PP7 virus-like particle as a functional peptide carrying platform

Virus-like particles (VLPs) have attracted attention as therapeutic platforms for the delivery of peptide-based motifs for immunology, cell targeting, and drug delivery. The functional peptide sequences of interest are covalently attached to the VLP surface by either genetic fusion or bioconjugation techniques. Here, we report our initial exploration of the Leviviridae PP7 bacteriophage capsid as a platform for the genetically-programmed display of multiple peptide sequences of therapeutic and targeting interest. These peptides include short and long sequences that bind cell-surface EGF or transferrin receptors, as well as examples of other functional (Z-domain) and antigenic (OVA) peptides. The PP7 structure is far more tolerant than the closely related Q VLP to self-assembly of C- or N-terminally extended capsid proteins. Some of these constructs were able to form stable and homogeneous particles entirely from such proteins, thereby displaying exactly 180 copies of the functional peptide on the VLP surface, a property not shared by other Leviviridae-based platforms. Preliminary exploration of the chemical reactivity of the PP7 particle also shows it to be highly tolerant toward standard bioconjugation techniques. PP7 is therefore an excellent candidate for elaboration into useful diagnostic and therapeutic agents

Crosslinking of and Coupling to Viral Capsid Proteins by Tyrosine Oxidation

AbstractCowpea mosaic virus is composed of 60 identical copies of a two-subunit protein organized in pentameric assemblies around the icosahedral 5-fold symmetry axis. Treatment of the virus with the Ni(II) complex of the tripeptide GGH and a peroxide oxidant, or irradiation in the presence of Ru(bpy)32+ and persulfate generates covalent crosslinks across the pentameric subunit boundaries, effectively stitching the subunits together. Intersubunit crosslinking was found to occur exclusively at adjacent tyrosine residues (Y52-Y103), as predicted from the X-ray crystal structure of the capsid, and to be more extensive with the photochemical ruthenium system. The Ni/GGH oxidative procedure was also used to make covalent attachments to the virion by trapping with a functionalized disulfide reagent

Introducing new functions into (and onto) virus-like particles

Leviphage Qß and PP7 are well studied viruses that infect E. coli. They also provide highly stable and tailorable capsid protein structures that can be manipulated in a number of ways by the molecular biologist and chemist. We will describe our work with both particles, designed to give them new binding, shielding, and catalytic properties. This involves the expression of hybrid particles bearing catalytic protein domains on the inside or outside, the use of standard polymerization methods to grow organic polymers from the surface or into the interior of the particles, and the marriage of these particles with degradable hydrogel carriers Please click Additional Files below to see the full abstract

Foreign nationals who receive science or engineering Ph.D.`s from US universities: Stay rates and characteristics of stayers

This report studies the behavior of foreign nationals who received Ph.D. degrees in science or engineering from US universities during the period 1984--1990. It addresses two distinct questions: What proportion of foreign students stay to work in the United States after graduation; and do foreign students who leave the United States differ from those who stay? Descriptive statistics are provided to answer the first question. These estimates of stay rates have small margins of error because they were produced from the tax payment records of the Social Security Administration. The estimates of stay rates in also provide a partial answer to the second question as well as we are able to provide stay rates for different degree fields and different countries of citizenship, thereby identifying country-specific and field-specific differences in stay rates

Effects of finite arm-length of LISA on analysis of gravitational waves from MBH binaries

Response of an interferometer becomes complicated for gravitational wave shorter than the arm-length of the detector, as nature of wave appears strongly. We have studied how parameter estimation for merging massive black hole binaries are affected by this complicated effect in the case of LISA. It is shown that three dimensional positions of some binaries might be determined much better than the past estimations that use the long wave approximation. For equal mass binaries this improvement is most prominent at \sim 10^5\sol.Comment: 10 pages, 3 figures, to appear in Phys.Rev.

Graviton Mass from Close White Dwarf Binaries Detectable with LISA

The arrival times of gravitational waves and optical light from orbiting binaries provide a mechanism to understand the propagation speed of gravity when compared to that of light or electromagnetic radiation. This is achieved with a measurement of any offset between optically derived orbital phase related to that derived from gravitational wave data, at a specified location of one binary component with respect to the other. Using a sample of close white dwarf binaries (CWDBs) detectable with the Laser Interferometer Space Antenna (LISA) and optical light curve data related to binary eclipses from meter-class telescopes for the same sample, we determine the accuracy to which orbital phase differences can be extracted. We consider an application of these measurements involving a variation to the speed of gravity, when compared to the speed of light, due to a massive graviton. For a subsample of $\sim$ 400 CWDBs with high signal-to-noise gravitational wave and optical data with magnitudes brighter than 25, the combined upper limit on the graviton mass is at the level of $\sim 6 \times 10^{-24}$ eV. This limit is two orders of magnitude better than the present limit derived by Yukawa-correction arguments related to the Newtonian potential and applied to the Solar-system.Comment: revised version, 8 pages, 5 figures, to appear in PR

A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000

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