification of ‘variant codons’, containing mixtures of bases, at any position. For example, specifying the variant codon TNT (where N is any nucleotide) will generate an equimolar mixture of the codons TAT, TCT, TGT and TTT at that position, encoding a mixture of the amino acids Tyr, Ser, Cys and Phe. This facility is demonstrated through the use of GeneGenie to develop and synthesize a library of enhanced green fluorescent protein variants. PMID:24782527

  7. Oligomer Formation of Tau Protein Hyperphosphorylated in Cells*

    PubMed Central

    Tepper, Katharina; Biernat, Jacek; Kumar, Satish; Wegmann, Susanne; Timm, Thomas; Hübschmann, Sabrina; Redecke, Lars; Mandelkow, Eva-Maria; Müller, Daniel J.; Mandelkow, Eckhard

    2014-01-01

    Abnormal phosphorylation (“hyperphosphorylation”) and aggregation of Tau protein are hallmarks of Alzheimer disease and other tauopathies, but their causative connection is still a matter of debate. Tau with Alzheimer-like phosphorylation is also present in hibernating animals, mitosis, or during embryonic development, without leading to pathophysiology or neurodegeneration. Thus, the role of phosphorylation and the distinction between physiological and pathological phosphorylation needs to be further refined. So far, the systematic investigation of highly phosphorylated Tau was difficult because a reliable method of preparing reproducible quantities was not available. Here, we generated full-length Tau (2N4R) in Sf9 cells in a well defined phosphorylation state containing up to ∼20 phosphates as judged by mass spectrometry and Western blotting with phospho-specific antibodies. Despite the high concentration in living Sf9 cells (estimated ∼230 μm) and high phosphorylation, the protein was not aggregated. However, after purification, the highly phosphorylated protein readily formed oligomers, whereas fibrils were observed only rarely. Exposure of mature primary neuronal cultures to oligomeric phospho-Tau caused reduction of spine density on dendrites but did not change the overall cell viability. PMID:25339173

  8. Carboxybetaine methacrylate oligomer modified nylon for circulating tumor cells capture.

    PubMed

    Dong, Chaoqun; Wang, Huiyu; Zhang, Zhuo; Zhang, Tao; Liu, Baorui

    2014-10-15

    Circulating tumor cells (CTC) capture is one of the most effective approaches in diagnosis and treatment of cancers in the field of personalized cancer medicine. In our study, zwitterionic carboxybetaine methacrylate (CBMA) oligomers were grafted onto nylon via atomic transfer random polymerization (ATRP) which would serve as a novel material for the development of convenient CTC capture interventional medical devices. The chemical, physical and biological properties of pristine and modified nylon surfaces were assessed by Fourier transform infrared spectra, atomic force microscope, water contact angle measurements, X-ray photoelectron spectroscopy, protein adsorption, platelet adhesion, and plasma recalcification time (PRT) determinations, etc. The results, including the significant decrease of proteins adsorption and platelets adhesion, as well as prolonged PRTs demonstrated the extraordinary biocompatibility and blood compatibility of the modified surface. Furthermore, we showed that upon immobilization of anti-epithelial cell adhesion molecular (anti-EpCAM) antibody onto the CBMA moiety, the modified nylon surface can selectively capture EpCAM positive tumor cells from blood with high efficiency, indicating the potential of the modified nylon in the manufacture of convenient interventional CTC capture medical devices.

  9. Cloud forming potential of oligomers relevant to secondary organic aerosols

    NASA Astrophysics Data System (ADS)

    Xu, Wen; Guo, Song; Gomez-Hernandez, Mario; Zamora, Misti L.; Secrest, Jeremiah; Marrero-Ortiz, Wilmarie; Zhang, Annie L.; Collins, Don R.; Zhang, Renyi

    2014-09-01

    The hygroscopic growth factor (HGF) and cloud condensation nuclei (CCN) activity are measured for surrogates that mimic atmospherically relevant oligomers, including glyoxal trimer dihydrate, methyl glyoxal trimer dihydrate, sucrose, methyl glyoxal mixtures with sulfuric acid and glycolic acid, and 2,4-hexandienal mixtures with sulfuric acid and glycolic acid. For the single-component aerosols, the measured HGF ranges from 1.3 to 1.4 at a relative humidity of 90%, and the hygroscopicity parameter (κ) is in the range of 0.06 to 0.19 on the basis of the measured CCN activity and 0.13 to 0.22 on the basis of the measured HGF, compared to the calculated values of 0.08 to 0.16. Large differences exist in the κ values derived using the measured HGF and CCN data for the multi-component aerosols. Our results reveal that, in contrast to the oxidation process, oligomerization decreases particle hygroscopicity and CCN activity and provides guidance for analyzing the organic species in ambient aerosols.

  10. Intracellular soluble α‐synuclein oligomers reduce pyramidal cell excitability

    PubMed Central

    Kaufmann, Timothy J.; Harrison, Paul M.; Richardson, Magnus J. E.; Pinheiro, Teresa J. T.

    2016-01-01

    Key points The presynaptic protein α‐synuclein forms aggregates during Parkinson's disease.Accumulating evidence suggests that the small soluble oligomers of α‐synuclein are more toxic than the larger aggregates appearing later in the disease.The link between oligomer toxicity and structure still remains unclear.In the present study, we have produced two structurally‐defined oligomers that have a similar morphology but differ in secondary structure.These oligomers were introduced into neocortical pyramidal cells during whole‐cell recording and, using a combination of experimentation and modelling, electrophysiological parameters were extracted.Both oligomeric species had similar effects on neuronal properties reducing input resistance, time constant and increasing capacitance. The net effect was a marked reduction in neuronal excitability that could impact on network activity. Abstract The presynaptic protein α‐synuclein (αSyn) aggregates during Parkinson's disease (PD) to form large proteinaceous amyloid plaques, the spread of which throughout the brain clinically defines the severity of the disease. During early stages of aggregation, αSyn forms soluble annular oligomers that show greater toxicity than much larger fibrils. These oligomers produce toxicity via a number of possible mechanisms, including the production of pore‐forming complexes that permeabilize membranes. In the present study, two well‐defined species of soluble αSyn oligomers were produced by different protocols: by polymerization of monomer and by sonication of fibrils. The two oligomeric species produced were morphologically similar, with both having an annular structure and consisting of approximately the same number of monomer subunits, although they differed in their secondary structure. Oligomeric and monomeric αSyn were injected directly into the soma of pyramidal neurons in mouse neocortical brain slices during whole‐cell patch clamp recording. Using a combined

  11. Characteristic Fragmentation of Polysiloxane Monolayer Films by Bombardment with Monatomic and Polyatomic Primary Ions in TOF-SIMS

    NASA Astrophysics Data System (ADS)

    Moon, Hye Kyoung; Wells, David D.; Gardella, Joseph A.

    2012-01-01

    This study reports the characteristic fragmentation patterns from two polysiloxane polymers that form ordered overlayer on silver substrates. Results are compared for the bombardment of various monatomic and polyatomic projectiles of Cs+, C{60/+} (10 keV), Bi{1/+}, and Bi{3/+} (25 keV) in the high mass range time-of-flight secondary ion mass spectrometry (TOF-SIMS) spectra. Results are reported from sub-monolayer (solution cast) coverages of poly(dimethylsiloxane)s with the number average molecular weights (Mn) of 2200 and 6140 Da, respectively, and Langmuir-Blodgett monolayers of poly(methylphenylsiloxane) with molecular weights (MW) from 600 and 1000 Da. For each film, Bi projectiles resulted in the emission of positive silver cluster ions from the substrate under the polymer overlayer and peaks corresponding to silver cluster ions with larger mass were observed by impact of polyatomic 25 keV Bi{3/+} projectiles. In addition, depending on the change of energy of Bi{3/+}, a different pattern of fragments was observed. With Cs+ and C{60/+} impact, however, the emission of silver cluster ions was not detected. In the case of C{60/+} impact for PDMS-6140, peaks corresponding to silver-cationized intact oligomers were not observed. In this paper, these results are explained by the possible bombardment mechanism for each projectile, based on its mass, energy, and split trajectories of the component atoms under the polyatomic impact.

  12. Characteristic fragmentation of polysiloxane monolayer films by bombardment with monatomic and polyatomic primary ions in TOF-SIMS.

    PubMed

    Moon, Hye Kyoung; Wells, David D; Gardella, Joseph A

    2012-01-01

    This study reports the characteristic fragmentation patterns from two polysiloxane polymers that form ordered overlayer on silver substrates. Results are compared for the bombardment of various monatomic and polyatomic projectiles of Cs(+), C(60)(+) (10 keV), Bi(1)(+), and Bi(3)(+) (25 keV) in the high mass range time-of-flight secondary ion mass spectrometry (TOF-SIMS) spectra. Results are reported from sub-monolayer (solution cast) coverages of poly(dimethylsiloxane)s with the number average molecular weights (M(n)) of 2200 and 6140 Da, respectively, and Langmuir-Blodgett monolayers of poly(methylphenylsiloxane) with molecular weights (MW) from 600 and 1000 Da. For each film, Bi projectiles resulted in the emission of positive silver cluster ions from the substrate under the polymer overlayer and peaks corresponding to silver cluster ions with larger mass were observed by impact of polyatomic 25 keV Bi(3)(+) projectiles. In addition, depending on the change of energy of Bi (3) (+) , a different pattern of fragments was observed. With Cs(+) and C(60)(+) impact, however, the emission of silver cluster ions was not detected. In the case of C(60)(+) impact for PDMS-6140, peaks corresponding to silver-cationized intact oligomers were not observed. In this paper, these results are explained by the possible bombardment mechanism for each projectile, based on its mass, energy, and split trajectories of the component atoms under the polyatomic impact.

  13. Realization of continuous Zachariasen carbon monolayer.

    PubMed

    Joo, Won-Jae; Lee, Jae-Hyun; Jang, Yamujin; Kang, Seog-Gyun; Kwon, Young-Nam; Chung, Jaegwan; Lee, Sangyeob; Kim, Changhyun; Kim, Tae-Hoon; Yang, Cheol-Woong; Kim, Un Jeong; Choi, Byoung Lyong; Whang, Dongmok; Hwang, Sung-Woo

    2017-02-01

    Rapid progress in two-dimensional (2D) crystalline materials has recently enabled a range of device possibilities. These possibilities may be further expanded through the development of advanced 2D glass materials. Zachariasen carbon monolayer, a novel amorphous 2D carbon allotrope, was successfully synthesized on germanium surface. The one-atom-thick continuous amorphous layer, in which the in-plane carbon network was fully sp(2)-hybridized, was achieved at high temperatures (>900°C) and a controlled growth rate. We verified that the charge carriers within the Zachariasen carbon monolayer are strongly localized to display Anderson insulating behavior and a large negative magnetoresistance. This new 2D glass also exhibited a unique ability as an atom-thick interface layer, allowing the deposition of an atomically flat dielectric film. It can be adopted in conventional semiconductor and display processing or used in the fabrication of flexible devices consisting of thin inorganic layers.

  14. Ground state structures in ferrofluid monolayers.

    PubMed

    Prokopieva, Taisia A; Danilov, Victor A; Kantorovich, Sofia S; Holm, Christian

    2009-09-01

    A combination of analytical calculations and Monte Carlo simulations is used to find the ground state structures in monodisperse ferrofluid monolayers. Taking into account the magnetic dipole-dipole interaction between all particles in the system we observe different topological structures that are likely to exist at low temperatures. The most energetically favored structures we find are rings, embedded rings, and rings side by side, and we are able to derive analytical expressions for the total energy of these structures. A detailed analysis of embedded rings and rings side by side shows that the interring interactions are negligible. We furthermore find that a single ideal ring is the ground state structure for a ferrofluid monolayer. We compared our theoretical predictions to the results of simulated annealing data and found them to be in excellent agreement.

  15. Piezoelectric monolayers as nonlinear energy harvesters.

    PubMed

    López-Suárez, Miquel; Pruneda, Miguel; Abadal, Gabriel; Rurali, Riccardo

    2014-05-02

    We study the dynamics of h-BN monolayers by first performing ab-initio calculations of the deformation potential energy and then solving numerically a Langevine-type equation to explore their use in nonlinear vibration energy harvesting devices. An applied compressive strain is used to drive the system into a nonlinear bistable regime, where quasi-harmonic vibrations are combined with low-frequency swings between the minima of a double-well potential. Due to its intrinsic piezoelectric response, the nonlinear mechanical harvester naturally provides an electrical power that is readily available or can be stored by simply contacting the monolayer at its ends. Engineering the induced nonlinearity, a 20 nm2 device is predicted to harvest an electrical power of up to 0.18 pW for a noisy vibration of 5 pN.

  16. Collective cell motion in endothelial monolayers

    PubMed Central

    Szabó, A.; Ünnep, R.; Méhes, E.; Twal, W. O.; Argraves, S. W.; Cao, Y.; Czirók, A.

    2011-01-01

    Collective cell motility is an important aspect of several developmental and pathophysiological processes. Despite its importance, the mechanisms that allow cells to be both motile and adhere to one another are poorly understood. In this study we establish statistical properties of the random streaming behavior of endothelial monolayer cultures. To understand the reported empirical findings, we expand the widely used cellular Potts model to include active cell motility. For spontaneous directed motility we assume a positive feedback between cell displacements and cell polarity. The resulting model is studied with computer simulations, and is shown to exhibit behavior compatible with experimental findings. In particular, in monolayer cultures both the speed and persistence of cell motion decreases, transient cell chains move together as groups, and velocity correlations extend over several cell diameters. As active cell motility is ubiquitous both in vitro and in vivo, our model is expected to be a generally applicable representation of cellular behavior. PMID:21076204

  17. Visualizing Individual Nitrogen Dopants in Monolayer Graphene

    SciTech Connect

    L Zhao; R He; K Rim; T Schiros; K Kim; H Zhou; C Gutierrez; S Chockalingam; C Arguello; et al.

    2011-12-31

    In monolayer graphene, substitutional doping during growth can be used to alter its electronic properties. We used scanning tunneling microscopy, Raman spectroscopy, x-ray spectroscopy, and first principles calculations to characterize individual nitrogen dopants in monolayer graphene grown on a copper substrate. Individual nitrogen atoms were incorporated as graphitic dopants, and a fraction of the extra electron on each nitrogen atom was delocalized into the graphene lattice. The electronic structure of nitrogen-doped graphene was strongly modified only within a few lattice spacings of the site of the nitrogen dopant. These findings show that chemical doping is a promising route to achieving high-quality graphene films with a large carrier concentration.

  18. Fracture characteristics of monolayer CVD-graphene.

    PubMed

    Hwangbo, Yun; Lee, Choong-Kwang; Kim, Sang-Min; Kim, Jae-Hyun; Kim, Kwang-Seop; Jang, Bongkyun; Lee, Hak-Joo; Lee, Seoung-Ki; Kim, Seong-Su; Ahn, Jong-Hyun; Lee, Seung-Mo

    2014-03-24

    We have observed and analyzed the fracture characteristics of the monolayer CVD-graphene using pressure bulge testing setup. The monolayer CVD-graphene has appeared to undergo environmentally assisted subcritical crack growth in room condition, i.e. stress corrosion cracking arising from the adsorption of water vapor on the graphene and the subsequent chemical reactions. The crack propagation in graphene has appeared to be able to be reasonably tamed by adjusting applied humidity and stress. The fracture toughness, describing the ability of a material containing inherent flaws to resist catastrophic failure, of the CVD-graphene has turned out to be exceptionally high, as compared to other carbon based 3D materials. These results imply that the CVD-graphene could be an ideal candidate as a structural material notwithstanding environmental susceptibility. In addition, the measurements reported here suggest that specific non-continuum fracture behaviors occurring in 2D monoatomic structures can be macroscopically well visualized and characterized.

  19. Fracture Characteristics of Monolayer CVD-Graphene

    NASA Astrophysics Data System (ADS)

    Hwangbo, Yun; Lee, Choong-Kwang; Kim, Sang-Min; Kim, Jae-Hyun; Kim, Kwang-Seop; Jang, Bongkyun; Lee, Hak-Joo; Lee, Seoung-Ki; Kim, Seong-Su; Ahn, Jong-Hyun; Lee, Seung-Mo

    2014-03-01

    We have observed and analyzed the fracture characteristics of the monolayer CVD-graphene using pressure bulge testing setup. The monolayer CVD-graphene has appeared to undergo environmentally assisted subcritical crack growth in room condition, i.e. stress corrosion cracking arising from the adsorption of water vapor on the graphene and the subsequent chemical reactions. The crack propagation in graphene has appeared to be able to be reasonably tamed by adjusting applied humidity and stress. The fracture toughness, describing the ability of a material containing inherent flaws to resist catastrophic failure, of the CVD-graphene has turned out to be exceptionally high, as compared to other carbon based 3D materials. These results imply that the CVD-graphene could be an ideal candidate as a structural material notwithstanding environmental susceptibility. In addition, the measurements reported here suggest that specific non-continuum fracture behaviors occurring in 2D monoatomic structures can be macroscopically well visualized and characterized.

  20. Realization of continuous Zachariasen carbon monolayer

    PubMed Central

    Joo, Won-Jae; Lee, Jae-Hyun; Jang, Yamujin; Kang, Seog-Gyun; Kwon, Young-Nam; Chung, Jaegwan; Lee, Sangyeob; Kim, Changhyun; Kim, Tae-Hoon; Yang, Cheol-Woong; Kim, Un Jeong; Choi, Byoung Lyong; Whang, Dongmok; Hwang, Sung-Woo

    2017-01-01

    Rapid progress in two-dimensional (2D) crystalline materials has recently enabled a range of device possibilities. These possibilities may be further expanded through the development of advanced 2D glass materials. Zachariasen carbon monolayer, a novel amorphous 2D carbon allotrope, was successfully synthesized on germanium surface. The one-atom-thick continuous amorphous layer, in which the in-plane carbon network was fully sp2-hybridized, was achieved at high temperatures (>900°C) and a controlled growth rate. We verified that the charge carriers within the Zachariasen carbon monolayer are strongly localized to display Anderson insulating behavior and a large negative magnetoresistance. This new 2D glass also exhibited a unique ability as an atom-thick interface layer, allowing the deposition of an atomically flat dielectric film. It can be adopted in conventional semiconductor and display processing or used in the fabrication of flexible devices consisting of thin inorganic layers. PMID:28246635

  1. Fracture Characteristics of Monolayer CVD-Graphene

    PubMed Central

    Hwangbo, Yun; Lee, Choong-Kwang; Kim, Sang-Min; Kim, Jae-Hyun; Kim, Kwang-Seop; Jang, Bongkyun; Lee, Hak-Joo; Lee, Seoung-Ki; Kim, Seong-Su; Ahn, Jong-Hyun; Lee, Seung-Mo

    2014-01-01

    We have observed and analyzed the fracture characteristics of the monolayer CVD-graphene using pressure bulge testing setup. The monolayer CVD-graphene has appeared to undergo environmentally assisted subcritical crack growth in room condition, i.e. stress corrosion cracking arising from the adsorption of water vapor on the graphene and the subsequent chemical reactions. The crack propagation in graphene has appeared to be able to be reasonably tamed by adjusting applied humidity and stress. The fracture toughness, describing the ability of a material containing inherent flaws to resist catastrophic failure, of the CVD-graphene has turned out to be exceptionally high, as compared to other carbon based 3D materials. These results imply that the CVD-graphene could be an ideal candidate as a structural material notwithstanding environmental susceptibility. In addition, the measurements reported here suggest that specific non-continuum fracture behaviors occurring in 2D monoatomic structures can be macroscopically well visualized and characterized. PMID:24657996

  2. Solvent free low-melt viscosity imide oligomers and thermosetting polymide composites

    NASA Technical Reports Server (NTRS)

    Chuang, Chun-Hua (Inventor)

    2012-01-01

    .[.This invention relates to the composition and a solvent-free process for preparing novel imide oligomers and polymers specifically formulated with effective amounts of a dianhydride such as 2,3,3',4-biphenyltetra carboxylic dianydride (a-BPDA), at least one aromatic diamine and an endcapped of 4-phenylethynylphthalic anhydride (PEPA) or nadic anhydride to produce imide oligomers that possess a low-melt viscosity of 1-60 poise at 260-280.degree. C. When the imide oligomer melt is cured at about 371.degree. C. in a press or autoclave under 100-500 psi, the melt resulted in a thermoset polyimide having a glass transition temperature (T.sub.g) equal to and above 310.degree. C. A novel feature of this process is that the monomers; namely the dianhydrides, diamines and the endcaps, are melt processable to form imide oligomers at temperatures ranging between 232-280.degree. C. (450-535.degree. F.) without any solvent. These low-melt imide oligomers can be easily processed by resin transfer molding (RTM), vacuum-assisted resin transfer molding (VARTM) or the resin infusion process with fiber preforms e.g. carbon, glass or quartz preforms to produce polyimide matrix composites with 288-343.degree. C. (550-650.degree. F.) high temperature performance capability..]. .Iadd.This invention relates to compositions and a solvent-free reaction process for preparing imide oligomers and polymers specifically derived from effective amounts of dianhydrides such as 2,3,3',4'-biphenyltetracarboxylic dianhydride (a-BPDA), at least one aromatic polyamine and an end-cap such as 4-phenylethynyphthalic anhydride (PEPA) or nadic anhydride to produce imide oligomers that possess a low-melt viscosity of 1-60 poise at 260.degree. C.-280.degree. C..Iaddend.

  3. Novel demonstration of amyloid-β oligomers in sporadic inclusion-body myositis muscle fibers.

    PubMed

    Nogalska, Anna; D'Agostino, Carla; Engel, W King; Klein, William L; Askanas, Valerie

    2010-11-01

    Accumulation of amyloid-β (Aβ) within muscle fibers has been considered an upstream step in the development of the s-IBM pathologic phenotype. Aβ42, which is considered more cytotoxic than Aβ40 and has a higher propensity to oligomerize, is preferentially increased in s-IBM muscle fibers. In Alzheimer disease (AD), low-molecular weight Aβ oligomers and toxic oligomers, also referred to as "Aβ-Derived Diffusible Ligands" (ADDLs), are considered strongly cytotoxic and proposed to play an important pathogenic role. ADDLs have been shown to be increased in AD brain. We now report for the first time that in s-IBM muscle biopsies Aβ-dimer, -trimer, and -tetramer are identifiable by immunoblots. While all the s-IBM samples we studied had Aβ-oligomers, their molecular weights and intensity varied between the patient samples. None of the control muscle biopsies had Aβ oligomers. Dot-immunoblots using highly specific anti-ADDL monoclonal antibodies also showed highly increased ADDLs in all s-IBM biopsies studied, while controls were negative. By immunofluorescence, in some of the abnormal s-IBM muscle fibers ADDLs were accumulated in the form of plaque-like inclusions, and were often increased diffusely in very small fibers. Normal and disease-controls were negative. By gold-immuno-electron microscopy, ADDL-immunoreactivities were in close proximity to 6-10 nm amyloid-like fibrils, and also were immunodecorating amorphous and floccular material. In cultured human muscle fibers, we found that inhibition of autophagy led to the accumulation of Aβ oligomers. This novel demonstration of Aβ42 oligomers in s-IBM muscle biopsy provides additional evidence that intra-muscle fiber accumulation of Aβ42 oligomers in s-IBM may contribute importantly to s-IBM pathogenic cascade.

  4. Self-propagative replication of Aβ oligomers suggests potential transmissibility in Alzheimer disease.

    PubMed

    Kumar, Amit; Pate, Kayla M; Moss, Melissa A; Dean, Dexter N; Rangachari, Vijayaraghavan

    2014-01-01

    The aggregation of amyloid-β (Aβ) peptide and its deposition in parts of the brain form the central processes in the etiology of Alzheimer disease (AD). The low-molecular weight oligomers of Aβ aggregates (2 to 30 mers) are known to be the primary neurotoxic agents whose mechanisms of cellular toxicity and synaptic dysfunction have received substantial attention in the recent years. However, how these toxic agents proliferate and induce widespread amyloid deposition throughout the brain, and what mechanism is involved in the amplification and propagation of toxic oligomer species, are far from clear. Emerging evidence based on transgenic mice models indicates a transmissible nature of Aβ aggregates and implicates a prion-like mechanism of oligomer propagation, which manifests as the dissemination and proliferation of Aβ toxicity. Despite accumulating evidence in support of a transmissible nature of Aβ aggregates, a clear, molecular-level understanding of this intriguing mechanism is lacking. Recently, we reported the characterization of unique replicating oligomers of Aβ42 (12-24 mers) in vitro called Large Fatty Acid-derived Oligomers (LFAOs) (Kumar et al., 2012, J. Biol. Chem). In the current report, we establish that LFAOs possess physiological activity by activating NF-κB in human neuroblastoma cells, and determine the experimental parameters that control the efficiency of LFAO replication by self-propagation. These findings constitute the first detailed report on monomer - oligomer lateral propagation reactions that may constitute potential mechanism governing transmissibility among Aβ oligomers. These data support the previous reports on transmissible mechanisms observed in transgenic animal models.

  5. Discrete Molecular Dynamics Study of Oligomer Formation by N-Terminally Truncated Amyloid β-Protein

    PubMed Central

    Meral, Derya; Urbanc, Brigita

    2013-01-01

    In Alzheimer’s disease (AD), amyloid β-protein (Aβ) self–assembles into toxic oligomers. Of the two predominant Aβ alloforms, Aβ1–40 and Aβ1–42, the latter is particularly strongly linked to AD. N-terminally truncated and pyroglutamated Aβ peptides were recently shown to seed Aβ aggregation and contribute significantly to Aβ–mediated toxicity, yet their folding and assembly were not explored computationally. Discrete molecular dynamics (DMD) approach previously captured in vitro–derived distinct Aβ1–40 and Aβ1–42 oligomer size distributions and predicted that the more toxic Aβ1–42 oligomers had more flexible and solvent exposed N-termini than Aβ1–40 oligomers. Here, we examined oligomer formation of Aβ3–40, Aβ3–42, Aβ11–40, and Aβ11–42 by the DMD approach. The four N-terminally truncated peptides showed increased oligomerization propensity relative to the full–length peptides, consistent with in vitro findings. Conformations formed by Aβ3–40/42 had significantly more flexible and solvent–exposed N-termini than Aβ1–40/42 conformations. In contrast, in Aβ11–40/42 conformations the N-termini formed more contacts and were less accessible to the solvent. The compactness of the Aβ11–40/42 conformations was in part facilitated by Val12. Two single amino acid substitutions that reduced and abolished hydrophobicity at position 12, respectively, resulted in a proportionally increased structural variability. Our results suggest that Aβ11–40 and Aβ11–42 oligomers might be less toxic than Aβ1–40 and Aβ1–42 oligomers and offer a plausible explanation for the experimentally–observed increased toxicity of Aβ3–40 and Aβ3–42 and their pyroglutamated forms. PMID:23500806

  6. Humanin Specifically Interacts with Amyloid-β Oligomers and Counteracts Their in vivo Toxicity.

    PubMed

    Romeo, Margherita; Stravalaci, Matteo; Beeg, Marten; Rossi, Alessandro; Fiordaliso, Fabio; Corbelli, Alessandro; Salmona, Mario; Gobbi, Marco; Cagnotto, Alfredo; Diomede, Luisa

    2017-03-06

    The 24-residue peptide humanin (HN) has been proposed as peptide-based inhibitors able to interact directly with amyloid-β (Aβ) oligomers and interfere with the formation and/or biological properties of toxic Aβ species. When administered exogenously HN, or its synthetic S14G-derivative (HNG), exerted multiple cytoprotective effects, counteracting the Aβ-induced toxicity. Whether these peptides interact directly with Aβ, particularly with the soluble oligomeric assemblies, remains largely unknown. We here investigated the ability of HN and HNG to interact directly with highly aggregating Aβ42, and interfere with the formation and toxicity of its oligomers. Experiments were run in cell-free conditions and in vivo in a transgenic C. elegans strain in which the Aβ toxicity was specifically due to oligomeric species. Thioflavin-T assay indicated that both HN and HNG delay the formation and reduce the final amount of Aβ42 fibrils. In vitro surface plasmon resonance studies indicated that they interact with Aβ42 oligomers favoring the formation of amorphous larger assemblies, observed with turbidity and electron microscopy. In vivo studies indicated that both HN and HNG decrease the relative abundance of A11-positive prefibrillar oligomers as well as OC-positive fibrillar oligomers and had similar protective effects. However, while HN possibly decreased the oligomers by promoting their assembly into larger aggregates, the reduction of oligomers caused by HNG can be ascribed to a marked decrease of the total Aβ levels, likely the consequence of the HNG-induced overexpression of the Aβ-degrading enzyme neprilysin. These findings provide information on the mechanisms underlying the anti-oligomeric effects of HN and HNG and illustrate the role of S14G substitution in regulating the in vivo mechanism of action.

  7. Grafted silane monolayers: reconsideration of growth mechanisms

    NASA Astrophysics Data System (ADS)

    Ivanov, D. A.; Nysten, B.; Jonas, A. M.; Legras, R.

    1998-03-01

    Chemical force microscopy is a new technique devised to image chemical heterogeneities on surfaces. It requires the chemical modification of Atomic Force Microscopy (AFM) tips in order to create chemical probes. In this respect, self-assembled monolayers (SAM) of alkylchlorosilanes are particularly interesting as modifying agents for AFM tips. We report here our results on the kinetics of silanization and on the structure of such SAM's grafted on model surfaces (hydroxylated Si(100) wafers). AFM, contact angle measurements, X-ray reflectivity and X-ray photoelectron spectroscopy were used to characterize SAM's of octadecyltrichlorosilane (OTS) and octadecyldimethylchlorosilane (ODMS) grown from hexadecane and toluene solutions. The mechanism of grafting of OTS follows two stages. The first rapid stage corresponds to the nucleation and growth of island-like monolayer domains. The second slower stage is related to the densification of the monolayer. SAM's of ODMS were found to form thinner layers as compared to OTS, due to their lower grafting density probably resulting in a more disordered state of grafted alkyl chains. We also address the problems concerning the relationships between the quality of final SAM structures and the water content as well as the nature of the solvent used for silanization.

  8. Exploring atomic defects in molybdenum disulphide monolayers

    PubMed Central

    Hong, Jinhua; Hu, Zhixin; Probert, Matt; Li, Kun; Lv, Danhui; Yang, Xinan; Gu, Lin; Mao, Nannan; Feng, Qingliang; Xie, Liming; Zhang, Jin; Wu, Dianzhong; Zhang, Zhiyong; Jin, Chuanhong; Ji, Wei; Zhang, Xixiang; Yuan, Jun; Zhang, Ze

    2015-01-01

    Defects usually play an important role in tailoring various properties of two-dimensional materials. Defects in two-dimensional monolayer molybdenum disulphide may be responsible for large variation of electric and optical properties. Here we present a comprehensive joint experiment–theory investigation of point defects in monolayer molybdenum disulphide prepared by mechanical exfoliation, physical and chemical vapour deposition. Defect species are systematically identified and their concentrations determined by aberration-corrected scanning transmission electron microscopy, and also studied by ab-initio calculation. Defect density up to 3.5 × 1013 cm−2 is found and the dominant category of defects changes from sulphur vacancy in mechanical exfoliation and chemical vapour deposition samples to molybdenum antisite in physical vapour deposition samples. Influence of defects on electronic structure and charge-carrier mobility are predicted by calculation and observed by electric transport measurement. In light of these results, the growth of ultra-high-quality monolayer molybdenum disulphide appears a primary task for the community pursuing high-performance electronic devices. PMID:25695374

  9. Investigation on gallium ions impacting monolayer graphene

    SciTech Connect

    Wu, Xin; Zhao, Haiyan Yan, Dong; Pei, Jiayun

    2015-06-15

    In this paper, the physical phenomena of gallium (Ga{sup +}) ion impacting monolayer graphene in the nanosculpting process are investigated experimentally, and the mechanisms are explained by using Monte Carlo (MC) and molecular dynamics (MD) simulations. Firstly, the MC method is employed to clarify the phenomena happened to the monolayer graphene target under Ga{sup +} ion irradiation. It is found that substrate has strong influence on the damage mode of graphene. The mean sputtering yield of graphene under 30 keV Ga{sup +} ion irradiation is 1.77 and the least ion dose to completely remove carbon atoms in graphene is 21.6 ion/nm{sup 2}. Afterwards, the focused ion beam over 21.6 ion/nm{sup 2} is used for the irradiation on a monolayer graphene supported by SiO2 experimentally, resulting in the nanostructures, i.e., nanodot and nanowire array on the graphene. The performances of the nanostructures are characterized by atomic force microscopy and Raman spectrum. A plasma plume shielding model is put forward to explain the nanosculpting results of graphene under different irradiation parameters. In addition, two damage mechanisms are found existing in the fabrication process of the nanostructures by using empirical MD simulations. The results can help us open the possibilities for better control of nanocarbon devices.

  10. Phase transitions of monolayers on graphene

    NASA Astrophysics Data System (ADS)

    Kahn, Joshua; Dzyubenko, Boris; Vilches, Oscar; Cobden, David

    We have studied physisorbed layers of monatomic and diatomic gases on graphene. We used devices in which few-layer graphene, ranging from monolayer to trilayer, is suspended across a trench between two platinum contacts and are cleaned by thermal and current annealing. We found that the density of adsorbates is revealed by the conductance, similar to the case with nanotubes. The conductance change for a monolayer can be large. On trilayer graphene the adsorbed gases can be seen to exhibit transitions between two-dimensional phases identical to those on bulk graphite, including incommensurate and commensurate solid, fluid and vapor and multiple layers. New features appear in the conductance at the boundaries of the commensurate phase of Kr. We are able to measure single-particle binding energies very accurately and see how it depends on thickness; investigate the effects of changing disorder by gradually current annealing; and search for new phases in the case of monolayer graphene where atoms adsorbed on both sides can interact. We can map out the 2d phase diagrams very quickly by ohmic heating, which gives nearly instantaneous control of the temperature.

  11. Biocompatible Ferromagnetic Cr-Trihalide Monolayers

    NASA Astrophysics Data System (ADS)

    Sun, Qiang

    Cr with an electronic configuration of 3d54s1 possesses the largest atomic magnetic moment (6µB) of all elements in the 3d transition metal series. Furthermore, the trivalent chromium (Cr3+) is biocompatible and is widely found in food and supplements. Here using first principles calculations combined with Monte Carlo simulations based on Ising model, we systematically study a class of 2D ferromagnetic monolayers CrX3 (X = Cl, Br, I). The feasibility of exfoliation from their layered bulk phase is confirmed by the small cleavage energy and high in-plane stiffness. Spin-polarized calculations, combined with self consistently determined Hubbard U that accounts for strong correlation energy, demonstrate that CrX3 (X =Cl, Br, I) monolayers are ferromagnetic and Cr is trivalent and carries a magnetic moment of 3µB, the resulting Cr3+ ions are biocompatible. The corresponding Curie temperatures for CrCl3 CrBr3 CrI3 are are found to 66, 86, and 107 K, respectively, which can be increased to 323, 314, 293 K by hole doping. The biocompatibility and ferromagnetism render these Cr-containing trichalcogenide monolayers unique for applications.

  12. Aromatic oligomers that form hetero duplexes in aqueous solution.

    PubMed

    Gabriel, Gregory J; Iverson, Brent L

    2002-12-25

    The electron-deficient 1,4,5,8-naphthalenetetracarboxylic diimide (Ndi) and electron-rich 1,5-dialkoxynaphthalene (Dan) have been shown to complex strongly with each other in water due to the hydrophobic effect as modulated through the electrostatic complementarity of the stacked dimer. Previously, oligomers of alternating Ndi and Dan units, termed aedamers, were the first foldamers to employ intramolecular aromatic stacking to effect the formation of secondary structure of nonnatural chains in aqueous solution. Described here is the use of this aromatic-aromatic (or pi-pi) interaction, this time in an intermolecular format, to demonstrate the self-assembly of stable hetero duplexes from a set of molecular strands (1a-4a) and (1b-4b) incorporating Ndi and Dan units, respectively. A 1-to-1 binding stoichiometry was determined from NMR and isothermal titration calorimetry (ITC) investigations, and these experiments indicated that association is enthalpically favored with the tetra-Ndi (4a) and tetra-Dan (4b) strands forming hetero duplexes (4a:4b) with a stability constant of 350 000 M-1 at T = 318 K. Polyacrylamide gel electrophoresis (PAGE) also illustrated the strong interaction between 4a and 4b and support a 1-to-1 binding mode even when one component is in slight excess. Overall, this system is the first to utilize complementary aromatic units to drive discrete self-assembly in aqueous solution. This new approach for designing assemblies is encouraging for future development of duplex systems with highly programmable modes of binding in solution or on surfaces.

  13. Computational design of organometallic oligomers featuring 1,3-metal-carbon bonding and planar tetracoordinate carbon atoms.

    PubMed

    Zhao, Xue-Feng; Yuan, Cai-Xia; Wang, Xiang; Li, Jia-Jia; Wu, Yan-Bo; Wang, Xiaotai

    2016-01-15

    Density functional theory computations (B3LYP) have been used to explore the chemistry of titanium-aromatic carbon "edge complexes" with 1,3-metal-carbon (1,3-MC) bonding between Ti and planar tetracoordinate Cβ . The titanium-coordinated, end-capping chlorides are replaced with OH or SH groups to afford two series of difunctional monomers that can undergo condensation to form oxide- and sulfide-bridged oligomers. The sulfide-linked oligomers have less molecular strain and are more exergonic than the corresponding oxide-linked oligomers. The HOMO-LUMO gap of the oligomers varies with their composition and decreases with growing oligomer chain. This theoretical study is intended to enrich 1,3-MC bonding and planar tetracoordinate carbon chemistry and provide interesting ideas to experimentalists. Organometallic complexes with the TiE2 (E = OH and SH) decoration on the edge of aromatic hydrocarbons have been computationally designed, which feature 1,3-metal-carbon (1,3-MC) bonding between titanium and planar tetracoordinate β-carbon. Condensation of these difunctional monomers by eliminating small molecules (H2O and H2S) produce chain-like oligomers. The HOMO-LUMO gaps of the oligomers decreases with growing oligomer chain, a trend that suggests possible semiconductor properties for oligomers with longer chains.

  14. Synthesis of paucidisperse poly(gamma-benzyl-alpha,L-glutamate) oligomers and star polymers with rigid arms.

    PubMed

    Wang, X; Daly, W H; Russo, P; Ngu-Schwemlein, M

    2001-01-01

    The synthesis of highly uniform gamma-benzyl-alpha,L-glutamate (BLG) oligomers via a convergent solution phase approach is reported. BLG oligomers were produced with designed lengths of 4, 8, 12, and 16 as a first step to production of BLG-4-mer and BLG-8-mer rod stars. The star oligomers were purified by size-exclusion chromatography and reversed phase HPLC, and characterized by MALDI-TOF mass spectrometry and reversed phase HPLC. These star-shaped BLG oligomers could be used as initiators for growing larger stars.

  15. Solvent Free Low-Melt Viscosity Imide Oligomers And Thermosetting Polyimide Composites

    NASA Technical Reports Server (NTRS)

    Chuang, CHun-Hua (Inventor)

    2006-01-01

    This invention relates to the composition and a solvent-free process for preparing novel imide oligomers and polymers specifically formulated with effective amounts of a dianhydride such as 2,3,3',4-biphenyltetra carboxylic dianydride (a-BPDA), at least one aromatic diamine' and an endcapped of 4-phenylethynylphthalic anhydride (PEPA) or nadic anhydride to produce imide oligomers that possess a low-melt viscosity of 1-60 poise at 260-280" C. When the imide oligomer melt is cured at about 371 C. in a press or autoclave under 100-500 psi, the melt resulted in a thermoset polyimide having a glass transition temperature (T(sub g)) equal to and above 310 C. A novel feature of this process is that the monomers; namely the dianhydrides, diamines and the endcaps, are melt processable to form imide oligomers at temperatures ranging between 232-280 C. (450-535 F) without any solvent. These low-melt imide oligomers can be easily processed by resin transfer molding (RTM), vacuum-assisted resin transfer molding (VARTM) or the resin infusion process with fiber preforms e.g. carbon, glass or quartz preforms to produce polyimide matrix composites with 288-343C (550-650 F) high temperature performance capability.

  16. In vitro release of a water-soluble agent from low viscosity biodegradable, injectable oligomers.

    PubMed

    Sharifpoor, Soroor; Amsden, Brian

    2007-03-01

    Low-molecular-weight poly(epsilon-caprolactone-co-1,3-trimethylene carbonate) and poly(1,3-trimethylene carbonate) are potential vehicles for the regio-specific delivery of water-soluble agents. In this paper, the characteristics and the mechanism governing the in vitro release of a model water-soluble drug, vitamin B12, from these polymer vehicles were determined. The loading of vitamin B12 was kept to 1 w/w%. The oligomers examined ranged from amorphous, high viscosity to crystalline but low viscosity. The oligomers did not degrade appreciably in vitro. The total fraction of vitamin B12 released increased as the crystallinity of the oligomers decreased, reaching nearly total release only for the completely amorphous oligomers. The rate of release was fastest for the amorphous oligomers and dependent on their viscosity. Inclusion of a more osmotically active agent, trehalose, into the vitamin B12 particles through co-lyophilization resulted in enhanced total fraction released and a faster release rate. The results are consistent with an osmotically driven release mechanism.

