Slow release and delivery of antisense oligonucleotide drug by self-assembled peptide amphiphile nanofibers

Cataloged from PDF version of article.Antisense oligonucleotides provide a promising therapeutic approach for several disorders including cancer. Chemical stability, controlled release, and intracellular delivery are crucial factors determining their efficacy. Gels composed of nanofibrous peptide network have been previously suggested as carriers for controlled delivery of drugs to improve stability and to provide controlled release, but have not been used for oligonucleotide delivery. In this work, a self-assembled peptide nanofibrous system is formed by mixing a cationic peptide amphiphile (PA) with Bcl-2 antisense oligodeoxynucleotide (ODN), G3139, through electrostatic interactions. The self-assembly of PA-ODN gel was characterized by circular dichroism, rheology, atomic force microscopy (AFM) and scanning electron microscopy (SEM). AFM and SEM images revealed establishment of the nanofibrous PA-ODN network. Due to the electrostatic interactions between PA and ODN, ODN release can be controlled by changing PA and ODN concentrations in the PA-ODN gel. Cellular delivery of the ODN by PA-ODN nanofiber complex was observed by using fluorescently labeled ODN molecule. Cells incubated with PA-ODN complex had enhanced cellular uptake compared to cells incubated with naked ODN. Furthermore, Bcl-2 mRNA amounts were lower in MCF-7 human breast cancer cells in the presence of PA-ODN complex compared to naked ODN and mismatch ODN evidenced by quantitative RT-PCR studies. These results suggest that PA molecules can control ODN release, enhance cellular uptake and present a novel efficient approach for gene therapy studies and oligonucleotide based drug deliver

Template-Directed Synthesis of Silica Nanotubes for Explosive Detection

Cataloged from PDF version of article.Fluorescent porous organic-inorganic thin films are of interest of explosive detection because of their vapor phase fluorescence quenching property. In this work, we synthesized fluorescent silica nanotubes using a biomineralization process through self-assembled peptidic nanostructures. We designed and synthesized an amyloid-like peptide self-assembling into nanofibers to be used as a template for silica nanotube formation. The amine groups on the peptide nanofibrous system were used for nucleation of silica nanostructures. Silica nanotubes were used to prepare highly porous surfaces, and they were doped with a fluorescent dye by physical adsorption for explosive sensing. These porous surfaces exhibited fast, sensitive, and highly selective fluorescence quenching against nitro-explosive vapors. The materials developed in this work have vast potential in sensing applications due to enhanced surface area. © 2011 American Chemical Society

Self-Assembled Peptide Nanofiber Templated One-Dimensional Gold Nanostructures Exhibiting Resistive Switching

Cataloged from PDF version of article.An amyloid-like peptide molecule self-assembling into one-dimensional nanofiber structure in ethanol was designed and synthesized with functional groups that can bind to gold ions. The peptide nanofibers were used as templates for nucleation and growth of one-dimensional gold nanostructures in the presence of ascorbic acid as reducing agent. We performed multistep seed-mediated synthesis of gold nanoparticles by changing peptide/gold precursor and peptide/reducing agent ratios. Gold nanostructures with a wide range of morphologies such as smooth nanowires, noodle-like one-dimensional nanostructures, and uniform aggregates of spherical nanoparticles were synthesized by use of an environmentally friendly synthesis method. Nanoscale electrical properties of gold-peptide nanofibers were investigated using atomic force microscopy. Bias dependent current (IV) measurements on thin films of gold-peptide nanofiber hybrid revealed tunneling dominated transport and resistive switching. Gold-peptide nanofiber composite nanostructures can provide insight into electrical conduction in biomolecular/inorganic composites, highlighting their potential applications in electronics and optics. © 2012 American Chemical Society

Encapsulation of a zinc phthalocyanine derivative in self-assembled peptide nanofibers

