Engineering the vaccinia virus L1 protein for increased neutralizing antibody response after DNA immunization

<p>Abstract</p> <p>Background</p> <p>The licensed smallpox vaccine, comprised of infectious vaccinia virus, has associated adverse effects, particularly for immunocompromised individuals. Therefore, safer DNA and protein vaccines are being investigated. The L1 protein, a component of the mature virion membrane that is conserved in all sequenced poxviruses, is required for vaccinia virus entry into host cells and is a target for neutralizing antibody. When expressed by vaccinia virus, the unglycosylated, myristoylated L1 protein attaches to the viral membrane via a C-terminal transmembrane anchor without traversing the secretory pathway. The purpose of the present study was to investigate modifications of the gene expressing the L1 protein that would increase immunogenicity in mice when delivered by a gene gun.</p> <p>Results</p> <p>The L1 gene was codon modified for optimal expression in mammalian cells and potential N-glycosylation sites removed. Addition of a signal sequence to the N-terminus of L1 increased cell surface expression as shown by confocal microscopy and flow cytometry of transfected cells. Removal of the transmembrane domain led to secretion of L1 into the medium. Induction of binding and neutralizing antibodies in mice was enhanced by gene gun delivery of L1 containing the signal sequence with or without the transmembrane domain. Each L1 construct partially protected mice against weight loss caused by intranasal administration of vaccinia virus.</p> <p>Conclusion</p> <p>Modifications of the vaccinia virus L1 gene including codon optimization and addition of a signal sequence with or without deletion of the transmembrane domain can enhance the neutralizing antibody response of a DNA vaccine.</p

Wing force and surface pressure data from a hover test of a 0.658-scale V-22 rotor and wing

A hover test of a 0.658-scale V-22 rotor and wing was conducted in the 40 x 80 foot wind tunnel at Ames Research Center. The principal objective of the test was to measure the surface pressures and total download on a large scale V-22 wing in hover. The test configuration consisted of a single rotor and semispan wing on independent balance systems. A large image plane was used to represent the aircraft plane of symmetry. Wing flap angles ranging from 45 to 90 degrees were examined. Data were acquired for both directions of the rotor rotation relative to the wing. Steady and unsteady wing surface pressures, total wing forces, and rotor performance data are presented for all of the configurations that were tested

Surface MIMO: Using Conductive Surfaces For MIMO Between Small Devices

As connected devices continue to decrease in size, we explore the idea of leveraging everyday surfaces such as tabletops and walls to augment the wireless capabilities of devices. Specifically, we introduce Surface MIMO, a technique that enables MIMO communication between small devices via surfaces coated with conductive paint or covered with conductive cloth. These surfaces act as an additional spatial path that enables MIMO capabilities without increasing the physical size of the devices themselves. We provide an extensive characterization of these surfaces that reveal their effect on the propagation of EM waves. Our evaluation shows that we can enable additional spatial streams using the conductive surface and achieve average throughput gains of 2.6-3x for small devices. Finally, we also leverage the wideband characteristics of these conductive surfaces to demonstrate the first Gbps surface communication system that can directly transfer bits through the surface at up to 1.3 Gbps.Comment: MobiCom '1

Irreducible characters of GSp(4, q) and dimensions of spaces of fixed vectors

In this paper, we compute the conjugacy classes and the list of irreducible characters of GSp(4,q), where q is odd. We also determine precisely which irreducible characters are non-cuspidal and which are generic. These characters are then used to compute dimensions of certain subspaces of fixed vectors of smooth admissible non-supercuspidal representations of GSp(4,F), where F is a non-archimedean local field of characteristic zero with residue field of order q.Comment: 48 pages, 21 tables. Corrected an error in Table 16 for type V* representations (theta_11 and theta_12 were switched

Percolation on the average and spontaneous magnetization for q-states Potts model on graph

We prove that the q-states Potts model on graph is spontaneously magnetized at finite temperature if and only if the graph presents percolation on the average. Percolation on the average is a combinatorial problem defined by averaging over all the sites of the graph the probability of belonging to a cluster of a given size. In the paper we obtain an inequality between this average probability and the average magnetization, which is a typical extensive function describing the thermodynamic behaviour of the model