  17. Alzheimer's-associated Abeta oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthal.

    PubMed

    Pitt, Jason; Roth, William; Lacor, Pascale; Smith, Amos B; Blankenship, Matthew; Velasco, Pauline; De Felice, Fernanda; Breslin, Paul; Klein, William L

    2009-10-15

    It now appears likely that soluble oligomers of amyloid-beta1-42 peptide, rather than insoluble fibrils, act as the primary neurotoxin in Alzheimer's disease (AD). Consequently, compounds capable of altering the assembly state of these oligomers (referred to as ADDLs) may have potential for AD therapeutics. Phenolic compounds are of particular interest for their ability to disrupt Abeta oligomerization and reduce pathogenicity. This study has focused on oleocanthal (OC), a naturally-occurring phenolic compound found in extra-virgin olive oil. OC increased the immunoreactivity of soluble Abeta species, when assayed with both sequence- and conformation-specific Abeta antibodies, indicating changes in oligomer structure. Analysis of oligomers in the presence of OC showed an upward shift in MW and a ladder-like distribution of SDS-stable ADDL subspecies. In comparison with control ADDLs, oligomers formed in the presence of OC (Abeta-OC) showed equivalent colocalization at synapses but exhibited greater immunofluorescence as a result of increased antibody recognition. The enhanced signal at synapses was not due to increased synaptic binding, as direct detection of fluorescently-labeled ADDLs showed an overall reduction in ADDL signal in the presence of OC. Decreased binding to synapses was accompanied by significantly less synaptic deterioration assayed by drebrin loss. Additionally, treatment with OC improved antibody clearance of ADDLs. These results indicate oleocanthal is capable of altering the oligomerization state of ADDLs while protecting neurons from the synaptopathological effects of ADDLs and suggest OC as a lead compound for development in AD therapeutics.

  18. Nitrogen Containing Organic Compounds and Oligomers in Secondary Organic Aerosol Formed by Photooxidation of Isoprene

    SciTech Connect

    Nguyen, Tran B.; Laskin, Julia; Laskin, Alexander; Nizkorodov, Serguei

    2011-07-06

    Electrospray ionization high-resolution mass spectrometry (ESI HR-MS) was used to probe molecular structures of oligomers in secondary organic aerosol (SOA) generated in laboratory experiments on isoprene photooxidation at low- and high-NOx conditions. Up to 80-90% of the observed products are oligomers and up to 33% are nitrogen-containing organic compounds (NOC). We observe oligomers with up to 8 monomer units in length. Tandem mass spectrometry (MSn) confirms NOC compounds are organic nitrates and elucidates plausible chemical building blocks contributing to oligomer formation. Most organic nitrates are comprised of methylglyceric acid units. Other important multifunctional C2-C5 monomer units are identified including methylglyoxal, hydroxyacetone, hydroxyacetic acid, glycolaldehyde, and 2-methyltetrols. The majority of the NOC oligomers contain only one nitrate moiety resulting in a low average N:C ratio of 0.019. Average O:C ratios of the detected SOA compounds are 0.54 under the low-NOx conditions and 0.83 under the high-NOx conditions. Our results underscore the importance of isoprene photooxidation as a source of NOC in organic particulate matter.

  19. Oligomer and SOA formation through aqueous phase photooxidation of methacrolein and methyl vinyl ketone

    NASA Astrophysics Data System (ADS)

    Liu, Yao; Siekmann, Frank; Renard, Pascal; El Zein, Atallah; Salque, Guillaume; El Haddad, Imad; Temime-Roussel, Brice; Voisin, Didier; Thissen, Roland; Monod, Anne

    2012-03-01

    This work investigates the ability of methacrolein (MACR) and methyl vinyl ketone (MVK) (the two main gas phase atmospheric oxidation products of isoprene) to form oligomers and secondary organic aerosol (SOA) upon aqueous phase OH-oxidation and subsequent water evaporation. For the two precursors, electrospray mass spectrometry (in infusion and coupled to liquid chromatography) analysis of the reacting solutions brought clear evidence for the formation of oligomer systems having a mass range of up to 1400 Da. More than 11 series of oligomers were found. For MVK, the intensity and masses of oligomers became increasingly important as MVK initial concentrations increased from 0.2 to 20 mM. For both precursors, the oligomers were responsible for the SOA formation during nebulization experiments. The evaluated SOA mass yield ranged from 3.9 to 9.9% for MVK. These yields were time dependent and were in good agreement with the range (1.6-11.7%) obtained for MACR under the same conditions by El Haddad et al. (2009).

  20. The Effect of Difunctional Oligomer Concentration and Processing Temperature on the Reactive Processing of Polymer Blends

    NASA Astrophysics Data System (ADS)

    O'Brien, Charles; Rice, Kevin; Dadmun, Mark

    2001-03-01

    Reactive processing is an interesting method to form compatibilizers for polymer blends in-situ. A model blend composed of poly(bisphenol A-co-epichlorohydrin) and poly(ethylene oxide) that is compatibilized with difunctional oligomers that are the same structure as the homopolymers is currently under investigation. It is expected that blocky copolymers will form at the bipahasic interface during processing as the difunctional oligomers undergo an addition copolymerization. Previous results have shown that the addition of the reactive oligomers improves the properties of the blend and thus this reactive process scheme is feasible. Additionally, these results indicate that the difunctioanal oligomers may act as plasticizers and continue to polymerize at room temperature after the blend is removed from the melt mixer. In this presentation, we will discuss our research that is focused on optimizing the reactive compatibilization process by controlling the amount of reactive oligomer added and the processing temperature and evaluating the effect of these parameters on the ultimate properties of the blend.

  1. Large-scale motif discovery using DNA Gray code and equiprobable oligomers

    PubMed Central

    Ichinose, Natsuhiro; Yada, Tetsushi; Gotoh, Osamu

    2012-01-01

    Motivation: How to find motifs from genome-scale functional sequences, such as all the promoters in a genome, is a challenging problem. Word-based methods count the occurrences of oligomers to detect excessively represented ones. This approach is known to be fast and accurate compared with other methods. However, two problems have hampered the application of such methods to large-scale data. One is the computational cost necessary for clustering similar oligomers, and the other is the bias in the frequency of fixed-length oligomers, which complicates the detection of significant words. Results: We introduce a method that uses a DNA Gray code and equiprobable oligomers, which solve the clustering problem and the oligomer bias, respectively. Our method can analyze 18 000 sequences of ~1 kbp long in 30 s. We also show that the accuracy of our method is superior to that of a leading method, especially for large-scale data and small fractions of motif-containing sequences. Availability: The online and stand-alone versions of the application, named Hegma, are available at our website: http://www.genome.ist.i.kyoto-u.ac.jp/~ichinose/hegma/ Contact: ichinose@i.kyoto-u.ac.jp; o.gotoh@i.kyoto-u.ac.jp PMID:22057160

  2. Chain-length and mode-delocalization dependent amide-I anharmonicity in peptide oligomers.

    PubMed

    Zhao, Juan; Wang, Jianping

    2012-06-07

    The diagonal anharmonicities of the amide-I mode in the alanine oligomers are examined in the normal-mode basis by ab initio calculations. The selected oligomers range from dimer to heptamer, in either the α-helical or β-sheet conformations. It is found that the anharmonicity varies from mode to mode within the same oligomer. For a given amide-I mode, the anharmonicity is closely related to the delocalization extent of the mode: the less it delocalizes, the larger the anharmonicity it has. Thus, the single-mode potential energy distribution (PED(max)) can be used as an indicator of the magnitude of the anharmonicity. It is found that as the peptide chain length increases, the averaged diagonal anharmonicity generally decreases; however, the sum of the averaged diagonal and off-diagonal anharmonicities within a peptide roughly remains a constant for all the oligomers examined, indicating the excitonic characteristics of the amide-I modes. Excitonic coupling tends to decrease the diagonal anharmonicities in a coupled system with multiple chromophores, which explains the observed behavior of the anharmonicities. The excitonic nature of the amide-I band in peptide oligomers is thus verified by the anharmonic computations. Isotopic substitution effect on the anharmonicities and mode localizations of the amide-I modes in peptides is also discussed.

  3. Amyloid Oligomers and Mature Fibrils Prepared from an Innocuous Protein Cause Diverging Cellular Death Mechanisms*

    PubMed Central

    Harte, Níal P.; Klyubin, Igor; McCarthy, Eoin K.; Min, Soyoung; Garrahy, Sarah Ann; Xie, Yongjing; Davey, Gavin P.; Boland, John J.; Rowan, Michael J.; Mok, K. Hun

    2015-01-01

    Despite significant advances, the molecular identity of the cytotoxic species populated during in vivo amyloid formation crucial for the understanding of neurodegenerative disorders is yet to be revealed. In this study lysozyme prefibrillar oligomers and fibrils in both mature and sonicated states have been isolated through an optimized ultrafiltration/ultracentrifugation method and characterized with various optical spectroscopic techniques, atomic force microscopy, and transmission electron microscopy. We examined their level and mode of toxicity on rat pheochromocytoma (PC12) cells in both differentiated and undifferentiated states. We find that oligomers and fibrils display cytotoxic capabilities toward cultured cells in vitro, with oligomers producing elevated levels of cellular injury toward undifferentiated PC12 cells (PC12undiff). Furthermore, dual flow cytometry staining experiments demonstrate that the oligomers and mature fibrils induce divergent cellular death pathways (apoptosis and secondary necrosis, respectively) in these PC12 cells. We have also shown that oligomers but not sonicated mature fibrils inhibit hippocampal long term potentiation, a form of synaptic plasticity implicated in learning and memory, in vivo. We conclude that our in vitro and in vivo findings confer a level of resistance toward amyloid fibrils, and that the PC 12-based comparative cytotoxicity assay can provide insights into toxicity differences between differently aggregated protein species. PMID:26221033

  4. Prefibrillar transthyretin oligomers and cold stored native tetrameric transthyretin are cytotoxic in cell culture

    SciTech Connect

    Soergjerd, Karin; Klingstedt, Therese; Lindgren, Mikael; Kagedal, Katarina; Hammarstroem, Per

    2008-12-26

    Recent studies suggest that soluble, oligomeric species, which are intermediates in the fibril formation process in amyloid disease, might be the key species in amyloid pathogenesis. Soluble oligomers of human wild type transthyretin (TTR) were produced to elucidate oligomer properties. Employing ThT fluorescence, time-resolved fluorescence anisotropy of pyrene-labeled TTR, chemical cross-linking, and electron microscopy we demonstrated that early formed soluble oligomers (within minutes) from A-state TTR comprised on the average 20-30 TTR monomers. When administered to neuroblastoma cells these early oligomers proved highly cytotoxic and induced apoptosis after 48 h of incubation. More mature fibrils (>24 h of fibrillation) were non-toxic. Surprisingly, we also found that native tetrameric TTR, when purified and stored under cold conditions (4 deg. C) was highly cytotoxic. The effect could be partially restored by increasing the temperature of the protein. The cytotoxic effects of native tetrameric TTR likely stems from a hitherto unexplored low temperature induced rearrangement of the tetramer conformation that possibly is related to the conformation of misfolded TTR in amyloigogenic oligomers.

  5. Sugar monomer and oligomer solubility: data and predictions for application to biomass hydrolysis.

    PubMed

    Gray, Matthew C; Converse, Alvin O; Wyman, Charles E

    2003-01-01

    Oligomer solubility could potentially play an important role in controlling the rates and yields in the thermochemical hydrolysis of hemicellulose as a pretreatment for subsequent enzymatic conversion of cellulose. However, limited data or models are available to describe the aqueous solubility of sugar monomers and oligomers. In this work, we measured the solubilities of sugars common to many biomass feedstocks in the temperature range of 25-30 degrees C. Then we reviewed solubility models for sugars from the open literature. Finally, we applied models to test their ability to describe this and other data reported in the literature. It was found that the solubility of sugar monomers was not well described by the ideal solubility law or other more complex models. However, with an empirical adjustment to the enthalpy of fusion, the ideal solubility law was able to approximately predict the solubility of cello-oligomers. Based on these results, solubilities for low molecular weight xylo-oligomers are predicted to investigate their possible importance in pretreatment and define further experimental measurements needed to improve our understanding of sugar and oligomer solubility.

  6. Comparison of mass spectrometric techniques for generating molecular weight information on a class of ethoxylated oligomers.

    PubMed

    Parees, D M; Hanton, S D; Clark, P A; Willcox, D A

    1998-04-01

    The results of fast atom bombardment (FAB), time-of-flight secondary ion mass spectrometry (ToF-SIMS), matrix-assisted laser desorption/ionization (MALD/I), electrospray ionization (ESI), and field desorption (FD) analyses of ethoxylated oligomers of 2,4,7,9-tetramethyl-5-decyne-4,7-diol (Surfynol(®) 104) were compared.Each of these desorption mass spectrometry (MS) techniques can produce spectra of unfragmented cationized oligomers. From the observed ion series we calculate average molecular weight information. We have compared the results of mass spectrometric analyses of a series of ethoxylated Surfynol surfactants. Our data indicate that FAB, ToF-SIMS, MALDI/I, and ESI produce similar results for the lower molecular weight species, but that as the average molecular weight increases FAB and SIMS produce slightly lower results than MALD/I and FD. This could be due to increased fragmentation. ESI produced a result similar to FAB and SIMS for the highest average molecular weight material. Further experiments compare the mass spectral results with gas chromatographic quantitative data. Although gas chromatography is not expected to accurately analyze the higher mass oligomers, we observe significant differences in intensities of the short-chain oligomers (especially the 0- and 1-mers) when compared to the desorption mass spectrometer results. These differences may reflect poor cationization efficiency for very short oligomer chains in the mass spectrometric analyses.

  7. Biodegradable polyester-based eco-composites containing hemp fibers modified with macrocyclic oligomers

    NASA Astrophysics Data System (ADS)

    Conzatti, Lucia; Utzeri, Roberto; Hodge, Philip; Stagnaro, Paola

    2016-05-01

    An original compatibilizing pathway for hemp fibers/poly(1,4-butylene adipate-co-terephtalate) (PBAT) eco-composites was explored exploiting the capability of macrocyclic oligomers (MCOs), obtained by cyclodepolymerization (CDP) of PBAT at high dilution, of being re-converted into linear chains by entropically-driven ring-opening polymerization (ED-ROP) that occurs simply heating the MCOS in the bulk. CDP reaction of PBAT was carried out varying solvent, catalyst and reaction time. Selected MCOs were used to adjust the conditions of the ED-ROP reaction. The best experimental conditions were then adopted to modify hemp fibers. Eco-composites based on PBAT and hemp fibers as obtained or modified with PBAT macrocyclics or oligomers were prepared by different process strategies. The best fiber-PBAT compatibility was observed when the fibers were modified with PBAT oligomers before incorporation in the polyester matrix.

  8. Mitochondrial oligomers boost glycolysis in cancer stem cells to facilitate blebbishield-mediated transformation after apoptosis

    PubMed Central

    Jinesh, GG; Molina, JR; Huang, L; Laing, NM; Mills, GB; Bar-Eli, M; Kamat, AM

    2016-01-01

    Apoptosis culminates in secondary necrosis due to lack of ATP. Cancer stem cells form spheres after apoptosis by evoking the blebbishield emergency program. Hence, determining how blebbishields avoid secondary necrosis is crucial. Here we demonstrate that N-Myc and VEGFR2 control transformation from blebbishields, during which oligomers of K-Ras, p27, BAD, Bax, and Bak boost glycolysis to avoid secondary necrosis. Non-apoptotic cancer cells also utilize oligomers to boost glycolysis, which differentiates the glycolytic function of oligomers from their apoptotic action. Smac mimetic in combination with TNF-α or TRAIL but not in combination with FasL abrogates transformation from blebbishields by inducing secondary necrosis. Thus blebbishield-mediated transformation is dependent on glycolysis, and Smac mimetics represent potential candidates to abrogate the blebbishield emergency program. PMID:27551498

  9. Exploring the assembly mechanism of tetrapeptide oligomers using the Activation-Relaxation Technique

    NASA Astrophysics Data System (ADS)

    Wei, Guanghong; Mousseau, Normand; Derreumaux, Philippe

    2004-03-01

    Alzheimer's disease and Parkinson's disease are associated with formation of amyloid fibrils. All amyloid fibrils seem to share a common cross β-sheet structure. Experimental studies have shown that peptides as short as 4 amino acids can form amyloid fibrils. It has also been shown that the oligomers that form early in the aggregation process of even non-disease-related proteins may be cytotoxic. We report a detailed study of the assembly mechanisms of the tetrapeptides into different size oligomers: trimers, hexamers and more. The assembly of the oligomers, in which the peptides form β-sheets through interpeptide interactions, are studied using the activation-relaxation technique (ART) in combination with a reduced off-lattice energy model (OPEP). We also describe the multiple pathways of oligomerization as well as categorize the various oligomeric intermediates, providing information of the early events of β-sheet formation.

  10. New insight into the dynamical system of αB-crystallin oligomers

    PubMed Central

    Inoue, Rintaro; Takata, Takumi; Fujii, Norihiko; Ishii, Kentaro; Uchiyama, Susumu; Sato, Nobuhiro; Oba, Yojiro; Wood, Kathleen; Kato, Koichi; Fujii, Noriko; Sugiyama, Masaaki

    2016-01-01

    α-Crystallin possesses a dynamic quaternary structure mediated by its subunit dynamics. Elucidation of a mechanism of subunit dynamics in homo-oligomers of αB-crystallin was tackled through deuteration-assisted small-angle neutron scattering (DA-SANS) and electrospray ionization (ESI) native mass spectrometry (nMS). The existence of subunit exchange was confirmed with DA-SANS, and monomers liberated from the oligomers were observed with nMS. With increasing temperature, an increase in both the exchange rate and monomer population was observed despite the absence of oligomer collapse. It is proposed that transiently liberated subunits, namely, “traveling subunits,” play a role in subunit exchange. Moreover, we propose that protein function is regulated by these traveling subunits. PMID:27381175

  11. Simple extrapolation method to predict the electronic structure of conjugated polymers from calculations on oligomers

    SciTech Connect

    Larsen, Ross E.

    2016-04-12

    In this study, we introduce two simple tight-binding models, which we call fragment frontier orbital extrapolations (FFOE), to extrapolate important electronic properties to the polymer limit using electronic structure calculations on only a few small oligomers. In particular, we demonstrate by comparison to explicit density functional theory calculations that for long oligomers the energies of the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), and of the first electronic excited state are accurately described as a function of number of repeat units by a simple effective Hamiltonian parameterized from electronic structure calculations on monomers, dimers and, optionally, tetramers. For the alternating copolymer materials that currently comprise some of the most efficient polymer organic photovoltaic devices one can use these simple but rigorous models to extrapolate computed properties to the polymer limit based on calculations on a small number of low-molecular-weight oligomers.

  12. Excitonic Coupling and Femtosecond Relaxation of Zinc Porphyrin Oligomers Linked with Triazole Bridge: Dynamics and Modeling.

    PubMed

    Bukreev, Alexey; Mikhailov, Konstantin; Shelaev, Ivan; Gostev, Fedor; Polevaya, Yuliya; Tyurin, Vladimir; Beletskaya, Irina; Umansky, Stanislav; Nadtochenko, Victor

    2016-03-31

    The synthesis of new zinc porphyrin oligomers linked by a triazole bridge was carried out via "click" reaction. A split in the porphyrin oligomer B-band was observed. It was considered as evidence of exciton-excitonic coupling. The relaxation of excited states in Q-band porphyrin oligomers was studied by the femtosecond laser spectroscopy technique with a 20 fs pump pulse. The transient oscillations of two B-band excitonic peaks have a π-radian shift. For explanation of the coherent oscillation, a theoretical model was developed. The model considered the combination of the exciton-excitonic coupling between porphyrin rings in dimer and weak exciton-vibronic coupling in one porphyrin ring. By varying the values of the structural parameters of porphyrins (the strength values of this couplings and measure of symmetry breaking), we obtained correspondence between the experimental data (phase shift and amplitudes of the spectrum oscillations) and the predictions of the model developed here.

  13. Simple extrapolation method to predict the electronic structure of conjugated polymers from calculations on oligomers

    DOE PAGES

    Larsen, Ross E.

    2016-04-12

    In this study, we introduce two simple tight-binding models, which we call fragment frontier orbital extrapolations (FFOE), to extrapolate important electronic properties to the polymer limit using electronic structure calculations on only a few small oligomers. In particular, we demonstrate by comparison to explicit density functional theory calculations that for long oligomers the energies of the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), and of the first electronic excited state are accurately described as a function of number of repeat units by a simple effective Hamiltonian parameterized from electronic structure calculations on monomers, dimers and, optionally,more » tetramers. For the alternating copolymer materials that currently comprise some of the most efficient polymer organic photovoltaic devices one can use these simple but rigorous models to extrapolate computed properties to the polymer limit based on calculations on a small number of low-molecular-weight oligomers.« less

  14. Solution state structure determination of silicate oligomers by 29SI NMR spectroscopy and molecular modeling.

    PubMed

    Cho, Herman; Felmy, Andrew R; Craciun, Raluca; Keenum, J Patrick; Shah, Neil; Dixon, David A

    2006-02-22

    Evidence for nine new solution state silicate oligomers has been discovered by (29)Si NMR homonuclear correlation experiments of (29)Si-enriched samples. In addition to enhancing signal sensitivity, the isotopic enrichment increases the probability of the (29)Si-(29)Si two-bond scalar couplings that are necessary for the observation of internuclear correlations in 2-D experiments. The proposed assignments are validated by comparisons of experimental and simulated cross-peaks obtained with high digital resolution. The internuclear connectivity indicated by the NMR data suggests that several of these oligomers can have multiple stereoisomers, including conformers and/or diastereomers. The stabilities of these oligomers and their possible stereoisomers have been investigated by electronic structure calculations.

  15. A mechanistic model of tau amyloid aggregation based on direct observation of oligomers

    NASA Astrophysics Data System (ADS)

    Shammas, Sarah L.; Garcia, Gonzalo A.; Kumar, Satish; Kjaergaard, Magnus; Horrocks, Mathew H.; Shivji, Nadia; Mandelkow, Eva; Knowles, Tuomas P. J.; Mandelkow, Eckhard; Klenerman, David

    2015-04-01

    Protein aggregation plays a key role in neurodegenerative disease, giving rise to small oligomers that may become cytotoxic to cells. The fundamental microscopic reactions taking place during aggregation, and their rate constants, have been difficult to determine due to lack of suitable methods to identify and follow the low concentration of oligomers over time. Here we use single-molecule fluorescence to study the aggregation of the repeat domain of tau (K18), and two mutant forms linked with familial frontotemporal dementia, the deletion mutant ΔK280 and the point mutant P301L. Our kinetic analysis reveals that aggregation proceeds via monomeric assembly into small oligomers, and a subsequent slow structural conversion step before fibril formation. Using this approach, we have been able to quantitatively determine how these mutations alter the aggregation energy landscape.

  16. Solution State Structure Determination of Silicate Oligomers by 29Si NMR Spectroscopy and Molecular Modeling

    SciTech Connect

    Cho, Herman M.; Felmy, Andrew R.; Craciun, Raluca; Keenum, Johnathan P.; Shah, Neil K.; Dixon, David A.

    2006-02-22

    Evidence for nine new solution state silicate oligomers has been discovered by 29Si NMR homonuclear correlation experiments of 29Si-enriched samples. In addition to enhancing signal sensitivity, the isotopic enrichment increases the probability of the 29Si–29Si two-bond scalar couplings that are necessary for the observation of internuclear correlations in 2-D experiments. The proposed assignments are validated by comparisons of experimental and simulated crosspeaks obtained with high digital resolution. The internuclear connectivity indicated by the NMR data suggests that several of these oligomers can have multiple stereoisomers, including conformers and/or diastereomers. The stability of these oligomers and their possible stereoisomers have been investigated by electronic structure calculations.

  17. Influence of bioregulators on the phospholipid Langmuir monolayers.

    PubMed

    Mogilevich, A S; Mogilevich, S E; Luik, A L

    1997-01-01

    Influence of bioregulators on the phospholipid Langmuir monolayers made of distearoylphosphatidylcholine and its equimolar mixture with dimitrystoylphosphatidylcholine was investigated. The results obtained allow concluding that the presence of physiologically active compounds in the subphase weakens the lipid-lipid interaction and increases the free energy change of air-liquid interface in the case of pure distearoylphosphatidylcholine monolayers, but in the case of mixed monolayers it leads both to the increase and decrease of these parameters. Presence of the dimirystoylphosphatidylcholine molecules with the short fatty acyl chains in the monolayer destabilizes it. This effect is partially compensated by the interaction between lipid and subphase molecules.

  18. Carbon phosphide monolayers with superior carrier mobility

    NASA Astrophysics Data System (ADS)

    Wang, Gaoxue; Pandey, Ravindra; Karna, Shashi P.

    2016-04-01

    Two dimensional (2D) materials with a finite band gap and high carrier mobility are sought after materials from both fundamental and technological perspectives. In this paper, we present the results based on the particle swarm optimization method and density functional theory which predict three geometrically different phases of the carbon phosphide (CP) monolayer consisting of sp2 hybridized C atoms and sp3 hybridized P atoms in hexagonal networks. Two of the phases, referred to as α-CP and β-CP with puckered or buckled surfaces are semiconducting with highly anisotropic electronic and mechanical properties. More remarkably, they have the lightest electrons and holes among the known 2D semiconductors, yielding superior carrier mobility. The γ-CP has a distorted hexagonal network and exhibits a semi-metallic behavior with Dirac cones. These theoretical findings suggest that the binary CP monolayer is a yet unexplored 2D material holding great promise for applications in high-performance electronics and optoelectronics.Two dimensional (2D) materials with a finite band gap and high carrier mobility are sought after materials from both fundamental and technological perspectives. In this paper, we present the results based on the particle swarm optimization method and density functional theory which predict three geometrically different phases of the carbon phosphide (CP) monolayer consisting of sp2 hybridized C atoms and sp3 hybridized P atoms in hexagonal networks. Two of the phases, referred to as α-CP and β-CP with puckered or buckled surfaces are semiconducting with highly anisotropic electronic and mechanical properties. More remarkably, they have the lightest electrons and holes among the known 2D semiconductors, yielding superior carrier mobility. The γ-CP has a distorted hexagonal network and exhibits a semi-metallic behavior with Dirac cones. These theoretical findings suggest that the binary CP monolayer is a yet unexplored 2D material holding great

  19. Thio-urethane oligomers improve the properties of light-cured resin cements

    PubMed Central

    Bacchi, Ataís; Consani, Rafael L.; Martim, Gedalias C.; Pfeifer, Carmem S.

    2015-01-01

    Thio-urethanes were synthesized by combining 1,6-Hexanediol-diissocyante (aliphatic) with pentaerythritol tetra-3-mercaptopropionate (PETMP) or 1,3-bis(1-isocyanato-1-methylethyl)benzene (aromatic) with trimethylol-tris-3-mercaptopropionate (TMP), at 1:2 isocyanate:thiol, leaving pendant thiols. Oligomers were added at 10–30 phr to BisGMA-UDMA-TEGDMA (5:3:2, BUT). 25wt% silanated inorganic fillers were added. Commercial cement (Relyx Veneer, 3M-ESPE) was also evaluated with 10–20 phr of aromatic oligomer. Near-IR was used to follow methacrylate conversion (DC) and rate of polymerization (Rpmax). Mechanical properties were evaluated in three-point bending (ISO 4049) for flexural strength/modulus (FS/FM, and toughness), and notched specimens (ASTM Standard E399-90) for fracture toughness (KIC). Polymerization stress (PS) was measured on the Bioman. Volumetric shrinkage (VS, %) was measured with the bonded disk technique. Results were analyzed with ANOVA/Tukey’s test (α=5%). In general terms, for BUT cements, conversion and mechanical properties in flexure increased for selected groups with the addition of thio-urethane oligomers. The aromatic versions resulted in greater FS/FM than aliphatic. Fracture toughness increased by twofold in the experimental groups (from 1.17±0.36 to around 3.23±0.22 MPa.m1/2). Rpmax decreased with the addition of thio-urethanes, though the vitrification point was not statistically different from the control. VS and PS decreased with both oligomers. For the commercial cement, 20 phr of oligomer increased DC, vitrification, reduced Rpmax and also significantly increased KIC, and reduced PS and FM. Thio-urethane oligomers were shown to favorably modify conventional dimethacrylate networks. Significant reductions in polymerization stress were achieved at the same time conversion and fracture toughness increased. PMID:25740124

  20. Air-Stable n-channel Diketopyrrolopyrrole-Diketopyrrolopyrrole Oligomers for High Performance Ambipolar Organic Transistors.

    PubMed

    Mukhopadhyay, Tushita; Puttaraju, Boregowda; Senanayak, Satyaprasad P; Sadhanala, Aditya; Friend, Richard; Faber, Hendrik A; Anthopoulos, Thomas D; Salzner, Ulrike; Meyer, Andreas; Patil, Satish

    2016-09-28

    n-channel organic semiconductors are prone to oxidation upon exposed to ambient conditions. Herein, we report design and synthesis of diketopyrrolopyrrole (DPP)-based oligomers for ambipolar organic thin-film transistors (OFETs) with excellent air and bias stability at ambient conditions. The cyclic voltammetry measurements reveal exceptional electrochemical stability during the redox cycle of oligomers. Structural properties including aggregation, crystallinity, and morphology in thin film were investigated by UV-visible spectroscopy, atomic force microscopy (AFM), thin-film X-ray diffraction (XRD), and grazing incidence small-angle X-ray scattering (GISAXS) measurements. AFM reveals morphological changes induced by different processing conditions whereas GISAXS measurements show an increase in the population of face-on oriented crystallites in films subjected to a combination of solvent and thermal treatments. These measurements also highlight the significance of chalcogen atom from sulfur to selenium on the photophysical, optical, electronic, and solid-state properties of DPP-DPP oligomers. Charge carrier mobilities of the oligomers were investigated by fabricating top-gate bottom-contact (TG-BC) thin-film transistors by annealing the thin films under various conditions. Combined solvent and thermal annealing of DPP-DPP oligomer thin films results in consistent electron mobilities as high as ∼0.2 cm(2) V(-1) s(-1) with an on/off ratio exceeding 10(4). Field-effect behavior was retained for up to ∼4 weeks, which illustrates remarkable air and bias stability. This work paves the way toward the development of n-channel DPP-DPP-based oligomers exhibiting retention of field-effect behavior with superior stability at ambient conditions.

  1. Chiral solidification of a phospholipid monolayer

    NASA Technical Reports Server (NTRS)

    Langer, J. S.

    1985-01-01

    The formation of chiral solidlike domains observed by Weiss and McConnell (1984) in monolayers of depalmitoylphosphatidylcholine (DPPC) floating on an air-water interface is investigated theoretically. It is proposed that the diffusion tensor for the two-dimensional fluidlike phase of the DPPC molecules has a chiral component acting perpendicular to the concentration gradient and coupled to the rotational motion of a pinwheellike molecule by the viscous forces. Diagrams are provided, and numerical estimates of the forces involved are shown to be in agreement with the observed behavior of the structures.

  2. Processing of monolayer materials via interfacial reactions

    DOEpatents

    Sutter, Peter Werner; Sutter, Eli Anguelova

    2014-05-20

    A method of forming and processing of graphene is disclosed based on exposure and selective intercalation of the partially graphene-covered metal substrate with atomic or molecular intercalation species such as oxygen (O.sub.2) and nitrogen oxide (NO.sub.2). The process of intercalation lifts the strong metal-carbon coupling and restores the characteristic Dirac behavior of isolated monolayer graphene. The interface of graphene with metals or metal-decorated substrates also provides for controlled chemical reactions based on novel functionality of the confined space between a metal surface and a graphene sheet.

  3. Fluidization of a horizontally driven granular monolayer.

    PubMed

    Heckel, Michael; Sack, Achim; Kollmer, Jonathan E; Pöschel, Thorsten

    2015-06-01

    We consider the transition of a horizontally vibrated monodisperse granular monolayer between its condensed state and its three-dimensional gaseous state as a function of the vibration parameters, amplitude, and frequency as well as particle number density. The transition is characterized by an abrupt change of the dynamical state which leaves its fingerprints in several measurable quantities including dissipation rate, sound emission, and a gap size which characterizes the sloshing motion of the material. The transition and its pronounced hysteresis is explained through the energy due to the collective motion of the particles relative to the container.

  4. Synthesis and Properties of Phenylethynyl-Terminated, Star-Branched, Phenylquinoxaline Oligomers

    NASA Technical Reports Server (NTRS)

    Ooi, I. H.; Hergenrother, P. M.; Harris, F. W.

    2000-01-01

    The primary objective of this work was to prepare readily melt and solution processable phenylquinoxaline (PQ) oligomers that could be thermally crosslinked to solvent-resistant resins. Thus, a mixture of 2-(4-hydroxyphenyl)-3-phenyl-6-fluoroquinoxaline and 3-(4-hydroxyphenyl)-2-phenyl-6-fluoroquinoxaline (HPFQ) was used to prepare star-branched PQ oligomers end-capped with 4-fluoro-4-phenylethynylbenzophenone (FPEB). 1,1,1-Tris(4-hydroxyphenyl)ethane (THPE) was used as the branching unit. The oligomer number-average molecular weights (M (bar) (sub n) S) as determined by size exclusion chromatography (SEC) were close to the calculated values of 2922, 4698, 6474, and 13,578 g/mol, and their intrinsic viscosities ranged from 0.16 to 0.57 dl/g (m-cresol at 30 C). The oligomers, which were quite soluble in common organic solvents, had glass transition temperatures (T (sub g) S) that ranged from 181 to 233 C (DSC, DELTA T = 20 C/min). They also underwent an exothermic cure with maxima from 377 to 443 C. The T (sub g) S of the cured oligomers ranged from 259 to 284 C depending on the oligomer M (bar) (sub n) and the curing conditions. The oligomers had low melt viscosities, e.g. an oligomer (SPQ-46) with an M (bar) (sub n) of 4816 g/mol (SEC) had a melt viscosity of 150 Pa s at 348 C. A cured thin film of SPQ-46, which was insoluble in common organic solvents, had a room temperature (RT) tensile strength of 100 MPa, a RT modulus of 2358 MPa, and a RT elongation of 5.9%. A cured sample of SPQ-46 displayed a RT titanium-titanium lap shear tensile strength of 35.2 MPa. SPQ-46/carbon fiber(IM-7) composites, were prepared that displayed a RT flexural strength of 1902 MPa, a RT modulus of 1.38 GPa and a RT open hole compressive strength of 433 MPa.

  5. Folding and self-assembly of aromatic and aliphatic urea oligomers: towards connecting structure and function.

    PubMed

    Fischer, Lucile; Guichard, Gilles

    2010-07-21

    Folding and self-assembly of biomacromolecules has inspired the development of discrete, non-natural oligomers that fold and/or self-assemble in a controlled manner. Though aromatic and aliphatic oligoamides remain unmatched for structural diversity and synthetic versatility, oligomers based on amide bond surrogates, such as urea backbones, also demonstrated a propensity for folding and self-assembly. In this Perspective, we review the advances in the design of oligomeric aromatic and aliphatic urea sequences (essentially N,N'-linked) that fold and/or self-assemble. Whenever applicable, the relationship between structure and function will be highlighted.

  6. Synthesis and incorporation of thienylene vinylene oligomers in main-chain copolymers

    SciTech Connect

    Madrigal, L.G.; Elandaloussi, E.H.; Spangler, C.W.

    1998-07-01

    Poly [2,5-thienylene vinylene] (PTV) has been studied extensively over the past decade for both its metallic conductivity behavior upon chemical doping, as well as its interesting third order nonlinear optical properties. PTV oligomers have been synthesized by the group, as well as others, and the formation of polaron-like radical-cations or bipolaron-like dications by oxidative doping has been demonstrated. In this paper the authors describe a general synthetic approach to PTV oligomers functionalized for copolymer formation by step-growth reaction.

  7. Energy Aspects of Thermal Molecular Switching: Molecular Thermal Hysteresis of Helicene Oligomers.

    PubMed

    Shigeno, Masanori; Kushida, Yo; Yamaguchi, Masahiko

    2015-07-20

    Molecular switching is a phenomenon by which a molecule reversibly changes its structure and state in response to external stimuli or energy. Herein, molecular switching is discussed from thermodynamic and kinetic aspects in terms of energy supply with an emphasis on the thermal switching exhibited by helicene oligomers. It includes the inversion of relative thermodynamic stability induced by temperature changes and molecular thermal hysteresis in a closed system. The thermal phenomenon associated with the oligomers involves population/concentration changes between metastable states under nonequilibrium thermodynamic control.

  8. Asymmetric synthesis of vinylogous β-amino acids and their incorporation into mixed backbone oligomers.

    PubMed

    Wu, Hao; An, Hongchan; Mo, Shuting Cynthia; Kodadek, Thomas

    2017-03-27

    Chiral vinylogous β-amino acids (VBAA) were synthesized using enantioselective Mannich reactions of aldehydes with in situ generated N-carbamoyl imines followed by a Horner-Wadsworth-Emmons reaction. The efficiency with which these units could be incorporated into oligomers with different moieties on the C- and N-terminal sides was established, as was the feasibility of sequencing oligomers containing VBAAs by tandem mass spectrometry. The data show that VBAAs will be useful building blocks for the construction of combinatorial libraries of peptidomimetic compounds.

  9. Synthesis and G-Quadruplex-Binding Properties of Defined Acridine Oligomers

    PubMed Central

    Ferreira, Rubén; Aviñó, Anna; Pérez-Tomás, Ricardo; Gargallo, Raimundo; Eritja, Ramon

    2010-01-01

    The synthesis of oligomers containing two or three acridine units linked through 2-aminoethylglycine using solid-phase methodology is described. Subsequent studies on cell viability showed that these compounds are not cytotoxic. Binding to several DNA structures was studied by competitive dialysis, which showed a clear affinity for DNA sequences that form G-quadruplexes and parallel triplexes. The fluorescence spectra of acridine oligomers were affected strongly upon binding to DNA. These spectral changes were used to calculate the binding constants (K). Log K were found to be in the order of 4–6. PMID:20725626

  10. Thermo-reversible gelation of atactic poly(methyl methacrylate) in poly(ethylene glycol) oligomers.

    PubMed

    Gao, Yun; Yu, Chunhong; Chen, Minzhi; Wang, Xiaoliang; Zhou, Dongshan; Xue, Gi

    2013-04-01

    The temperature-concentration behavior of physical gel by atactic poly(methyl methacrylate) (aPMMA) in poly(ethylene glycol) oligomer (PEG400) was investigated. A liquid-liquid demixing interferes with a glass transition during cooling. The combination of demixing and T g leads to the formation of amorphous gels at low temperature. We suggest that the gelation of aPMMA/PEG400 is a glassy gel, in which short-range attractive depletion interaction in the polymer/oligomer system was the driving force at molecular level.

  11. Absorption enhancing effects of chitosan oligomers on the intestinal absorption of low molecular weight heparin in rats.

    PubMed

    Zhang, Hailong; Mi, Jie; Huo, Yayu; Huang, Xiaoyan; Xing, Jianfeng; Yamamoto, Akira; Gao, Yang

    2014-05-15

    Absorption enhancing effects of chitosan oligomers with different type and varying concentration on the intestinal absorption of low molecular weight heparin (LMWH) were examined by an in situ closed loop method in different intestinal sections of rats. Chitosan hexamer with the optimal concentration of 0.5% (w/v) showed the highest absorption enhancing ability both in the small intestine and large intestine. The membrane toxicities of chitosan oligomers were evaluated by morphological observation and determining the biological markers including amount of protein and activity of lactate dehydrogenase (LDH) released from intestinal epithelium cells. There was no obvious change both in levels of protein and LDH and morphology in the intestinal membrane between control and various chitosan oligomers groups, suggesting that chitosan oligomers did not induce any significant membrane damage to the intestinal epithelium. In addition, zeta potentials became less negative and amount of free LMWH gradually decreased when various chitosan oligomers were added to LMWH solution, revealing that electrostatic interaction between positively charged chitosan oligomers and negative LMWH was included in the absorption enhancing mechanism of chitosan oligomers. In conclusion, chitosan oligomers, especially chitosan hexamer, are safe and efficient absorption enhancers and can be used promisingly to improve oral absorption of LMWH.

  12. Single-Molecule Imaging Reveals Aβ42:Aβ40 Ratio-Dependent Oligomer Growth on Neuronal Processes

    PubMed Central

    Johnson, Robin D.; Schauerte, Joseph A.; Chang, Chun-Chieh; Wisser, Kathleen C.; Althaus, John Christian; Carruthers, Cynthia J.L.; Sutton, Michael A.; Steel, Duncan G.; Gafni, Ari

    2013-01-01

    Soluble oligomers of the amyloid-β peptide have been implicated as proximal neurotoxins in Alzheimer’s disease. However, the identity of the neurotoxic aggregate(s) and the mechanisms by which these species induce neuronal dysfunction remain uncertain. Physiologically relevant experimentation is hindered by the low endogenous concentrations of the peptide, the metastability of Aβ oligomers, and the wide range of observed interactions between Aβ and biological membranes. Single-molecule microscopy represents one avenue for overcoming these challenges. Using this technique, we find that Aβ binds to primary rat hippocampal neurons at physiological concentrations. Although amyloid-β(1–40) as well as amyloid-β(1–42) initially form larger oligomers on neurites than on glass slides, a 1:1 mix of the two peptides result in smaller neurite-bound oligomers than those detected on-slide or for either peptide alone. With 1 nM peptide in solution, Aβ40 oligomers do not grow over the course of 48 h, Aβ42 oligomers grow slightly, and oligomers of a 1:1 mix grow substantially. Evidently, small Aβ oligomers are capable of binding to neurons at physiological concentrations and grow at rates dependent on local Aβ42:Aβ40 ratios. These results are intriguing in light of the increased Aβ42:Aβ40 ratios shown to correlate with familial Alzheimer’s disease mutations. PMID:23442968

  13. The effects of a multifunctional oligomer and its incorporation strategies on the gene delivery efficiency of poly(L-lysine).

