UNLV Jazz Ensemble II and III

Program listing performers and works performe

Transferrin-polycation-DNA complexes. The effect of polycations on the structure of the complex and DNA delivery to cells.

We have previously described a gene delivery system based upon the receptor-mediated endocytosis of DNA complexed with transferrin-polycation conjugates. This delivery system has been found to be very effective for both the internalization and the expression of genetic material in cells that have many transferrin receptors. Upon scrutinization of the parameters involved in this method, which we have termed transferrinfection, we note two important features of the process: the polycation in polycation-transferrin conjugates, as expected, serves to attach the transferrin moiety to the DNA and, in addition, the polycation functions to condense the DNA into a doughnut structure. Electron microscopic analysis of a range of poorly active to highly active transferrinfection samples reveals a strong correlation between DNA condensation and cellular DNA uptake. Furthermore, we demonstrate that the transfection activity of the DNA complex can be increased by addition of free polycation as long as a sufficient quantity of polycation-transferrin conjugates remains in the complex to ensure its binding to the cellular receptor

DNA-binding transferrin conjugates as functional gene-delivery agents: synthesis by linkage of polylysine or ethidium homodimer to the transferrin carbohydrate moiety

We have previously demonstrated that transferrin-polycation conjugates are efficient carrier molecules for the introduction of genes into eucariotic cells. We describe here a more specific method for conjugation of transferrin with DNA-binding compounds involving attachment at the transferrin carbohydrate moiety. We used the polycation poly(L-lysine) or the DNA intercalator, ethidium homodimer as DNAbinding domains. Successful transferrin-receptor-mediatedd elivery and expression of the Photinus pyralis luciferase gene in K562 cells has been shown with these new transferrin conjugates. The activity of the transferrin-ethidium homodimer (TfEtD) conjugates is low relative to transferrin-polylysine conjugates; probably because of incomplete condensation of the DNA. However, DNA delivery with TfEtD is drastically improved when ternary complexes of the DNA with TfEtD and the DNA condensing agent polylysine are prepared. The gene delivery with the carbohydrate-linked transferrin-polylysine conjugates is equal or superior to described conjugates containing disulfide linkage. The new ligation method facilitates the synthesis of large quantities (>lo0 mg) of conjugates. INTRODUCTION Transferrin-polycation conjugates are efficient carriers for the uptake of DNA into eucariotic cells (I). This gene transfer technique, termed tramferrinfection, is based on receptor-mediated endocytosis of DNA complexed with polycation-transferrin conjugates (2,3). Our initial conjugate synthesis (1) involved the modification of one to two amino groups on the transferrin molecule with the bifunctional reagent succinimidyl34 2-pyridy1dithio)propionate (SPDP), followed by ligation to similarly modified polycations (polylysine or protamine) through the formation of disulfide bonds. Because there are more than 50 lysines on the large (about 80 kDa) transferrin protein, the actual site (or sites) of ligation to the polycation is unknown with this method. In this paper we describe the synthesis of new transferrin conjugates that are ligated with DNA-binding compounds in a specific manner through modification of the transferrin carbohydrate moiety. The conjugates thus obtained are free of any groups derived from chemical linking agents, since the connecting atoms are already present within the starting compounds. The carbohydrate group acts as anatural spacer that puts a 32-atom distance between the transferrin and the DNA binding moiety. This spacer effect may be important for appropriate presentation of the ligand to its receptor. As a DNA-binding compound, the polycation polylysine was used, similar to the use described in ref 1 or to the asialo-orosomucoid conjugates prepared by Wu and Wu (4). We have also prepared a novel type of transferrin conjugate that contains the DNA intercalator ethidium homodimer (5) as the DNAbinding group and demonstrate successful receptormediated gene delivery with these conjugates. EXPERIMENTAL PROCEDURES Human transferrin (iron-free), conalbumin (iron-free), and poly(L-lysine) were obtained from Sigma. Liquid chro- Abbreviations used: FITC, fluorescein ieothiocyenate; TfEtD, traneferrin-ethidium homodimer conjugate; TfpL, traneferrinpolytL- lysine) conjugate; HEPES, 4-(2-hydroxyethyl)-l-piperazineethanesulfonic acid

Transferrin-polycation conjugates as carriers for DNA uptake into cells.