Cataloged from PDF version of article.In this article, we demonstrate encapsulation of octakis(hexylthio) zinc phthalocyanine molecules by non-covalent supramolecular organization within self-assembled peptide nanofibers. Peptide nanofibers containing octakis(hexylthio) zinc phthalocyanine molecules were obtained via a straight-forward one-step self-assembly process under aqueous conditions. Nanofiber formation results in the encapsulation and organization of the phthalocyanine molecules, promoting ultrafast intermolecular energy transfer. The morphological, mechanical, spectroscopic and non-linear optical properties of phthalocyanine containing peptide nanofibers were characterized by TEM, SEM, oscillatory rheology, UV-Vis, fluorescence, ultrafast pump-probe and circular dichroism spectroscopy techniques. The ultrafast pump-probe experiments of octakis(hexylthio) zinc phthalocyanine molecules indicated pH controlled non-linear optical characteristics of the encapsulated molecules within self-assembled peptide nanofibers. This method can provide a versatile approach for bottom-up fabrication of supramolecular organic electronic devices. © 2012 The Royal Society of Chemistry

Rho primes in analyzing e+e- annihilation, MARK III, LASS and ARGUS data

The results of an analysis are presented of some recent data on the reactions $e^+e^-\to\pi^+\pi^-\pi^+\pi^-$, $e^+e^-\to\pi^+\pi^-\pi^0\pi^0$ with the subtracted $\omega\pi^0$ events, $e^+e^-\to\omega\pi^0$, $e^+e^-\to\eta \pi^+\pi^-$, $e^+e^-\to\pi^+\pi^-$, $K^-p\to\pi^+\pi^-\Lambda$, the decays $J/\psi\to\pi^+\pi^-\pi^0$, $tau^-\to\nu_tau\pi^+\pi^-\pi^-\pi^0$ $tau^-\to\nu_\tau\omega\pi^-$, upon taking into account both the strong energy dependence of the partial widths on energy and the previously neglected mixing of the $\rho$ type resonances. The above effects are shown to exert an essential influence on the specific values of masses and coupling constants of heavy resonances and hence are necessary to be accounted for in establishing their true nature.Comment: 20 pages, ReVTeX, 9 Postscript figures As compared to hep-ph/9607398, new material concerning the analysis of the ARGUS data on the tau decays into four pion hadronic states is adde

Amyloid Inspired Self-Assembled Peptide Nanofibers

Cataloged from PDF version of article.Amyloid peptides are important components in many degenerative diseases as well as in maintaining cellular metabolism. Their unique stable structure provides new insights in developing new materials. Designing bioinspired selfassembling peptides is essential to generate new forms of hierarchical nanostructures. Here we present oppositely charged amyloid inspired peptides (AIPs), which rapidly self-assemble into nanofibers at pH 7 upon mixing in water caused by noncovalent interactions. Mechanical properties of the gels formed by selfassembled AIP nanofibers were analyzed with oscillatory rheology. AIP gels exhibited strong mechanical characteristics superior to gels formed by self-assembly of previously reported synthetic short peptides. Rheological studies of gels composed of oppositely charged mixed AIP molecules (AIP-1 + 2) revealed superior mechanical stability compared to individual peptide networks (AIP-1 and AIP-2) formed by neutralization of net charges through pH change. Adhesion and elasticity properties of AIP mixed nanofibers and charge neutralized AIP-1, AIP-2 nanofibers were analyzed by high resolution force− distance mapping using atomic force microscopy (AFM). Nanomechanical characterization of self-assembled AIP-1 + 2, AIP-1, and AIP-2 nanofibers also confirmed macroscopic rheology results, and mechanical stability of AIP mixed nanofibers was higher compared to individual AIP-1 and AIP-2 nanofibers self-assembled at acidic and basic pH, respectively. Experimental results were supported with molecular dynamics simulations by considering potential noncovalent interactions between the amino acid residues and possible aggregate forms. In addition, HUVEC cells were cultured on AIP mixed nanofibers at pH 7 and biocompatibility and collagen mimetic scaffold properties of the nanofibrous system were observed. Encapsulation of a zwitterionic dye (rhodamine B) within AIP nanofiber network was accomplished at physiological conditions to demonstrate that this network can be utilized for inclusion of soluble factors as a scaffold for cell culture studies. Copyright © 2012 American Chemical Societ

Size-controlled conformal nanofabrication of biotemplated three-dimensional TiO2 and ZnO nanonetworks