    PubMed

    Zhou, Dezhong; Li, Congxin; Hu, Yuling; Zhou, Hao; Chen, Jiatong; Zhang, Zhengpu; Guo, Tianying

    2012-05-14

    A novel multifunctional oligomer is synthesized and incorporated to enhance the gene delivery efficiency of PLL via non-electrostatic assembly and covalent grafting strategies. The improvement of the gene delivery efficiency is dependent on the gene carrying complex properties, and the properties are dependent on the oligomer incorporation strategy.

  14. Enzymatic production of defined chitosan oligomers with a specific pattern of acetylation using a combination of chitin oligosaccharide deacetylases

    NASA Astrophysics Data System (ADS)

    Hamer, Stefanie Nicole; Cord-Landwehr, Stefan; Biarnés, Xevi; Planas, Antoni; Waegeman, Hendrik; Moerschbacher, Bruno Maria; Kolkenbrock, Stephan

    2015-03-01

    Chitin and chitosan oligomers have diverse biological activities with potentially valuable applications in fields like medicine, cosmetics, or agriculture. These properties may depend not only on the degrees of polymerization and acetylation, but also on a specific pattern of acetylation (PA) that cannot be controlled when the oligomers are produced by chemical hydrolysis. To determine the influence of the PA on the biological activities, defined chitosan oligomers in sufficient amounts are needed. Chitosan oligomers with specific PA can be produced by enzymatic deacetylation of chitin oligomers, but the diversity is limited by the low number of chitin deacetylases available. We have produced specific chitosan oligomers which are deacetylated at the first two units starting from the non-reducing end by the combined use of two different chitin deacetylases, namely NodB from Rhizobium sp. GRH2 that deacetylates the first unit and COD from Vibrio cholerae that deacetylates the second unit starting from the non-reducing end. Both chitin deacetylases accept the product of each other resulting in production of chitosan oligomers with a novel and defined PA. When extended to further chitin deacetylases, this approach has the potential to yield a large range of novel chitosan oligomers with a fully defined architecture.

  15. Enzymatic production of defined chitosan oligomers with a specific pattern of acetylation using a combination of chitin oligosaccharide deacetylases

    PubMed Central

    Hamer, Stefanie Nicole; Cord-Landwehr, Stefan; Biarnés, Xevi; Planas, Antoni; Waegeman, Hendrik; Moerschbacher, Bruno Maria; Kolkenbrock, Stephan

    2015-01-01

    Chitin and chitosan oligomers have diverse biological activities with potentially valuable applications in fields like medicine, cosmetics, or agriculture. These properties may depend not only on the degrees of polymerization and acetylation, but also on a specific pattern of acetylation (PA) that cannot be controlled when the oligomers are produced by chemical hydrolysis. To determine the influence of the PA on the biological activities, defined chitosan oligomers in sufficient amounts are needed. Chitosan oligomers with specific PA can be produced by enzymatic deacetylation of chitin oligomers, but the diversity is limited by the low number of chitin deacetylases available. We have produced specific chitosan oligomers which are deacetylated at the first two units starting from the non-reducing end by the combined use of two different chitin deacetylases, namely NodB from Rhizobium sp. GRH2 that deacetylates the first unit and COD from Vibrio cholerae that deacetylates the second unit starting from the non-reducing end. Both chitin deacetylases accept the product of each other resulting in production of chitosan oligomers with a novel and defined PA. When extended to further chitin deacetylases, this approach has the potential to yield a large range of novel chitosan oligomers with a fully defined architecture. PMID:25732514

  16. Enzymatic production of defined chitosan oligomers with a specific pattern of acetylation using a combination of chitin oligosaccharide deacetylases.

    PubMed

    Hamer, Stefanie Nicole; Cord-Landwehr, Stefan; Biarnés, Xevi; Planas, Antoni; Waegeman, Hendrik; Moerschbacher, Bruno Maria; Kolkenbrock, Stephan

    2015-03-03

    Chitin and chitosan oligomers have diverse biological activities with potentially valuable applications in fields like medicine, cosmetics, or agriculture. These properties may depend not only on the degrees of polymerization and acetylation, but also on a specific pattern of acetylation (PA) that cannot be controlled when the oligomers are produced by chemical hydrolysis. To determine the influence of the PA on the biological activities, defined chitosan oligomers in sufficient amounts are needed. Chitosan oligomers with specific PA can be produced by enzymatic deacetylation of chitin oligomers, but the diversity is limited by the low number of chitin deacetylases available. We have produced specific chitosan oligomers which are deacetylated at the first two units starting from the non-reducing end by the combined use of two different chitin deacetylases, namely NodB from Rhizobium sp. GRH2 that deacetylates the first unit and COD from Vibrio cholerae that deacetylates the second unit starting from the non-reducing end. Both chitin deacetylases accept the product of each other resulting in production of chitosan oligomers with a novel and defined PA. When extended to further chitin deacetylases, this approach has the potential to yield a large range of novel chitosan oligomers with a fully defined architecture.

  17. Spontaneously adsorbed monolayer films: Fabrication, characterization, and application of monolayers of alkanethiol and sulfur-bearing cyclodestrin derivatives

    SciTech Connect

    Chinkap, Chung.

    1991-03-12

    Monolayers of n-alkanethiols (CH{sub 3}(CH{sub 2}){sub n}SH, n=1--17) and sulfur-bearing cyclodextrin derivatives spontaneously adsorbed on Ag and Au have been studied with a variety of surface characterization methods, such as infrared inflection spectroscopy, contact angle measurements, electro-chemistry, optical ellipsometry, and scanning tunneling microscopy. Long chain n-alkanethiols monolayers on Ag and Au are insulating to electron transfer and have contact angles indicative of well-ordered hydrocarbon terminated structures. Infrared and contact angle data indicate a different orientation of the methyl group with respect to the surface for chains with odd and even numbers of methylene groups. Compared to monolayers on Au, the alkanethiol monolayers on Ag are oriented more towards the surface normal. The observed odd-even effect methyl group orientation for these monolayers on Ag is offset by a methylene group from that on Au. The relationships between the structure and packing of the monolayers on Ag and Au and the composition, roughness, and crystallinity of the substrate are also discussed. Monolayers of sulfur-bearing cyclodextrin derivatives on Au and Ag are fabricated by spontaneous adsorption and characterized by the above techniques. Size-selectively and molecular recognition of the {alpha}- and {beta}- cyclodextrin cavity are shown with our monolayers. Because of molecular recognition, p-nitrophenol is retained preferrentially by the cyclodextrin monolayers over o-nitrophenol. 146 refs., 44 figs., 5 tabs.

  18. Glycosyl-Templated Chiral Helix Stapling of Ethynylpyridine Oligomers by Alkene Metathesis between Inter-Pitch Side Chains.

    PubMed

    Abe, Hajime; Kayamori, Fumihiro; Inouye, Masahiko

    2015-06-22

    Ethynylpyridine polymers and oligomers consisting of 4-substituted pyridine rings linked by acetylene bonds at the 2- and 6-positions have been investigated. Ethynylpyridine oligomers covalently linked with a glycosyl chiral template form chiral helical complexes by intramolecular hydrogen bonding, in which the chirality of the template is translated to the helix. With a view to fixation of the chiral architecture, D/L-galactosyl- and D/L-mannosyl-linked ethynylpyridine oligomers have been developed with 4-(3-butenyloxy)pyridine units having alkene side chains. The helical structures are successfully stapled by alkene metathesis of the side chains. Subsequent removal of the chiral templates by acidolysis produces template-free stapled oligomers. The chiral, template-free, stapled oligomers show chiral helicity, which is resistant to polar solvents and heating.

  19. Crystallization and preliminary crystallographic study of oligomers of the haemolytic lectin CEL-III from the sea cucumber Cucumaria echinata.

    PubMed

    Unno, Hideaki; Hisamatsu, Keigo; Nagao, Tomonao; Tateya, Yuki; Matsumoto, Naoki; Goda, Shuichiro; Hatakeyama, Tomomitsu

    2013-04-01

    CEL-III is a Ca(2+)-dependent haemolytic lectin isolated from the marine invertebrate Cucumaria echinata. This lectin binds to Gal/GalNAc-containing carbohydrate chains on the cell surface and, after conformational changes, oligomerizes to form ion-permeable pores in cell membranes. CEL-III also forms soluble oligomers similar to those formed in cell membranes upon binding of specific carbohydrates in high-pH and high-salt solutions. These soluble and membrane CEL-III oligomers were crystallized and X-ray diffraction data were collected. Crystals of soluble oligomers and membrane oligomers diffracted X-rays to 3.3 and 4.2 Å resolution, respectively, using synchrotron radiation and the former was found to belong to space group C2. Self-rotation functional analysis of the soluble oligomer crystal suggested that it might be composed of heptameric CEL-III.

  20. Predicting Two-Dimensional Silicon Carbide Monolayers.

    PubMed

    Shi, Zhiming; Zhang, Zhuhua; Kutana, Alex; Yakobson, Boris I

    2015-10-27

    Intrinsic semimetallicity of graphene and silicene largely limits their applications in functional devices. Mixing carbon and silicon atoms to form two-dimensional (2D) silicon carbide (SixC1-x) sheets is promising to overcome this issue. Using first-principles calculations combined with the cluster expansion method, we perform a comprehensive study on the thermodynamic stability and electronic properties of 2D SixC1-x monolayers with 0 ≤ x ≤ 1. Upon varying the silicon concentration, the 2D SixC1-x presents two distinct structural phases, a homogeneous phase with well dispersed Si (or C) atoms and an in-plane hybrid phase rich in SiC domains. While the in-plane hybrid structure shows uniform semiconducting properties with widely tunable band gap from 0 to 2.87 eV due to quantum confinement effect imposed by the SiC domains, the homogeneous structures can be semiconducting or remain semimetallic depending on a superlattice vector which dictates whether the sublattice symmetry is topologically broken. Moreover, we reveal a universal rule for describing the electronic properties of the homogeneous SixC1-x structures. These findings suggest that the 2D SixC1-x monolayers may present a new "family" of 2D materials, with a rich variety of properties for applications in electronics and optoelectronics.

  1. Abscisic acid-lipid interactions: a phospholipid monolayer study.

    PubMed

    Bürner, H; Benz, R; Gimmler, H; Hartung, W; Stillwell, W

    1993-08-15

    Lipid monolayer studies were performed on a Langmuir trough in the absence and in the presence of the plant hormone abscisic acid (ABA). The ABA-induced effects on the lipid monolayers can be summarized as follows: (i) ABA as the free acid (pH below 5.3) increased the molecular area and slightly decreased the surface pressure in the collapse points of monolayers made of saturated, unsaturated and of mixed lipids; ABA as the anion showed only minor effects. (ii) The ABA-induced area increase of the lipid monolayers decreased when the surface pressure increased, but some ABA remained in the monolayers made of unsaturated phospholipids even at collapse pressure. (iii) The incorporation of ABA into the monolayers could be inhibited by adding the plant sterol beta-sitosterol to the monolayer forming phospholipids. (iv) There was no substantial difference of ABA action on plant phospholipids as compared with other phospholipids. (v) ABA had a much stronger influence on unsaturated phospholipids than on saturated ones. (vi) ABA decreased the phase-transition temperature of saturated phospholipids. These results, which agree with those obtained from phospholipid vesicle studies, indicate that the physical state of the lipid is important for the ability of ABA penetrating into the lipid monolayer. Finally, a possible relevance of these results is discussed in terms of the action of ABA on guard cell membranes of plants.

  2. Synthesis of copper monolayer and particles at aqueous organic interface

    NASA Astrophysics Data System (ADS)

    Yang, Jian-guang; Yang, Sheng-hai; Okamoto, Takeshi; Bessho, Takeshi; Satake, Shigeru; Ichino, Ryoichi; Okido, Masazumi

    2006-12-01

    Using aqueous-organic interface (water-oleic acid) reduction of Cu 2+ by ascorbic acid, hydrophobic copper monolayer and copper particles have been prepared and characterized. The resultant monolayer could be transferred from the interface onto solid substrate or be dissolved to yield an organosol and copper nanoparticles.

  3. Hydrogen exchange mass spectrometry of proteins at Langmuir monolayers

    PubMed Central

    Pirrone, Gregory F.; Vernon, Briana C.; Kent, Michael S.; Engen, John R.

    2015-01-01

    Hydrogen exchange (HX) mass spectrometry (MS) is valuable for providing conformational information for proteins/peptides that are very difficult to analyze with other methods such as peripheral membrane proteins and peptides that interact with membranes. We developed a new type of HX MS measurement that integrates Langmuir monolayers. A lipid monolayer was generated, a peptide or protein associated with it, and then the monolayer-associated peptide or protein was exposed to deuterium. The deuterated species was recovered from the monolayer, digested, and deuterium incorporation monitored by MS. Test peptides showed that deuterium recovery in an optimized protocol was equivalent to deuterium recovery in conventional solution HX MS. The reproducibility of the measurements was high despite the requirement of generating a new monolayer for each deuterium labeling time. We validated that known conformational changes in the presence of a monolayer/membrane could be observed with the peptide melittin and the myristoylated protein Arf-1. Results in an accompanying paper show that the method can reveal details of conformational changes in a protein (HIV-1 Nef) which adopts a different conformation depending on if it can insert into the lipid layer. Overall, the HX MS Langmuir monolayer method provided new and meaningful conformational information for proteins that associate with lipid layers. The combination of HX MS results with neutron or X-ray reflection of the same proteins in Langmuir monolayers can be more informative than isolated use of either method. PMID:26134943

  4. Topological, Valleytronic, and Optical Properties of Monolayer PbS.

    PubMed

    Wan, Wenhui; Yao, Yugui; Sun, Liangfeng; Liu, Cheng-Cheng; Zhang, Fan

    2017-03-01

    A PbS monolayer is demonstrated to be a novel platform for topological, valleytronic, and optical phenomena. Compressive strain can turn the trivial monolayer into a topological insulator. Optical pumping can facilitate charge, spin, and valley Hall effects tunable by external strain and light ellipticity. Similar results apply to other IV-VI semiconductors.

  5. SYNCHROTRON X - RAY OBSERVATIONS OF A MONOLAYER TEMPLATE FOR MINERALIZATION.

    SciTech Connect

    DIMASI,E.; GOWER,L.B.

    2000-11-27

    Mineral nucleation at a Langmuir film interface has been studied by synchrotron x-ray scattering. Diluted calcium bicarbonate solutions were used as subphases for arachidic and stearic acid monolayers, compressed in a Langmuir trough. Self-assembly of the monolayer template is observed directly, and subsequent crystal growth monitored in-situ.

  6. Amphiphilic siloxane phosphonate macromolecule monolayers at the air/water interface: effects of structure and temperature.

    PubMed

    Cabasso, Israel; Stesikova, Elvira

    2008-11-20

    A comprehensive study is reported of Langmuir-Blodgett (LB) films (spread at the air/water interface using the Langmuir balance technique) composed of surface active, nonionic, and OH-free amphiphilic siloxane phosphonate ester macromolecules. Analysis is made on three molecular structures in the form of linear polymer poly(diethylphosphono-benzyl-alphabeta-ethyl methylsiloxane) (PPEMS), cyclic oligomer methylphosphonobenzyl-alphabeta-ethyl cyclosiloxane (MPECS), and copolymer poly(PEMS-co-DMS). The surface pressure-surface area (pi -A) isotherms of homopolymer at 3-40 degrees C show a clear temperature-induced phase transition (plateaus at pit approximately 17-19 mN/m) below 10 degrees C. The magnitude of the transition substantially increases upon lowering the temperature (partial differential DeltaAt/ partial differential T approximately -0.1 nm2 unit(-1) deg(-1) and partial differential pi t / partial differential T approximately -0.25 mN m(-1) deg(-1)). The positive entropy and enthalpy gain infers that strong coupling with the subphase and excess hydration attributed to hydrogen bonding between the P=O bond and the subphase prevails at low temperatures. The cyclic oligomer MPECS forms a condensed monolayer at the air/water interface that does not display a similar transition in the experimental temperature range. The temperature sensitivity of MPECS film is observed only in the collapsed region. The nature of the interaction with the subphase is similar for MPECS and PPEMS, indicating that the size and thermal mobility are the controlling factors in these processes. The elasticity plot reveals two distinct states (above and below transition). This observation is supported by BAM images that show irregular spiral structures below 10 degrees C. The transition occurring in the copolymer at 20 degrees C is due to relaxation of the PDMS component. The two maxima shown in the elasticity plot indicate additive fractions of PPEMS and PDMS. The surface areas of these

  7. Methylene blue adsorption on a DMPA lipid langmuir monolayer.

    PubMed

    Giner Casares, Juan José; Camacho, Luis; Martín-Romero, Maria Teresa; López Cascales, José Javier

    2010-07-12

    Adsorption of methylene blue (MB) onto a dimyristoylphosphatidic acid (DMPA) Langmuir air/water monolayer is studied by molecular dynamics (MD) simulations, UV reflection spectroscopy and surface potential measurements. The free-energy profile associated with MB transfer from water to the lipid monolayer shows two minima of -66 and -60 kJ mol(-1) for its solid and gas phase, respectively, corresponding to a spontaneous thermodynamic process. From the position of the free-energy minima, it is possible to predict the precise location of MB in the interior of the DMPA monolayer. Thus, MB is accommodated in the phosphoryl or carbonyl region of the DMPA Langmuir air/water interface, depending on the isomorphic state (solid or gas phase, respectively). Reorientation of MB, measured from the bulk solution to the interior of the lipid monolayer, passes from a random orientation in bulk solution to an orientation parallel to the surface of the lipid monolayer when MB is absorbed.

  8. Reorientation of a dipolar monolayer and dipolar solvent.

    PubMed

    Yi, Taeil; Lichter, Seth

    2014-06-01

    The reliable persistence of an adhered monolayer film on a substrate is critical for film function. The process by which monolayers degrade or disperse remains unclear. Our study investigates the properties and dynamics of a solute of dipolar molecules initially adhered as a monolayer on a substrate in a water-like Stockmayer solvent. We find that for a rigid solute, both the solute and solvent show qualitatively different dynamics than for a flexible solute and its solvent. For the rigid solute, spreading is hindered and solvent orientation is more pronounced. We formulate a simple kinetic model that shows qualitatively similar results to the molecular dynamics simulations of the time evolution of the monolayer. Simple kinetics of molecules on substrates is a starting point for understanding important industrial monolayer applications and complex interactions on membranes.

  9. Monolayer-by-monolayer stacked pyramid-like MoS2 nanodots on monolayered MoS2 flakes with enhanced photoluminescence.

    PubMed

    Yuan, Cailei; Cao, Yingjie; Luo, Xingfang; Yu, Ting; Huang, Zhenping; Xu, Bo; Yang, Yong; Li, Qinliang; Gu, Gang; Lei, Wen

    2015-11-07

    The precise control of the morphology and crystal shape of MoS2 nanostructures is of particular importance for their application in nanoelectronic and optoelectronic devices. Here, we describe a single step route for the synthesis of monolayer-by-monolayer stacked pyramid-like MoS2 nanodots on monolayered MoS2 flakes using a chemical vapor deposition method. First-principles calculations demonstrated that the bandgap of the pyramid-like MoS2 nanodot is a direct bandgap. Enhanced local photoluminescence emission was observed in the pyramid-like MoS2 nanodot, in comparison with monolayered MoS2 flakes. The findings presented here provide new opportunities to tailor the physical properties of MoS2via morphology-controlled synthesis.

  10. A strategy for designing a peptide probe for detection of β-amyloid oligomers.

    PubMed

    Hu, Yang; Su, Baihao; Kim, Chung-Sei; Hernandez, Michael; Rostagno, Agueda; Ghiso, Jorge; Kim, Jin Ryoun

    2010-11-22

    Aggregation of β-amyloid (Aβ) is implicated in the pathology of Alzheimer's disease. Development of a robust strategy to detect Aβ oligomeric intermediates, which have been identified as significant toxic agents, would be highly beneficial in the screening of drug candidates as well as enhancing our understanding of Aβ oligomerization. Rapid, specific and quantitative detection, currently unavailable, would be highly preferred for accurate and reliable probing of transient Aβ oligomers. Here, we report the development of a novel peptide probe, PG46, based on the nature of Aβ self-assembly and the conformation-sensitive fluorescence of the biarsenical dye, FlAsH. PG46 was found to bind to Aβ oligomers and displayed an increase in FlAsH fluorescence upon binding. No such event was observed when PG46 was co-incubated with Aβ low-molecular-weight species or Aβ fibrils. Aβ oligomer detection was fast, and occurred within one hour without any additional sample incubation or preparation. We anticipate that the development of a strategy for detection of amyloid oligomers described in this study will be directly relevant to a host of other amyloidogenic proteins.

  11. The Effect of Molecular Weight on the Composite Properties of Cured Phenylethynyl Terminated Imide Oligomers

    NASA Technical Reports Server (NTRS)

    Smith, J. G., Jr.; Connell, J. W.; Hergenrother, P. M.

    1997-01-01

    As part of a program to develop high temperature/high performance structural resins for aeronautical applications, imide oligomers containing terminal phenylethynyl groups with calculated number average molecular weights of 1250, 2500 and 5000 g/mol were prepared, characterized, and evaluated as adhesives and composite matrix resins. The goal of this work was to develop resin systems that are processable using conventional processing equipment into void free composites that exhibit high mechanical properties with long term high temperature durability, and are not affected by exposure to common aircraft fluids. The imide oligomers containing terminal phenylethynyl groups were fabricated into titanium adhesive specimens and IM-7 carbon fiber laminates under 0.1 - 1.4 MPa for 1 hr at 350-371 C. The lower molecular weight oligomers exhibited higher cured Tg, better processability, and better retention of mechanical properties at elevated temperature without significantly sacrificing toughness or damage tolerance than the higher molecular weight oligomer. The neat resin, adhesive and composite properties of the cured polymers will be presented.

  12. Methyl-esterified 3-hydroxybutyrate oligomers protect bacteria from hydroxyl radicals.

    PubMed

    Koskimäki, Janne J; Kajula, Marena; Hokkanen, Juho; Ihantola, Emmi-Leena; Kim, Jong H; Hautajärvi, Heidi; Hankala, Elina; Suokas, Marko; Pohjanen, Johanna; Podolich, Olga; Kozyrovska, Natalia; Turpeinen, Ari; Pääkkönen, Mirva; Mattila, Sampo; Campbell, Bruce C; Pirttilä, Anna Maria

    2016-05-01

    Bacteria rely mainly on enzymes, glutathione and other low-molecular weight thiols to overcome oxidative stress. However, hydroxyl radicals are the most cytotoxic reactive oxygen species, and no known enzymatic system exists for their detoxification. We now show that methyl-esterified dimers and trimers of 3-hydroxybutyrate (ME-3HB), produced by bacteria capable of polyhydroxybutyrate biosynthesis, have 3-fold greater hydroxyl radical-scavenging activity than glutathione and 11-fold higher activity than vitamin C or the monomer 3-hydroxybutyric acid. We found that ME-3HB oligomers protect hypersensitive yeast deletion mutants lacking oxidative stress-response genes from hydroxyl radical stress. Our results show that phaC and phaZ, encoding polymerase and depolymerase, respectively, are activated and polyhydroxybutyrate reserves are degraded for production of ME-3HB oligomers in bacteria infecting plant cells and exposed to hydroxyl radical stress. We found that ME-3HB oligomer production is widespread, especially in bacteria adapted to stressful environments. We discuss how ME-3HB oligomers could provide opportunities for numerous applications in human health.

  13. High-resolution NMR characterization of low abundance oligomers of amyloid-β without purification.

    PubMed

    Kotler, Samuel A; Brender, Jeffrey R; Vivekanandan, Subramanian; Suzuki, Yuta; Yamamoto, Kazutoshi; Monette, Martine; Krishnamoorthy, Janarthanan; Walsh, Patrick; Cauble, Meagan; Holl, Mark M Banaszak; Marsh, E Neil G; Ramamoorthy, Ayyalusamy

    2015-07-03

    Alzheimer's disease is characterized by the misfolding and self-assembly of the amyloidogenic protein amyloid-β (Aβ). The aggregation of Aβ leads to diverse oligomeric states, each of which may be potential targets for intervention. Obtaining insight into Aβ oligomers at the atomic level has been a major challenge to most techniques. Here, we use magic angle spinning recoupling (1)H-(1)H NMR experiments to overcome many of these limitations. Using (1)H-(1)H dipolar couplings as a NMR spectral filter to remove both high and low molecular weight species, we provide atomic-level characterization of a non-fibrillar aggregation product of the Aβ1-40 peptide using non-frozen samples without isotopic labeling. Importantly, this spectral filter allows the detection of the specific oligomer signal without a separate purification procedure. In comparison to other solid-state NMR techniques, the experiment is extraordinarily selective and sensitive. A resolved 2D spectra could be acquired of a small population of oligomers (6 micrograms, 7% of the total) amongst a much larger population of monomers and fibers (93% of the total). By coupling real-time (1)H-(1)H NMR experiments with other biophysical measurements, we show that a stable, primarily disordered Aβ1-40 oligomer 5-15 nm in diameter can form and coexist in parallel with the well-known cross-β-sheet fibrils.

  14. A simple procedure for preparing chitin oligomers through acetone precipitation after hydrolysis in concentrated hydrochloric acid.

    PubMed

    Kazami, Nao; Sakaguchi, Masayoshi; Mizutani, Daisuke; Masuda, Tatsuhiko; Wakita, Satoshi; Oyama, Fumitaka; Kawakita, Masao; Sugahara, Yasusato

    2015-11-05

    Chitin oligomers are of interest because of their numerous biologically relevant properties. To prepare chitin oligomers containing 4-6 GlcNAc units [(GlcNAc)4-6], α- and β-chitin were hydrolyzed with concentrated hydrochloric acid at 40 °C. The reactant was mixed with acetone to recover the acetone-insoluble material, and (GlcNAc)4-6 was efficiently recovered after subsequent water extraction. Composition analysis using gel permeation chromatography and MALDI-TOF mass spectrometry indicated that (GlcNAc)4-6 could be isolated from the acetone-insoluble material with recoveries of approximately 17% and 21% from the starting α-chitin and β-chitin, respectively. The acetone precipitation method is highly useful for recovering chitin oligomers from the acid hydrolysate of chitin. The changes in the molecular size and higher-order structure of chitin during the course of hydrolysis were also analyzed, and a model that explains the process of oligomer accumulation is proposed.

  15. A method for the 32P labeling of peptides or peptide nucleic acid oligomers

    NASA Technical Reports Server (NTRS)

    Kozlov, I. A.; Nielsen, P. E.; Orgel, L. E.; Bada, J. L. (Principal Investigator)

    1998-01-01

    A novel approach to the radioactive labeling of peptides and PNA oligomers is described. It is based on the conjugation of a deoxynucleoside 3'-phosphate with the terminal amine of the substrate, followed by phosphorylation of the 5'-hydroxyl group of the nucleotide using T4 polynucleotide kinase and [gamma-32P]ATP.

  16. Efficient synthesis of oxygenated terphenyls and other oligomers: sequential arylation reactions through phenol oxidation-rearomatization.

    PubMed

    Dohi, Toshifumi; Kamitanaka, Tohru; Watanabe, Shohei; Hu, Yinjun; Washimi, Naohiko; Kita, Yasuyuki

    2012-10-22

    One by one: starting from simple phenols, a diverse series of oxygenated terphenyl compounds can be prepared in a concise and practical manner using sequential arylation reactions involving phenol oxidation/rearomatization and quinone monoacetal intermediates. Many of the terphenyl products can be used for preparing well-defined oligomers and, furthermore, contain valuable functional groups that can be transformed for further diversification.

  17. Conformational Flexibility of Soluble Cellulose Oligomers: Chain Length and Temperature Dependence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Structures, dynamics, and stabilities of different sized cellulosic oligomers need to be considered when designing enzymatic cocktails for the conversion of biomass to biofuels since they can be both productive substrates and inhibitors of the overall process. In the present work, the conformational...

  18. Complement Protein C1q Forms a Complex with Cytotoxic Prion Protein Oligomers

    PubMed Central

    Erlich, Paul; Dumestre-Pérard, Chantal; Ling, Wai Li; Lemaire-Vieille, Catherine; Schoehn, Guy; Arlaud, Gérard J.; Thielens, Nicole M.; Gagnon, Jean; Cesbron, Jean-Yves

    2010-01-01

    A growing number of studies have investigated the interaction between C1q and PrP, but the oligomeric form of PrP involved in this interaction remains to be determined. Aggregation of recombinant full-length murine PrP in the presence of 100 mm NaCl allowed us to isolate three different types of oligomers by size-exclusion chromatography. In contrast to PrP monomers and fibrils, these oligomers activate the classical complement pathway, the smallest species containing 8–15 PrP protomers being the most efficient. We used Thioflavine T fluorescence to monitor PrP aggregation and showed that, when added to the reaction, C1q has a cooperative effect on PrP aggregation and leads to the formation of C1q-PrP complexes. In these complexes, C1q interacts through its globular domains preferentially with the smallest oligomers, as shown by electron microscopy, and retains the ability to activate the classical complement pathway. Using two cell lines, we also provide evidence that C1q inhibits the cytotoxicity induced by the smallest PrP oligomers. The cooperative interaction between C1q and PrP could represent an early step in the disease, where it prevents elimination of the prion seed, leading to further aggregation. PMID:20410306

  19. UV curable lens production using molecular weight controlled PEEK based acrylic oligomer (Ac-PEEK).

    PubMed

    İnan, Tulay Y; Yıldız, Emel; Karaca, Birsen; Dogan, Hacer; Vatansever, Alican; Nalbant, Muhammed; Eken, Koray

    2014-08-01

    We produced UV curable lenses with properties blocking short wave UV light. In the UV-curable formulations, we used an oligomer (Ac-PEEK) with another urethan oligomer (Mw = 2000). Radically active, molecular weight controlled Ac-PEEK was obtained by reacting 2-hydroxyl ethyl methacrylate with molecular- weight- controlled and isocyanate terminated PEEK (Mn = 4500). We characterized all synthesized monomer, oligomer and optical materials with UV/Vis spectrophotometer with interferogram, elemental analyser, mass spectrophotometer, proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, thermal gravimetric analyzer, differential scanning calorimeter, scanning electron microscopy and gas chromatography. Results suggested that newly synthesized oligomer with the structure of PEEK absorbs short wave UV-light. Ageing tests [ISO 11979-5, Ophthalmic implants-intraocular lenses (IOL)-Part 5: Biocompatibility] performed on the IOL materials were successful. High contact angle of the obtained lenses suggests that all lenses were hydrophobic and SEM results revealed that lenses are morphologically homogeneous. Based on all positive properties just mentioned, we safely conclude that the lenses produced in this study are very promising for IOL production.

  20. Structural characterization of toxic oligomers that are kinetically trapped during α-synuclein fibril formation

    PubMed Central

    Chen, Serene W.; Drakulic, Srdja; Deas, Emma; Ouberai, Myriam; Aprile, Francesco A.; Arranz, Rocío; Ness, Samuel; Roodveldt, Cintia; Guilliams, Tim; De-Genst, Erwin J.; Klenerman, David; Wood, Nicholas W.; Knowles, Tuomas P.J.; Alfonso, Carlos; Rivas, Germán; Abramov, Andrey Y.; Valpuesta, José María; Dobson, Christopher M.; Cremades, Nunilo

    2015-01-01

    We describe the isolation and detailed structural characterization of stable toxic oligomers of α-synuclein that have accumulated during the process of amyloid formation. Our approach has allowed us to identify distinct subgroups of oligomers and to probe their molecular architectures by using cryo-electron microscopy (cryoEM) image reconstruction techniques. Although the oligomers exist in a range of sizes, with different extents and nature of β-sheet content and exposed hydrophobicity, they all possess a hollow cylindrical architecture with similarities to certain types of amyloid fibril, suggesting that the accumulation of at least some forms of amyloid oligomers is likely to be a consequence of very slow rates of rearrangement of their β-sheet structures. Our findings reveal the inherent multiplicity of the process of protein misfolding and the key role the β-sheet geometry acquired in the early stages of the self-assembly process plays in dictating the kinetic stability and the pathological nature of individual oligomeric species. PMID:25855634

  1. Structural characterization of toxic oligomers that are kinetically trapped during α-synuclein fibril formation.

    PubMed

    Chen, Serene W; Drakulic, Srdja; Deas, Emma; Ouberai, Myriam; Aprile, Francesco A; Arranz, Rocío; Ness, Samuel; Roodveldt, Cintia; Guilliams, Tim; De-Genst, Erwin J; Klenerman, David; Wood, Nicholas W; Knowles, Tuomas P J; Alfonso, Carlos; Rivas, Germán; Abramov, Andrey Y; Valpuesta, José María; Dobson, Christopher M; Cremades, Nunilo

    2015-04-21

    We describe the isolation and detailed structural characterization of stable toxic oligomers of α-synuclein that have accumulated during the process of amyloid formation. Our approach has allowed us to identify distinct subgroups of oligomers and to probe their molecular architectures by using cryo-electron microscopy (cryoEM) image reconstruction techniques. Although the oligomers exist in a range of sizes, with different extents and nature of β-sheet content and exposed hydrophobicity, they all possess a hollow cylindrical architecture with similarities to certain types of amyloid fibril, suggesting that the accumulation of at least some forms of amyloid oligomers is likely to be a consequence of very slow rates of rearrangement of their β-sheet structures. Our findings reveal the inherent multiplicity of the process of protein misfolding and the key role the β-sheet geometry acquired in the early stages of the self-assembly process plays in dictating the kinetic stability and the pathological nature of individual oligomeric species.

  2. An update on the physiological and therapeutic relevance of GPCR oligomers.

    PubMed

    Farran, Batoul

    2017-03-01

    The traditional view on GPCRs held that they function as single monomeric units composed of identical subunits. This notion was overturned by the discovery that GPCRs can form homo- and hetero-oligomers, some of which are obligatory, and can further assemble into receptor mosaics consisting of three or more protomers. Oligomerisation exerts significant impacts on receptor function and physiology, offering a platform for the diversification of receptor signalling, pharmacology, regulation, crosstalk, internalization and trafficking. Given their involvement in the modulation of crucial physiological processes, heteromers could constitute important therapeutic targets for a wide range of diseases, including schizophrenia, Parkinson's disease, substance abuse or obesity. This review aims at depicting the current developments in GPCR oligomerisation research, documenting various class A, B and C GPCR heteromers detected in vitro and in vivo using biochemical and biophysical approaches, as well as recently identified higher-order oligomeric complexes. It explores the current understanding of dimerization dynamics and the possible interaction interfaces that drive oligomerisation. Most importantly, it provides an inventory of the wide range of physiological processes and pathophysiological conditions to which GPCR oligomers contribute, surveying some of the oligomers that constitute potential drug targets. Finally, it delineates the efforts to develop novel classes of ligands that specifically target and tether to receptor oligomers instead of a single monomeric entity, thus ameliorating their ability to modulate GPCR function.

  3. The Role of Initial Oligomers in Amyloid Fibril Formation by Human Stefin B

    PubMed Central

    Taler-Verčič, Ajda; Kirsipuu, Tiina; Friedemann, Merlin; Noormägi, Andra; Polajnar, Mira; Smirnova, Julia; Žnidarič, Magda Tušek; Žganec, Matjaž; Škarabot, Miha; Vilfan, Andrej; Staniforth, Rosemary A.; Palumaa, Peep; Žerovnik, Eva

    2013-01-01

    Oligomers are commonly observed intermediates at the initial stages of amyloid fibril formation. They are toxic to neurons and cause decrease in neural transmission and long-term potentiation. We describe an in vitro study of the initial steps in amyloid fibril formation by human stefin B, which proved to be a good model system. Due to relative stability of the initial oligomers of stefin B, electrospray ionization mass spectrometry (ESI MS) could be applied in addition to size exclusion chromatography (SEC). These two techniques enabled us to separate and detect distinguished oligomers from the monomers: dimers, trimers, tetramers, up to decamers. The amyloid fibril formation process was followed at different pH and temperatures, including such conditions where the process was slow enough to detect the initial oligomeric species at the very beginning of the lag phase and those at the end of the lag phase. Taking into account the results of the lower-order oligomers transformations early in the process, we were able to propose an improved model for the stefin B fibril formation. PMID:24013380

  4. Studies in the Mineral and Salt-Catalyzed Formation of RNA Oligomers

    NASA Astrophysics Data System (ADS)

    Miyakawa, Shin; Joshi, Prakash C.; Gaffey, Michael J.; Gonzalez-Toril, Elena; Hyland, Callen; Ross, Teresa; Rybij, Kristin; Ferris, James P.

    2006-08-01

    Activated mononucleotides oligomerize in the presence of montmorillonite clay to form RNA oligomers. In the present study, effects of salts, temperature and pH on the clay-catalyzed synthesis of RNA oligomers were investigated. This reaction is favored by relatively high concentration of salts, such as 1 M NaCl. It was shown that the presence of divalent cations was not required for this reaction. High concentrations of NH4 + and HCO3 - and 0.01 M HPO4 2- inhibit the reaction. The yields of RNA oligomers decreased as the temperature was raised from 4 ^∘C to 50 ^∘C. A5' ppA was the major product at pH's below 6. The catalytic activity of a variety of minerals and three meteorites were investigated but none of them except galena catalyzed the oligomerization. ATP was generated from ADP but it was due to the presence of HEPES buffer and not due to the minerals. Meteorites catalyzed the hydrolysis of the pyrophosphate bonds of ATP. The results suggest that oligomers of RNA could have formed in pH 7-9 solutions of alkali metal salts in the presence of montmorillonite clay.

  5. Chemistry and properties of imide oligomers containing pendant and terminal phenylethynyl groups

    SciTech Connect

    Smith, J.G. Jr.

    1996-12-31

    As part of a continuing effort to develop high performance/high temperature structural resins for aeronautical applications, oligomers containing latent reactive groups have been under investigation. Material requirements include ease of processability, retention of mechanical properties at elevated temperature, and no loss of mechanical properties after exposure to aircraft fluids such as hydraulic fluid, jet fuel, and cleaning fluids. The phenylethynyl group is an ideal latent reactive group. It has a relatively high cure temperature ({approximately}350{degrees}C) and a large processing window can be obtained with materials possessing the proper glass transition temperature. The thermally cured materials exhibit good retention of mechanical properties at elevated temperatures with no significant loss of properties after exposure to various solvents. To date, the phenylethynyl group has been incorporated either terminal or pendant to a variety of imide oligomers. Upon thermal cure, the phenylethynyl group undergoes chain extension, branching and/or crosslinking; however, the final cured product has not been well defined. As an extension of this work, a series of imide oligomers containing both pendant and terminal phenylethynyl groups (PTPEIs) were prepared as a means to improve retention of mechanical properties at elevated temperature while maintaining processability. The PTPEI oligomers were characterized, thermally cured and the cured polymers evaluated as unoriented thin films and adhesives. The chemistry, physical, and mechanical properties of these materials will be discussed.

  6. Alzheimer's disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers

    PubMed Central

    De Felice, Fernanda G.; Wu, Diana; Lambert, Mary P.; Fernandez, Sara J.; Velasco, Pauline T.; Lacor, Pascale N.; Bigio, Eileen H.; Jerecic, Jasna; Acton, Paul J.; Shughrue, Paul J.; Chen-Dodson, Elizabeth; Kinney, Gene G.; Klein, William L.

    2008-01-01

    Alzheimer’s disease (AD) is characterized by presence of extracellular fibrillar Aβ in amyloid plaques, intraneuronal neurofibrillary tangles consisting of aggregated hyperphosphorylated tau and elevated brain levels of soluble Aβ oligomers (ADDLs). A major question is how these disparate facets of AD pathology are mechanistically related. Here we show that, independent of the presence of fibrils, ADDLs stimulate tau phosphorylation in mature cultures of hippocampal neurons and in neuroblastoma cells at epitopes characteristically hyperphosphorylated in AD. A monoclonal antibody that targets ADDLs blocked their attachment to synaptic binding sites and prevented tau hyperphosphorylation. Tau phosphorylation was blocked by the Src family tyrosine kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7(t-butyl)pyrazol(3,4-D)pyramide (PP1), and by the phosphatidylinositol-3-kinase inhibitor LY294002. Significantly, tau hyperphosphorylation was also induced by a soluble aqueous extract containing Aβ oligomers from AD brains, but not by an extract from non-AD brains. Aβ oligomers have been increasingly implicated as the main neurotoxins in AD, and the current results provide a unifying mechanism in which oligomer activity is directly linked to tau hyperphosphorylation in AD pathology. PMID:17403556

  7. Enhanced Volatile Organic Compounds emissions and organic aerosol mass increase the oligomer content of atmospheric aerosols.