We have developed a high-efficiency nucleic acid delivery system that uses receptor-mediated endocytosis to carry DNA macromolecules into cells. We accomplished this by conjugating the iron-transport protein transferrin to polycations that bind nucleic acids. Human transferrin, as well as the chicken homologue conalbumin, has been covalently linked to the small DNA-binding protein protamine or to polylysines of various sizes through a disulfide linkage. These modified transferrin molecules maintain their ability to bind their cognate receptor and to mediate efficient iron transport into the cell. The transferrin-polycation molecules form electrophoretically stable complexes with double-stranded DNA, single-stranded DNA, and modified RNA molecules independent of nucleic acid size (from short oligonucleotides to DNA of 21 kilobase pairs). When complexes of transferrin-polycation and a bacterial plasmid DNA containing the gene for Photinus pyralis luciferase are supplied to eukaryotic cells, high-level expression of the luciferase gene occurs, demonstrating transferrin receptor-mediated endocytosis and expression of the imported DNA. We refer to this delivery system as "transferrinfection.

Evolved solar systems in Praesepe

"Copyright 2011 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics." Original paper can be found at: http://scitation.aip.org/"We have obtained near-IR photometry for the 11 Praesepe white dwarfs, to search for an excess indicative of a dusty debris disk. All the white dwarfs are in the DAZ temperature regime, however we find no indications of a disk around any white dwarf. We have, however determined that the radial velocity variable white dwarf WD0837+185 could have an unresolved T8 dwarf companion that would not be seen as a near-IR excess.Final Accepted Versio

A (Bounded) Bestiary of Feynman Integral Calabi-Yau Geometries

We define the rigidity of a Feynman integral to be the smallest dimension over which it is non-polylogarithmic. We argue that massless Feynman integrals in four dimensions have a rigidity bounded by 2(L-1) at L loops, and we show that this bound may be saturated for integrals that we call marginal: those with (L+1)D/2 propagators in (even) D dimensions. We show that marginal Feynman integrals in D dimensions generically involve Calabi-Yau geometries, and we give examples of finite four-dimensional Feynman integrals in massless $\phi^4$ theory that saturate our predicted bound in rigidity at all loop orders.Comment: 5+2 pages, 11 figures, infinite zoo of Calabi-Yau manifolds. v2 reflects minor changes made for publication. This version is authoritativ

The XMM-Newton view of the relativistic spectral features in AXJ0447-0627

The XMM-Newton observation of the optically Type 1 AGN AXJ0447-0627 (z=0.214) unambiguously reveals a complex, bright and prominent set of lines in the 4-8 keV rest frame energy range. Although, from a phenomenological point of view, the observed properties can be described by a simple power law model plus 5 narrow Gaussian lines (at rest frame energies of nearly 4.49, 5.55, 6.39, 7.02 and 7.85 keV), we find that a model comprising a power law (Gamma of the order of 2.2), a reflected relativistic continuum, a narrow Fe I Kalpha line from neutral material as well as a broad Fe Kalpha relativistic line from a ionized accretion disk represents a good physical description of the data. The ''double horned'' profile of the relativistic line implies an inclination of the accretion disk of the order of 45 degree, and an origin in a narrow region of the disk, from R_in of the order of 19 GM/c^2 to R_out of the order of 30 GM/c^2. The narrow Fe I Kalpha line from neutral material is probably produced far from the central black hole, most likely in the putative molecular torus. Although some of these properties have been already found in other Type 1 AGN and discussed in the literature, at odd with the objects reported so far we measure high equivalent widths (EWs) of the observed lines: nearly 1.4 keV for the ``double horned'' relativistic line and nearly 0.4 keV for the narrow line.Comment: 16 pages, 3 figures, Latex manuscript; accepted for publication in Ap