Cataloged from PDF version of article.A solvent-free fabrication of TiO2 and ZnO nanonetworks is demonstrated by using supramolecular nanotemplates with high coating conformity, uniformity, and atomic scale size control. Deposition of TiO2 and ZnO on three-dimensional nanofibrous network template is accomplished. Ultrafine control over nanotube diameter allows robust and systematic evaluation of the electrochemical properties of TiO2 and ZnO nanonetworks in terms of size-function relationship. We observe hypsochromic shift in UV absorbance maxima correlated with decrease in wall thickness of the nanotubes. Photocatalytic activities of anatase TiO2 and hexagonal wurtzite ZnO nanonetworks are found to be dependent on both the wall thickness and total surface area per unit of mass. Wall thickness has effect on photoexcitation properties of both TiO2 and ZnO due to band gap energies and total surface area per unit of mass. The present work is a successful example that concentrates on nanofabrication of intact three-dimensional semiconductor nanonetworks with controlled band gap energies

Effects of Symmetry Breaking on the Strong and Electroweak Interactions of the Vector Nonet

Starting from a chiral invariant and quark line rule conserving Lagrangian of pseudoscalar and vector nonets we introduce first and second order symmetry breaking as well as quark line rule violating terms and fit the parameters, at tree level, to many strong and electroweak processes. A number of predictions are made. The electroweak interactions are included in a manifestly gauge invariant manner. The resulting symmetry breaking pattern is discussed in detail. Specifically, for the ``strong'' interactions, we study all the vector meson masses and V -> \phi \phi decays, including isotopic spin violations. In the electroweak sector we study the { rho^0 , omega , phi } -> e^+e^- decays, { pi^+ , K^+ , K^0 } ``charge radii'', K_{l3} ``slope factor'' and the overall e^+e^- -> pi^+ pi^- process. It is hoped that the resulting model may be useful as a reasonable description of low energy physics in the range up to about 1 GeV.Comment: 43 pages (LaTeX), 5 PostScript figures are included as uuencoded-compressed-tar file at the en

A New Era in the Quest for Dark Matter

There is a growing sense of `crisis' in the dark matter community, due to the absence of evidence for the most popular candidates such as weakly interacting massive particles, axions, and sterile neutrinos, despite the enormous effort that has gone into searching for these particles. Here, we discuss what we have learned about the nature of dark matter from past experiments, and the implications for planned dark matter searches in the next decade. We argue that diversifying the experimental effort, incorporating astronomical surveys and gravitational wave observations, is our best hope to make progress on the dark matter problem.Comment: Published in Nature, online on 04 Oct 2018. 13 pages, 1 figur

Proper Motions, Orbits, and Tidal Influences of Milky Way Dwarf Spheroidal Galaxies

We combine Gaia EDR3 astrometry with accurate photometry and utilize a probabilistic mixture model to measure the systemic proper motion of 52 dwarf spheroidal (dSph) satellite galaxies of the Milky Way (MW). For the 46 dSphs with literature line-of-sight velocities we compute orbits in both a MW and a combined MW + Large Magellanic Cloud (LMC) potential and identify Car II, Car III, Hor I, Hyi I, Phx II, and Ret II as likely LMC satellites. 40% of our dSph sample has a >25% change in pericenter and/or apocenter with the MW + LMC potential. For these orbits, we Monte Carlo sample over the observational uncertainties for each dSph and the uncertainties in the MW and LMC potentials. We predict that Ant II, Boo III, Cra II, Gru II, and Tuc III should be be tidally disrupting by comparing each dSph's average density relative to the MW density at its pericenter. dSphs with large ellipticity (CVn I, Her, Tuc V, UMa I, UMa II, UMi, Wil 1) show a preference for their orbital direction to align with their major axis even for dSphs with large pericenters. We compare the dSph radial orbital phase to subhalos in MW-like N-body simulations and infer that there is not an excess of satellites near their pericenter. With projections of future Gaia data releases, we find dSph orbital precision will be limited by uncertainties in the distance and/or MW potential rather than proper motion precision. Finally, we provide our membership catalogs to enable community follow-up.Comment: 26 pages, 13 figures + appendix with extra figures. ApJ accepted. Catalogs with membership, additional figures, and a machine readable compilation of tables 1-4 are available at https://zenodo.org/record/653329