    PubMed

    Kourtchev, Ivan; Giorio, Chiara; Manninen, Antti; Wilson, Eoin; Mahon, Brendan; Aalto, Juho; Kajos, Maija; Venables, Dean; Ruuskanen, Taina; Levula, Janne; Loponen, Matti; Connors, Sarah; Harris, Neil; Zhao, Defeng; Kiendler-Scharr, Astrid; Mentel, Thomas; Rudich, Yinon; Hallquist, Mattias; Doussin, Jean-Francois; Maenhaut, Willy; Bäck, Jaana; Petäjä, Tuukka; Wenger, John; Kulmala, Markku; Kalberer, Markus

    2016-10-13

    Secondary organic aerosol (SOA) accounts for a dominant fraction of the submicron atmospheric particle mass, but knowledge of the formation, composition and climate effects of SOA is incomplete and limits our understanding of overall aerosol effects in the atmosphere. Organic oligomers were discovered as dominant components in SOA over a decade ago in laboratory experiments and have since been proposed to play a dominant role in many aerosol processes. However, it remains unclear whether oligomers are relevant under ambient atmospheric conditions because they are often not clearly observed in field samples. Here we resolve this long-standing discrepancy by showing that elevated SOA mass is one of the key drivers of oligomer formation in the ambient atmosphere and laboratory experiments. We show for the first time that a specific organic compound class in aerosols, oligomers, is strongly correlated with cloud condensation nuclei (CCN) activities of SOA particles. These findings might have important implications for future climate scenarios where increased temperatures cause higher biogenic volatile organic compound (VOC) emissions, which in turn lead to higher SOA mass formation and significant changes in SOA composition. Such processes would need to be considered in climate models for a realistic representation of future aerosol-climate-biosphere feedbacks.

  8. Allosteric modulation in monomers and oligomers of a G protein-coupled receptor

    PubMed Central

    Shivnaraine, Rabindra V; Kelly, Brendan; Sankar, Krishana S; Redka, Dar'ya S; Han, Yi Rang; Huang, Fei; Elmslie, Gwendolynne; Pinto, Daniel; Li, Yuchong; Rocheleau, Jonathan V; Gradinaru, Claudiu C; Ellis, John; Wells, James W

    2016-01-01

    The M2 muscarinic receptor is the prototypic model of allostery in GPCRs, yet the molecular and the supramolecular determinants of such effects are unknown. Monomers and oligomers of the M2 muscarinic receptor therefore have been compared to identify those allosteric properties that are gained in oligomers. Allosteric interactions were monitored by means of a FRET-based sensor of conformation at the allosteric site and in pharmacological assays involving mutants engineered to preclude intramolecular effects. Electrostatic, steric, and conformational determinants of allostery at the atomic level were examined in molecular dynamics simulations. Allosteric effects in monomers were exclusively negative and derived primarily from intramolecular electrostatic repulsion between the allosteric and orthosteric ligands. Allosteric effects in oligomers could be positive or negative, depending upon the allosteric-orthosteric pair, and they arose from interactions within and between the constituent protomers. The complex behavior of oligomers is characteristic of muscarinic receptors in myocardial preparations. DOI: http://dx.doi.org/10.7554/eLife.11685.001 PMID:27151542

  9. Use of Doubly Charged Precursors to Validate Dissociation Mechanisms of Singly Charged Poly(Dimethylsiloxane) Oligomers

    NASA Astrophysics Data System (ADS)

    Fouquet, Thierry; Toniazzo, Valérie; Ruch, David; Charles, Laurence

    2013-07-01

    Collision-induced dissociation of doubly charged poly(dimethylsiloxane) (PDMS) molecules was investigated to provide experimental evidence for fragmentation reactions proposed to occur upon activation of singly charged oligomers. This study focuses on two PDMS species holding trimethylsilyl or methoxy end-groups and cationized with ammonium. In both cases, introduction of the additional charge did not induce significant differences in dissociation behavior, and the use of doubly charged precursors enabled the occurrence of charge-separation reactions, allowing molecules always eliminated as neutrals upon activation of singly charged oligomers to be detected as cationized species. In the case of trimethylsilyl-terminated oligomers, random location of the adducted charge combined with rapid consecutive reactions proposed to occur from singly charged precursors could be validated based on MS/MS data of doubly charged oligomers. In the case of methoxy-terminated PDMS, favored interaction of the adducted ammonium with both end-groups, proposed to rationalize the dissociation behavior of singly charged molecules, was also supported by MS/MS data obtained for molecules adducted with two ammonium cations.

  10. Stabilizing Off-pathway Oligomers by Polyphenol Nanoassemblies for IAPP Aggregation Inhibition

    NASA Astrophysics Data System (ADS)

    Nedumpully-Govindan, Praveen; Kakinen, Aleksandr; Pilkington, Emily H.; Davis, Thomas P.; Chun Ke, Pu; Ding, Feng

    2016-01-01

    Experimental studies have shown that many naturally occurring polyphenols have inhibitory effect on the aggregation of several proteins. Here, we use discrete molecular dynamics (DMD) simulations and high-throughput dynamic light scattering (DLS) experiments to study the anti-aggregation effects of two polyphenols, curcumin and resveratrol, on the aggregation of islet amyloid polypeptide (IAPP or amylin). Our DMD simulations suggest that the aggregation inhibition is caused by stabilization of small molecular weight IAPP off-pathway oligomers by the polyphenols. Our analysis indicates that IAPP-polyphenol hydrogen bonds and π-π stacking combined with hydrophobic interactions are responsible for the stabilization of oligomers. The presence of small oligomers is confirmed with DLS measurements in which nanometer-sized oligomers are found to be stable for up to 7.5 hours, the time frame within which IAPP aggregates in the absence of polyphenols. Our study offers a general anti-aggregation mechanism for polyphenols, and further provides a computational framework for the future design of anti-amyloid aggregation therapeutics.

  11. Chemical evolution. XXII - The hydantoins released on hydrolysis of HCN oligomers

    NASA Technical Reports Server (NTRS)

    Ferris, J. P.; Wos, J. D.; Lobo, A. P.

    1974-01-01

    The isolation of three hydantoins from HCN oligomers is described. One of these hydantoins, 5-carboxymethylidine hydantoin (5-CMH), rearranges to pyrimidine orotic acid in basic solution. The isolation of 5-CMH suggests the possibility that pyrimidines were formed directly from HCN on the primitive earth.

  12. WASP-1, a canonical Wnt signaling potentiator, rescues hippocampal synaptic impairments induced by Aβ oligomers.

    PubMed

    Vargas, Jessica Y; Ahumada, Juan; Arrázola, Macarena S; Fuenzalida, Marco; Inestrosa, Nibaldo C

    2015-02-01

    Amyloid-β (Aβ) oligomers are a key factor in Alzheimer's disease (AD)-associated synaptic dysfunction. Aβ oligomers block the induction of hippocampal long-term potentiation (LTP) in rodents. The activation of Wnt signaling prevents Aβ oligomer-induced neurotoxic effects. The compound WASP-1 (Wnt-activating small molecule potentiator-1), has been described as a synergist of the ligand Wnt-3a, enhancing the activation of Wnt/β-catenin signaling. Herein, we report that WASP-1 administration successfully rescued Aβ-induced synaptic impairments both in vitro and in vivo. The activation of canonical Wnt/β-catenin signaling by WASP-1 increased synaptic transmission and rescued hippocampal LTP impairments induced by Aβ oligomers. Additionally, intra-hippocampal administration of WASP-1 to the double transgenic APPswe/PS1dE9 mouse model of AD prevented synaptic protein loss and reduced tau phosphorylation levels. Moreover, we found that WASP-1 blocked Aβ aggregation in vitro and reduced pathological tau phosphorylation in vivo. These results indicate that targeting canonical Wnt signaling with WASP-1 could have value for treating AD.

  13. Enhanced Volatile Organic Compounds emissions and organic aerosol mass increase the oligomer content of atmospheric aerosols

    NASA Astrophysics Data System (ADS)

    Kourtchev, Ivan; Giorio, Chiara; Manninen, Antti; Wilson, Eoin; Mahon, Brendan; Aalto, Juho; Kajos, Maija; Venables, Dean; Ruuskanen, Taina; Levula, Janne; Loponen, Matti; Connors, Sarah; Harris, Neil; Zhao, Defeng; Kiendler-Scharr, Astrid; Mentel, Thomas; Rudich, Yinon; Hallquist, Mattias; Doussin, Jean-Francois; Maenhaut, Willy; Bäck, Jaana; Petäjä, Tuukka; Wenger, John; Kulmala, Markku; Kalberer, Markus

    2016-10-01

    Secondary organic aerosol (SOA) accounts for a dominant fraction of the submicron atmospheric particle mass, but knowledge of the formation, composition and climate effects of SOA is incomplete and limits our understanding of overall aerosol effects in the atmosphere. Organic oligomers were discovered as dominant components in SOA over a decade ago in laboratory experiments and have since been proposed to play a dominant role in many aerosol processes. However, it remains unclear whether oligomers are relevant under ambient atmospheric conditions because they are often not clearly observed in field samples. Here we resolve this long-standing discrepancy by showing that elevated SOA mass is one of the key drivers of oligomer formation in the ambient atmosphere and laboratory experiments. We show for the first time that a specific organic compound class in aerosols, oligomers, is strongly correlated with cloud condensation nuclei (CCN) activities of SOA particles. These findings might have important implications for future climate scenarios where increased temperatures cause higher biogenic volatile organic compound (VOC) emissions, which in turn lead to higher SOA mass formation and significant changes in SOA composition. Such processes would need to be considered in climate models for a realistic representation of future aerosol-climate-biosphere feedbacks.

  14. Student-Driven Design of Peptide Mimetics: Microwave-Assisted Synthesis of Peptoid Oligomers

    ERIC Educational Resources Information Center

    Pohl, Nicola L. B.; Kirshenbaum, Kent; Yoo, Barney; Schulz, Nathan; Zea, Corbin J.; Streff, Jennifer M.; Schwarz, Kimberly L.

    2011-01-01

    An experiment for the undergraduate organic laboratory is described in which peptide mimetic oligomers called "peptoids" are built stepwise on a solid-phase resin. Students employ two modern strategies to facilitate rapid multistep syntheses: solid-phase techniques to obviate the need for intermediate purifications and microwave irradiation to…

  15. Rapid Multistep Synthesis of a Bioactive Peptidomimetic Oligomer for the Undergraduate Laboratory

    ERIC Educational Resources Information Center

    Utku, Yeliz; Rohatgi, Abhinav; Yoo, Barney; Kirshenbaum, Kent; Zuckermann, Ronald N.; Pohl, Nicola L.

    2010-01-01

    Peptidomimetic compounds are increasingly important in drug-discovery applications. We introduce the synthesis of an N-substituted glycine oligomer, a bioactive "peptoid" trimer. The six-step protocol is conducted on solid-phase resin, enabling the synthesis to be performed by undergraduate organic chemistry students. This synthesis lab was…

  16. Synthesis and Properties of Bis(aniline, methyl)siloxy-octaphenylsilsesquioxane Modified Thermosetting Polyimide Oligomers

    DTIC Science & Technology

    2011-08-19

    Conference Paper 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Synthesis and Properties of Bis( aniline , methyl)siloxy...SYNTHESIS AND PROPERTIES OF BIS( ANILINE , METHYL)SILOXY-OCTAPHENYLSILSESQUIOXANE MODIFIED THERMOSETTING POLYIMIDE OLIGOMERS Gregory R. Yandek1...oxydiphenylene aniline (Kapton™) reduced its moisture uptake by 83% concurrently improving mechanical properties.4 The objective of this work is to

  17. Stabilizing Off-pathway Oligomers by Polyphenol Nanoassemblies for IAPP Aggregation Inhibition

    PubMed Central

    Nedumpully-Govindan, Praveen; Kakinen, Aleksandr; Pilkington, Emily H.; Davis, Thomas P.; Chun Ke, Pu; Ding, Feng

    2016-01-01

    Experimental studies have shown that many naturally occurring polyphenols have inhibitory effect on the aggregation of several proteins. Here, we use discrete molecular dynamics (DMD) simulations and high-throughput dynamic light scattering (DLS) experiments to study the anti-aggregation effects of two polyphenols, curcumin and resveratrol, on the aggregation of islet amyloid polypeptide (IAPP or amylin). Our DMD simulations suggest that the aggregation inhibition is caused by stabilization of small molecular weight IAPP off-pathway oligomers by the polyphenols. Our analysis indicates that IAPP-polyphenol hydrogen bonds and π-π stacking combined with hydrophobic interactions are responsible for the stabilization of oligomers. The presence of small oligomers is confirmed with DLS measurements in which nanometer-sized oligomers are found to be stable for up to 7.5 hours, the time frame within which IAPP aggregates in the absence of polyphenols. Our study offers a general anti-aggregation mechanism for polyphenols, and further provides a computational framework for the future design of anti-amyloid aggregation therapeutics. PMID:26763863

  18. Optimization of the All-D Peptide D3 for Aβ Oligomer Elimination.

    PubMed

    Klein, Antonia Nicole; Ziehm, Tamar; Tusche, Markus; Buitenhuis, Johan; Bartnik, Dirk; Boeddrich, Annett; Wiglenda, Thomas; Wanker, Erich; Funke, Susanne Aileen; Brener, Oleksandr; Gremer, Lothar; Kutzsche, Janine; Willbold, Dieter

    2016-01-01

    The aggregation of amyloid-β (Aβ) is postulated to be the crucial event in Alzheimer's disease (AD). In particular, small neurotoxic Aβ oligomers are considered to be responsible for the development and progression of AD. Therefore, elimination of thesis oligomers represents a potential causal therapy of AD. Starting from the well-characterized d-enantiomeric peptide D3, we identified D3 derivatives that bind monomeric Aβ. The underlying hypothesis is that ligands bind monomeric Aβ and stabilize these species within the various equilibria with Aβ assemblies, leading ultimately to the elimination of Aβ oligomers. One of the hereby identified d-peptides, DB3, and a head-to-tail tandem of DB3, DB3DB3, were studied in detail. Both peptides were found to: (i) inhibit the formation of Thioflavin T-positive fibrils; (ii) bind to Aβ monomers with micromolar affinities; (iii) eliminate Aβ oligomers; (iv) reduce Aβ-induced cytotoxicity; and (v) disassemble preformed Aβ aggregates. The beneficial effects of DB3 were improved by DB3DB3, which showed highly enhanced efficacy. Our approach yielded Aβ monomer-stabilizing ligands that can be investigated as a suitable therapeutic strategy against AD.

  19. The Volumetric Diversity of Misfolded Prion Protein Oligomers Revealed by Pressure Dissociation*

    PubMed Central

    Torrent, Joan; Lange, Reinhard; Rezaei, Human

    2015-01-01

    Protein oligomerization has been associated with a wide range of diseases. High pressure approaches offer a powerful tool for deciphering the underlying molecular mechanisms by revealing volume changes associated with the misfolding and assembly reactions. We applied high pressure to induce conformational changes in three distinct β-sheet-rich oligomers of the prion protein PrP, a protein characterized by a variety of infectious quaternary structures that can propagate stably and faithfully and cause diseases with specific phenotypic traits. We show that pressure induces dissociation of the oligomers and leads to a lower volume monomeric PrP state that refolds into the native conformation after pressure release. By measuring the different pressure and temperature sensitivity of the tested PrP oligomers, we demonstrate significantly different void volumes in their quaternary structure. In addition, by focusing on the kinetic and energetic behavior of the pressure-induced dissociation of one specific PrP oligomer, we reveal a large negative activation volume and an increase in both apparent activation enthalpy and entropy. This suggests a transition state ensemble that is less structured and significantly more hydrated than the oligomeric state. Finally, we found that site-specific fluorescent labeling allows monitoring of the transient population of a kinetic intermediate in the dissociation reaction. Our results indicate that defects in atomic packing may deserve consideration as a new factor that influences differences between PrP assemblies and that could be relevant also for explaining the origin of prion strains. PMID:26126829

  20. Enhanced Volatile Organic Compounds emissions and organic aerosol mass increase the oligomer content of atmospheric aerosols

    PubMed Central

    Kourtchev, Ivan; Giorio, Chiara; Manninen, Antti; Wilson, Eoin; Mahon, Brendan; Aalto, Juho; Kajos, Maija; Venables, Dean; Ruuskanen, Taina; Levula, Janne; Loponen, Matti; Connors, Sarah; Harris, Neil; Zhao, Defeng; Kiendler-Scharr, Astrid; Mentel, Thomas; Rudich, Yinon; Hallquist, Mattias; Doussin, Jean-Francois; Maenhaut, Willy; Bäck, Jaana; Petäjä, Tuukka; Wenger, John; Kulmala, Markku; Kalberer, Markus

    2016-01-01

    Secondary organic aerosol (SOA) accounts for a dominant fraction of the submicron atmospheric particle mass, but knowledge of the formation, composition and climate effects of SOA is incomplete and limits our understanding of overall aerosol effects in the atmosphere. Organic oligomers were discovered as dominant components in SOA over a decade ago in laboratory experiments and have since been proposed to play a dominant role in many aerosol processes. However, it remains unclear whether oligomers are relevant under ambient atmospheric conditions because they are often not clearly observed in field samples. Here we resolve this long-standing discrepancy by showing that elevated SOA mass is one of the key drivers of oligomer formation in the ambient atmosphere and laboratory experiments. We show for the first time that a specific organic compound class in aerosols, oligomers, is strongly correlated with cloud condensation nuclei (CCN) activities of SOA particles. These findings might have important implications for future climate scenarios where increased temperatures cause higher biogenic volatile organic compound (VOC) emissions, which in turn lead to higher SOA mass formation and significant changes in SOA composition. Such processes would need to be considered in climate models for a realistic representation of future aerosol-climate-biosphere feedbacks. PMID:27733773

  1. Secondary Ion Mass Spectrometry of Zeolite Materials: Observation of Abundant Aluminosilicate Oligomers Using an Ion Trap

    SciTech Connect

    Groenewold, Gary Steven; Kessinger, Glen Frank; Scott, Jill Rennee; Gianotto, Anita Kay; Appelhans, Anthony David; Delmore, James Edward

    2000-12-01

    Oligomeric oxyanions were observed in the secondary ion mass spectra (SIMS) of zeolite materials. The oxyanions have the general composition AlmSinO2(m+n)H(m-1)- (m + n = 2 to 8) and are termed dehydrates. For a given mass, multiple elemental compositions are possible because (Al + H) is an isovalent and isobaric substitute for Si. Using 18 keV Ga+ as a projectile, oligomer abundances are low relative to the monomers. Oligomer abundance can be increased by using the polyatomic projectile ReO4- (~5 keV). Oligomer abundance can be further increased using an ion trap (IT-) SIMS; in this instrument, long ion lifetimes (tens of ms) and relatively high He pressure result in significant collisional stabilization and increased high-mass abundance. The dehydrates rapidly react with adventitious H2O present in the IT-SIMS to form mono-, di-, and trihydrates. The rapidity of the reaction and comparison to aluminum oxyanion hydration suggest that H2O adds to the aluminosilicate oxyanions in a dissociative fashion, forming covalently bound product ions. In addition to these findings, it was noted that production of abundant oligomeric aluminosilicates could be significantly increased by substituting the countercation (NH4+) with the larger alkali ions Rb+ and Cs+. This constitutes a useful tactic for generating large aluminosilicate oligomers for surface characterization and ion-molecule reactivity studies.

  2. DOPAL derived alpha-synuclein oligomers impair synaptic vesicles physiological function

    PubMed Central

    Plotegher, N.; Berti, G.; Ferrari, E.; Tessari, I.; Zanetti, M.; Lunelli, L.; Greggio, E.; Bisaglia, M.; Veronesi, M.; Girotto, S.; Dalla Serra, M.; Perego, C.; Casella, L.; Bubacco, L.

    2017-01-01

    Parkinson’s disease is a neurodegenerative disorder characterized by the death of dopaminergic neurons and by accumulation of alpha-synuclein (aS) aggregates in the surviving neurons. The dopamine catabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is a highly reactive and toxic molecule that leads to aS oligomerization by covalent modifications to lysine residues. Here we show that DOPAL-induced aS oligomer formation in neurons is associated with damage of synaptic vesicles, and with alterations in the synaptic vesicles pools. To investigate the molecular mechanism that leads to synaptic impairment, we first aimed to characterize the biochemical and biophysical properties of the aS-DOPAL oligomers; heterogeneous ensembles of macromolecules able to permeabilise cholesterol-containing lipid membranes. aS-DOPAL oligomers can induce dopamine leak in an in vitro model of synaptic vesicles and in cellular models. The dopamine released, after conversion to DOPAL in the cytoplasm, could trigger a noxious cycle that further fuels the formation of aS-DOPAL oligomers, inducing neurodegeneration. PMID:28084443

  3. Synthesis of a new π-conjugated redox oligomer: Electrochemical and optical investigation

    NASA Astrophysics Data System (ADS)

    Blili, Saber; Zaâboub, Zouhour; Maaref, Hassen; Haj Said, Ayoub

    2017-01-01

    A new π-conjugated redox oligomer was prepared according a two-Step Synthesis. Firstly, an oligophenylene (OMPA) was obtained from the anodic oxidation of the (4-methoxyphenyl)acetonitrile. Then, the resulting material was chemically modified by the Knoevenagel condensation with the ferrocenecarboxaldehyde. This reaction led to a redox-conjugated oligomer the Fc-OMPA. The synthesized material was characterized using different spectroscopic techniques: NMR, FTIR, UV-vis and photoluminescence (PL) spectroscopy. The Fc-OMPA was used to modify a platinum electrode surface and the electrochemical response of the ferrocene redox-center was investigated by cyclic voltammetry. Moreover, the room temperature PL spectra of Fc-OMPA revealed that the ferrocene moiety, which acts as an electron donor, can effectively quench the oligomer luminescence. However, when ferrocene was oxidized to ferrocenium ion, the intramolecular charge transfer process was prevented which consequently enhanced the light emission. Thus, the oligomer light-emission can be, chemically or electrochemically tuned. The obtained results showed that the prepared material is a good candidate for the elaboration of electrochemical sensors and for the development of luminescent Redox-switchable devices.

  4. Structural Insights into Amyloid Oligomers of the Parkinson Disease-related Protein α-Synuclein*

    PubMed Central

    Gallea, J. Ignacio; Celej, M. Soledad

    2014-01-01

    The presence of intraneuronal deposits mainly formed by amyloid fibrils of the presynaptic protein α-synuclein (AS) is a hallmark of Parkinson disease. Currently, neurotoxicity is attributed to prefibrillar oligomeric species rather than the insoluble aggregates, although their mechanisms of toxicity remain elusive. Structural details of the supramolecular organization of AS oligomers are critically needed to decipher the structure-toxicity relationship underlying their pathogenicity. In this study, we employed site-specific fluorescence to get a deeper insight into the internal architecture of AS oligomeric intermediates. We demonstrate that AS oligomers are ordered assemblies possessing a well defined pattern of intermolecular contacts. Some of these contacts involve regions that form the β-sheet core in the fibrillar state, although their spatial arrangement may differ in the two aggregated forms. However, even though the two termini are excluded from the fibrillar core, they are engaged in a number of intermolecular interactions within the oligomer. Therefore, substantial structural remodeling of early oligomeric interactions is essential for fibril growth. The intermolecular contacts identified in AS oligomers can serve as targets for the rational design of anti-amyloid compounds directed at preventing oligomeric interactions/reorganizations. PMID:25143382

  5. Glycan arrays containing synthetic Clostridium difficile lipoteichoic acid oligomers as tools toward a carbohydrate vaccine.

    PubMed

    Martin, Christopher E; Broecker, Felix; Eller, Steffen; Oberli, Matthias A; Anish, Chakkumkal; Pereira, Claney L; Seeberger, Peter H

    2013-08-18

    Clostridium difficile is a leading cause of severe nosocomial infections. Cell-surface carbohydrate antigens are promising vaccine candidates. Here we report the first total synthesis of oligomers of the lipoteichoic acid antigen repeating unit. Synthetic glycan microarrays revealed anti-glycan antibodies in the blood of patients that help to define epitopes for vaccine development.

  6. Facile Synthesis of Highly Crystalline and Large Areal Hexagonal Boron Nitride from Borazine Oligomers

    NASA Astrophysics Data System (ADS)

    Park, Sungchan; Seo, Tae Hoon; Cho, Hyunjin; Min, Kyung Hyun; Lee, Dong Su; Won, Dong-Il; Kang, Sang Ook; Kim, Myung Jong

    2017-01-01

    A novel and facile synthetic method for h-BN films from borazine oligomer (B3N3H4)x precursors has been developed. This method only includes spin-coating of borazine oligomer onto nickel catalysts and a subsequent annealing step. Large areal and highly crystalline h-BN films were obtained. The stoichiometric B/N ratio of borazine oligomer precursor was preserved in the final h-BN product such that it was close to 1 as revealed by XPS. Catalytic effect of nickel for h-BN formation was clearly demonstrated by lowering crystallization temperature compared to the growth condition in the absence of catalyst. The graphene field effect transistor (GFET) characterization has proved the high quality synthesis of h-BN films, showing the shift of neutrality point and the increase of the mobility. This method can also provide functional h-BN coating on various surfaces by annealing Ni-coated borazine oligomer films and subsequent removal of Ni catalyst.

  7. High-Capacity Conductive Nanocellulose Paper Sheets for Electrochemically Controlled Extraction of DNA Oligomers

    PubMed Central

    Razaq, Aamir; Nyström, Gustav; Strømme, Maria; Mihranyan, Albert; Nyholm, Leif

    2011-01-01

    Highly porous polypyrrole (PPy)-nanocellulose paper sheets have been evaluated as inexpensive and disposable electrochemically controlled three-dimensional solid phase extraction materials. The composites, which had a total anion exchange capacity of about 1.1 mol kg−1, were used for extraction and subsequent release of negatively charged fluorophore tagged DNA oligomers via galvanostatic oxidation and reduction of a 30–50 nm conformal PPy layer on the cellulose substrate. The ion exchange capacity, which was, at least, two orders of magnitude higher than those previously reached in electrochemically controlled extraction, originated from the high surface area (i.e. 80 m2 g−1) of the porous composites and the thin PPy layer which ensured excellent access to the ion exchange material. This enabled the extractions to be carried out faster and with better control of the PPy charge than with previously employed approaches. Experiments in equimolar mixtures of (dT)6, (dT)20, and (dT)40 DNA oligomers showed that all oligomers could be extracted, and that the smallest oligomer was preferentially released with an efficiency of up to 40% during the reduction of the PPy layer. These results indicate that the present material is very promising for the development of inexpensive and efficient electrochemically controlled ion-exchange membranes for batch-wise extraction of biomolecules. PMID:22195031

  8. Synthesis of DNA mimics representing HypNA-pPNA hetero-oligomers.

    PubMed

    Efimov, Vladimir A; Chakhmakhcheva, Oksana G

    2005-01-01

    The methods for the synthesis and purification of negatively charged peptide nucleic acid (PNA)-relative deoxyribonucleic acid (DNA) mimics containing alternating residues of phosphono peptide nucleic acid (pPNA) monomers and PNA-like monomers on the base of trans-4-hydroxy-L-proline are described. Examples of the chimeric oligomers hybridization with complementary DNA and ribonucleic acid fragments are demonstrated.

  9. Facile Synthesis of Highly Crystalline and Large Areal Hexagonal Boron Nitride from Borazine Oligomers

    PubMed Central

    Park, Sungchan; Seo, Tae Hoon; Cho, Hyunjin; Min, Kyung Hyun; Lee, Dong Su; Won, Dong-Il; Kang, Sang Ook; Kim, Myung Jong

    2017-01-01

    A novel and facile synthetic method for h-BN films from borazine oligomer (B3N3H4)x precursors has been developed. This method only includes spin-coating of borazine oligomer onto nickel catalysts and a subsequent annealing step. Large areal and highly crystalline h-BN films were obtained. The stoichiometric B/N ratio of borazine oligomer precursor was preserved in the final h-BN product such that it was close to 1 as revealed by XPS. Catalytic effect of nickel for h-BN formation was clearly demonstrated by lowering crystallization temperature compared to the growth condition in the absence of catalyst. The graphene field effect transistor (GFET) characterization has proved the high quality synthesis of h-BN films, showing the shift of neutrality point and the increase of the mobility. This method can also provide functional h-BN coating on various surfaces by annealing Ni-coated borazine oligomer films and subsequent removal of Ni catalyst. PMID:28074854

  10. High-resolution NMR characterization of low abundance oligomers of amyloid-β without purification

    NASA Astrophysics Data System (ADS)

    Kotler, Samuel A.; Brender, Jeffrey R.; Vivekanandan, Subramanian; Suzuki, Yuta; Yamamoto, Kazutoshi; Monette, Martine; Krishnamoorthy, Janarthanan; Walsh, Patrick; Cauble, Meagan; Holl, Mark M. Banaszak; Marsh, E. Neil. G.; Ramamoorthy, Ayyalusamy

    2015-07-01

    Alzheimer’s disease is characterized by the misfolding and self-assembly of the amyloidogenic protein amyloid-β (Aβ). The aggregation of Aβ leads to diverse oligomeric states, each of which may be potential targets for intervention. Obtaining insight into Aβ oligomers at the atomic level has been a major challenge to most techniques. Here, we use magic angle spinning recoupling 1H-1H NMR experiments to overcome many of these limitations. Using 1H-1H dipolar couplings as a NMR spectral filter to remove both high and low molecular weight species, we provide atomic-level characterization of a non-fibrillar aggregation product of the Aβ1-40 peptide using non-frozen samples without isotopic labeling. Importantly, this spectral filter allows the detection of the specific oligomer signal without a separate purification procedure. In comparison to other solid-state NMR techniques, the experiment is extraordinarily selective and sensitive. A resolved 2D spectra could be acquired of a small population of oligomers (6 micrograms, 7% of the total) amongst a much larger population of monomers and fibers (93% of the total). By coupling real-time 1H-1H NMR experiments with other biophysical measurements, we show that a stable, primarily disordered Aβ1-40 oligomer 5-15 nm in diameter can form and coexist in parallel with the well-known cross-β-sheet fibrils.

  11. Oligomer formation during gas-phase ozonolysis of small alkenes and enol ethers: new evidence for the central role of the Criegee Intermediate as oligomer chain unit

    NASA Astrophysics Data System (ADS)

    Sadezky, A.; Winterhalter, R.; Kanawati, B.; Römpp, A.; Spengler, B.; Mellouki, A.; Le Bras, G.; Chaimbault, P.; Moortgat, G. K.

    2008-05-01

    An important fraction of secondary organic aerosol (SOA) formed by atmospheric oxidation of diverse volatile organic compounds (VOC) has recently been shown to consist of high-molecular weight oligomeric species. In our previous study (Sadezky et al., 2006), we reported the identification and characterization of oligomers as main constituents of SOA from gas-phase ozonolysis of small enol ethers. These oligomers contained repeated chain units of the same chemical composition as the main Criegee Intermediates (CI) formed during the ozonolysis reaction, which were CH2O2 (mass 46) for alkyl vinyl ethers (AVE) and C2H4O2 (mass 60) for ethyl propenyl ether (EPE). In the present work, we extend our previous study to another enol ether (ethyl butenyl ether EBE) and a variety of structurally related small alkenes (trans-3-hexene, trans-4-octene and 2,3-dimethyl-2-butene). Experiments have been carried out in a 570 l spherical glass reactor at atmospheric conditions in the absence of seed aerosol. SOA formation was measured by a scanning mobility particle sizer (SMPS). SOA filter samples were collected and chemically characterized off-line by ESI(+)/TOF MS and ESI(+)/TOF MS/MS, and elemental compositions were determined by ESI(+)/FTICR MS and ESI(+)/FTICR MS/MS. The results for all investigated unsaturated compounds are in excellent agreement with the observations of our previous study. Analysis of the collected SOA filter samples reveal the presence of oligomeric compounds in the mass range 200 to 800 u as major constituents. The repeated chain units of these oligomers are shown to systematically have the same chemical composition as the respective main Criegee Intermediate (CI) formed during ozonolysis of the unsaturated compounds, which is C3H6O2 (mass 74) for ethyl butenyl ether (EBE), trans-3-hexene, and 2,3-dimethyl-2-butene, and C4H8O2 (mass 88) for trans-4-octene. Analogous fragmentation pathways among the oligomers formed by gas-phase ozonolysis of the different

  12. Novel chemo-enzymatic oligomers of cinnamic acids as direct and indirect inhibitors of coagulation proteinases.

    PubMed

    Monien, Bernhard H; Henry, Brian L; Raghuraman, Arjun; Hindle, Michael; Desai, Umesh R

    2006-12-01

    Thrombin and factor Xa, two important procoagulant enzymes, have been prime targets for regulation of clotting through the direct and indirect mechanism of inhibition. Our efforts on exploiting the indirect mechanism led us to study a carboxylic acid-based scaffold, which displayed major acceleration in the inhibition of these enzymes [J. Med. Chem.2005, 48, 1269, 5360]. This work advances the study to chemo-enzymatically prepared oligomers of 4-hydroxycinnamic acids, DHPs, which display interesting anticoagulant properties. Oligomers, ranging in size from tetramers to pentadecamers, were prepared through peroxidase-catalyzed oxidative coupling of caffeic, ferulic, and sinapic acids, and sulfated using triethylamine-sulfur trioxide complex. Chromatographic, spectroscopic, and elemental studies suggest that the DHPs are heterogeneous, polydisperse preparations composed of inter-monomer linkages similar to those found in natural lignins. Measurement of activated thromboplastin and prothrombin time indicates that both the sulfated and unsulfated derivatives of the DHPs display anticoagulant activity, which is dramatically higher than that of the reference polyacrylic acids. More interestingly, this activity approaches that of low-molecular-weight heparin with the sulfated derivative showing approximately 2- to 3-fold greater potency than the unsulfated parent. Studies on the inhibition of factor Xa and thrombin indicate that the oligomers exert their anticoagulant effect through both direct and indirect inhibition mechanisms. This dual inhibition property of 4-hydroxycinnamic acid-based DHP oligomers is the first example in inhibitors of coagulation. This work puts forward a novel, non-heparin structure, which may be exploited for the design of potent, dual action inhibitors of coagulation through combinatorial virtual screening on a library of DHP oligomers.

  13. PrPSc-Specific Antibodies with the Ability to Immunodetect Prion Oligomers

    PubMed Central

    Tayebi, Mourad; Jones, Daryl Rhys; Taylor, William Alexander; Stileman, Benjamin Frederick; Chapman, Charlotte; Zhao, Deming; David, Monique

    2011-01-01

    The development of antibodies with binding capacity towards soluble oligomeric forms of PrPSc recognised in the aggregation process in early stage of the disease would be of paramount importance in diagnosing prion diseases before extensive neuropathology has ensued. As blood transfusion appears to be efficient in the transmission of the infectious prion agent, there is an urgent need to develop reagents that would specifically recognize oligomeric forms of the abnormally folded prion protein, PrPSc. To that end, we show that anti-PrP monoclonal antibodies (called PRIOC mAbs) derived from mice immunised with native PrP-coated microbeads are able to immunodetect oligomers/multimers of PrPSc. Oligomer-specific immunoreactivity displayed by these PRIOC mAbs was demonstrated as large aggregates of immunoreactive deposits in prion-permissive neuroblastoma cell lines but not in equivalent non-infected or prn-p0/0 cell lines. In contrast, an anti-monomer PrP antibody displayed diffuse immunoreactivity restricted to the cell membrane. Furthermore, our PRIOC mAbs did not display any binding with monomeric recombinant and cellular prion proteins but strongly detected PrPSc oligomers as shown by a newly developed sensitive and specific ELISA. Finally, PrioC antibodies were also able to bind soluble oligomers formed of Aβ and α-synuclein. These findings demonstrate the potential use of anti-prion antibodies that bind PrPSc oligomers, recognised in early stage of the disease, for the diagnosis of prion diseases in blood and other body fluids. PMID:21625515

  14. Postsynaptic Receptors for Amyloid-β Oligomers as Mediators of Neuronal Damage in Alzheimer's Disease.

    PubMed

    Dinamarca, Margarita C; Ríos, Juvenal A; Inestrosa, Nibaldo C

    2012-01-01

    The neurotoxic effect of amyloid-β peptide (Aβ) over the central synapses has been described and is reflected in the decrease of some postsynaptic excitatory proteins, the alteration in the number and morphology of the dendritic spines, and a decrease in long-term potentiation. Many studies has been carried out to identify the putative Aβ receptors in neurons, and is still no clear why the Aβ oligomers only affect the excitatory synapses. Aβ oligomers bind to neurite and preferentially to the postsynaptic region, where the postsynaptic protein-95 (PSD-95) is present in the glutamatergic synapse, and interacts directly with the N-methyl-D-aspartate receptor (NMDAR) and neuroligin (NL). NL is a postsynaptic protein which binds to the presynaptic protein, neurexin to form a heterophilic adhesion complex, the disruption of this interaction affects the integrity of the synaptic contact. Structurally, NL has an extracellular domain homolog to acetylcholinesterase, the first synaptic protein that was found to interact with Aβ. In the present review we will document the interaction between Aβ and the extracellular domain of NL-1 at the excitatory synapse, as well as the interaction with other postsynaptic components, including the glutamatergic receptors (NMDA and mGluR5), the prion protein, the neurotrophin receptor, and the α7-nicotinic acetylcholine receptor. We conclude that several Aβ oligomers receptors exist at the excitatory synapse, which could be the responsible for the neurotoxic effect described for the Aβ oligomers. The characterization of the interaction between Aβ receptors and Aβ oligomers could help to understand the source of the neurologic damage observed in the brain of the Alzheimer's disease patients.

  15. Valley depolarization in monolayer WSe2

    PubMed Central

    Yan, Tengfei; Qiao, Xiaofen; Tan, Pingheng; Zhang, Xinhui

    2015-01-01

    We have systematically examined the circular polarization of monolayer WSe2 at different temperature, excitation energy and exciton density. The valley depolarization in WSe2 is experimentally confirmed to be governed by the intervalley electron-hole exchange interaction. More importantly, a non-monotonic dependence of valley circular polarization on the excitation power density has been observed, providing the experimental evidence for the non-monotonic dependence of exciton intervalley scattering rate on the excited exciton density. The physical origination of our experimental observations has been proposed to be in analogy to the D′yakonov-Perel′ mechanism that is operative in conventional GaAs quantum well systems. Our experimental results are fundamentally important for well understanding the valley pseudospin relaxation in atomically thin transition metal dichalcogenides. PMID:26490157

  16. Ultrafast response of monolayer molybdenum disulfide photodetectors

    PubMed Central

    Wang, Haining; Zhang, Changjian; Chan, Weimin; Tiwari, Sandip; Rana, Farhan

    2015-01-01

    The strong light emission and absorption exhibited by single atomic layer transitional metal dichalcogenides in the visible to near-infrared wavelength range make them attractive for optoelectronic applications. In this work, using two-pulse photovoltage correlation technique, we show that monolayer molybdenum disulfide photodetector can have intrinsic response times as short as 3 ps implying photodetection bandwidths as wide as 300 GHz. The fast photodetector response is a result of the short electron–hole and exciton lifetimes in this material. Recombination of photoexcited carriers in most two-dimensional metal dichalcogenides is dominated by nonradiative processes, most notable among which is Auger scattering. The fast response time, and the ease of fabrication of these devices, make them interesting for low-cost ultrafast optical communication links. PMID:26572726

  17. Phospholipid monolayers between fluid and solid states.

    PubMed Central

    Helm, C A; Möhwald, H; Kjaer, K; Als-Nielsen, J

    1987-01-01

    Monolayers of the phospholipid dimyristoyl phosphatidic acid on the surface of water have been studied by a combination of the new techniques of synchrotron x-ray diffraction and fluorescence microscopy with classical surface pressure data. The pressure vs. area isotherm changes slope at the surface pressures pi c and pi s. The optical technique demonstrates that between pi c and pi s the fluid phase coexists with a denser "gel" phase. Electron diffraction data have shown that the gel phase has bond orientational order over tens of micrometers. However, the x-ray data demonstrate that positional correlations extend only over tens of angstroms. Thus, the gel phase is not crystalline. Above pi s a solid phase is formed with a positional correlation range that is eight times longer for the chemically purest films. Images FIGURE 1 FIGURE 2 PMID:3651557

  18. Metastability of a Supercompressed Fluid Monolayer

    PubMed Central

    Smith, Ethan C.; Crane, Jonathan M.; Laderas, Ted G.; Hall, Stephen B.

    2003-01-01

    Previous studies showed that monomolecular films of extracted calf surfactant collapse at the equilibrium spreading pressure during quasi-static compressions but become metastable at much higher surface pressures when compressed faster than a threshold rate. To determine the mechanism by which the films become metastable, we studied single-component films of 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC). Initial experiments confirmed similar metastability of POPC if compressed above a threshold rate. Measurements at different surface pressures then showed that rates of collapse, although initially increasing above the equilibrium spreading pressure, reached a sharply defined maximum and then slowed considerably. When heated, rapidly compressed films recovered their ability to collapse with no discontinuous change in area, arguing that the metastability does not reflect transition of the POPC film to a new phase. These observations indicate that in several respects, the supercompression of POPC monolayers resembles the supercooling of three-dimensional liquids toward a glass transition. PMID:14581205

  19. Covalently networked monolayer-protected nanoparticle films.

    PubMed

    Tognarelli, D J; Miller, Robert B; Pompano, Rebecca R; Loftus, Andrew F; Sheibley, Daniel J; Leopold, Michael C

    2005-11-22

    Covalently networked films of nanoparticles can be assembled on various substrates from functionalized monolayer-protected clusters (MPCs) via ester coupling reactions. Exposure of a specifically modified substrate to alternating solutions of 11-mercaptoundecanoic acid exchanged and 11-mercaptoundecanol exchanged MPCs, in the presence of ester coupling reagents, 1,3-dicyclohexylcarbodiimide and 4-(dimethylamino)pyridine, results in the formation of a multilayer film with ester bridges between individual nanoparticles. These films can be grown in a controlled manner to various thicknesses and exhibit certain properties that are consistent with films having other types of interparticle connectivity, including chemical vapor response behavior and quantized double layer charging. Ester coupling of MPCs into assembled films is a straightforward and highly versatile approach that results in robust films that can endure harsher chemical environments than other types of films. The stability of these covalent films is assessed and compared to other more traditional MPC film assemblies.

  20. Chitosan oligomers as potential and safe absorption enhancers for improving the pulmonary absorption of interferon-alpha in rats.

    PubMed

    Yamada, Keigo; Odomi, Masaaki; Okada, Naoki; Fujita, Takuya; Yamamoto, Akira

    2005-11-01

    Effects of chitosan oligomers on pulmonary absorption of interferon-alpha (IFN) were examined by means of an in vivo pulmonary absorption experiment. Chitosan oligomers used in this study were chitosan dimer, tetramer, hexamer, and water-soluble (WS) chitosan. A significant increase in serum IFN concentrations was observed after intratracheal administration of IFN with these oligomers. Of these chitosan oligomers, 0.5% w/v chitosan hexamer appeared to be more effective in enhancing the pulmonary absorption of IFN than other oligomers at the same concentration, and the AUC value of IFN with chitosan hexamer increased 2.6-fold as compared with the control. On the other hand, chitosan polymers, which have relatively high molecular weights (22-96 kDa), were not effective in enhancing the pulmonary absorption of IFN due to their low solubility in water. Additionally, the effect of different concentrations (0.1%-1% w/v) of chitosan hexamer on the pulmonary absorption of IFN was studied. Of these different concentrations of chitosan hexamers, the highest AUC value of IFN was obtained in the presence of 0.5% w/v chitosan hexamer. Furthermore, chitosan oligomers did not cause any membrane damage to the rat pulmonary tissues, as determined by leakage of protein and lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid. Therefore, these findings indicated that the use of chitosan oligomers would be a promising approach for improving of the pulmonary absorption of biologically active peptides including IFN.

  1. Direct observation of single amyloid-β(1-40) oligomers on live cells: binding and growth at physiological concentrations.

    PubMed

    Johnson, Robin D; Schauerte, Joseph A; Wisser, Kathleen C; Gafni, Ari; Steel, Duncan G

    2011-01-01

    Understanding how amyloid-β peptide interacts with living cells on a molecular level is critical to development of targeted treatments for Alzheimer's disease. Evidence that oligomeric Aβ interacts with neuronal cell membranes has been provided, but the mechanism by which membrane binding occurs and the exact stoichiometry of the neurotoxic aggregates remain elusive. Physiologically relevant experimentation is hindered by the high Aβ concentrations required for most biochemical analyses, the metastable nature of Aβ aggregates, and the complex variety of Aβ species present under physiological conditions. Here we use single molecule microscopy to overcome these challenges, presenting direct optical evidence that small Aβ(1-40) oligomers bind to living neuroblastoma cells at physiological Aβ concentrations. Single particle fluorescence intensity measurements indicate that cell-bound Aβ species range in size from monomers to hexamers and greater, with the majority of bound oligomers falling in the dimer-to-tetramer range. Furthermore, while low-molecular weight oligomeric species do form in solution, the membrane-bound oligomer size distribution is shifted towards larger aggregates, indicating either that bound Aβ oligomers can rapidly increase in size or that these oligomers cluster at specific sites on the membrane. Calcium indicator studies demonstrate that small oligomer binding at physiological concentrations induces only mild, sporadic calcium leakage. These findings support the hypothesis that small oligomers are the primary Aβ species that interact with neurons at physiological concentrations.

  2. Acute amnestic encephalopathy in amyloid-β oligomer-injected mice is due to their widespread diffusion in vivo.

    PubMed

    Epelbaum, Stéphane; Youssef, Ihsen; Lacor, Pascale N; Chaurand, Pierre; Duplus, Eric; Brugg, Bernard; Duyckaerts, Charles; Delatour, Benoît

    2015-06-01

    Amyloid-β (Aβ) oligomers are the suspected culprit as initiators of Alzheimer's disease (AD). However, their diffusion in the brain remains unknown. Here, we studied Aβ oligomers' dissemination and evaluated their in vivo toxicity. Wild-type mice were injected with 50 pmol of synthetic Aβ oligomers (of different size) in the hippocampus. Oligomers diffused largely in the brain as soon as 1 hour and up to 7 days after injection. A transient encephalopathy with memory impairment was induced by this unique injection. The immunoreactivity of the postsynaptic marker PSD95 was diffusely decreased. Similar results (both on memory and PSD95 immunoreactivity) were obtained with delipidated and high molecular weight oligomers (>50 kDa) but not with smaller assemblies. Tau hyperphosphorylation was observed in the oligomer-injected brains. Finally, fos immunostaining was increased in Aβ-derived diffusible ligands-injected mice, suggesting neuronal hyperactivity. Rapid and widespread diffusion of Aβ oligomers was demonstrated in vivo and associated with decreased synaptic markers and memory deficits which gives new insight to the pathogenicity of Aβ.

  3. Protective spin-labeled fluorenes maintain amyloid beta peptide in small oligomers and limit transitions in secondary structure

    PubMed Central

    Altman, Robin; Ly, Sonny; Hilt, Silvia; Petrlova, Jitka; Maezawa, Izumi; Kálai, Tamás; Hideg, Kálmán; Jin, Lee-Way; Laurence, Ted A.; Voss, John C.

    2015-01-01

    Alzheimer’s disease is characterized by the presence of extracellular plaques comprised of amyloid beta (Aβ) peptides. Soluble oligomers of the Aβ peptide underlie a cascade of neuronal loss and dysfunction associated with Alzheimer’s disease. Single particle analyses of Aβ oligomers in solution by fluorescence correlation spectroscopy (FCS) were used to provide real-time descriptions of how spin-labeled fluorenes (SLFs; bi-functional small molecules that block the toxicity of Aβ) prevent and disrupt oligomeric assemblies of Aβ in solution. Furthermore, the circular dichroism (CD) spectrum of untreated Aβ shows a continuous, progressive change over a 24-hour period, while the spectrum of Aβ treated with SLF remains relatively constant following initial incubation. These findings suggest the conformation of Aβ within the oligomer provides a complementary determinant of Aβ toxicity in addition to oligomer growth and size. Although SLF does not produce a dominant state of secondary structure in Aβ, it does induce a net reduction in beta secondary content compared to untreated samples of Aβ. The FCS results, combined with electron paramagnetic resonance spectroscopy and CD spectroscopy, demonstrate SLFs can inhibit the growth of Aβ oligomers and disrupt existing oligomers, while retaining Aβ as a population of smaller, yet largely disordered oligomers. PMID:26374940

  4. Matrix-assisted laser desorption/ionization mass spectrometry of discrete mass poly(butylene glutarate) oligomers.

    PubMed

    Williams, John B; Chapman, Toby M; Hercules, David M

    2003-07-01

    The mass dependency of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) response has been studied using equimolar mixtures of synthetic discrete mass poly(butylene glutarate) (PBG) oligomers of known structure having degrees of polymerization of 8, 16, 32, and 64. Mass discrimination observed was attributed to choice of matrix and detector saturation caused by higher laser intensity and inclusion of matrix ions in the MALDI spectra. Optimization of sample preparation and instrumental parameters provided uniform response over the mass ranged spanned by these four oligomers. The oligomer mixture was shown to serve as a model of more complex polymer distributions in the mass range 780-6000 Da, and application of the discrete mass oligomers as internal and calibration standards was demonstrated. Inclusion of PBG discrete mass oligomers as an internal standard in a quasi-equimolar mixture with polydispersed poly(butylene adipate) (PBA) indicated that some diminution of response occurred during the analysis of this mixture of materials. Reasons for differences in the corrected molecular weight averages of the polydispersed PBA obtained from measurements using MALDI and GPC were studied using individual discrete mass oligomers as calibration standards for GPC. The data indicated that differences in hydrodynamic volumes of PBG oligomers and PEG standards at similar masses resulted in an overestimation by GPC of the molecular weight averages of the PBA distribution.

  5. Protective spin-labeled fluorenes maintain amyloid beta peptide in small oligomers and limit transitions in secondary structure

    SciTech Connect

    Altman, Robin; Ly, Sonny; Hilt, Silvia; Petrlova, Jitka; Maezawa, Izumi; Kálai, Tamás; Hideg, Kálmán; Jin, Lee-Way; Laurence, Ted A.; Voss, John C.

    2015-12-01

    Alzheimer’s disease is characterized by the presence of extracellular plaques comprised of amyloid beta (Aβ) peptides. Soluble oligomers of the Aβ peptide underlie a cascade of neuronal loss and dysfunction associated with Alzheimer's disease. Single particle analyses of Aβ oligomers in solution by fluorescence correlation spectroscopy (FCS) were used to provide real-time descriptions of how spin-labeled fluorenes (SLFs; bi-functional small molecules that block the toxicity of Aβ) prevent and disrupt oligomeric assemblies of Aβ in solution. The FCS results, combined with electron paramagnetic resonance spectroscopy and circular dichroism spectroscopy, demonstrate SLFs can inhibit the growth of Aβ oligomers and disrupt existing oligomers while retaining Aβ in a largely disordered state. Furthermore, while the ability of SLF to block Aβ toxicity correlates with a reduction in oligomer size, our results suggest the conformation of Aβ within the oligomer determines the toxicity of the species. Attenuation of Aβ toxicity, which has been associated primarily with the soluble oligomeric form, can be achieved through redistribution of the peptides into smaller oligomers and arrest of the fractional increase in beta secondary structure.

  6. Antigenic implications of human immunodeficiency virus type 1 envelope quaternary structure: oligomer-specific and -sensitive monoclonal antibodies.

    PubMed Central

    Broder, C C; Earl, P L; Long, D; Abedon, S T; Moss, B; Doms, R W

    1994-01-01

    A majority of monoclonal antibodies (mAbs) raised against soluble oligomeric human immunodeficiency virus type 1 isolate IIIB (HIV-1IIIB) envelope (env) glycoprotein reacted with conformational epitopes within the gp120 or gp41 subunits. Of 35 mAbs directed against gp41, 21 preferentially reacted with oligomeric env. A subset of these mAbs reacted only with env oligomers (oligomer-specific mAbs). In contrast, only 1 of 27 mAbs directed against the gp120 subunit reacted more strongly with env oligomers than with monomers, and none were oligomer-specific. However, 50% of anti-gp120 mAbs preferentially recognized monomeric env, suggesting that some epitopes in gp120 are partially masked or altered by intersubunit contacts in the native env oligomer. Two mAbs to oligomer-dependent epitopes in gp41 neutralized HIV-1IIIB and HIV-1SF2, and binding of these mAbs to env was blocked by preincubation with HIV-1-positive human serum. Thus, immunization with soluble, oligomeric env elicits antibodies to conserved, conformational epitopes including a newly defined class of neutralizing antibodies that bind to oligomer-specific epitopes in gp41, and may also minimize the production of antibodies that preferentially react with monomeric env protein. Images PMID:7972127

  7. Effects of secreted oligomers of amyloid β-protein on hippocampal synaptic plasticity: a potent role for trimers

    PubMed Central

    Townsend, Matthew; Shankar, Ganesh M; Mehta, Tapan; Walsh, Dominic M; Selkoe, Dennis J

    2006-01-01

    The accumulation of amyloid β-protein (Aβ) in brain regions serving memory and cognition is a central pathogenic feature of Alzheimer's disease (AD). We have shown that small soluble oligomers of human Aβ that are naturally secreted by cultured cells inhibit hippocampal long-term potentiation (LTP) in vitro and in vivo and transiently impair the recall of a complex learned behaviour in rats. These results support the hypothesis that diffusible oligomers of Aβ initiate a synaptic dysfunction that may be an early event in AD. We now report detailed electrophysiological analyses that define conditions under which acute application of soluble Aβ inhibits hippocampal synaptic plasticity in wild-type mice. To ascertain which Aβ assemblies contribute to the impairment of LTP, we fractionated oligomers by size-exclusion chromatography and found that Aβ trimers fully inhibit LTP, whereas dimers and tetramers have an intermediate potency. Natural Aβ oligomers are sensitive to heat denaturation, primarily inhibit the induction phase of LTP, and cause a sustained impairment of LTP even after extensive washout. We observed no effects of Aβ oligomers on presynaptic vesicle release. LTP in juvenile mice is resistant to the effects of Aβ oligomers, as is brain-derived-neurotrophic-factor-induced LTP in adult hippocampus. We conclude that specific assemblies, particularly timers, of naturally secreted Aβ oligomers are potent and selective inhibitors of certain forms of hippocampal LTP. PMID:16469784

  8. Monolayer semiconductor nanocavity lasers with ultralow thresholds.

    PubMed

    Wu, Sanfeng; Buckley, Sonia; Schaibley, John R; Feng, Liefeng; Yan, Jiaqiang; Mandrus, David G; Hatami, Fariba; Yao, Wang; Vučković, Jelena; Majumdar, Arka; Xu, Xiaodong

    2015-04-02

    Engineering the electromagnetic environment of a nanometre-scale light emitter by use of a photonic cavity can significantly enhance its spontaneous emission rate, through cavity quantum electrodynamics in the Purcell regime. This effect can greatly reduce the lasing threshold of the emitter, providing a low-threshold laser system with small footprint, low power consumption and ultrafast modulation. An ultralow-threshold nanoscale laser has been successfully developed by embedding quantum dots into a photonic crystal cavity (PCC). However, several challenges impede the practical application of this architecture, including the random positions and compositional fluctuations of the dots, extreme difficulty in current injection, and lack of compatibility with electronic circuits. Here we report a new lasing strategy: an atomically thin crystalline semiconductor--that is, a tungsten diselenide monolayer--is non-destructively and deterministically introduced as a gain medium at the surface of a pre-fabricated PCC. A continuous-wave nanolaser operating in the visible regime is thereby achieved with an optical pumping threshold as low as 27 nanowatts at 130 kelvin, similar to the value achieved in quantum-dot PCC lasers. The key to the lasing action lies in the monolayer nature of the gain medium, which confines direct-gap excitons to within one nanometre of the PCC surface. The surface-gain geometry gives unprecedented accessibility and hence the ability to tailor gain properties via external controls such as electrostatic gating and current injection, enabling electrically pumped operation. Our scheme is scalable and compatible with integrated photonics for on-chip optical communication technologies.

  9. Anomalous thermal conductivity of monolayer boron nitride

    NASA Astrophysics Data System (ADS)

    Tabarraei, Alireza; Wang, Xiaonan

    2016-05-01

    In this paper, we use nonequilibrium molecular dynamics modeling to investigate the thermal properties of monolayer hexagonal boron nitride nanoribbons under uniaxial strain along their longitudinal axis. Our simulations predict that hexagonal boron nitride shows an anomalous thermal response to the applied uniaxial strain. Contrary to three dimensional materials, under uniaxial stretching, the thermal conductivity of boron nitride nanoribbons first increases rather than decreasing until it reaches its peak value and then starts decreasing. Under compressive strain, the thermal conductivity of monolayer boron nitride ribbons monolithically reduces rather than increasing. We use phonon spectrum and dispersion curves to investigate the mechanism responsible for the unexpected behavior. Our molecular dynamics modeling and density functional theory results show that application of longitudinal tensile strain leads to the reduction of the group velocities of longitudinal and transverse acoustic modes. Such a phonon softening mechanism acts to reduce the thermal conductivity of the nanoribbons. On the other hand, a significant increase in the group velocity (stiffening) of the flexural acoustic modes is observed, which counteracts the phonon softening effects of the longitudinal and transverse modes. The total thermal conductivity of the ribbons is a result of competition between these two mechanisms. At low tensile strain, the stiffening mechanism overcomes the softening mechanism which leads to an increase in the thermal conductivity. At higher tensile strain, the softening mechanism supersedes the stiffening and the thermal conductivity slightly reduces. Our simulations show that the decrease in the thermal conductivity under compressive strain is attributed to the formation of buckling defects which reduces the phonon mean free path.

  10. Monolayer semiconductor nanocavity lasers with ultralow thresholds

    SciTech Connect

    Wu, Sanfeng; Buckley, Sonia; Schaibley, John R.; Feng, Liefeng; Yan, Jiaqiang; Mandrus, David G.; Hatami, Fariba; Yao, Wang; Vučković, Jelena; Majumdar, Arka; Xu, Xiaodong

    2015-03-16

    Engineering the electromagnetic environment of a nanoscale light emitter by a photonic cavity can significantly enhance its spontaneous emission rate through cavity quantum electrodynamics in the Purcell regime. This effect can greatly reduce the lasing threshold of the emitter1–5, providing the ultimate low-threshold laser system with small footprint, low power consumption and ultrafast modulation. A state-of-the-art ultra-low threshold nanolaser has been successfully developed though embedding quantum dots into photonic crystal cavity (PhCC)6–8. However, several core challenges impede the practical applications of this architecture, including the random positions and compositional fluctuations of the dots7, extreme difficulty in current injection8, and lack of compatibility with electronic circuits7,8. Here, we report a new strategy to lase, where atomically thin crystalline semiconductor, i.e., a tungsten-diselenide (WSe2) monolayer, is nondestructively and deterministically introduced as a gain medium at the surface of a pre-fabricated PhCC. A new type of continuous-wave nanolaser operating in the visible regime is achieved with an optical pumping threshold as low as 27 nW at 130 K, similar to the value achieved in quantum dot PhCC lasers7. The key to the lasing action lies in the monolayer nature of the gain medium, which confines direct-gap excitons to within 1 nm of the PhCC surface. The surface-gain geometry allows unprecedented accessibilities to multi-functionalize the gain, enabling electrically pumped operation. Our scheme is scalable and compatible with integrated photonics for on-chip optical communication technologies.

  11. Monolayer semiconductor nanocavity lasers with ultralow thresholds

    DOE PAGES

    Wu, Sanfeng; Buckley, Sonia; Schaibley, John R.; ...

    2015-03-16

    Engineering the electromagnetic environment of a nanoscale light emitter by a photonic cavity can significantly enhance its spontaneous emission rate through cavity quantum electrodynamics in the Purcell regime. This effect can greatly reduce the lasing threshold of the emitter1–5, providing the ultimate low-threshold laser system with small footprint, low power consumption and ultrafast modulation. A state-of-the-art ultra-low threshold nanolaser has been successfully developed though embedding quantum dots into photonic crystal cavity (PhCC)6–8. However, several core challenges impede the practical applications of this architecture, including the random positions and compositional fluctuations of the dots7, extreme difficulty in current injection8, and lackmore » of compatibility with electronic circuits7,8. Here, we report a new strategy to lase, where atomically thin crystalline semiconductor, i.e., a tungsten-diselenide (WSe2) monolayer, is nondestructively and deterministically introduced as a gain medium at the surface of a pre-fabricated PhCC. A new type of continuous-wave nanolaser operating in the visible regime is achieved with an optical pumping threshold as low as 27 nW at 130 K, similar to the value achieved in quantum dot PhCC lasers7. The key to the lasing action lies in the monolayer nature of the gain medium, which confines direct-gap excitons to within 1 nm of the PhCC surface. The surface-gain geometry allows unprecedented accessibilities to multi-functionalize the gain, enabling electrically pumped operation. Our scheme is scalable and compatible with integrated photonics for on-chip optical communication technologies.« less

  12. Electronic correlations in monolayer VS2

    NASA Astrophysics Data System (ADS)

    Isaacs, Eric B.; Marianetti, Chris A.

    2016-07-01

    The layered transition metal dichalcogenide vanadium disulfide (VS2), which nominally has one electron in the 3 d shell, is potent for strong-correlation physics and is possibly another realization of an effective one-band model beyond the cuprates. Here monolayer VS2 in both the trigonal prismatic and the octahedral phases is investigated using density functional theory plus Hubbard U (DFT +U ) calculations. Trigonal prismatic VS2 has an isolated low-energy band that emerges from a confluence of crystal-field splitting and direct V-V hopping. Within spin density functional theory, ferromagnetism splits the isolated band of the trigonal prismatic structure, leading to a low-band-gap, S =1/2 , ferromagnetic Stoner insulator; the octahedral phase is higher in energy. Including the on-site interaction U increases the band gap, leads to Mott insulating behavior, and, for sufficiently high values, stabilizes the ferromagnetic octahedral phase. The validity of DFT and DFT +U for these two-dimensional materials with potential for strong electronic correlations is discussed. A clear benchmark is given by examining the experimentally observed charge density wave in octahedral VS2, for which DFT grossly overestimates the bond length differences compared to known experiments; the presence of charge density waves is also probed for the trigonal prismatic phase. Finally, we investigate why only the octahedral phase has been observed in experiments and discuss the possibility of realizing the trigonal prismatic phase. Our work suggests that trigonal prismatic VS2 is a promising candidate for strongly correlated electron physics that, if realized, could be experimentally probed in an unprecedented fashion due to its monolayer nature.

  13. Surface-segregated monolayers: a new type of ordered monolayer for surface modification of organic semiconductors.

    PubMed

    Wei, Qingshuo; Tajima, Keisuke; Tong, Yujin; Ye, Shen; Hashimoto, Kazuhito

    2009-12-09

    We report a new type of ordered monolayer for the surface modification of organic semiconductors. Fullerene derivatives with fluorocarbon chains ([6,6]-phenyl-C(61)-buryric acid 1H,1H-perfluoro-1-alkyl ester or FC(n)) spontaneously segregated as a monolayer on the surface of a [6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM) film during a spin-coating process from the mixture solutions, as confirmed by X-ray photoelectron spectroscopy (XPS). Ultraviolet photoelectron spectroscopy (UPS) showed the shift of ionization potentials (IPs) depending on the fluorocarbon chain length, indicating the formation of surface dipole moments. Surface-sensitive vibrational spectroscopy, sum frequency generation (SFG) revealed the ordered molecular orientations of the C(60) moiety in the surface FC(n) layers. The intensity of the SFG signals from FC(n) on the surface showed a clear odd-even effect when the length of the fluorocarbon chain was changed. This new concept of the surface-segregated monolayer provides a facile and versatile approach to modifying the surface of organic semiconductors and is applicable to various organic optoelectronic devices.

  14. The load of amyloid-β oligomers is decreased in the cerebrospinal fluid of Alzheimer's disease patients.

    PubMed

    Sancesario, Giulia M; Cencioni, Maria T; Esposito, Zaira; Borsellino, Giovanna; Nuccetelli, Marzia; Martorana, Alessandro; Battistini, Luca; Sorge, Roberto; Spalletta, Gianfranco; Ferrazzoli, Davide; Bernardi, Giorgio; Bernardini, Sergio; Sancesario, Giuseppe

    2012-01-01

    Amyloid-β (Aβ) oligomers are heterogeneous and instable compounds of variable molecular weight. Flow cytometry and fluorescence resonance energy transfer (FRET)-based methods allow the simultaneous detection of Aβ oligomers with low and high molecular weight in their native form. We evaluated whether an estimate of different species of Aβ oligomers in the cerebrospinal fluid (CSF) with or without dilution with RIPA buffer could be more useful in the diagnosis of Alzheimer's disease (AD) than the measurement of Aβ42 monomers, total tau (t-tau), and phosphorylated tau (p-tau). Increased t-tau (p < 0.01) and p-tau (p < 0.01), and decreased Aβ42 (p < 0.01), were detected in the CSF of patients with AD (n = 46), compared to patients with other dementia (OD) (n = 35) or with other neurological disorders (OND) (n = 56). In native CSF (n = 137), the levels of Aβ oligomers were lower (p < 0.05) in AD than in OD and OND patients; in addition, the ratio Aβ oligomers/p-tau was lower in AD than in OD (p < 0.01) and OND (p < 0.05) patients, yielding a sensitivity of 75% and a specificity of 64%. However, in CSF diluted with RIPA (n = 30), Aβ oligomers appeared higher (p < 0.05) in AD than in OND patients, suggesting they become partially disaggregated and more easily detectable after RIPA. In conclusion, FRET analysis in native CSF is essential to correctly determine the composition of Aβ oligomers. In this experimental setting, the simultaneous estimate of low and high molecular weight Aβ oligomers is as useful as the other biomarkers in the diagnosis of AD. The low amount of Aβ oligomers detected in native CSF of AD may be inversely related to their levels in the brain, as occurs for Aβ monomers, representing a biomarker for the amyloid pathogenic cascade.

  15. Translational Diffusion in Phospholipid Monolayers Measured by Fluorescence Microphotolysis

    NASA Astrophysics Data System (ADS)

    Peters, Reiner; Beck, Konrad

    1983-12-01

    A method is described that eliminates surface flow in monolayers at the air-water interface and makes possible diffusion measurements by fluorescence microphotolysis (``photobleaching''). In contrast to previous studies that did not account for surface flow, lipid probe diffusion has been found to be similar in densely packed monolayers and in related bilayers. Furthermore, it seems that lipid diffusion is based on the same molecular mechanism in monolayers, bilayers, and potentially also cell membranes. In monolayers of L-α -dilauroylphosphatidylcholine (Lau2-PtdCho) the translational diffusion coefficient D of the fluorescent lipid probe N-4-nitrobenzo-2-oxa-1,3 diazole egg phosphatidylethanolamine decreased from 110 μ m2/s at a surface pressure Pi =1 mN/m to 15 μ m2/s at Pi =38 mN/m (T = 21-22 degrees C). Data could be fitted by the ``free volume model.'' In monolayers of L-α -dipalmitoylphosphatidylcholine (Pam2-PtdCho) D decreased by >3 orders of magnitude upon increasing Pi at constant temperature, thus indicating a fluid-to-crystalline phase transition. In Lau2-PtdCho/Pam2-PtdCho monolayers phase separation has been visualized in the fluorescence microscope and the effect on D measured. These results suggest that monolayers are a promising model system for studying the molecular mobility of lipids and other cell membrane components.

  16. Optically Reconfigurable Monolayer of Azobenzene Donor Molecules on Oxide Surfaces.

    PubMed

    McElhinny, Kyle M; Huang, Peishen; Joo, Yongho; Kanimozhi, Catherine; Lakkham, Arunee; Sakurai, Kenji; Evans, Paul G; Gopalan, Padma

    2017-03-07

    The structural configuration of molecules assembled at organic-inorganic interfaces within electronic materials strongly influences the functional electronic and vibrational properties relevant to applications ranging from energy storage to photovoltaics. Controlling and characterizing the structural state of an interface and its evolution under external stimuli is crucial both for the fundamental understanding of the factors influenced by molecular structure and for the development of methods for material synthesis. It has been challenging to create complete molecular monolayers that exhibit external reversible control of the structure and electronic configuration. We report a monolayer/inorganic interface consisting of an organic monolayer assembled on an oxide surface, exhibiting structural and electronic reconfiguration under ultraviolet illumination. The molecular monolayer is linked to the surface through a carboxylate link, with the backbone bearing an azobenzene functional group and the head group consisting of a rhenium-bipyridine group. Optical spectroscopy, X-ray photoelectron spectroscopy, atomic force microscopy, and X-ray reflectivity show that closely packed monolayers are formed from these molecules via the Langmuir-Blodgett technique. Reversible photoisomerization is observed in solution and in monolayers assembled on Si and quartz substrates. The reconfiguration of these monolayers provides additional means to control excitation and charge transfer processes that are important in applications in catalysis, molecular electronics, and solar energy conversion.

  17. The Modeling of Pulmonary Particulate Matter Transport Using Langmuir Monolayers

    NASA Astrophysics Data System (ADS)

    Eaton, Jeremy M.

    The effects of a barrier in proximity to the air-water interface on the dynamics of a Langmuir monolayer system are observed. A monolayer of Survanta, bovine lung surfactant, is deposited onto the interface of an aqueous buffer solution. Polystyrene particles one micron in diameter and tagged with fluorescent carboxylate groups are distributed evenly throughout the monolayer surface. The bead-monolayer system is compressed and expanded to induce folding. A polydimethylsiloxane (PDMS) substrate is placed below the monolayer in the buffer solution to study interactions between the folding monolayer and a barrier. The presence of the substrate is shown to shift surface pressure-area isotherms toward regions of lower area by an average of 8.9 mN/m. The surface of the PDMS substrate can be imaged using fluorescence microscopy to detect the presence of particles or surfactant that may have been transported there from the air-water interface during folding. Images show the transferral of particles and monolayer together suggesting the pinch-off of a fold or the direct interaction of a fold with the barrier.

  18. EXCESS FIBRINOGEN ADSORPTION TO MONOLAYERS OF MIXED LIPIDS

    PubMed Central

    Deshmukh, V.; Britt, D.W.; Hlady, V.

    2010-01-01

    Adsorption of fibrinogen to the monolayers of mixed lipids, dipalmitoyl phosphatidyl choline (DPPC) and eicosylamine (EA) was measured at a surface pressure of 20 mN/m by an in situ surface plasmon resonance technique. Pressure-area isotherms of DPPC+EA mixtures on water and buffer subphases indicated good lipid miscibility and some contraction of the monolayers at intermediate and higher surface pressures. Surface electric potential of the DPPC+EA monolayers showed excess values for intermediate DPPC:EA ratios. Fibrinogen adsorption and its adsorption rates from a dilute solution (0.03 mg/ml) were proportional to the fraction of EA in the monolayer indicating that protein binding was primarily driven by electrostatic interactions between positive EA charges in the monolayer and a net negative protein charge. At a higher protein concentration (0.06 mg/ml) both the fibrinogen adsorbed amount and its maximum adsorption rate showed excess values relative to the pure EA for 1:1, 2:1 and 3:1 DPPC+EA monolayers. This excess adsorption could be explained, in part, by the contraction of the monolayers with intermediate DPPC:EA ratios which resulted in an excess surface electric potential. PMID:20829000

  19. Dynamics of a monolayer of microspheres on an elastic substrate

    NASA Astrophysics Data System (ADS)

    Wallen, S. P.; Maznev, A. A.; Boechler, N.

    2015-11-01

    We present a model for wave propagation in a monolayer of spheres on an elastic substrate. The model, which considers sagittally polarized waves, includes: horizontal, vertical, and rotational degrees of freedom; normal and shear coupling between the spheres and substrate, as well as between adjacent spheres; and the effects of wave propagation in the elastic substrate. For a monolayer of interacting spheres, we find three contact resonances, whose frequencies are given by simple closed-form expressions. For a monolayer of isolated spheres, only two resonances are present. The contact resonances couple to surface acoustic waves in the substrate, leading to mode hybridization and "avoided crossing" phenomena. We present dispersion curves for a monolayer of silica microspheres on a silica substrate, assuming adhesive Hertzian interactions, and compare calculations using an effective medium approximation (including elasticity of the substrate) to a discrete model of a monolayer on a rigid substrate. While the effective medium model does not describe discrete lattice effects occurring at short wavelengths, we find that it is well suited for describing the interaction between the monolayer and substrate in the long wavelength limit. We suggest that a complete picture of the dynamics of a monolayer adhered to an elastic substrate can be found by combining the dispersion curves generated with the effective medium model for the elastic substrate and the discrete model for the rigid substrate. This model is potentially scalable for use with nano- to macroscale systems, and offers the prospect of experimentally extracting contact stiffnesses from measurements of acoustic dispersion.

  20. Nonenzymatic synthesis of RNA and DNA oligomers on hexitol nucleic acid templates: the importance of the A structure

    NASA Technical Reports Server (NTRS)

    Kozlov, I. A.; Politis, P. K.; Van Aerschot, A.; Busson, R.; Herdewijn, P.; Orgel, L. E.; Bada, J. L. (Principal Investigator); Dolan, M. (Principal Investigator)

    1999-01-01

    Hexitol nucleic acid (HNA) is an analogue of DNA containing the standard nucleoside bases, but with a phosphorylated 1,5-anhydrohexitol backbone. HNA oligomers form duplexes having the nucleic acid A structure with complementary DNA or RNA oligomers. The HNA decacytidylate oligomer is an efficient template for the oligomerization of the 5'-phosphoroimidazolides of guanosine or deoxyguanosine. Comparison of the oligomerization efficiencies on HNA, RNA, and DNA decacytidylate templates under various conditions suggests strongly that only nucleic acid double helices with the A structure support efficient template-directed synthesis when 5'-phosphoroimidazolides of nucleosides are used as substrates.

  1. Purified high molecular weight synthetic Aβ(1-42) and biological Aβ oligomers are equipotent in rapidly inducing MTT formazan exocytosis.

    PubMed

    Weidner, Adam M; Housley, Molly; Murphy, M Paul; Levine, Harry

    2011-06-15

    Synthetic soluble Aβ oligomers are often used as a surrogate for biologic material in a number of model systems. We compared the activity of Aβ oligomers (synthetic and cell culture media derived) on the human SH-SY5Y neuroblastoma and C2C12 mouse myoblast cell lines in a novel, modified MTT assay. Separating oligomers from monomeric peptide by size exclusion chromatography produced effects at peptide concentrations approaching physiologic levels (10-100 nM). Purified oligomers, but not monomers or fibrils, elicited an increase of a detergent-insoluble form of MTT formazan within 2h as opposed to a control toxin (H(2)O(2)). This effect was comparable for biological and synthetic peptide in both cell types. Monomeric Aβ attenuated the effect of soluble oligomers. This study suggests that the activities of biological and synthetic oligomers are indistinguishable during early stages of Aβ oligomer-cell interaction.

  2. Oligomer formation during gas-phase ozonolysis of small alkenes and enol ethers: new evidence for the central role of the Criegee Intermediate as oligomer chain unit

    NASA Astrophysics Data System (ADS)

    Sadezky, A.; Winterhalter, R.; Kanawati, B.; Römpp, A.; Spengler, B.; Mellouki, A.; Le Bras, G.; Chaimbault, P.; Moortgat, G. K.

    2007-10-01

    An important fraction of secondary organic aerosol (SOA) formed by atmospheric oxidation of diverse volatile organic compounds (VOC) has recently been shown to consist of high-molecular weight oligomeric species. In our previous study (Sadezky et al., 2006), we reported the identification and characterization of oligomers as main constituents of SOA from gas-phase ozonolysis of small enol ethers. These oligomers contained repeated chain units of the same chemical composition as the main Criegee Intermediates (CI) formed during the ozonolysis reaction, which were CH2O2 (mass 46) for alkyl vinyl ethers (AVE) and C2H4O2 (mass 60) for ethyl propenyl ether (EPE). In the present work, we extend our previous study (Sadezky et al., 2006) to another enol ether (ethyl butenyl ether EBE) and a variety of structurally related small alkenes (trans-3-hexene, trans-4-octene and 2,3-dimethyl-2-butene). Experiments have been carried out in a 570 l spherical glass reactor at atmospheric conditions in the absence of seed aerosol. SOA formation was measured by a scanning mobility particle sizer (SMPS). SOA filter samples were collected and chemically characterized off-line by ESI(+)/MS-TOF and ESI(+)/MS/MS-TOF, and elemental compositions were confirmed by ESI(+)/MS/MS-FTICR. The results for all investigated unsaturated compounds are in excellent agreement with the observations of our previous study (Sadezky et al., 2006). Analysis of the collected SOA filter samples reveal the presence of oligomeric compounds in the mass range 200 to 800 u as major constituents. The repeated chain units of these oligomers are shown to systematically have the same chemical composition as the respective main Criegee Intermediate (CI) formed during ozonolysis of the unsaturated compounds, which is C3H6O2 (mass 74) for ethyl butenyl ether (EBE), trans-3-hexene, and 2,3-dimethyl-2-butene, and C4H8O2 (mass 88) for trans-4-octene. Analogous fragmentation pathways among the oligomers formed by gas

  3. Ordered Porous Pd Octahedra Covered with Monolayer Ru Atoms.

    PubMed

    Ge, Jingjie; He, Dongsheng; Bai, Lei; You, Rui; Lu, Haiyuan; Lin, Yue; Tan, Chaoliang; Kang, Yan-Biao; Xiao, Bin; Wu, Yuen; Deng, Zhaoxiang; Huang, Weixin; Zhang, Hua; Hong, Xun; Li, Yadong

    2015-11-25

    Monolayer Ru atoms covered highly ordered porous Pd octahedra have been synthesized via the underpotential deposition and thermodynamic control. Shape evolution from concave nanocube to octahedron with six hollow cavities was observed. Using aberration-corrected high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy, we provide quantitative evidence to prove that only a monolayer of Ru atoms was deposited on the surface of porous Pd octahedra. The as-prepared monolayer Ru atoms covered Pd nanostructures exhibited excellent catalytic property in terms of semihydrogenation of alkynes.

  4. Optical Control of Spin Polarization in Monolayer Transition Metal Dichalcogenides.

    PubMed

    Chen, Xi; Yan, Tengfei; Zhu, Bairen; Yang, Siyuan; Cui, Xiaodong

    2017-02-28

    Optical excitation could generate electrons' spin polarization in some semiconductors with the control of the field polarization. In this article, we report a series of spin-resolved photocurrent experiments on monolayer tungsten disulfide. The experiments demonstrate that the optical excitations with the same helicity could generate opposite spin polarization around the Fermi level by tuning the excitation energy. The mechanism lies in the valley-dependent optical selection rules, the giant spin-orbit coupling, and spin-valley locking in monolayer transition metal dichalcogenides (TMDs). These exotic features make monolayer TMDs promising candidates for conceptual semiconductor-based spintronics.

  5. Amyloid β oligomers induce interleukin-1β production in primary microglia in a cathepsin B- and reactive oxygen species-dependent manner

    SciTech Connect

    Taneo, Jun; Adachi, Takumi; Yoshida, Aiko; Takayasu, Kunio; Takahara, Kazuhiko; Inaba, Kayo

    2015-03-13

    Amyloid β (Aβ) peptide, a causative agent of Alzheimer's disease, forms two types of aggregates: oligomers and fibrils. These aggregates induce inflammatory responses, such as interleukin-1β (IL-1β) production by microglia, which are macrophage-like cells located in the brain. In this study, we examined the effect of the two forms of Aβ aggregates on IL-1β production in mouse primary microglia. We prepared Aβ oligomer and fibril from Aβ (1–42) peptide in vitro. We analyzed the characteristics of these oligomers and fibrils by electrophoresis and atomic force microscopy. Interestingly, Aβ oligomers but not Aβ monomers or fibrils induced robust IL-1β production in the presence of lipopolysaccharide. Moreover, Aβ oligomers induced endo/phagolysosome rupture, which released cathepsin B into the cytoplasm. Aβ oligomer-induced IL-1β production was inhibited not only by the cathepsin B inhibitor CA-074-Me but also by the reactive oxygen species (ROS) inhibitor N-acetylcysteine. Random chemical crosslinking abolished the ability of the oligomers to induce IL-1β. Thus, multimerization and fibrillization causes Aβ oligomers to lose the ability to induce IL-1β. These results indicate that Aβ oligomers, but not fibrils, induce IL-1β production in primary microglia in a cathepsin B- and ROS-dependent manner. - Highlights: • We prepared amyloid β (Aβ) fibrils with minimum contamination of Aβ oligomers. • Primary microglia (MG) produced IL-1β in response to Aβ oligomers, but not fibrils. • Only Aβ oligomers induced leakage of cathepsin B from endo/phagolysosomes. • IL-1β production in response to Aβ oligomers depended on both cathepsin B and ROS. • Crosslinking reduced the ability of the Aβ oligomers to induce IL-1β from MG.

  6. Conformation-specific antibodies to target amyloid β oligomers and their application to immunotherapy for Alzheimer's disease.

    PubMed

    Murakami, Kazuma

    2014-01-01

    Amyloid β-protein (Aβ) oligomers, intermediates of Aβ aggregation, cause cognitive impairment and synaptotoxicity in the pathogenesis of Alzheimer's disease (AD). Immunotherapy using anti-Aβ antibody is one of the most promising approaches for AD treatment. However, most clinical trials using conventional sequence-specific antibodies have proceeded with difficulty. This is probably due to the unintended removal of the non-pathological monomer and fibrils of Aβ as well as the pathological oligomers by these antibodies that recognize Aβ sequence, which is not involved in synaptotoxicity. Several efforts have been made recently to develop conformation-specific antibodies that target the tertiary structure of Aβ oligomers. Here, we review the recent findings of Aβ oligomers and anti-Aβ antibodies including our own, and discuss their potential as therapeutic and diagnostic tools.

  7. Saccharide recognition-induced transformation of pyridine-pyridone alternate oligomers from self-dimer to helical complex.

    PubMed

    Abe, Hajime; Machiguchi, Hiroshi; Matsumoto, Shinya; Inouye, Masahiko

    2008-06-20

    Co-oligomers involving (1H)-4-pyridone and 4-alkoxypyridine rings were studied, and it was found that their supramolecular transformation was caused by saccharide recognition. In the co-oligomers, pyridone and pyridine rings are alternately linked at their 2,6-position with an acetylene bond. The pyridine rings behave as a hydrogen bonding acceptor, and the pyridone rings and tautomerized 4-pyridinol work as a donor. Pyridine-pyridone-pyridine 3-mer was found to self-dimerize on the basis of vapor pressure osmometry in CHCl(3), and the association constant was obtained as 2.3 x 10(3) M(-1) by (1)H NMR titration. Longer 5-, 7-, 9-, and 11-mer oligomers showed considerable broadening and anisotropy in the (1)H NMR spectra due to self-association. These longer oligomers recognized octyl beta-D-glucopyranoside and changed their form into a chiral helical complex, showing characteristic circular dichroism.

  8. Montmorillonite-catalysed formation of RNA oligomers: the possible role of catalysis in the origins of life

    PubMed Central

    Ferris, James P

    2006-01-01

    Large deposits of montmorillonite are present on the Earth today and it is believed to have been present at the time of the origin of life and has recently been detected on Mars. It is formed by aqueous weathering of volcanic ash. It catalyses the formation of oligomers of RNA that contain monomer units from 2 to 30–50. Oligomers of this length are formed because this catalyst controls the structure of the oligomers formed and does not generate all possible isomers. Evidence of sequence-, regio- and homochiral selectivity in these oligomers has been obtained. Postulates on the role of selective versus specific catalysts on the origins of life are discussed. An introduction to the origin of life is given with an emphasis on reaction conditions based on the recent data obtained from zircons 4.0–4.5 Ga. PMID:17008218

  9. Synthesis and characterizations of heterojunction of monolayer semiconductors

    NASA Astrophysics Data System (ADS)

    Lee, Yi-Hsien; Zhang, Xin-Quan; Tseng, Yu-Wen; Huang, Kuan-Hua; Chen, Chun-An; Chen, Bo-Han

    Monolayers of van der Waals materials, including graphene, and MoS2, offered a burgeoning field in fundamental physics, and optoelectronics.[1-5] Recently, atomically thin heterostructures of monolayer TMDc with various geometrical and energy band alignments are expected to be the key materials for next generation flexible optoelectronics. The individual TMDc monolayers can be adjoined vertically or laterally to construct diverse heterostructures which are difficult to reach with the laborious pick up-and-transfer method of the exfoliated flakes. The ability to produce copious amounts of high quality layered heterostructures on diverse surfaces is highly desirable but it has remained a challenging issue. Here, we have achieved a direct synthesis of various heterostructures of monolayer TMDc. The synthesis was performed using CVD with aromatic molecules as seeding promoters. We will discuss possible growth behaviors, and we examine the symmetry and the interface of these heterostructures using optical analysis and scanning TEM.

  10. Thiophene-based monolayer OFETs prepared by Langmuir techniques

    NASA Astrophysics Data System (ADS)

    Agina, Elena V.; Sizov, Alexey S.; Anisimov, Daniil S.; Trul, Askold A.; Borshchev, Oleg V.; Paraschuk, Dmitry Y.; Shcherbina, Maxim A.; Chvalun, Sergey N.; Ponomarenko, Sergey A.

    2015-08-01

    A novel fast, easily processible and highly reproducible approach to thiophene-based monolayer OFETs fabrication by Langmuir-Blodgett or Langmuir-Schaefer techniques was developed and successfully applied. It is based on selfassembly of organosilicon derivatives of oligothiophenes or benzothienobenzothiophene on the water-air interface. Influence of the conjugation length and the anchor group chemistry of the self-assembling molecules on the monolayer structure and electric performance of monolayer OFETs was systematically investigated. The efficient monolayer OFETs with the charge carrier mobilities up to 0.01 cm2/Vs and on/off ratio up to 106 were fabricated, and their functionality in integrated circuits under normal air conditions was demonstrated.

  11. Phase emerging from intramonolayer cycloaddition on micro-patterned monolayer

    SciTech Connect

    Tajuddin, Hairul A.; Manning, Robert J.; Leggett, Graham J.; Williams, Nicholas H.

    2012-11-27

    Cu(I)-catalyzed cycloaddition between azide and acetylene, followed by hydrolysis of ester were performed on micro-patterned self-assembled monolayer to produce smaller features. The reactions were initially performed on mixed monolayers and analysed by water contact angle (CA) and confirmed by X-ray Photoelectron Spectroscopy (XPS). The contact angle measurement has shown a drastic wetting of water on the surface of mixed monolayer indicating that the terminal groups on mixed monolayer has changed into carboxylic acid and hydroxyl terminals. The reactions work in a similar way on micro-patterned SAM and analyzed by using friction force microscope. The emerging of the new lines with high friction force on the border suggested a successful intramonolayer reactions on the border of the patterned SAM.

  12. The Formation and Stability of Alkylthiol Monolayers on Carbon Substrates

    PubMed Central

    Lockett, Matthew R.; Smith, Lloyd M.

    2010-01-01

    The formation and stability of alkylthiol monolayers on amorphous carbon thin films are investigated. Alkylthiol monolayers were prepared via a two-step, wet chemical process in which the carbon surface was first halogenated and then incubated with (4-(trifluoromethyl)phenyl)methanethiol (4tBM). The 4tBM covalently attaches to the surface in a substitution reaction in which the 4tBM thiol replaces the surface halogen. Studies of the substitution mechanism showed that monolayer formation is affected by the nature of the surface-bound halogen as well as the concentration and nucleophilicity of the 4tBM sulfur atom, consistent with a bimolecular (SN2) substitution reaction mechanism. The alkylthiol monolayers are stable over a wide range of solvent, pH, and temperature conditions. PMID:20706614

  13. Growth of rare-earth monolayers on synthetic fluorine mica

    NASA Astrophysics Data System (ADS)

    Tsui, F.; Han, P. D.; Flynn, C. P.

    1993-05-01

    We have grown single-crystal rare-earth films on cleaved faces of synthetic fluorine mica fluorophlogopite by molecular-beam-epitaxy techniques. This has made it possible to measure material properties such as magnetism in monolayer structures.

  14. Optical emission and vibrational modes of uniform pentacene monolayers (*)

    NASA Astrophysics Data System (ADS)

    He, Rui; Tassi, Nancy; Blanchet, Graciela; Pinczuk, Aron

    2006-03-01

    Pentacene monolayers are probed by photoluminescence and resonant Raman spectroscopies below 10K. Monolayers grown on polymeric substrate of poly-alpha-methyl-styrene (PAMS) exhibit high uniformity within micron size clusters. These films show sharp exciton luminescence bands, and the energy of the exciton optical emission displays a red-shift as the average film thickness increases. The large resonance enhancements of Raman scattering intensities enable the measurements of low-lying (40- 200cm-1) optical lattice vibrations from these monolayers. These experiments demonstrate that luminescence and resonant Raman scattering from single pentacene monolayers are venues for probing 2D properties, studies of interface effects, and thin film characterization. (*) Supported primarily by the Nanoscale Science and Engineering Initiative of the National Science Foundation under NSF Award No. CHE-0117752 and by the New York State Office of Science, Technology, and Academic Research (NYSTAR), and by a research grant of the W. M. Keck Foundation.

  15. Oxidized Monolayers of Epitaxial Silicene on Ag(111)

    PubMed Central

    Johnson, Neil W.; Muir, David I.; Moewes, Alexander

    2016-01-01

    The properties of epitaxial silicene monolayers on Ag(111) at various levels of oxidation are determined through complementary density functional theory calculations and soft X-ray spectroscopy experiments. Our calculations indicate that moderate levels of oxidation do not cause a significant bandgap opening in the epitaxial silicene monolayer, suggesting that oxygen functionalization is not a viable mechanism for bandgap tuning while the silicene monolayer remains on its metallic substrate. In addition, moderate oxidation is calculated to strongly distort the hexagonal Si lattice, causing it to cluster in regions of highest oxygen adatom concentration but retain its 2D sheet structure. However, our experiments reveal that beam-induced oxidation is consistent with the formation of islands of bulk-like SiO2. Complete exposure of the monolayer to ambient conditions results in a fully oxidized sample that closely resembles bulk SiO2, of which a significant portion is completely detached from the substrate. PMID:26936144

  16. Recognition of Salmonella typhimurium by immobilized phage P22 monolayers

    NASA Astrophysics Data System (ADS)

    Handa, Hitesh; Gurczynski, Stephen; Jackson, Matthew P.; Auner, Gregory; Walker, Jeremy; Mao, Guangzhao

    2008-04-01

    Phages are promising alternatives to antibodies as the biorecognition element in a variety of biosensing applications. In this study, a monolayer of bacteriophage P22 whose tailspike proteins specifically recognize Salmonella serotypes was covalently bound to glass substrates through a bifunctional cross linker 3-aminopropyltrimethoxysilane. The specific binding of Salmonella typhimurium to the phage monolayer was studied by enzyme-linked immunosorbent assay and atomic force microscopy. Escherichia coli and a Gram-positive bacterium Listeria monocytogenes were also studied as control bacteria. The P22 particles show strong binding affinity to S. typhimurium. In addition, the dried P22 monolayer maintained 50% binding capacity to S. typhimurium after a one-week storage time. This is a promising method to prepare phage monolayer coatings on surface plasmon resonance and acoustic biosensor substrates in order to utilize the nascent phage display technology.

  17. Monolayers of hard rods on planar substrates. I. Equilibrium.

    PubMed

    Oettel, M; Klopotek, M; Dixit, M; Empting, E; Schilling, T; Hansen-Goos, H

    2016-08-21

    The equilibrium properties of hard rod monolayers are investigated in a lattice model (where position and orientation of a rod are restricted to discrete values) as well as in an off-lattice model featuring spherocylinders with continuous positional and orientational degrees of freedom. Both models are treated using density functional theory and Monte Carlo simulations. Upon increasing the density of rods in the monolayer, there is a continuous ordering of the rods along the monolayer normal ("standing up" transition). The continuous transition also persists in the case of an external potential which favors flat-lying rods in the monolayer. This behavior is found in both the lattice and the continuum models. For the lattice model, we find very good agreement between the results from the specific DFT used (lattice fundamental measure theory) and simulations. The properties of lattice fundamental measure theory are further illustrated by the phase diagrams of bulk hard rods in two and three dimensions.

  18. Monolayers of hard rods on planar substrates. I. Equilibrium

    NASA Astrophysics Data System (ADS)

    Oettel, M.; Klopotek, M.; Dixit, M.; Empting, E.; Schilling, T.; Hansen-Goos, H.

    2016-08-01

    The equilibrium properties of hard rod monolayers are investigated in a lattice model (where position and orientation of a rod are restricted to discrete values) as well as in an off-lattice model featuring spherocylinders with continuous positional and orientational degrees of freedom. Both models are treated using density functional theory and Monte Carlo simulations. Upon increasing the density of rods in the monolayer, there is a continuous ordering of the rods along the monolayer normal ("standing up" transition). The continuous transition also persists in the case of an external potential which favors flat-lying rods in the monolayer. This behavior is found in both the lattice and the continuum models. For the lattice model, we find very good agreement between the results from the specific DFT used (lattice fundamental measure theory) and simulations. The properties of lattice fundamental measure theory are further illustrated by the phase diagrams of bulk hard rods in two and three dimensions.

  19. Unsupported single-atom-thick copper oxide monolayers

    NASA Astrophysics Data System (ADS)

    Yin, Kuibo; Zhang, Yu-Yang; Zhou, Yilong; Sun, Litao; Chisholm, Matthew F.; Pantelides, Sokrates T.; Zhou, Wu

    2017-03-01

    Oxide monolayers may present unique opportunities because of the great diversity of properties of these materials in bulk form. However, reports on oxide monolayers are still limited. Here we report the formation of single-atom-thick copper oxide layers with a square lattice both in graphene pores and on graphene substrates using aberration-corrected scanning transmission electron microscopy. First-principles calculations find that CuO is energetically stable and its calculated lattice spacing matches well with the measured value. Furthermore, free-standing copper oxide monolayers are predicted to be semiconductors with band gaps ∼3 eV. The new wide-bandgap single-atom-thick copper oxide monolayers usher a new frontier to study the highly diverse family of two-dimensional oxides and explore their properties and their potential for new applications.

  20. Electrochemical Properties of Organosilane Self Assembled Monolayers on Aluminum 2024

    NASA Technical Reports Server (NTRS)

    Hintze, Paul E.; Calle, Luz Marina

    2004-01-01

    Self assembled monolayers are commonly used to modify surfaces. Within the last 15 years, self assembled monolayers have been investigated as a way to protect from corrosion[1,2] or biofouling.[3] In this study, self assembled monolayers of decitriethoxysilane (C10H21Si(OC2H5)3) and octadecyltriethoxysilane (C18H37Si(OC2H5)3) were formed on aluminum 2024-T3. The modified surfaces and bare Al 2024 were characterized by dynamic water contact angle measurements, x-ray photoelectron spectroscopy (XIPS) and infrared spectroscopy. Electrochemical impedance spectroscopy (EIS) in 0.5 M NaCl was used to characterize the monolayers and evaluate their corrosion protection properties. The advancing water contact angle and infrared measurements show that the mono layers form a surface where the hydrocarbon chains are packed and oriented away from the surface, consistent with what is found in similar systems. The contact angle hysteresis measured in these systems is relatively large, perhaps indicating that the hydrocarbon chains are not as well packed as monolayers formed on other substrates. The results of the EIS measurements were modeled using a Randle's circuit modified by changing the capacitor to a constant phase element. The constant phase element values were found to characterize the monolayer. The capacitance of the monolayer modified surface starts lower than the bare Al 2024, but approaches values similar to the bare Al 2024 within 24 hours as the monolayer is degraded. The n values found for bare Al 2024 quickly approach the value of a true capacitor and are greater than 0.9 within hours after the start of exposure. For the monolayer modified structure, n can stay lower than 0.9 for a longer period of time. In fact, n for the monolayer modified surfaces is different from the bare surface even after the capacitance values have converged. This indicates that the deviation from ideal capacitance is the most sensitive indicator of the presence of the monolayer.

  1. Sequence-Defined Oligomers from Hydroxyproline Building Blocks for Parallel Synthesis Applications.

    PubMed

    Kanasty, Rosemary L; Vegas, Arturo J; Ceo, Luke M; Maier, Martin; Charisse, Klaus; Nair, Jayaprakash K; Langer, Robert; Anderson, Daniel G

    2016-08-08

    The functionality of natural biopolymers has inspired significant effort to develop sequence-defined synthetic polymers for applications including molecular recognition, self-assembly, and catalysis. Conjugation of synthetic materials to biomacromolecules has played an increasingly important role in drug delivery and biomaterials. We developed a controlled synthesis of novel oligomers from hydroxyproline-based building blocks and conjugated these materials to siRNA. Hydroxyproline-based monomers enable the incorporation of broad structural diversity into defined polymer chains. Using a perfluorocarbon purification handle, we were able to purify diverse oligomers through a single solid-phase extraction method. The efficiency of synthesis was demonstrated by building 14 unique trimers and 4 hexamers from 6 diverse building blocks. We then adapted this method to the parallel synthesis of hundreds of materials in 96-well plates. This strategy provides a platform for the screening of libraries of modified biomolecules.

  2. Coplanar switching of polarization in thin films of vinylidene fluoride oligomers

    SciTech Connect

    Sharma, Pankaj Fursina, Alexandra; Poddar, Shashi; Ducharme, Stephen; Gruverman, Alexei

    2014-11-03

    Switching characteristics of vinylidene fluoride oligomer thin films with molecular chains aligned normal to the substrate and exhibiting a preferential in-plane polarization have been investigated using coplanar geometry of inter-digital electrodes via high-resolution piezoresponse force microscopy. It has been shown that in-plane switching proceeds via non-180° rotation of dipoles mediated by non-stochastic nucleation, expansion, and coalescence of domains. As-grown multidomain configuration is found to be strongly pinned aided by charged domain walls, and the electrically induced (in-plane) mono-domain states relax to the as-grown state. The observed coercive field (approximately 0.6 MV/m) is two to three orders of magnitude smaller than that for the oligomer films with out-of-plane polarization. It is suggested that the low steric hindrance to the rotation of molecular dipoles gives rise to the observed low coercive field.

  3. Soybean Ferritin Forms an Iron-Containing Oligomer in Tofu Even after Heat Treatment.

    PubMed

    Masuda, Taro

    2015-10-14

    Ferritin, a multimeric iron storage protein distributed in almost all living kingdoms, has been highlighted recently as a nutritional iron source in plant-derived foodstuffs, because ferritin iron is suggested to have high bioavailability. In soybean seeds, ferritin contributes largely to the net iron contents. Here, the oligomeric states and iron contents of soybean ferritin during food processing (especially tofu gel formation) were analyzed. Ferritin was purified from tofu gel as an iron-containing oligomer (approximately 1000 Fe atoms per oligomer), which was composed of two types of subunits similar to the native soybean seed ferritin. Circular dichroism spectra also showed no differences in α-helical structure between native soybean ferritin and tofu ferritin. The present data demonstrate that ferritin was stable during the heat treatment (boiling procedure) in food processing, although partial denaturation was observed at temperatures higher than 80 °C.

  4. Liquid Crystalline Thermosets from Ester, Ester-imide, and Ester-amide Oligomers

    NASA Technical Reports Server (NTRS)

    Dingemans, Theodorus J. (Inventor); Weiser, Erik S. (Inventor); St. Clair, Terry L. (Inventor)

    2009-01-01

    Main chain thermotropic liquid crystal esters, ester-imides, and ester-amides were prepared from AA, BB, and AB type monomeric materials and end-capped with phenylacetylene, phenylmaleimide, or nadimide reactive end-groups. The end-capped liquid crystal oligomers are thermotropic and have, preferably, molecular weights in the range of approximately 1000-15,000 grams per mole. The end-capped liquid crystaloligomers have broad liquid crystalline melting ranges and exhibit high melt stability and very low melt viscosities at accessible temperatures. The end-capped liquid crystal oli-gomers are stable forup to an hour in the melt phase. They are highly processable by a variety of melt process shape forming and blending techniques. Once processed and shaped, the end-capped liquid crystal oigomers were heated to further polymerize and form liquid crystalline thermosets (LCT). The fully cured products are rubbers above their glass transition temperatures.

  5. Similarities and differences in the influence of polycations and oligomers on DNA conformation and packaging.

    PubMed

    Kasyanenko, Nina; Dribinsky, Boris

    2016-05-01

    A comparison of DNA conformational changes in a solution containing the poly-l-lysine with the number of monomers z=3, 5, 17, 20, 270, 325 and polyamines (spermine and spermidine) was carried out in 1M and 5mM NaCl solutions. It was shown that despite the identical results of DNA condensation induced by compounds, their influence on the DNA conformation prior to packaging depends on whether they belong to a long polycations or short oligomers. DNA secondary and tertiary structures were examined using Circular Dichroism, UV-vis Spectrophotometry, Dynamic Light Scattering, Low Gradient Viscometry, Flow Birefringence, and AFM. The phase diagrams for systems of DNA-polycations, DNA-oligomers, DNA-polyamines were drawn.

  6. Liquid Crystal Ordering and Isotropic Gelation in Solutions of Four-Base-Long DNA Oligomers.

    PubMed

    Fraccia, Tommaso P; Smith, Gregory P; Bethge, Lucas; Zanchetta, Giuliano; Nava, Giovanni; Klussmann, Sven; Clark, Noel A; Bellini, Tommaso

    2016-09-27

    Liquid crystal ordering is reported in aqueous solutions of the oligomer 5'-ATTAp-3' and of the oligomer 5'-GCCGp-3'. In both systems, we quantitatively interpret ordering as stemming from the chaining of molecules via a "running-bond" type of pairing, a self-assembly process distinct from the duplex aggregation previously reported for longer oligonucleotides. While concentrated solutions of 5'-ATTAp-3' show only a columnar liquid crystal phase, solutions of 5'-GCCGp-3' display a rich phase diagram, featuring a chiral nematic phase analogous to those observed in solutions of longer oligonucleotides and two unconventional phases, a columnar crystal and, at high concentration, an isotropic amorphous gel. The appearance of these phases, which can be interpreted on the basis of features of 5'-GCCGp-3'molecular structure, suggests distinctive assembly motifs specific to ultrashort oligonucleotides.

  7. Self-assembly of human MxA GTPase into highly ordered dynamin-like oligomers.

    PubMed

    Kochs, Georg; Haener, Markus; Aebi, Ueli; Haller, Otto

    2002-04-19

    Human MxA protein is a member of the interferon-induced Mx protein family and an important component of the innate host defense against RNA viruses. The Mx family belongs to a superfamily of large GTPases that also includes the dynamins and the interferon-regulated guanylate-binding proteins. A common feature of these large GTPases is their ability to form high molecular weight oligomers. Here we determined the capacity of MxA to self-assemble into homo-oligomers in vitro. We show that recombinant MxA protein assembles into long filamentous structures with a diameter of about 20 nm at physiological salt concentration as demonstrated by sedimentation assays and electron microscopy. In the presence of guanosine nucleotides the filaments rearranged into rings and more compact helical arrays. Our data indicate that binding and hydrolysis of GTP induce conformational changes in MxA that may be essential for viral target recognition and antiviral activity.

  8. QIAD assay for quantitating a compound’s efficacy in elimination of toxic Aβ oligomers

    PubMed Central

    Brener, Oleksandr; Dunkelmann, Tina; Gremer, Lothar; van Groen, Thomas; Mirecka, Ewa A.; Kadish, Inga; Willuweit, Antje; Kutzsche, Janine; Jürgens, Dagmar; Rudolph, Stephan; Tusche, Markus; Bongen, Patrick; Pietruszka, Jörg; Oesterhelt, Filipp; Langen, Karl-Josef; Demuth, Hans-Ulrich; Janssen, Arnold; Hoyer, Wolfgang; Funke, Susanne A.; Nagel-Steger, Luitgard; Willbold, Dieter

    2015-01-01

    Strong evidence exists for a central role of amyloid β-protein (Aβ) oligomers in the pathogenesis of Alzheimer’s disease. We have developed a fast, reliable and robust in vitro assay, termed QIAD, to quantify the effect of any compound on the Aβ aggregate size distribution. Applying QIAD, we studied the effect of homotaurine, scyllo-inositol, EGCG, the benzofuran derivative KMS88009, ZAβ3W, the D-enantiomeric peptide D3 and its tandem version D3D3 on Aβ aggregation. The predictive power of the assay for in vivo efficacy is demonstrated by comparing the oligomer elimination efficiency of D3 and D3D3 with their treatment effects in animal models of Alzheimer´s disease. PMID:26394756

  9. Multidimensional Self-Assembled Structures of Alkylated Cellulose Oligomers Synthesized via in Vitro Enzymatic Reactions.

    PubMed

    Yataka, Yusuke; Sawada, Toshiki; Serizawa, Takeshi

    2016-10-04

    The self-assembly of biomolecules into highly ordered nano-to-macroscale structures is essential in the construction of biological tissues and organs. A variety of biomolecular assemblies composed of nucleic acids, peptides, and lipids have been used as molecular building units for self-assembled materials. However, crystalline polysaccharides have rarely been utilized in self-assembled materials. In this study, we describe multidimensional self-assembled structures of alkylated cellulose oligomers synthesized via in vitro enzymatic reactions. We found that the alkyl chain length drastically affected the assembled morphologies and allomorphs of cellulose moieties. The modulation of the intermolecular interactions of cellulose oligomers by alkyl substituents was highly effective at controlling their assembly into multidimensional structures. This study proposes a new potential of crystalline oligosaccharides for structural components of molecular assemblies with controlled morphologies and crystal structures.

  10. Scaling laws for buckling instability in monolayer networks

    NASA Technical Reports Server (NTRS)

    Noever, David A.

    1992-01-01

    In this comment a power law is argued to govern the thickening of cell widths relative to their lengths in buckling monolayer networks. A scaling relation is derived for general instabilities in cellular networks, and a reply is given that questions the use of the amplitude of the buckling undulation in an already buckled wall in the Euler relation. Both treatments provided shed light on the stability/instability of wavelengths for buckling monolayer networks.

  11. Nonequilibrium 2-Hydroxyoctadecanoic Acid Monolayers: Effect of Electrolytes

    SciTech Connect

    Lendrum, Conrad D.; Ingham, Bridget; Lin, Binhua; Meron, Mati; Toney, Michael F.; McGrath, Kathryn M.

    2012-02-06

    2-Hydroxyacids display complex monolayer phase behavior due to the additional hydrogen bonding afforded by the presence of the second hydroxy group. The placement of this group at the position {alpha} to the carboxylic acid functionality also introduces the possibility of chelation, a utility important in crystallization including biomineralization. Biomineralization, like many biological processes, is inherently a nonequilibrium process. The nonequilibrium monolayer phase behavior of 2-hydroxyoctadecanoic acid was investigated on each of pure water, calcium chloride, sodium bicarbonate and calcium carbonate crystallizing subphases as a precursor study to a model calcium carbonate biomineralizing system, each at a pH of {approx}6. The role of the bicarbonate co-ion in manipulating the monolayer structure was determined by comparison with monolayer phase behavior on a sodium chloride subphase. Monolayer phase behavior was probed using surface pressure/area isotherms, surface potential, Brewster angle microscopy, and synchrotron-based grazing incidence X-ray diffraction and X-ray reflectivity. Complex phase behavior was observed for all but the sodium chloride subphase with hydrogen bonding, electrostatic and steric effects defining the symmetry of the monolayer. On a pure water subphase hydrogen bonding dominates with three phases coexisting at low pressures. Introduction of calcium ions into the aqueous subphase ensures strong cation binding to the surfactant head groups through chelation. The monolayer becomes very unstable in the presence of bicarbonate ions within the subphase due to short-range hydrogen bonding interactions between the monolayer and bicarbonate ions facilitated by the sodium cation enhancing surfactant solubility. The combined effects of electrostatics and hydrogen bonding are observed on the calcium carbonate crystallizing subphase.

  12. Montmorillonite catalysis of RNA oligomer formation in aqueous solution. A model for the prebiotic formation of RNA

    NASA Technical Reports Server (NTRS)

    Ferris, J. P.; Ertem, G.

    1993-01-01

    Oligomers of adenylic acid of up to the 11-mer in length are formed by the reaction of the phosphorimidazolide of adenosine (ImpA) in pH 8 aqueous solution at room temperature in the presence of Na(+)-montmorillonite. These oligomers are joined by phosphodiester bonds in which the 3',5'-linkage predominates over the 2',5'-linkage by a 2:1 ratio. Reaction of a 9:1 mixture of ImpA, A5'ppA results in the formation of oligomers with a 3:1 ratio of 3',5'- to 2',5'-linked phosphodiester bonds. A high proportion of these oligomers contain the A5'ppA grouping. A5'ppA reacts much more rapidly with ImpA than does 5'-ADP (ppA) or 5'-ATP (pppA). The exchangeable cation associated with the montmorillonite effects the observed catalysis with Li+, Na+, NH4+, and Ca2+ being the more effective while Mg2+ and Al3+ are almost ineffective catalysts. 2',5'-Linked oligomers, up to the tetramer in length, are formed using UO2(2+)-montmorillonite. The structure analysis of individual oligomer fractions was performed by selective enzymatic and KOH hydrolytic studies followed by HPLC analysis of the reaction products. It is concluded from the composition of the oligomers that the rate of addition ImpA to a 3'-terminus containing a 2',5'-linkage is slower than the addition to a nucleoside joined by a 3',5'-linked phosphodiester bond. The potential importance of mineral catalysis of the formation of RNA and other oligomers on primitive Earth is discussed.

  13. Considerable Enhancement of Emission Yields of [Au(CN)2(-)] Oligomers in Aqueous Solutions by Coexisting Cations.

    PubMed

    Wakabayashi, Ryo; Maeba, Junichi; Nozaki, Koichi; Iwamura, Munetaka

    2016-08-01

    The photophysical properties of [Au(CN)2(-)] oligomers in aqueous solutions were investigated as functions of coexisting cations as well as the viscosity and temperature of solutions. A solution of [Au(CN)2(-)] in the concentration range of 0.03-0.2 mol/dm(3) exhibited emission peaks at 460-480 nm because of the presence of oligomers larger than trimers. Although the emission yields (ϕem) of K[Au(CN)2] solutions were <1%, it considerably increased to 43% when 1.0 mol/dm(3) tetraethylammonium chloride (Et4NCl) was added. The lifetimes of the main emission bands were also significantly varied with additional salts, e.g., KCl, 15 ns; Et4NCl, 520 ns. The time-resolved emission measurements of [Au(CN)2(-)] in a water/glycerol mixture indicated that the lifetimes were almost directly proportional to the inverse of the viscosity of the solution. On the other hand, the intrinsic lifetimes of dimers and trimers with weak emission in shorter wavelength regions were very short and independent of the viscosity of the solutions and coexisting cations (dimer, ∼25 ps; trimer, ∼2 ns). These results indicated that the deactivation of the excited-state [Au(CN)2(-)]n oligomers (n ≥ 4) was dominated by the dissociation of the oligomers to a shorter species (dimer or trimer). The hydrophobic interactions between tetraalkylammonium cations and CN ligands remarkably stabilized the larger oligomers and suppressed the dissociation of the excited-state oligomers, which enhanced the emission yield of the oligomers. This work provides a new method of "exciplex tuning" by changing the environment of excited-state [Au(CN)2(-)]n oligomers.

  14. Tau Oligomers Associate with Inflammation in the Brain and Retina of Tauopathy Mice and in Neurodegenerative Diseases

    PubMed Central

    Nilson, Ashley N.; English, Kelsey C.; Gerson, Julia E.; Barton Whittle, T.; Nicolas Crain, C.; Xue, Judy; Sengupta, Urmi; Castillo-Carranza, Diana L.; Zhang, Wenbo; Gupta, Praveena; Kayed, Rakez

    2016-01-01

    It is well-established that inflammation plays an important role in Alzheimer’s disease (AD) and frontotemporal lobar dementia (FTLD). Inflammation and synapse loss occur in disease prior to the formation of larger aggregates, but the contribution of tau to inflammation has not yet been thoroughly investigated. Tau pathologically aggregates to form large fibrillar structures known as tangles. However, evidence suggests that smaller soluble aggregates, called oligomers, are the most toxic species and form prior to tangles. Furthermore, tau oligomers can spread to neighboring cells and between anatomically connected brain regions. In addition, recent evidence suggests that inspecting the retina may be a window to brain pathology. We hypothesized that there is a relationship between tau oligomers and inflammation, which are hallmarks of early disease. We conducted immunofluorescence and biochemical analyses on tauopathy mice, FTLD, and AD subjects. We showed that oligomers co-localize with astrocytes, microglia, and HMGB1, a pro-inflammatory cytokine. Additionally, we show that tau oligomers are present in the retina and are associated with inflammatory cells suggesting that the retina may be a valid non-invasive biomarker for brain pathology. These results suggest that there may be a toxic relationship between tau oligomers and inflammation. Therefore, the ability of tau oligomers to spread may initiate a feed-forward cycle in which tau oligomers induce inflammation, leading to neuronal damage, and thus more inflammation. Further mechanistic studies are warranted in order to understand this relationship, which may have critical implications for improving the treatment of tauopathies. PMID:27716675

  15. Characterisation of proanthocyanidins from black soybeans: isolation and characterisation of proanthocyanidin oligomers from black soybean seed coats.

    PubMed

    Ito, Chiaki; Oki, Tomoyuki; Yoshida, Tadashi; Nanba, Fumio; Yamada, Katsushige; Toda, Toshiya

    2013-12-01

    Proanthocyanidin oligomers (dimers to tetramers) were isolated from black soybean seed coats, using Sephadex LH-20 column chromatography and reversed-phase preparative HPLC. The isolated oligomers consisted of only (-)-epicatechin units, which were linked through either 4β→8 or 4β→6 (B-type) bonds. Procyanidin B2, procyanidin C1, and cinnamtannin A2 were identified as the main compounds of the proanthocyanidin dimers, trimers, and tetramers, respectively.

  16. A quantification method for heat-decomposable methylglyoxal oligomers and its application on 1,3,5-trimethylbenzene SOA

    NASA Astrophysics Data System (ADS)

    Rodigast, Maria; Mutzel, Anke; Herrmann, Hartmut

    2017-03-01

    Methylglyoxal forms oligomeric compounds in the atmospheric aqueous particle phase, which could establish a significant contribution to the formation of aqueous secondary organic aerosol (aqSOA). Thus far, no suitable method for the quantification of methylglyoxal oligomers is available despite the great effort spent for structure elucidation. In the present study a simplified method was developed to quantify heat-decomposable methylglyoxal oligomers as a sum parameter. The method is based on the thermal decomposition of oligomers into methylglyoxal monomers. Formed methylglyoxal monomers were detected using PFBHA (o-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride) derivatisation and gas chromatography-mass spectrometry (GC/MS) analysis. The method development was focused on the heating time (varied between 15 and 48 h), pH during the heating process (pH = 1-7), and heating temperature (50, 100 °C). The optimised values of these method parameters are presented. The developed method was applied to quantify heat-decomposable methylglyoxal oligomers formed during the OH-radical oxidation of 1,3,5-trimethylbenzene (TMB) in the Leipzig aerosol chamber (LEipziger AerosolKammer, LEAK). Oligomer formation was investigated as a function of seed particle acidity and relative humidity. A fraction of heat-decomposable methylglyoxal oligomers of up to 8 % in the produced organic particle mass was found, highlighting the importance of those oligomers formed solely by methylglyoxal for SOA formation. Overall, the present study provides a new and suitable method for quantification of heat-decomposable methylglyoxal oligomers in the aqueous particle phase.

  17. Energetic contributions of residues to the formation of early amyloid-β oligomers.

    PubMed

    Pouplana, R; Campanera, J M

    2015-01-28

    Low-weight amyloid-β (Aβ) oligomers formed at early stages of oligomerization rather than fibril assemblies seem to be the toxic components that drive neurodegeneration in Alzheimer's disease. Unfortunately, detailed knowledge of the structure of these early oligomers at the residue level is not yet available. In this study, we performed all-atom explicit solvent molecular dynamics simulations to examine the oligomerization process of Aβ10-35 monomers when forming dimers, trimers, tetramers and octamers, with four independent simulations of a total simulated time of 3 μs for each oligomer system. The decomposition of the stability free energy by MM-GBSA methodology allowed us to unravel the network of energetic interactions that stabilize such oligomers. The contribution of the intermonomeric van der Waals term is the most significant energy feature of the oligomerization process, consistent with the so-called hydrophobic effect. Furthermore, the decomposition of the stability free energy into residues and residue-pairwise terms revealed that it is mainly apolar interactions between the three specific hydrophobic fragments 31-35 (C-terminal region), 17-20 (central hydrophobic core) and 12-14 (N-terminal region) that are responsible for such a favourable effect. The conformation in which the hydrophobic cthr-chc interaction is oriented perpendicularly is particularly important. We propose three other model substructures that favour the oligomerization process and can thus be considered as molecular targets for future inhibitors. Understanding Aβ oligomerization at the residue level could lead to more efficient design of inhibitors of this process.

  18. Yeast prion-protein, sup35, fibril formation proceeds by addition and substraction of oligomers.

    PubMed

    Narayanan, Saravanakumar; Walter, Stefan; Reif, Bernd

    2006-05-01

    In analogy to human prions, a domain of the translation-termination protein in Saccharomyces cerevisiae, Sup35, can switch its conformation from a soluble functional state, [psi-], to a conformation, [PSI+], that facilitates aggregation and impairs its native function. Overexpression of the molecular chaperone Hsp104 abolishes the [PSI+] phenotype and restores the normal function of Sup35. We have recently shown that Hsp104 interacts preferably with low oligomeric species of a Sup35 derived peptide, Sup35[5-26]; however, due to possible exchange between different oligomeric states, it was not possible to obtain information on the distribution and stability of the oligomeric state. We show here, that low-molecular-weight oligomers (Sup35[5-26])n (n approximately = 4-6) are indeed important for the fibril formation and disassembly process. We find that Hsp104 is able to disaggregate Sup35[5-26] fibrils by substraction of hexameric to decameric Sup35[5-26] oligomers. This disaggregation effect does not require assistance from other chaperones and is independent of ATP at high Hsp104 concentrations. Furthermore, we demonstrate that critical oligomers have a preference for alpha-helical conformations. The conformational reorganization into beta-sheet structures seems to occur only upon incorporation of these oligomers into fibrillar structures. The results are demonstrated by using an equilibrium dialysis experiment that employed different molecular-weight cut-off membranes. A combination of thioflavin-T (ThT) fluorescence and UV measurements allowed the quantification of fibril formation and the amount of peptide diffusing out of the dialysis bag. CD and NMR spectroscopy data were combined to obtain structural information.

  19. Probing and trapping a sensitive conformation: amyloid-β fibrils, oligomers, and dimers.

    PubMed

    Fawver, Janelle N; Duong, Karen T; Wise-Scira, Olivia; Petrofes Chapa, Rachel; Schall, Hayley E; Coskuner, Orkid; Zhu, Xiongwei; Colom, Luis V; Murray, Ian V J

    2012-01-01

    Alzheimer's disease (AD) is a devastating neurodegenerative disease with pathological misfolding of amyloid-β protein (Aβ). The recent interest in Aβ misfolding intermediates necessitates development of novel detection methods and ability to trap these intermediates. We speculated that two regions of Aβ may allow for detection of specific Aβ species: the N-terminal and 22-35, both likely important in oligomer interaction and formation. We determined via epitomics, proteomic assays, and electron microscopy that the Aβ(42) species (wild type, ΔE22, and MetOx) predominantly formed fibrils, oligomers, or dimers, respectively. The 2H4 antibody to the N-terminal of Aβ, in the presence of 2% SDS, primarily detected fibrils, and an antibody to the 22-35 region detected low molecular weight Aβ species. Simulated molecular modeling provided insight into these SDS-induced structural changes. We next determined if these methods could be used to screen anti-Aβ drugs as well as identify compounds that trap Aβ in various conformations. Immunoblot assays determined that taurine, homotaurine (Tramiprosate), myoinositol, methylene blue, and curcumin did not prevent Aβ aggregation. However, calmidazolium chloride trapped Aβ at oligomers, and berberine reduced oligomer formation. Finally, pretreatment of AD brain tissues with SDS enhanced 2H4 antibody immunostaining of fibrillar Aβ. Thus we identified and characterized Aβs that adopt specific predominant conformations (modified Aβ or via interactions with compounds), developed a novel assay for aggregated Aβ, and applied it to drug screening and immunohistochemistry. In summary, our novel approach facilitates drug screening, increases the probability of success of antibody therapeutics, and improves antibody-based detection and identification of different conformations of Aβ.

  20. Structural fingerprints and their evolution during oligomeric vs. oligomer-free amyloid fibril growth

    NASA Astrophysics Data System (ADS)

    Foley, Joseph; Hill, Shannon E.; Miti, Tatiana; Mulaj, Mentor; Ciesla, Marissa; Robeel, Rhonda; Persichilli, Christopher; Raynes, Rachel; Westerheide, Sandy; Muschol, Martin

    2013-09-01

    Deposits of fibrils formed by disease-specific proteins are the molecular hallmark of such diverse human disorders as Alzheimer's disease, type II diabetes, or rheumatoid arthritis. Amyloid fibril formation by structurally and functionally unrelated proteins exhibits many generic characteristics, most prominently the cross β-sheet structure of their mature fibrils. At the same time, amyloid formation tends to proceed along one of two separate assembly pathways yielding either stiff monomeric filaments or globular oligomers and curvilinear protofibrils. Given the focus on oligomers as major toxic species, the very existence of an oligomer-free assembly pathway is significant. Little is known, though, about the structure of the various intermediates emerging along different pathways and whether the pathways converge towards a common or distinct fibril structures. Using infrared spectroscopy we probed the structural evolution of intermediates and late-stage fibrils formed during in vitro lysozyme amyloid assembly along an oligomeric and oligomer-free pathway. Infrared spectroscopy confirmed that both pathways produced amyloid-specific β-sheet peaks, but at pathway-specific wavenumbers. We further found that the amyloid-specific dye thioflavin T responded to all intermediates along either pathway. The relative amplitudes of thioflavin T fluorescence responses displayed pathway-specific differences and could be utilized for monitoring the structural evolution of intermediates. Pathway-specific structural features obtained from infrared spectroscopy and Thioflavin T responses were identical for fibrils grown at highly acidic or at physiological pH values and showed no discernible effects of protein hydrolysis. Our results suggest that late-stage fibrils formed along either pathway are amyloidogenic in nature, but have distinguishable structural fingerprints. These pathway-specific fingerprints emerge during the earliest aggregation events and persist throughout the

  1. A model for non-obligate oligomer formation in protein aggregration

    PubMed Central

    Healy, Eamonn F.

    2015-01-01

    Using solvent-exposed intramolecular backbone hydrogen bonds as physico-chemical descriptors for protein packing, a role for transient, non-obligate oligomers in the formation of aberrant protein aggregates is presented. Oligomeric models of the both wild type (wt) and select mutant variants of superoxide dismutase (SOD1) are proposed to provide a structural basis for investigating the etiology of Amyotrophic Lateral Sclerosis (ALS). PMID:26282203

  2. Conformational control in a bipyridine linked π-conjugated oligomer: cation mediated helix unfolding and refolding.

    PubMed

    Divya, Kizhumuri P; Sreejith, Sivaramapanicker; Suresh, Cherumuttathu H; Ajayaghosh, Ayyappanpillai

    2010-11-28

    A chiral π-conjugated oligomer having alternate bipyridine and carbazole moieties connected through acetylinic bonds undergoes helical folding in chloroform-acetonitrile (40/60, v/v) as evident by fluorescence and circular dichroism changes. In the presence of transition metal cations such as Zn(2+) defolding of the helical conformation occurs. Upon decomplexation of the cation with EDTA, the helical conformation is regained.

  3. Quaternized chitosan oligomers as novel gene delivery vectors in epithelial cell lines.

    PubMed

    Thanou, M; Florea, B I; Geldof, M; Junginger, H E; Borchard, G

    2002-01-01

    Quaternized modifications of chitosan present characteristics that might be useful in DNA condensing and efficient gene delivery. Trimethylated chitosan (TMO) was synthesized from oligomeric chitosan (<20 monomer units). TMOs spontaneously formed complexes (chitoplexes) with RSV-alpha3 luciferase plasmid DNA. These complexes were characterized by photon correlation spectroscopy and were investigated for their ability to transfect COS-1 and Caco-2 cell lines in the presence and absence of fetal calf serum and compared with DOTAP (N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium sulphate) lipoplexes. Additionally, their effect on the viability of the respective cell cultures was investigated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Results showed that quaternized chitosan oligomers were able to condense DNA and form complexes with a size ranging from 200 to 500 nm. Chitoplexes proved to transfect COS-1 cells, however, to a lesser extent than DOTAP-DNA lipoplexes. The quaternized oligomer derivatives appeared to be superior to oligomeric chitosan. The presence of fetal calf serum (FCS) did not affect the transfection efficiency of the chitoplexes, whereas the transfection efficiency of DOTAP DNA complexes was decreased. Cells remained 100% viable in the presence of chitosan oligomers whereas viability of DOTAP treated cells decreased to approximately 50% in both cell lines. Both DOTAP-DNA lipoplexes and chitoplexes resulted in less transfection efficiency in Caco-2 cell cultures than in COS-1 cells; however quaternized chitosan oligomers proved to be superior to DOTAP. Effects on the viability of Caco-2 cells were similar to the effects observed in COS-1 cells. We conclude that trimethylated chitosan-DNA complexes present suitable characteristics and the potential to be used as gene delivery vectors.

  4. Chemical evolution. XXI - The amino acids released on hydrolysis of HCN oligomers

    NASA Technical Reports Server (NTRS)

    Ferris, J. P.; Wos, J. D.; Nooner, D. W.; Oro, J.

    1974-01-01

    Major amino acids released by hydrolysis of acidic and basic HCN oligomers are identified by chromatography as Gly, Asp, and diaminosuccinic acid. Smaller amounts of Ala, Ile and alpha-aminoisobutyric acid are also detected. The amino acids released did not change appreciably when the hydrolysis medium was changed from neutral to acidic or basic. The presence of both meso and d, l-diaminosuccinic acids was established by paper chromatography and on an amino acid analyzer.

  5. Effect of shear on the desorption of oligomers in nanoscopically confined films

    NASA Astrophysics Data System (ADS)

    Manias, E.; Hadziioannou, G.; ten Brinke, G.

    1994-07-01

    Bitsanis et al. J. Chem. Phys. 99, 5520 (1993) found that in nanoscopically confined films between strongly physisorbing surfaces chains with many contacts with the walls are irreversibly adsorbed. When shear is imposed to these systems molecular dynamics (MD) simulations show that the majority of the adsorbed oligomers adopts flat conformations on top of the walls. Although these conformations are characterized by high molecular adsorption energies, the same MD simulations show that desorption is strongly promoted by shear. The underlying mechanism is discussed.

  6. Nonenzymatic template-directed reactions on altritol oligomers, preorganized analogues of oligonucleotides

    NASA Technical Reports Server (NTRS)

    Kozlov, I. A.; Zielinski, M.; Allart, B.; Kerremans, L.; Van Aerschot, A.; Busson, R.; Herdewijn, P.; Orgel, L. E.; Bada, J. L. (Principal Investigator)

    2000-01-01

    Altritol nucleic acids (ANAs) are RNA analogues with a phosphorylated D-altritol backbone. The nucleobase is attached at the 2-(S)-position of the carbohydrate moiety. We report that ANA oligomers are superior to the corresponding DNA, RNA, and HNA (hexitol nucleic acid) in supporting efficient nonenzymatic template-directed synthesis of complementary RNAs from nucleoside-5'-phosphoro-2-methyl imidazolides. Activated ANA and HNA monomers do not oligomerize efficiently on DNA, RNA, HNA, or ANA templates.

  7. Thermal stability of hydrophobic helical oligomers: a lattice simulation study in explicit water.

    PubMed

    Romero-Vargas Castrillón, Santiago; Matysiak, Silvina; Stillinger, Frank H; Rossky, Peter J; Debenedetti, Pablo G

    2012-08-23

    We investigate the thermal stability of helical hydrophobic oligomers using a three-dimensional, water-explicit lattice model and the Wang-Landau Monte Carlo method. The degree of oligomer helicity is controlled by the parameter ε(mm) < 0, which mimics monomer-monomer hydrogen bond interactions leading to the formation of helical turns in atomistic proteins. We vary |ε(mm)| between 0 and 4.5 kcal/mol and therefore investigate systems ranging from flexible homopolymers (i.e., those with no secondary structure) to helical oligomers that are stable over a broad range of temperatures. We find that systems with |ε(mm)| ≤ 2.0 kcal/mol exhibit a broad thermal unfolding transition at high temperature, leading to an ensemble of random coils. In contrast, the structure of conformations involved in a second, low-temperature, transition is strongly dependent on |ε(mm)|. Weakly helical oligomers are observed when |ε(mm)| ≤ 1.0 kcal/mol and exhibit a low-temperature, cold-unfolding-like transition to an ensemble of strongly water-penetrated globular conformations. For higher |ε(mm)| (1.7 kcal/mol ≤ |ε(mm)| ≤ 2.0 kcal/mol), cold unfolding is suppressed, and the low-temperature conformational transition becomes a "crystallization", in which a "molten" helix is transformed into a defect-free helix. The molten helix preserves ≥50% of the helical contacts observed in the "crystal" at a lower temperature. When |ε(mm)| = 4.5 kcal/mol, we find that conformational transitions are largely suppressed within the range of temperatures investigated.

  8. A Recombinant Fungal Chitin Deacetylase Produces Fully Defined Chitosan Oligomers with Novel Patterns of Acetylation.

    PubMed

    Naqvi, Shoa; Cord-Landwehr, Stefan; Singh, Ratna; Bernard, Frank; Kolkenbrock, Stephan; El Gueddari, Nour Eddine; Moerschbacher, Bruno M

    2016-11-15

    Partially acetylated chitosan oligosaccharides (paCOS) are potent biologics with many potential applications, and their bioactivities are believed to be dependent on their structure, i.e., their degrees of polymerization and acetylation, as well as their pattern of acetylation. However, paCOS generated via chemical N-acetylation or de-N-acetylation of GlcN or GlcNAc oligomers, respectively, typically display random patterns of acetylation, making it difficult to control and predict their bioactivities. In contrast, paCOS produced from chitin deacetylases (CDAs) acting on chitin oligomer substrates may have specific patterns of acetylation, as shown for some bacterial CDAs. However, compared to what we know about bacterial CDAs, we know little about the ability of fungal CDAs to produce defined paCOS with known patterns of acetylation. Therefore, we optimized the expression of a chitin deacetylase from the fungus Puccinia graminis f. sp. tritici in Escherichia coli The best yield of functional enzyme was obtained as a fusion protein with the maltose-binding protein (MBP) secreted into the periplasmic space of the bacterial host. We characterized the MBP fusion protein from P. graminis (PgtCDA) and tested its activity on different chitinous substrates. Mass spectrometric sequencing of the products obtained by enzymatic deacetylation of chitin oligomers, i.e., tetramers to hexamers, revealed that PgtCDA generated paCOS with specific acetylation patterns of A-A-D-D, A-A-D-D-D, and A-A-D-D-D-D, respectively (A, GlcNAc; D, GlcN), indicating that PgtCDA cannot deacetylate the two GlcNAc units closest to the oligomer's nonreducing end. This unique property of PgtCDA significantly expands the so far very limited library of well-defined paCOS available to test their bioactivities for a wide variety of potential applications.

  9. A Foldamer-Dendrimer Conjugate Neutralizes Synaptotoxic β-Amyloid Oligomers

    PubMed Central

    Fülöp, Lívia; Mándity, István M.; Juhász, Gábor; Szegedi, Viktor; Hetényi, Anasztázia; Wéber, Edit; Bozsó, Zsolt; Simon, Dóra; Benkő, Mária; Király, Zoltán; Martinek, Tamás A.

    2012-01-01

    Background and Aims Unnatural self-organizing biomimetic polymers (foldamers) emerged as promising materials for biomolecule recognition and inhibition. Our goal was to construct multivalent foldamer-dendrimer conjugates which wrap the synaptotoxic β-amyloid (Aβ) oligomers with high affinity through their helical foldamer tentacles. Oligomeric Aβ species play pivotal role in Alzheimer's disease, therefore recognition and direct inhibition of this undruggable target is a great current challenge. Methods and Results Short helical β-peptide foldamers with designed secondary structures and side chain chemistry patterns were applied as potential recognition segments and their binding to the target was tested with NMR methods (saturation transfer difference and transferred-nuclear Overhauser effect). Helices exhibiting binding in the µM region were coupled to a tetravalent G0-PAMAM dendrimer. In vitro biophysical (isothermal titration calorimetry, dynamic light scattering, transmission electron microscopy and size-exclusion chromatography) and biochemical tests (ELISA and dot blot) indicated the tight binding between the foldamer conjugates and the Aβ oligomers. Moreover, a selective low nM interaction with the low molecular weight fraction of the Aβ oligomers was found. Ex vivo electrophysiological experiments revealed that the new material rescues the long-term potentiation from the toxic Aβ oligomers in mouse hippocampal slices at submicromolar concentration. Conclusions The combination of the foldamer methodology, the fragment-based approach and the multivalent design offers a pathway to unnatural protein mimetics that are capable of specific molecular recognition, and has already resulted in an inhibitor for an extremely difficult target. PMID:22859942

  10. Colloidal polycrystalline monolayers under oscillatory shear

    NASA Astrophysics Data System (ADS)

    Buttinoni, Ivo; Steinacher, Mathias; Spanke, Hendrik Th.; Pokki, Juho; Bahmann, Severin; Nelson, Bradley; Foffi, Giuseppe; Isa, Lucio

    2017-01-01

    In this paper we probe the structural response to oscillatory shear deformations of polycrystalline monolayers of soft repulsive colloids with varying area fraction over a broad range of frequencies and amplitudes. The particles are confined at a fluid interface, sheared using a magnetic microdisk, and imaged through optical microscopy. The structural and mechanical response of soft materials is highly dependent on their microstructure. If crystals are well understood and deform through the creation and mobilization of specific defects, the situation is much more complex for disordered jammed materials, where identifying structural motifs defining plastically rearranging regions remains an elusive task. Our materials fall between these two classes and allow the identification of clear pathways for structural evolution. In particular, we demonstrate that large enough strains are able to fluidize the system, identifying critical strains that fulfill a local Lindemann criterion. Conversely, smaller strains lead to localized and erratic irreversible particle rearrangements due to the motion of structural defects. In this regime, oscillatory shear promotes defect annealing and leads to the growth of large crystalline domains. Numerical simulations help identify the population of rearranging particles with those exhibiting the largest deviatoric stresses and indicate that structural evolution proceeds towards the minimization of the stress stored in the system. The particles showing high deviatoric stresses are localized around grain boundaries and defects, providing a simple criterion to spot regions likely to rearrange plastically under oscillatory shear.

  11. Hopping magnetoresistance in ion irradiated monolayer graphene

    NASA Astrophysics Data System (ADS)

    Shlimak, I.; Zion, E.; Butenko, A. V.; Wolfson, L.; Richter, V.; Kaganovskii, Yu.; Sharoni, A.; Haran, A.; Naveh, D.; Kogan, E.; Kaveh, M.

    2016-02-01

    Magnetoresistance (MR) of ion irradiated monolayer graphene samples with a variable-range hopping (VRH) mechanism of conductivity was measured at temperatures down to T=1.8 K in magnetic fields up to B=8 T. It was observed that in perpendicular magnetic fields, hopping resistivity R decreases, which corresponds to negative MR (NMR), while parallel magnetic field results in positive MR (PMR) at low temperatures. NMR is explained on the basis of the "orbital" model in which perpendicular magnetic field suppresses the destructive interference of many paths through the intermediate sites in the total probability of the long-distance tunneling in the VRH regime. At low fields, a quadratic dependence (| ΔR / R | ∼ B2) of NMR is observed, while at B > B*, the quadratic dependence is replaced by the linear one. It was found that all NMR curves for different samples and different temperatures could be merged into common dependence when plotted as a function of B/B*. It is shown that B* ∼ T1/2 in agreement with predictions of the "orbital" model. The obtained values of B* also allowed us to estimate the localization radius ξ of charge carriers for samples with a different degree of disorder. PMR in parallel magnetic fields is explained by suppression of hopping transitions via double occupied states due to alignment of electron spins.

  12. Photogalvanic effect in monolayer black phosphorus

    NASA Astrophysics Data System (ADS)

    Xie, Yiqun; Zhang, Lei; Zhu, Yu; Liu, Lei; Guo, Hong

    2015-11-01

    We report a first-principles theoretical approach for analyzing linear and circular photogalvanic effects (PGEs) based on density functional theory within the nonequilibrium Green’s function formalism. Using this approach we investigate the PGE phenomena in monolayer black phosphorus (MBP) doped with sulfur atoms. The impurity doping breaks the space inversion symmetry of pristine MBP, leading to a C s symmetry with a mirror reflection plane normal to the zigzag direction of the MBP lattice. Governed by this symmetry, a linear PGE is induced in both zigzag and armchair directions, and a circular PGE is induced along the zigzag direction. A robust broadband photoresponse is found from the near-infrared to the visible range for the MBP device. There is a strong anisotropy in PGE: photoresponse in the zigzag direction can be larger by an order of magnitude than that in the armchair direction. We identify the origin of the observed PGE as the inter-band transitions from the impurity and valence bands to the conduction bands, which involves a transfer of angular momentum from photons to electrons.

  13. Photogalvanic effect in monolayer black phosphorus.

    PubMed

    Xie, Yiqun; Zhang, Lei; Zhu, Yu; Liu, Lei; Guo, Hong

    2015-11-13

    We report a first-principles theoretical approach for analyzing linear and circular photogalvanic effects (PGEs) based on density functional theory within the nonequilibrium Green's function formalism. Using this approach we investigate the PGE phenomena in monolayer black phosphorus (MBP) doped with sulfur atoms. The impurity doping breaks the space inversion symmetry of pristine MBP, leading to a C s symmetry with a mirror reflection plane normal to the zigzag direction of the MBP lattice. Governed by this symmetry, a linear PGE is induced in both zigzag and armchair directions, and a circular PGE is induced along the zigzag direction. A robust broadband photoresponse is found from the near-infrared to the visible range for the MBP device. There is a strong anisotropy in PGE: photoresponse in the zigzag direction can be larger by an order of magnitude than that in the armchair direction. We identify the origin of the observed PGE as the inter-band transitions from the impurity and valence bands to the conduction bands, which involves a transfer of angular momentum from photons to electrons.

  14. Properties of Langmuir monolayers from semifluorinated alkanes

    NASA Astrophysics Data System (ADS)

    Broniatowski, M.; Macho, I. Sandez; Miñones, J.; Dynarowicz-Łątka, P.

    2005-06-01

    The aim of this study was to characterize several semifluorinated alkanes (SFA), of the general formula F(CF 2) m(CH 2) nH (in short F mH n), containing 25 carbon atoms in total (pentacosanes) differing in the m/ n ratio, as Langmuir monolayers at the free water surface. The following compounds have been studied: F6H19, F8H17, F10H15 and F12H13. Surface pressure ( π) and electric surface potential (Δ V) isotherms were recorded in addition to quantitative Brewster angle microscopy results. The negative sign of Δ V evidenced for the orientation of all the investigated semifluorinated pentacosanes, regardless the length of the hydrogenated segment, with their perfluorinated parts directed towards the air. As inferred from apparent dipole moment values and relative reflectivity results, the fluorinated pentacosanes with shorter perfluorinated fragment (F6H19 and F8H17) were found to be vertically oriented at the air/water interface, while those with longer perfluorinated moiety (F10H15 and F12H13) remain titled even in the vicinity of the film collapse.

  15. Surface dilatational viscosity of Langmuir monolayers

    NASA Astrophysics Data System (ADS)

    Lopez, Juan; Vogel, Michael; Hirsa, Amir

    2003-11-01

    With increased interest in microfluidic systems, interfacial phenomena is receiving more attention. As the length scales of fluid problems decrease, the surface to volume ratio increases and the coupling between interfacial flow and bulk flow becomes increasingly dominated by effects due to intrinsic surface viscosities (shear and dilatational), in comparison to elastic effects (due to surface tension gradients). The surface shear viscosity is well-characterized, as cm-scale laboratory experiments are able to isolate its effects from other interfacial processes (e.g., in the deep-channel viscometer). The same is not true for the dilatational viscosity, because it acts in the direction of surface tension gradients. Their relative strength scale with the capillary number, and for cm-scale laboratory flows, surface tension effects tend to dominate. In microfluidic scale flows, the scaling favors viscosity. We have devised an experimental apparatus which is capable of isolating and enhancing the effects of dilatational viscosity at the cm scales by driving the interface harmonically in time, while keeping the interface flat. In this talk, we shall present both the theory for how this works as well as experimental measurements of surface velocity from which we deduce the dilatational viscosity of several monolayers on the air-water interface over a substantial range of surface concentrations. Anomalous behavior over some range of concentration, which superficially indicates negative viscosity, maybe explained in terms of compositional effects due to large spatial and temporal variations in concentration and corresponding viscosity.

  16. Induction of homochirality in achiral enantiomorphous monolayers.

    PubMed

    Parschau, Manfred; Romer, Sara; Ernst, Karl-Heinz

    2004-12-01

    We report the induction of homochirality in enantiomorphous layers of achiral succinic acid on a Cu(110) surface after doping with tartaric acid (TA) enantiomers. Succinic acid becomes chiral upon adsorption due to symmetry-breaking interactions with the Cu(110) surface. The doubly deprotonated bisuccinate forms mirror domains on the surface, which leads to a superposition of (11,-90) and (90,-11) patterns observed by low-energy electron diffraction (LEED). On average, however, the surface layer is racemic. An amount of 2 mol % of (R,R)- or (S,S)-tartaric acid in the monolayer, corresponding to an absolute coverage of 0.001 tartaric acid molecule per surface copper atom, is sufficient to make the LEED spots of one enantiomorphous lattice disappear. After thermally induced desorption of TA, the succinic acid lattice turns racemic again. In analogy to the "sergeants-and-soldiers" principle described for helical polymers, this effect is explained by a lateral cooperative interaction within the two-dimensional lattice.

  17. Technique for etching monolayer and multilayer materials

    DOEpatents

    Bouet, Nathalie C. D.; Conley, Raymond P.; Divan, Ralu; Macrander, Albert

    2015-10-06

    A process is disclosed for sectioning by etching of monolayers and multilayers using an RIE technique with fluorine-based chemistry. In one embodiment, the process uses Reactive Ion Etching (RIE) alone or in combination with Inductively Coupled Plasma (ICP) using fluorine-based chemistry alone and using sufficient power to provide high ion energy to increase the etching rate and to obtain deeper anisotropic etching. In a second embodiment, a process is provided for sectioning of WSi.sub.2/Si multilayers using RIE in combination with ICP using a combination of fluorine-based and chlorine-based chemistries and using RF power and ICP power. According to the second embodiment, a high level of vertical anisotropy is achieved by a ratio of three gases; namely, CHF.sub.3, Cl.sub.2, and O.sub.2 with RF and ICP. Additionally, in conjunction with the second embodiment, a passivation layer can be formed on the surface of the multilayer which aids in anisotropic profile generation.

  18. Structural phase transitions in monolayer molybdenum dichalcogenides

    NASA Astrophysics Data System (ADS)

    Choe, Duk-Hyun; Sung, Ha June; Chang, Kee Joo

    2015-03-01

    The recent discovery of two-dimensional materials such as graphene and transition metal dichalcogenides (TMDs) has provided opportunities to develop ultimate thin channel devices. In contrast to graphene, the existence of moderate band gap and strong spin-orbit coupling gives rise to exotic electronic properties which vary with layer thickness, lattice structure, and symmetry. TMDs commonly appear in two structures with distinct symmetries, trigonal prismatic 2H and octahedral 1T phases which are semiconducting and metallic, respectively. In this work, we investigate the structural and electronic properties of monolayer molybdenum dichalcogenides (MoX2, where X = S, Se, Te) through first-principles density functional calculations. We find a tendency that the semiconducting 2H phase is more stable than the metallic 1T phase. We show that a spontaneous symmetry breaking of 1T phase leads to various distorted octahedral (1T') phases, thus inducing a metal-to-semiconductor transition. We discuss the effects of carrier doping on the structural stability and the modification of the electronic structure. This work was supported by the National Research Foundation of Korea (NRF) under Grant No. NRF-2005-0093845 and Samsung Science and Technology Foundation under Grant No. SSTFBA1401-08.

  19. Treponema pallidum Invades Intercellular Junctions of Endothelial Cell Monolayers

    NASA Astrophysics Data System (ADS)

    Thomas, D. Denee; Navab, Mahamad; Haake, David A.; Fogelman, Alan M.; Miller, James N.; Lovett, Michael A.

    1988-05-01

    The pathogenesis of syphilis reflects invasive properties of Treponema pallidum, but the actual mode of tissue invasion is unknown. We have found two in vitro parallels of treponemal invasiveness. We tested whether motile T. pallidum could invade host cells by determining the fate of radiolabeled motile organisms added to a HeLa cell monolayer; 26% of treponemes associated with the monolayer in a trypsin-resistant niche, presumably between the monolayer and the surface to which it adhered, but did not attain intracellularity. Attachment of T. pallidum to cultured human and rabbit aortic and human umbilical vein endothelial cells was 2-fold greater than to HeLa cells. We added T. pallidum to aortic endothelial cells grown on membrane filters under conditions in which tight intercellular junctions had formed. T. pallidum was able to pass through the endothelial cell monolayers without altering tight junctions, as measured by electrical resistance. In contrast, heat-killed T. pallidum and the nonpathogen Treponema phagedenis biotype Reiter failed to penetrate the monolayer. Transmission electron micrographs of sections of the monolayer showed T. pallidum in intercellular junctions. Our in vitro observations suggest that these highly motile spirochetes may leave the circulation by invading the junctions between endothelial cells.

  20. Thermoelectric properties of SnSe2 monolayer

    NASA Astrophysics Data System (ADS)

    Li, Guanpeng; Ding, Guangqian; Gao, Guoying

    2017-01-01

    The 2H (MoS2-type) phase of 2D transition metal dichalcogenides (TMDCs) has been extensively studied and exhibits excellent electronic and optoelectronic properties, but the high phonon thermal conductivity is detrimental to the thermoelectric performances. Here, we use first-principles methods combined with Boltzmann transport theory to calculate the electronic and phononic transport properties of 1T (CdI2-type) SnSe2 monolayer, a recently realized 2D metal dichalcogenide semiconductor. The calculated band gap is 0.85 eV, which is a little larger than the bulk value. Lower phonon thermal conductivity and higher power factor are obtained in 1T-SnSe2 monolayer compared to 2H-TMDCs monolayers. The low phonon thermal conductivity (3.27 W mK-1 at room temperature) is mainly due to the low phonon frequency of acoustic modes and the coupling of acoustic modes with optical modes. We also find that the p-type has better thermoelectric performance than the n-type, and the figure of merit within p-type can reach 0.94 at 600 K for 1T-SnSe2 monolayer, which is higher than those of most 2H-TMDCs monolayers, making 1T-SnSe2 monolayer a promising candidate for thermoelectric applications.

  1. Monolayer Contact Doping from a Silicon Oxide Source Substrate.

    PubMed

    Ye, Liang; González-Campo, Arántzazu; Kudernac, Tibor; Núñez, Rosario; de Jong, Michel; van der Wiel, Wilfred G; Huskens, Jurriaan

    2017-04-03

    Monolayer contact doping (MLCD) is a modification of the monolayer doping (MLD) technique that involves monolayer formation of a dopant-containing adsorbate on a source substrate. This source substrate is subsequently brought into contact with the target substrate, upon which the dopant is driven into the target substrate by thermal annealing. Here, we report a modified MLCD process, in which we replace the commonly used Si source substrate by a thermally oxidized substrate with a 100 nm thick silicon oxide layer, functionalized with a monolayer of a dopant-containing silane. The thermal oxide potentially provides a better capping effect and effectively prevents the dopants from diffusing back into the source substrate. The use of easily accessible and processable silane monolayers provides access to a general and modifiable process for the introduction of dopants on the source substrate. As a proof of concept, a boron-rich carboranyl-alkoxysilane was used here to construct the monolayer that delivers the dopant, to boost the doping level in the target substrate. X-ray photoelectron spectroscopy (XPS) showed a successful grafting of the dopant adsorbate onto the SiO2 surface. The achieved doping levels after thermal annealing were similar to the doping levels acessible by MLD as demonstrated by secondary ion mass spectrometry measurements. The method shows good prospects, e.g. for use in the doping of Si nanostructures.

  2. Using self-assembled monolayers to model the extracellular matrix.

    PubMed

    Mrksich, Milan

    2009-03-01

    The extracellular matrix is an insoluble aggregate of large proteins and glycosoaminoglycans that comprises the microenvironment of cells in tissue. The matrix displays a host of ligands that interact with cell-surface receptors to mediate the attachment and spreading of cells and regulate signaling processes. Studies of cell-matrix interactions and downstream signaling processes commonly employ substrates having an adsorbed layer of protein and are challenged by the difficulty in controlling the structure and activity of the immobilized protein. Significant effort has been directed towards the development of model substrates that present adhesion ligands in defined densities, orientations and environments. Among these approaches, self-assembled monolayers of alkanethiolates on gold offer a high level of control over the molecular structure of the surface and are well-suited to studies of cell adhesion. This review describes the design and use of monolayers for applications in cell biology, including the use of monolayers to evaluate the roles of peptide and protein ligands in cell-matrix interactions, the development of methods to pattern ligands on monolayers and applications to cell biology, the development of dynamic monolayers that can switch the activities of ligands presented to an adherent cell, and the rewiring of interactions between a cell and its substrate. These examples illustrate the flexibility inherent to monolayers for applications in cell biology.

  3. High Quality Factor Mechanical Resonators Based on WSe2 Monolayers

    PubMed Central

    2016-01-01

    Suspended monolayer transition metal dichalcogenides (TMD) are membranes that combine ultralow mass and exceptional optical properties, making them intriguing materials for opto-mechanical applications. However, the low measured quality factor of TMD resonators has been a roadblock so far. Here, we report an ultrasensitive optical readout of monolayer TMD resonators that allows us to reveal their mechanical properties at cryogenic temperatures. We find that the quality factor of monolayer WSe2 resonators greatly increases below room temperature, reaching values as high as 1.6 × 104 at liquid nitrogen temperature and 4.7 × 104 at liquid helium temperature. This surpasses the quality factor of monolayer graphene resonators with similar surface areas. Upon cooling the resonator, the resonant frequency increases significantly due to the thermal contraction of the WSe2 lattice. These measurements allow us to experimentally study the thermal expansion coefficient of WSe2 monolayers for the first time. High Q-factors are also found in resonators based on MoS2 and MoSe2 monolayers. The high quality-factor found in this work opens new possibilities for coupling mechanical vibrational states to two-dimensional excitons, valley pseudospins, and single quantum emitters and for quantum opto-mechanical experiments based on the Casimir interaction. PMID:27459399

  4. Growth of calcium oxalate monohydrate at phospholipid Langmuir monolayers

    NASA Astrophysics Data System (ADS)

    Whipps, Scott; Khan, Saeed R.; Jeffrey O'Palko, F.; Backov, Rénal; Talham, Daniel R.

    1998-08-01

    Calcium oxalate monohydrate crystals have been nucleated from metastable solutions at Langmuir monolayers of the phospholipids dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphatidylserine and dipalmitoylphosphatidylcholine and the fatty acid arachidic acid. The phospholipid monolayers were used as model systems for domains of pure lipid in cellular media as part of investigations of their potential role in the nucleation of calcium oxalate in the urinary tract. Crystal formation was monitored at the air/water interface using Brewster angle microscopy and in transferred films using SEM and TEM. For each Langmuir monolayer, it was observed that nucleation is heterogeneous and is selective with respect to the orientation and morphology of the precipitated crystals with up to 90% of crystals growing with the ( 1 0 1¯) face oriented towards the monolayer interface. The selectivity is attributed to calcium binding at the lipid monolayer favoring formation of the calcium-rich ( 1 0 1¯) face. The behavior at each monolayer was similar, although a higher rate of crystal formation was observed at the anionic DPPG interface.

  5. Aβ42-oligomer Interacting Peptide (AIP) neutralizes toxic amyloid-β42 species and protects synaptic structure and function

    NASA Astrophysics Data System (ADS)

    Barucker, Christian; Bittner, Heiko J.; Chang, Philip K.-Y.; Cameron, Scott; Hancock, Mark A.; Liebsch, Filip; Hossain, Shireen; Harmeier, Anja; Shaw, Hunter; Charron, François M.; Gensler, Manuel; Dembny, Paul; Zhuang, Wei; Schmitz, Dietmar; Rabe, Jürgen P.; Rao, Yong; Lurz, Rudi; Hildebrand, Peter W.; McKinney, R. Anne; Multhaup, Gerhard

    2015-10-01

    The amyloid-β42 (Aβ42) peptide is believed to be the main culprit in the pathogenesis of Alzheimer disease (AD), impairing synaptic function and initiating neuronal degeneration. Soluble Aβ42 oligomers are highly toxic and contribute to progressive neuronal dysfunction, loss of synaptic spine density, and affect long-term potentiation (LTP). We have characterized a short, L-amino acid Aβ-oligomer Interacting Peptide (AIP) that targets a relatively well-defined population of low-n Aβ42 oligomers, rather than simply inhibiting the aggregation of Aβ monomers into oligomers. Our data show that AIP diminishes the loss of Aβ42-induced synaptic spine density and rescues LTP in organotypic hippocampal slice cultures. Notably, the AIP enantiomer (comprised of D-amino acids) attenuated the rough-eye phenotype in a transgenic Aβ42 fly model and significantly improved the function of photoreceptors of these flies in electroretinography tests. Overall, our results indicate that specifically “trapping” low-n oligomers provides a novel strategy for toxic Aβ42-oligomer recognition and removal.

  6. Fabrication of an antibody-aptamer sandwich assay for electrochemical evaluation of levels of β-amyloid oligomers

    PubMed Central

    Zhou, Yanli; Zhang, Huanqing; Liu, Lantao; Li, Congming; Chang, Zhu; Zhu, Xu; Ye, Baoxian; Xu, Maotian

    2016-01-01

    Amyloid β-peptide (Aβ) in its oligomeric form is often considered as the most toxic species in Alzheimer’s disease (AD), and thus Aβ oligomer is a potentially promising candidate biomarker for AD diagnosis. The development of a sensitive and reliable method for monitoring the Aβ oligomer levels in body fluids is an urgent requirement in order to predict the severity and progression at early or preclinical stages of AD. Here, we show a proof of concept for a sensitive and specific detection of Aβ oligomers by an antibody-aptamer sandwich assay. The antibodies of Aβ oligomers and a nanocomposite of gold nanoparticles with aptamer and thionine (aptamer-Au-Th) were used as the recognition element and the detection probe for specifically binding to Aβ oligomers, respectively. The electrochemical signal of Th reduction could provide measurable electrochemical signals, and a low limit of detection (100 pM) was achieved due to the signal amplification by high loading of Th on the gold nanoparticles. The feasibility of the assay was verified by test of Aβ oligomers in artificial cerebrospinal fluid. The proposed strategy presents valuable information related to early diagnosis of AD process. PMID:27725775

  7. Aβ42 assembles into specific β-barrel pore-forming oligomers in membrane-mimicking environments

    PubMed Central

    Serra-Batiste, Montserrat; Ninot-Pedrosa, Martí; Bayoumi, Mariam; Gairí, Margarida; Maglia, Giovanni; Carulla, Natàlia

    2016-01-01

    The formation of amyloid-β peptide (Aβ) oligomers at the cellular membrane is considered to be a crucial process underlying neurotoxicity in Alzheimer’s disease (AD). Therefore, it is critical to characterize the oligomers that form within a membrane environment. To contribute to this characterization, we have applied strategies widely used to examine the structure of membrane proteins to study the two major Aβ variants, Aβ40 and Aβ42. Accordingly, various types of detergent micelles were extensively screened to identify one that preserved the properties of Aβ in lipid environments—namely the formation of oligomers that function as pores. Remarkably, under the optimized detergent micelle conditions, Aβ40 and Aβ42 showed different behavior. Aβ40 aggregated into amyloid fibrils, whereas Aβ42 assembled into oligomers that inserted into lipid bilayers as well-defined pores and adopted a specific structure with characteristics of a β-barrel arrangement that we named β-barrel pore-forming Aβ42 oligomers (βPFOsAβ42). Because Aβ42, relative to Aβ40, has a more prominent role in AD, the higher propensity of Aβ42 to form βPFOs constitutes an indication of their relevance in AD. Moreover, because βPFOsAβ42 adopt a specific structure, this property offers an unprecedented opportunity for testing a hypothesis regarding the involvement of βPFOs and, more generally, membrane-associated Aβ oligomers in AD. PMID:27621459

  8. Aβ42-oligomer Interacting Peptide (AIP) neutralizes toxic amyloid-β42 species and protects synaptic structure and function.

    PubMed

    Barucker, Christian; Bittner, Heiko J; Chang, Philip K-Y; Cameron, Scott; Hancock, Mark A; Liebsch, Filip; Hossain, Shireen; Harmeier, Anja; Shaw, Hunter; Charron, François M; Gensler, Manuel; Dembny, Paul; Zhuang, Wei; Schmitz, Dietmar; Rabe, Jürgen P; Rao, Yong; Lurz, Rudi; Hildebrand, Peter W; McKinney, R Anne; Multhaup, Gerhard

    2015-10-29

    The amyloid-β42 (Aβ42) peptide is believed to be the main culprit in the pathogenesis of Alzheimer disease (AD), impairing synaptic function and initiating neuronal degeneration. Soluble Aβ42 oligomers are highly toxic and contribute to progressive neuronal dysfunction, loss of synaptic spine density, and affect long-term potentiation (LTP). We have characterized a short, L-amino acid Aβ-oligomer Interacting Peptide (AIP) that targets a relatively well-defined population of low-n Aβ42 oligomers, rather than simply inhibiting the aggregation of Aβ monomers into oligomers. Our data show that AIP diminishes the loss of Aβ42-induced synaptic spine density and rescues LTP in organotypic hippocampal slice cultures. Notably, the AIP enantiomer (comprised of D-amino acids) attenuated the rough-eye phenotype in a transgenic Aβ42 fly model and significantly improved the function of photoreceptors of these flies in electroretinography tests. Overall, our results indicate that specifically "trapping" low-n oligomers provides a novel strategy for toxic Aβ42-oligomer recognition and removal.

  9. Aβ42-oligomer Interacting Peptide (AIP) neutralizes toxic amyloid-β42 species and protects synaptic structure and function

    PubMed Central

    Barucker, Christian; Bittner, Heiko J.; Chang, Philip K.-Y.; Cameron, Scott; Hancock, Mark A.; Liebsch, Filip; Hossain, Shireen; Harmeier, Anja; Shaw, Hunter; Charron, François M.; Gensler, Manuel; Dembny, Paul; Zhuang, Wei; Schmitz, Dietmar; Rabe, Jürgen P.; Rao, Yong; Lurz, Rudi; Hildebrand, Peter W.; McKinney, R. Anne; Multhaup, Gerhard

    2015-01-01

    The amyloid-β42 (Aβ42) peptide is believed to be the main culprit in the pathogenesis of Alzheimer disease (AD), impairing synaptic function and initiating neuronal degeneration. Soluble Aβ42 oligomers are highly toxic and contribute to progressive neuronal dysfunction, loss of synaptic spine density, and affect long-term potentiation (LTP). We have characterized a short, L-amino acid Aβ-oligomer Interacting Peptide (AIP) that targets a relatively well-defined population of low-n Aβ42 oligomers, rather than simply inhibiting the aggregation of Aβ monomers into oligomers. Our data show that AIP diminishes the loss of Aβ42-induced synaptic spine density and rescues LTP in organotypic hippocampal slice cultures. Notably, the AIP enantiomer (comprised of D-amino acids) attenuated the rough-eye phenotype in a transgenic Aβ42 fly model and significantly improved the function of photoreceptors of these flies in electroretinography tests. Overall, our results indicate that specifically “trapping” low-n oligomers provides a novel strategy for toxic Aβ42-oligomer recognition and removal. PMID:26510576

  10. Interaction of toxic and non-toxic HypF-N oligomers with lipid bilayers investigated at high resolution with atomic force microscopy

    PubMed Central

    Oropesa-Nuñez, Reinier; Seghezza, Silvia; Dante, Silvia; Diaspro, Alberto; Cascella, Roberta; Cecchi, Cristina; Stefani, Massimo; Chiti, Fabrizio; Canale, Claudio

    2016-01-01

    Protein misfolded oligomers are considered the most toxic species amongst those formed in the process of amyloid formation and the molecular basis of their toxicity, although not completely understood, is thought to originate from the interaction with the cellular membrane. Here, we sought to highlight the molecular determinants of oligomer-membrane interaction by atomic force microscopy. We monitored the interaction between multiphase supported lipid bilayers and two types of HypF-N oligomers displaying different structural features and cytotoxicities. By our approach we imaged with unprecedented resolution the ordered and disordered lipid phases of the bilayer and different oligomer structures interacting with either phase. We identified the oligomers and lipids responsible for toxicity and, more generally, we established the importance of the membrane lipid component in mediating oligomer toxicity. Our findings support the importance of GM1 ganglioside in mediating the oligomer-bilayer interaction and support a mechanism of oligomer cytotoxicity involving bilayer destabilization by globular oligomers within GM1-rich ordered raft regions rather than by annular oligomers in the surrounding disordered membrane domains. PMID:27391440

  11. Benzothienobenzothiophene-based conjugated oligomers as semiconductors for stable organic thin-film transistors.

    PubMed

    Yu, Han; Li, Weili; Tian, Hongkun; Wang, Haibo; Yan, Donghang; Zhang, Jingping; Geng, Yanhou; Wang, Fosong

    2014-04-09

    Two benzothienobenzothiophene (BTBT)-based conjugated oligomers, i.e., 2,2'-bi[1]benzothieno[3,2-b][1]benzothiophene (1) and 5,5'-bis([1]benzothieno[3,2-b][1]benzothiophen-2-yl)-2,2'-bithiophene (2), were prepared and characterized. Both oligomers exhibit excellent thermal stability, with 5% weight-loss temperatures (T(L)) above 370 °C; no phase transition was observed before decomposition. The highest occupied molecular orbital (HOMO) levels of 1 and 2 are -5.3 and -4.9 eV, respectively, as measured by ultraviolet photoelectron spectroscopy. Thin-film X-ray diffraction and atomic force microscopy characterizations indicate that both oligomers form highly crystalline films with large domain sizes on octadecyltrimethoxysilane-modified substrates. Organic thin-film transistors with top-contact and bottom-gate geometry based on 1 and 2 exhibited mobilities up to 2.12 cm(2)/V·s for 1 and 1.39 cm(2)/V·s for 2 in an ambient atmosphere. 1-based devices exhibited great air and thermal stabilities, as evidenced by the slight performance degradation after 2 months of storage under ambient conditions and after thermal annealing at temperatures below 250 °C.

  12. The adsorption of short single-stranded DNA oligomers to mineral surfaces.

    PubMed

    Cleaves, H James; Crapster-Pregont, Ellen; Jonsson, Caroline M; Jonsson, Christopher L; Sverjensky, Dimitri A; Hazen, Robert A

    2011-06-01

    We studied the adsorption of short single-stranded deoxyribonucleic acid (ssDNA) oligomers, of approximately 30 nucleotides (nt) in length, of varying sequence, adenine+guanine+cytosine (AGC) content, and propensity to form secondary structure, to equal surface area samples of olivine, pyrite, calcite, hematite, and rutile in 0.1M NaCl, 0.05M pH 8.1 KHCO(3) buffer. Although the mineral surfaces have widely varying points of zero charge, under these conditions they show remarkably similar adsorption of ssDNA regardless of oligomer characteristics. Mineral surfaces appear to accommodate ssDNA comparably, or ssDNA oligomers of this length are able to find binding sites of comparable strength and density due to their flexibility, despite the disparate surface properties of the different minerals. This may partially be due charge shielding by the ionic strength of the solutions tested, which are typical of many natural environments. These results may have some bearing on the adsorption and accumulation of biologically derived nucleic acids in sediments as well as the abiotic synthesis of nucleic acids before the origin of life.

  13. Supramolecular Order of 2,5-Bis(dodecanoxy)phenyleneethynylene-Butadiyne Oligomers in the Solid State.

    PubMed

    Vergara, Edgar; Arias, Eduardo; Moggio, Ivana; Gallardo-Vega, Carlos; Ziolo, Ronald F; Jiménez-Barrera, Rosa M; Navarro, Damaso; Rodríguez, Oliverio; Fernández, Salvador; Herrera, Manuel

    2015-06-23

    The supramolecular order of a 2,5-bis(dodecanoxy)phenyleneethynylene-butadiyne series of rod-like oligomers with 2, 4, 6, and 8 phenyleneethynylene moieties was studied in the solid state by differential scanning calorimetry (DSC), temperature-dependent small- and wide-angle X-ray scattering (SWAXS), selected area electron diffraction (SAED), polarized optical microscopy (POM), high-resolution transmission microscopy (HRTEM), and scanning tunneling microscopy (STM). It was found that all of the oligomers self-assemble in blocks of molecules that resemble bricks that are randomly oriented. These oligomers are described as sanidic liquid crystals as a term to classify their mesomorphic behavior because of their brick or board-like structure. The strong π-π interaction that governs the package of conjugated backbones was evidenced by the reiterative distances of 0.36 ± 0.017 nm found by SWAXS and 0.32 ± 0.017 nm found by HRTEM. A STM study of a cast film of the tetramer deposited on highly oriented pyrolitic graphite (HOPG) allowed for the visualization and determination of the conjugated backbone length of 2.48 nm and a phenyl-phenyl distance of 0.34 nm, suggesting that the molecules are stacked in lamellae perpendicularly aligned to the substrate.

  14. Aβ40 Oligomers Identified as a Potential Biomarker for the Diagnosis of Alzheimer's Disease

    PubMed Central

    Wang, Xuemei; Magdangal, Erika; Salisbury, Cleo; Peretz, David; Zuckermann, Ronald N.; Connolly, Michael D.; Hansson, Oskar; Minthon, Lennart; Zetterberg, Henrik; Blennow, Kaj; Fedynyshyn, Joseph P.; Allauzen, Sophie

    2010-01-01

    Alzheimer's Disease (AD) is the most prevalent form of dementia worldwide, yet the development of therapeutics has been hampered by the absence of suitable biomarkers to diagnose the disease in its early stages prior to the formation of amyloid plaques and the occurrence of irreversible neuronal damage. Since oligomeric Aβ species have been implicated in the pathophysiology of AD, we reasoned that they may correlate with the onset of disease. As such, we have developed a novel misfolded protein assay for the detection of soluble oligomers composed of Aβ x-40 and x-42 peptide (hereafter Aβ40 and Aβ42) from cerebrospinal fluid (CSF). Preliminary validation of this assay with 36 clinical samples demonstrated the presence of aggregated Aβ40 in the CSF of AD patients. Together with measurements of total Aβ42, diagnostic sensitivity and specificity greater than 95% and 90%, respectively, were achieved. Although larger sample populations will be needed to confirm this diagnostic sensitivity, our studies demonstrate a sensitive method of detecting circulating Aβ40 oligomers from AD CSF and suggest that these oligomers could be a powerful new biomarker for the early detection of AD. PMID:21209907

  15. Oligomers modulate interfibril branching and mass transport properties of collagen matrices.

    PubMed

    Whittington, Catherine F; Brandner, Eric; Teo, Ka Yaw; Han, Bumsoo; Nauman, Eric; Voytik-Harbin, Sherry L

    2013-10-01

    Mass transport within collagen-based matrices is critical to tissue development, repair, and pathogenesis, as well as the design of next-generation tissue engineering strategies. This work shows how collagen precursors, specified by intermolecular cross-link composition, provide independent control of collagen matrix mechanical and transport properties. Collagen matrices were prepared from tissue-extracted monomers or oligomers. Viscoelastic behavior was measured in oscillatory shear and unconfined compression. Matrix permeability and diffusivity were measured using gravity-driven permeametry and integrated optical imaging, respectively. Both collagen types showed an increase in stiffness and permeability hindrance with increasing collagen concentration (fibril density); however, different physical property–concentration relationships were noted. Diffusivity was not affected by concentration for either collagen type over the range tested. In general, oligomer matrices exhibited a substantial increase in stiffness and only a modest decrease in transport properties when compared with monomer matrices prepared at the same concentration. The observed differences in viscoelastic and transport properties were largely attributed to increased levels of interfibril branching within oligomer matrices. The ability to relate physical properties to relevant microstructure parameters, including fibril density and interfibril branching, is expected to advance the understanding of cell–matrix signaling, as well as facilitate model-based prediction and design of matrix-based therapeutic strategies.

  16. Cell-physiological effects of elastin derived (VGVAPG)n oligomers in a unicellular model system.

    PubMed

    Köhidai, László; Kun, Lídia; Eva, Pállinger; Csaba, György; Mihala, Nikolett; Majer, Zsuzsa; Süli-Vargha, Helga

    2004-07-01

    Elastin is one of the most significant components of the extracellular matrix, which supports the stretchiness of the blood vessels via its helical structure and cross-links. Enzymatic decomposition of this protein could induce chemotactic responses of cell populations in the surrounding tissues by several peptide sequences, e.g. XGXXPG. In our present work the VGVAPG variant and its oligomers were studied. The objective of the experiments was to learn (i) whether the chemotactic effect of these peptides is general in different levels of phylogeny: (ii) whether increasing the number of monomer units influences the chemotactic behaviour of the cell? The trimer had the strongest chemoattractant effect in a wide concentration range (10(-12) - 10(-7) M), while the monomer and the pentamer were chemorepellent. All tri-, tetra-, penta- and hexamers could chemotactically select subpopulations with a high chemotactic responsiveness to the identical peptide, in the long term. With regard to its repellent effect, the pentamer had a negative effect on phagocytosis. All six oligomers had a growth-promoter effect in Tetrahymena. The characteristic cell-physiological effects of VGVAPG oligomers signal that molecules of the extracellular matrix can induce identical responses even in lower levels of phylogeny, e.g. in the Ciliates.

  17. Bacterial adhesion and growth reduction by novel rubber-derived oligomers

    PubMed Central

    Badawy, Hope T.; Pasetto, Pamela; Mouget, Jean-Luc; Pilard, Jean-François; Cutright, Teresa J.

    2013-01-01

    In the medical field, attached bacteria can cause infections associated with catheters, incisions, burns, and medical implants especially in immunocompromised patients. The problem is exacerbated by the fact that attached bacteria are ~1000 times more resistant to antibiotics than planktonic cells. The rapid spread of antibiotic resistance in these and other organisms has led to a significant need to find new methods for preventing bacterial attachment. The goal of this research was to evaluate the effectiveness of novel polymer coatings to prevent the attachment of three medically relevant bacteria. Tests were conducted with Pseudomonas aeruginosa, Staphylococcus epidermidis, and Staphylococcus aureus for oligomers derived from modifications of natural rubber (cis 1,4-polyisoprene). The different oligomers were: PP04, with no quaternary ammonium (QA); MV067, one QA; PP06, three QA groups. In almost all experiments, cell attachment was inhibited to various extents as long as the oligomers were used. PP06 was the most effective as it decreased the planktonic cell numbers by at least 50% for all bacteria. Differences between species sensitivity were also observed. P. aeruginosa was the most resistant bacteria tested, S. aureus, the most sensitive. Further experiments are required to understand the full extent and mode of the antimicrobial properties of these surfaces. PMID:23921230

  18. Aβ1-42 monomers or oligomers have different effects on autophagy and apoptosis.

    PubMed

    Guglielmotto, Michela; Monteleone, Debora; Piras, Antonio; Valsecchi, Valeria; Tropiano, Marta; Ariano, Stefania; Fornaro, Michele; Vercelli, Alessandro; Puyal, Julien; Arancio, Ottavio; Tabaton, Massimo; Tamagno, Elena

    2014-10-01

    The role of autophagy and its relationship with apoptosis in Alzheimer disease (AD) pathogenesis is poorly understood. Disruption of autophagy leads to buildup of incompletely digested substrates, amyloid-β (Aβ) peptide accumulation in vacuoles and cell death. Aβ, in turn, has been found to affect autophagy. Thus, Aβ might be part of a loop in which it is both the substrate of altered autophagy and its cause. Given the relevance of different soluble forms of Aβ1-42 in AD, we have investigated whether monomers and oligomers of the peptide have a differential role in causing altered autophagy and cell death. Using differentiated SK-N-BE neuroblastoma cells, we found that monomers hamper the formation of the autophagic BCL2-BECN1/Beclin 1 complex and activate the MAPK8/JNK1-MAPK9/JNK2 pathway phosphorylating BCL2. Monomers also inhibit apoptosis and allow autophagy with intracellular accumulation of autophagosomes and elevation of levels of BECN1 and LC3-II, resulting in an inhibition of substrate degradation due to an inhibitory action on lysosomal activity. Oligomers, in turn, favor the formation of the BCL2-BECN1 complex favoring apoptosis. In addition, they cause a less profound increase in BECN1 and LC3-II levels than monomers without affecting the autophagic flux. Thus, data presented in this work show a link for autophagy and apoptosis with monomers and oligomers, respectively. These studies are likely to help the design of novel disease modifying therapies.

  19. Soluble amyloid-β oligomers as synaptotoxins leading to cognitive impairment in Alzheimer’s disease

    PubMed Central

    Ferreira, Sergio T.; Lourenco, Mychael V.; Oliveira, Mauricio M.; De Felice, Fernanda G.

    2015-01-01

    Alzheimer’s disease (AD) is the most common form of dementia in the elderly, and affects millions of people worldwide. As the number of AD cases continues to increase in both developed and developing countries, finding therapies that effectively halt or reverse disease progression constitutes a major research and public health challenge. Since the identification of the amyloid-β peptide (Aβ) as the major component of the amyloid plaques that are characteristically found in AD brains, a major effort has aimed to determine whether and how Aβ leads to memory loss and cognitive impairment. A large body of evidence accumulated in the past 15 years supports a pivotal role of soluble Aβ oligomers (AβOs) in synapse failure and neuronal dysfunction in AD. Nonetheless, a number of basic questions, including the exact molecular composition of the synaptotoxic oligomers, the identity of the receptor(s) to which they bind, and the signaling pathways that ultimately lead to synapse failure, remain to be definitively answered. Here, we discuss recent advances that have illuminated our understanding of the chemical nature of the toxic species and the deleterious impact they have on synapses, and have culminated in the proposal of an Aβ oligomer hypothesis for Alzheimer’s pathogenesis. We also highlight outstanding questions and challenges in AD research that should be addressed to allow translation of research findings into effective AD therapies. PMID:26074767

  20. Synaptic Amyloid-β Oligomers Precede p-Tau and Differentiate High Pathology Control Cases

    PubMed Central

    Bilousova, Tina; Miller, Carol A.; Poon, Wayne W.; Vinters, Harry V.; Corrada, Maria; Kawas, Claudia; Hayden, Eric Y.; Teplow, David B.; Glabe, Charles; Albay, Ricardo; Cole, Gregory M.; Teng, Edmond; Gylys, Karen H.

    2017-01-01

    Amyloid-β (Aβ) and hyperphosphorylated tau (p-tau) aggregates form the two discrete pathologies of Alzheimer disease (AD), and oligomeric assemblies of each protein are localized to synapses. To determine the sequence by which pathology appears in synapses, Aβ and p-tau were quantified across AD disease stages in parietal cortex. Nondemented cases with high levels of AD-related pathology were included to determine factors that confer protection from clinical symptoms. Flow cytometric analysis of synaptosome preparations was used to quantify Aβ and p-tau in large populations of individual synaptic terminals. Soluble Aβ oligomers were assayed by a single antibody sandwich enzyme-linked immunosorbent assay. Total in situ Aβ was elevated in patients with early- and late-stage AD dementia, but not in high pathology nondemented controls compared with age-matched normal controls. However, soluble Aβ oligomers were highest in early AD synapses, and this assay distinguished early AD cases from high pathology controls. Overall, synapse-associated p-tau did not increase until late-stage disease in human and transgenic rat cortex, and p-tau was elevated in individual Aβ-positive synaptosomes in early AD. These results suggest that soluble oligomers in surviving neocortical synaptic terminals are associated with dementia onset and suggest an amyloid cascade hypothesis in which oligomeric Aβ drives phosphorylated tau accumulation and synaptic spread. These results indicate that antiamyloid therapies will be less effective once p-tau pathology is developed. PMID:26718979

  1. Multifunctional oligomer incorporation: a potent strategy to enhance the transfection activity of poly(l-lysine).

    PubMed

    Liu, Shuai; Yang, Jixiang; Ren, Hongqi; O'Keeffe-Ahern, Jonathan; Zhou, Dezhong; Zhou, Hao; Chen, Jiatong; Guo, Tianying

    2016-03-01

    Natural polycations, such as poly(l-lysine) (PLL) and chitosan (CS), have inherent superiority as non-viral vectors due to their unparalleled biocompatibility and biodegradability. However, the application was constrained by poor transfection efficiency and safety concerns. Since previous modification strategies greatly weakened the inherent advantages of natural polycations, developing a strategy for functional group introduction with broad applicability to enhance the transfection efficiency of natural polycations without compromising their cationic properties is imperative. Herein, two uncharged functional diblock oligomers P(DMAEL-b-NIPAM) and P(DMAEL-b-Vlm) were prepared from a lactose derivative, N-iso-propyl acrylamide (NIPAM) as well as 1-vinylimidazole (Vlm) and further functionalized with four small ligands folate, glutathione, cysteine and arginine, respectively, aiming to enhance the interactions of complexes with cells, which were quantified utilizing a quartz crystal microbalance (QCM) biosensor, circumventing the tedious material screening process of cell transfection. Upon incorporation with PLL and DNA, the multifunctional oligomers endow the formulated ternary complexes with great properties suitable for transfection, such as anti-aggregation in serum, destabilized endosome membrane, numerous functional sites for promoted endocytosis and therefore robust transfection activity. Furthermore, different from the conventional strategy of decreasing cytotoxicity by reducing the charge density, the multifunctional oligomer incorporation strategy maintains the highly positive charge density, which is essential for efficient cellular uptake. This system develops a new platform to modify natural polycations towards clinical gene therapy.

  2. Synthesis of polyamide oligomers based on 14-amino-3,6,9, 12-tetraoxatetradecanoic acid.

    PubMed

    Dhawan, R; Kadijk, M G; Joikinen, T J; Feng, M; Ansell, S M

    2000-01-01

    A series of oligomers of polyamides based on 14-amino-3,6,9, 12-tetraoxatetradecanoic acid monomers (ATTAn) was synthesized. These materials were designed as monodisperse analogues of poly(ethylene glycol) for use in biomedical applications where reproducible behavior is important. Synthesis of the monomer was evaluated using two routes. For small-scale preparations, tetraethylene glycol (TEG) was monoprotected with dihydropyran, converted to an alkoxide, and alkylated with ethyl bromoacetate. On larger scales, TEG was alkylated directly by treatment with sodium, followed by ethyl bromoacetate. The amine function was introduced by mesylation followed by treatment with sodium azide. Reduction of the azide to amino groups was performed over Pd/C using either hydrogen or formic acid as proton sources. Assembly of the oligomers was accomplished using standard DCC/NHS chemistry and an iterative dimerization sequence after appropriate deprotection of a pair of monomers. The amino group was protected by retaining the azido group as a latent amine. A series of ATTAn oligomers was prepared (n = 1-8). A lipid conjugate of the octamer, ATTA8-DSPE, was synthesized.

  3. Comparison of automated pre-column and post-column analysis of amino acid oligomers

    NASA Technical Reports Server (NTRS)

    Chow, J.; Orenberg, J. B.; Nugent, K. D.

    1987-01-01

    It has been shown that various amino acids will polymerize under plausible prebiotic conditions on mineral surfaces, such as clays and soluble salts, to form varying amounts of oligomers (n = 2-6). The investigations of these surface reactions required a quantitative method for the separation and detection of these amino acid oligomers at the picomole level in the presence of nanomole levels of the parent amino acid. In initial high-performance liquid chromatography (HPLC) studies using a classical postcolumn o-phthalaldehyde (OPA) derivatization ion-exchange HPLC procedure with fluorescence detection, problems encountered included lengthy analysis time, inadequate separation and large relative differences in sensitivity for the separated species, expressed as a variable fluorescent yield, which contributed to poor quantitation. We have compared a simple, automated, pre-column OPA derivatization and reversed-phase HPLC method with the classical post-column OPA derivatization and ion-exchange HPLC procedure. A comparison of UV and fluorescent detection of the amino acid oligomers is also presented. The conclusion reached is that the pre-column OPA derivatization, reversed-phase HPLC and UV detection produces enhanced separation, improved sensitivity and faster analysis than post-column OPA derivatization, ion-exchange HPLC and fluorescence detection.

  4. Conformational analysis of o-phenylenes: helical oligomers with frayed ends.

    PubMed

    Hartley, C Scott; He, Jian

    2010-12-17

    The o-phenylenes represent a fundamental class of conjugated polymers that, unlike the isomeric p-phenylenes, should exhibit rich conformational behavior. Recently, we reported the synthesis and characterization of a series of o-phenylene oligomers featuring unusual electronic properties, including surprisingly long-range delocalization as measured by UV-vis spectroscopy and hypsochromic shifts in fluorescence maxima with increasing length. To rationalize these properties, we hypothesized that the oligomers predominantly assume a stacked helical conformation in solution. This assertion, however, was supported by only indirect evidence. Here we present a thorough investigation of the conformational behavior of this series of o-phenylenes by dynamic NMR spectroscopy and computational chemistry. EXSY experiments, in combination with other two-dimensional NMR techniques, provided full (1)H chemical shift assignments for at least the two most prevalent conformers for each member of the series (hexamer to dodecamer). GIAO density functional theory calculations were then used to relate the NMR data to specific molecular geometries. We have found that the o-phenylenes do indeed assume stacked helical conformations with disorder occurring at the ends. Thus, the o-phenylene motif appears to have great potential as a means to organize arenes into predictable three-dimensional arrangements. Our results also illustrate the power of (1)H NMR GIAO predictions in the solution-phase conformational analysis of oligomers, particularly those with a high density of aromatic subunits.

  5. NMR studies of DNA oligomers and their interactions with minor groove binding ligands

    SciTech Connect

    Fagan, Patricia A.

    1996-05-01

    The cationic peptide ligands distamycin and netropsin bind noncovalently to the minor groove of DNA. The binding site, orientation, stoichiometry, and qualitative affinity of distamycin binding to several short DNA oligomers were investigated by NMR spectroscopy. The oligomers studied contain A,T-rich or I,C-rich binding sites, where I = 2-desaminodeoxyguanosine. I•C base pairs are functional analogs of A•T base pairs in the minor groove. The different behaviors exhibited by distamycin and netropsin binding to various DNA sequences suggested that these ligands are sensitive probes of DNA structure. For sites of five or more base pairs, distamycin can form 1:1 or 2:1 ligand:DNA complexes. Cooperativity in distamycin binding is low in sites such as AAAAA which has narrow minor grooves, and is higher in sites with wider minor grooves such as ATATAT. The distamycin binding and base pair opening lifetimes of I,C-containing DNA oligomers suggest that the I,C minor groove is structurally different from the A,T minor groove. Molecules which direct chemistry to a specific DNA sequence could be used as antiviral compounds, diagnostic probes, or molecular biology tools. The author studied two ligands in which reactive groups were tethered to a distamycin to increase the sequence specificity of the reactive agent.

  6. Lysosomal Enzyme Glucocerebrosidase Protects against Aβ1-42 Oligomer-Induced Neurotoxicity

    PubMed Central

    Kam, Tae-In; Yun, Seungpil; Kim, Sangjune; Park, Hyejin; Hwang, Heehong; Pletnikova, Olga; Troncoso, Juan C.; Dawson, Valina L.; Dawson, Ted M.; Ko, Han Seok

    2015-01-01

    Glucocerebrosidase (GCase) functions as a lysosomal enzyme and its mutations are known to be related to many neurodegenerative diseases, including Gaucher’s disease (GD), Parkinson’s disease (PD), and Dementia with Lewy Bodies (DLB). However, there is little information about the role of GCase in the pathogenesis of Alzheimer’s disease (AD). Here we demonstrate that GCase protein levels and enzyme activity are significantly decreased in sporadic AD. Moreover, Aβ1–42 oligomer treatment results in neuronal cell death that is concomitant with decreased GCase protein levels and enzyme activity, as well as impairment in lysosomal biogenesis and acidification. Importantly, overexpression of GCase promotes the lysosomal degradation of Aβ1–42 oligomers, restores the lysosomal impairment, and protects against the toxicity in neurons treated with Aβ1–42 oligomers. Our findings indicate that a deficiency of GCase could be involved in progression of AD pathology and suggest that augmentation of GCase activity may be a potential therapeutic option for the treatment of AD. PMID:26629917

  7. New strategy for stable-isotope-aided, multidimensional NMR spectroscopy of DNA oligomers

    SciTech Connect

    Ono, Okira; Tate, Shin-Ichi; Kainosho, Masatsune

    1994-12-01

    Nuclear Magnetic Resonance (NMR) is the most efficient method for determining the solution structures of biomolecules. By applying multidimensional heteronuclear NMR techniques to {sup 13}C/{sup 15}N-labeled proteins, we can determine the solution structures of proteins with molecular mass of 20 to 30kDa at an accuracy similar to that of x-ray crystallography. Improvements in NMR instrumentation and techniques as well as the development of protein engineering methods for labeling proteins have rapidly advanced multidimensional heteronuclear NMR of proteins. In contrast, multidimensional heteronuclear NMR studies of nucleic acids is less advanced because there were no efficient methods for preparing large amounts of labeled DNA/RNA oligomers. In this report, we focused on the chemical synthesis of DNA oligomers labeled at specific residue(s). RNA oligomers with specific labels, which are difficult to synthesize by the enzyme method, can be synthesized by the chemical method. The specific labels are useful for conformational analysis of larger molecules such as protein-nucleic acid complexes.

  8. Amyloid-β oligomers are sequestered by both intracellular and extracellular chaperones

    PubMed Central

    Narayan, Priyanka; Meehan, Sarah; Carver, John A.; Wilson, Mark R.; Dobson, Christopher M.; Klenerman, David

    2016-01-01

    The aberrant aggregation of the amyloid-β peptide into β-sheet rich, fibrillar structures proceeds via a heterogeneous ensemble of oligomeric intermediates that have been associated with neurotoxicity in Alzheimer’s disease (AD). Of particular interest in this context are the mechanisms by which molecular chaperones, part of the primary biological defenses against protein misfolding, influence Aβ aggregation. We have used single-molecule fluorescence techniques to compare the interactions between distinct aggregation states (monomers, oligomers, amyloid fibrils) of the AD-associated amyloid-β(1-40) peptide, and two molecular chaperones, both of which are upregulated in the brains of patients with AD and have been found colocalized with Aβ in senile plaques. One of the chaperones, αB-crystallin, is primarily found inside cells while the other, clusterin, is predominantly located in the extracellular environment. We find that both chaperones bind to misfolded oligomeric species and form long-lived complexes thereby preventing both their further growth into fibrils and their dissociation. From these studies, we conclude that these chaperones have a common mechanism of action based on sequestering Aβ oligomers. This conclusion suggests that these chaperones, both of which are ATP-independent, are able to inhibit potentially pathogenic Aβ oligomer-associated processes whether they occur in the extracellular or intracellular environment. PMID:23106396

  9. Roles of poly(3-hydroxybutyrate) depolymerase and 3HB-oligomer hydrolase in bacterial PHB metabolism.

    PubMed

    Sugiyama, Akinori; Kobayashi, Teruyuki; Shiraki, Mari; Saito, Terumi

    2004-06-01

    Many poly-3-hydroxybutyrate (PHB)-degrading enzymes have been studied. But biological roles of 3HB-oligomer hydrolases (3HBOHs) and how PHB depolymerases (PHBDPs) and 3HBOHs cooperate in PHB metabolism are not fully elucidated. In this study, several PHBDPs and 3HBOHs from three types of bacteria were purified, and their substrate specificity, kinetic properties, and degradation products were investigated. From the results, PHBDP and 3HBOH seemed to play a role in PHB metabolism in three types of bacteria, as follows: (A) In Ralstonia pickettii T1, an extracellular PHBDP degrades extracellular PHB to various-sized 3HB-oligomers, which an extracellular 3HBOH hydrolyzes to 3HB-monomers. (B) In Acidovorax sp. SA1, an extracellular PHBDP hydrolyzes extracellular PHB to small 3HB-oligomers (dimer and trimer), which an intracellular 3HBOH efficiently degrades to 3HB in the cell. (C) In Ralstonia eutropha H16, an intracellular 3HBOH helps in the degradation of intracellular PHB inclusions by PHBDP.

  10. LptA Assembles into Rod-Like Oligomers Involving Disorder-to-Order Transitions

    NASA Astrophysics Data System (ADS)

    Santambrogio, Carlo; Sperandeo, Paola; Villa, Riccardo; Sobott, Frank; Polissi, Alessandra; Grandori, Rita

    2013-10-01

    LptA is a periplasmic protein involved in the transport of lipopolysaccharide (LPS) from the inner membrane (IM) to the outer membrane (OM) of Gram-negative bacteria. Growing evidence supports a model in which LptA assembles into oligomers, forming a physical bridge connecting IM and OM. This work investigates assembly and architecture of LptA oligomers. Circular dichroism and "native" electrospray-ionization ion-mobility mass spectrometry (ESI-IM-MS) are employed to test concentration dependence of LptA structural features and to analyze the morphology of higher-order aggregates. The results show that LptA progressively assembles into rod-like oligomers without fixed stoichiometry, and grows by an n + 1 mechanism up to at least the pentamer. The oligomerization process induces disorder-to-order transitions in the polypeptide chain. Comparison with crystallographic and computational data suggests that these conformational changes likely involve short disordered regions at the N- and C-termini of monomeric LptA. The protein response to thermal denaturation displays strong concentration dependence, indicating that oligomerization increases protein stability. LptA conformational stability can also be enhanced by in vitro LPS binding. The genesis of these fibrillar structures could be relevant for the correct transport of LPS across the bacterial periplasm.

  11. Structural Properties of HIV Integrase. Lens Epithelium-derived Growth Factor Oligomers

    SciTech Connect

    Gupta, K.; Diamond, T; Hwang, Y; Bushman, F; Van Duyne, G

    2010-01-01

    Integrase (IN) is the catalytic component of the preintegration complex, a large nucleoprotein assembly critical for the integration of the retroviral genome into a host chromosome. Although partial crystal structures of human immunodeficiency virus IN alone and its complex with the integrase binding domain of the host factor PSIP1/lens epithelium-derived growth factor (LEDGF)/p75 are available, many questions remain regarding the properties and structures of LEDGF-bound IN oligomers. Using analytical ultracentrifugation, multiangle light scattering, and small angle x-ray scattering, we have established the oligomeric state, stoichiometry, and molecular shapes of IN {center_dot} LEDGF complexes in solution. Analyses of intact IN tetramers bound to two different LEDGF truncations allow for placement of the integrase binding domain by difference analysis. Modeling of the small angle x-ray scattering envelopes using existing structural data suggests domain arrangements in the IN oligomers that support and extend existing biochemical data for IN {center_dot} LEDGF complexes and lend new insights into the quaternary structure of LEDGF-bound IN tetramers. These IN oligomers may be involved in stages of the viral life cycle other than integration, including assembly, budding, and early replication.

  12. Nanostructure formation by self-assembled monolayers: influence of the isomerization state of azobenzene ligands on monolayer formation

    NASA Astrophysics Data System (ADS)

    Vogel, Florian; Bretthauer, Frauke; Siemeling, Ulrich; Träger, Frank

    2011-03-01

    The monolayer formation of photoswitchable self-assembled monolayers of azobenzene-functionalized molecules was studied in situ and in real time by optical second-harmonic generation. Especially the influence of the isomerization state during the adsorption process was measured in our experiments. As will be shown, the isomerization state has a significant influence on the adsorption process of the investigated molecules. Based on the results of the second-harmonic generation experiments the kinetics of the adsorption process was determined.

  13. Low-magnification image analysis of Giemsa stained, electroporation and bleomycin treated endothelial monolayers provides reliable monolayer integrity data.

    PubMed

    Meulenberg, Cécil J W; Cemazar, Maja

    2014-06-01

    The aim of this study was to develop an in vitro cell model for studying the in vivo observed vascular effect, induced by exposing blood vessels to changing electric field strengths. Human microvascular endothelial cells (HMEC-1) were cultured as monolayers on 8 chamber glass slides as a model of capillary wall. Exposed to electric pulses alone, or in the presence of bleomycin (electrochemotherapy), monolayers were incubated with culture medium, fixed with methanol, stained with Giemsa, and photographed. Images of high-contrast low-magnification monolayers made under identical optimal light exposure were converted to greyscale, and the use of a threshold tool yielded a binary distribution, from which we determined two parameters of monolayer integrity: the covered surface area and the number of cells. We show that this low-magnification image analysis method for attached endothelial cells provides reliable control parameters of monolayer integrity, representing capillary wall. Besides, already within 2h post-treatment the data show distinct effects in the monolayer integrity parameters for electric pulses alone, or in the presence of bleomycin. The present method can be readily introduced to short and long-term toxicity assays with a variety of treatment conditions.

  14. Monte Carlo studies of model Langmuir monolayers.

    PubMed

    Opps, S B; Yang, B; Gray, C G; Sullivan, D E

    2001-04-01

    This paper examines some of the basic properties of a model Langmuir monolayer, consisting of surfactant molecules deposited onto a water subphase. The surfactants are modeled as rigid rods composed of a head and tail segment of diameters sigma(hh) and sigma(tt), respectively. The tails consist of n(t) approximately 4-7 effective monomers representing methylene groups. These rigid rods interact via site-site Lennard-Jones potentials with different interaction parameters for the tail-tail, head-tail, and head-head interactions. In a previous paper, we studied the ground-state properties of this system using a Landau approach. In the present paper, Monte Carlo simulations were performed in the canonical ensemble to elucidate the finite-temperature behavior of this system. Simulation techniques, incorporating a system of dynamic filters, allow us to decrease CPU time with negligible statistical error. This paper focuses on several of the key parameters, such as density, head-tail diameter mismatch, and chain length, responsible for driving transitions from uniformly tilted to untilted phases and between different tilt-ordered phases. Upon varying the density of the system, with sigma(hh)=sigma(tt), we observe a transition from a tilted (NNN)-condensed phase to an untilted-liquid phase and, upon comparison with recent experiments with fatty acid-alcohol and fatty acid-ester mixtures [M. C. Shih, M. K. Durbin, A. Malik, P. Zschack, and P. Dutta, J. Chem. Phys. 101, 9132 (1994); E. Teer, C. M. Knobler, C. Lautz, S. Wurlitzer, J. Kildae, and T. M. Fischer, J. Chem. Phys. 106, 1913 (1997)], we identify this as the L'(2)/Ov-L1 phase boundary. By varying the head-tail diameter ratio, we observe a decrease in T(c) with increasing mismatch. However, as the chain length was increased we observed that the transition temperatures increased and differences in T(c) due to head-tail diameter mismatch were diminished. In most of the present research, the water was treated as a hard

  15. Monte Carlo studies of model Langmuir monolayers

    NASA Astrophysics Data System (ADS)

    Opps, S. B.; Yang, B.; Gray, C. G.; Sullivan, D. E.

    2001-04-01

    This paper examines some of the basic properties of a model Langmuir monolayer, consisting of surfactant molecules deposited onto a water subphase. The surfactants are modeled as rigid rods composed of a head and tail segment of diameters σhh and σtt, respectively. The tails consist of nt~4-7 effective monomers representing methylene groups. These rigid rods interact via site-site Lennard-Jones potentials with different interaction parameters for the tail-tail, head-tail, and head-head interactions. In a previous paper, we studied the ground-state properties of this system using a Landau approach. In the present paper, Monte Carlo simulations were performed in the canonical ensemble to elucidate the finite-temperature behavior of this system. Simulation techniques, incorporating a system of dynamic filters, allow us to decrease CPU time with negligible statistical error. This paper focuses on several of the key parameters, such as density, head-tail diameter mismatch, and chain length, responsible for driving transitions from uniformly tilted to untilted phases and between different tilt-ordered phases. Upon varying the density of the system, with σhh=σtt, we observe a transition from a tilted (NNN)-condensed phase to an untilted-liquid phase and, upon comparison with recent experiments with fatty acid-alcohol and fatty acid-ester mixtures [M. C. Shih, M. K. Durbin, A. Malik, P. Zschack, and P. Dutta, J. Chem. Phys. 101, 9132 (1994); E. Teer, C. M. Knobler, C. Lautz, S. Wurlitzer, J. Kildae, and T. M. Fischer, J. Chem. Phys. 106, 1913 (1997)], we identify this as the L'2/Ov-L1 phase boundary. By varying the head-tail diameter ratio, we observe a decrease in Tc with increasing mismatch. However, as the chain length was increased we observed that the transition temperatures increased and differences in Tc due to head-tail diameter mismatch were diminished. In most of the present research, the water was treated as a hard surface, whereby the surfactants are only

  16. The melting of pulmonary surfactant monolayers.

    PubMed

    Yan, Wenfei; Biswas, Samares C; Laderas, Ted G; Hall, Stephen B

    2007-05-01

    Monomolecular films of phospholipids in the liquid-expanded (LE) phase after supercompression to high surface pressures (pi), well above the equilibrium surface pressure (pi(e)) at which fluid films collapse from the interface to form a three-dimensional bulk phase, and in the tilted-condensed (TC) phase both replicate the resistance to collapse that is characteristic of alveolar films in the lungs. To provide the basis for determining which film is present in the alveolus, we measured the melting characteristics of monolayers containing TC dipalmitoyl phosphatidylcholine (DPPC), as well as supercompressed 1-palmitoyl-2-oleoyl phosphatidylcholine and calf lung surfactant extract (CLSE). Films generated by appropriate manipulations on a captive bubble were heated from < or =27 degrees C to > or =60 degrees C at different constant pi above pi(e). DPPC showed the abrupt expansion expected for the TC-LE phase transition, followed by the contraction produced by collapse. Supercompressed CLSE showed no evidence of the TC-LE expansion, arguing that supercompression did not simply convert the mixed lipid film to TC DPPC. For both DPPC and CLSE, the melting point, taken as the temperature at which collapse began, increased at higher pi, in contrast to 1-palmitoyl-2-oleoyl phosphatidylcholine, for which higher pi produced collapse at lower temperatures. For pi between 50 and 65 mN/m, DPPC melted at 48-55 degrees C, well above the main transition for bilayers at 41 degrees C. At each pi, CLSE melted at temperatures >10 degrees C lower. The distinct melting points for TC DPPC and supercompressed CLSE provide the basis by which the nature of the alveolar film might be determined from the temperature-dependence of pulmonary mechanics.

  17. Clustering in vibrated monolayers of granular rods.

    PubMed

    González-Pinto, M; Borondo, F; Martínez-Ratón, Y; Velasco, E

    2017-04-05

    We investigate the ordering properties of vertically-vibrated monolayers of granular cylinders in a circular container at high packing fraction. In line with previous works by other groups, we identify liquid-crystalline ordering behaviour similar to that of two-dimensional hard rectangular particles subject to thermal equilibrium fluctuations. However, due to dissipation, there is a much stronger tendency for particles to cluster into parallel arrangements in the granular system. These clusters behave as a polydisperse mixture of long life-time 'superparticles', and some aspects of the system behaviour can be understood by applying mean-field theories for equilibrium hard rectangles, based on two-body correlations, to these 'superparticles'. Many other features of the granular system are different: (i) for small particle length-to-breadth ratio κ, we identify tetratic ordering at moderate packing fractions and smectic fluctuations at higher packing fractions, with no sharp transition between the two states. Both types of ordering can be explained in terms of clustering. (ii) For large κ, strong clustering precludes the stabilisation of a uniaxial nematic state, and the system exhibits a mixture of randomly-oriented clusters which, as packing fraction is increased, develops into states with smectic fluctuations, again through a diffuse transition. (iii) Vorticity excitations of the velocity field compete with smectic ordering, causing dynamic fluctuations and the absence of steady states at high densities; the tetratic state, by contrast, is very stiff against vorticity, and long-standing steady states, spatially and orientationally homogeneous except for four symmetrical defects located close to the wall, can be observed.

  18. Mysterious Lattice Rotations in Adsorbed Monolayers

    NASA Astrophysics Data System (ADS)

    Diehl, Renee D.

    1997-03-01

    Lattice rotations due to a mismatch in structure have been observed in film growth for many years, probably beginning in the 1930's with the Nishiyama-Wasserman and Kurdjumov-Sachs orientations observed when fcc(111) films grow on bcc(110) surfaces, or vice versa. Early analysis of this problem was carried out with the aid of Moiré patterns and the observation that the preferred lattice orientations are those which maximize the Moiré fringe spacing. Later energy calculations indicated that the structures which were predicted by the the Moiré technique actually do correspond to energy minima. Epitaxial rotation in adsorbed monolayers is a conceptually simpler problem since in principle it involves only two planes of atoms, and it was first observed in 1977 for Ar on a graphite surface(C. G. Shaw, M. D. Chinn, S. C. Fain, Jr. Phys. Rev. Lett. 41 (1978) 955.). This observation came only a few months after a new theory, based on the expected elastic behavior of an overlayer, was developed by A. D. Novaco and J. P. McTague(A. D. Novaco and J. P. McTague, Phys. Rev. Lett. 38 (1977) 1286.), and the agreement with the experimental results was remarkable. It was later shown that a few symmetry principles similar to those used for the film growth studies sometimes can also predict the observed structures. However, the situation for incommensurate layers physisorbed on metal surfaces currently looks bleak. None of the existing theories or models appears to describe the experimental results. New data for physisorbed gases on metal surfaces will be presented, along with some half-baked (and probably wrong) ideas for what might be happening. This work was supported by NSF.

  19. The melting of pulmonary surfactant monolayers

    PubMed Central

    Yan, Wenfei; Biswas, Samares C.; Laderas, Ted G.; Hall, Stephen B.

    2012-01-01

    Monomolecular films of phospholipids in the liquid-expanded (LE) phase after supercompression to high surface pressures (π), well above the equilibrium surface pressure (πe) at which fluid films collapse from the interface to form a three-dimensional bulk phase, and in the tilted-condensed (TC) phase both replicate the resistance to collapse that is characteristic of alveolar films in the lungs. To provide the basis for determining which film is present in the alveolus, we measured the melting characteristics of monolayers containing TC dipalmitoyl phosphatidylcholine (DPPC), as well as supercompressed 1-palmitoyl-2-oleoyl phosphatidylcholine and calf lung surfactant extract (CLSE). Films generated by appropriate manipulations on a captive bubble were heated from ≤27°C to ≥60°C at different constant π above πe. DPPC showed the abrupt expansion expected for the TC-LE phase transition, followed by the contraction produced by collapse. Supercompressed CLSE showed no evidence of the TC-LE expansion, arguing that supercompression did not simply convert the mixed lipid film to TC DPPC. For both DPPC and CLSE, the melting point, taken as the temperature at which collapse began, increased at higher π, in contrast to 1-palmitoyl-2-oleoyl phosphatidylcholine, for which higher π produced collapse at lower temperatures. For π between 50 and 65 mN/m, DPPC melted at 48–55°C, well above the main transition for bilayers at 41°C. At each π, CLSE melted at temperatures >10°C lower. The distinct melting points for TC DPPC and supercompressed CLSE provide the basis by which the nature of the alveolar film might be determined from the temperature-dependence of pulmonary mechanics. PMID:17194731

  20. Platinum monolayer electrocatalysts for oxygen reduction in fuel cells

    NASA Astrophysics Data System (ADS)

    Zhang, Junliang

    Fuel cells are expected to be one of the major clean energy sources in the near future. However, the slow kinetics of electrocatalytic oxygen reduction reaction (ORR) and the high loading of Pt for the cathode material are the urgent issues to be addressed since they determine the efficiency and the cost of this energy source. In this study, a new approach was developed for designing electrocatalysts for the ORR in fuel cells. These electrocatalysts consist of only one Pt monolayer, or mixed transition metal-Pt monolayer, on suitable carbon-supported metal, or alloy nanoparticles. The synthesis involved depositing a monolayer of Cu on a suitable transition metal or metal alloy surface at underpotentials, followed by galvanic displacement of the Cu monolayer with Pt or mixed metal-Pt. It was found that the electronic properties of Pt monolayer could be fine-tuned by the electronic and geometric effects introduced by the substrate metal (or alloy) and the lateral effects of the neighboring metal atoms. The role of substrates was found reflected in a "volcano" plot of the monolayer activity for the ORR as a function of their calculated d-band centers. The Pt mass-specific activity of the new Pt monolayer electrocatalysts was up to twenty times higher than the state-of-the-art commercial Pt/C catalysts. The enhancement of the activity is caused mainly by decreased formation of PtOH (the blocking species for ORR), and to a lesser degree by the electronic effects. Fuel cell tests showed a very good long term stability of the new electrocatalysts. Our results demonstrated a viable way to designing the electrocatalysts which could successfully alleviate two issues facing the commercialization of fuel cells---the costs of electrocatalysts and their efficiency.