Spontaneous magnetization of the Ising model on the Sierpinski carpet fractal, a rigorous result

We give a rigorous proof of the existence of spontaneous magnetization at finite temperature for the Ising spin model defined on the Sierpinski carpet fractal. The theorem is inspired by the classical Peierls argument for the two dimensional lattice. Therefore, this exact result proves the existence of spontaneous magnetization for the Ising model in low dimensional structures, i.e. structures with dimension smaller than 2.Comment: 14 pages, 8 figure

Sonic-Point Model of Kilohertz Quasi-Periodic Brightness Oscillations in Low-Mass X-ray Binaries

Strong, coherent, quasi-periodic brightness oscillations (QPOs) with frequencies ranging from about 300 Hz to 1200 Hz have been discovered with the Rossi X-ray Timing Explorer in the X-ray emission from some fifteen neutron stars in low-mass binary systems. Two simultaneous kilohertz QPOs differing in frequency by 250 to 350 Hertz have been detected in twelve of the fifteen sources. Here we propose a model for these QPOs. In this model the X-ray source is a neutron star with a surface magnetic field of 10^7 to 10^10 G and a spin frequency of a few hundred Hertz, accreting gas via a Keplerian disk. The frequency of the higher-frequency QPO in a kilohertz QPO pair is the Keplerian frequency at a radius near the sonic point at the inner edge of the Keplerian flow whereas the frequency of the lower-frequency QPO is approximately the difference between the Keplerian frequency at a radius near the sonic point and the stellar spin frequency. This model explains naturally many properties of the kilohertz QPOs, including their frequencies, amplitudes, and coherence. We show that if the frequency of the higher-frequency QPO in a pair is an orbital frequency, as in the sonic-point model, the frequencies of these QPOs place interesting upper bounds on the masses and radii of the neutron stars in the kilohertz QPO sources and provide new constraints on the equation of state of matter at high densities. Further observations of these QPOs may provide compelling evidence for the existence of a marginally stable orbit, confirming a key prediction of general relativity in the strong-field regime.Comment: 67 pages, including 15 figures and 5 tables; uses aas2pp4; final version to appear in the Astrophysical Journal on 1 December 199

Cytochromec−Crown Ether Complexes as Supramolecular Catalysts: Cold-Active Synzymes for Asymmetric Sulfoxide Oxidation in Methanol

A series of supramolecular complexes of various cytochrome c proteins with 18-crown-6 derivatives behave as cold-active synzymes in the H_2O_2 oxidation of racemic sulfoxides. This interesting behavior contrasts with native functionality, where the employed proteins act as electron transfer carriers. ESI-MS, UV, CD, and Raman spectroscopic characterizations reveal that four or five 18-crown-6 molecules strongly bind to the surface of the cytochrome c and also that nonnatural low-spin hexacoordinate heme structures are induced in methanol. Significantly, crown ether complexation can convert catalytically inactive biological forms to catalytically active artificial forms. Horse heart, pigeon breast, and yeast cytochromes c all stereoselectively oxidize (S)-isomers of methyl tolyl sulfoxide and related sulfoxides upon crown ether complexation. These supramolecular catalysts show the highest efficiency and enantiomer selectivity at −40 °C in the H_2O_2-dependent sulfoxide oxidation, while oxidative decomposition of the heme moieties predominantly occurs at room temperature. The oxidation reactivity of the employed sulfoxides is apparently related to steric constraints and electrochemical oxidation potentials of their S O bonds. Among the cytochrome c complexes, yeast cytochrome c demonstrates the lowest catalytic activity and degradation reactivity. It has a significantly different protein sequence, suggesting that crown ether complexation effectively activates heme coordination but may additionally alter the native backbone structure. The proper combination of cytochrome c proteins, 18-crown-6 receptors, and external circumstances can be used to successfully generate “protein-based supramolecular catalysts” exhibiting nonbiological reactivities

Recent X-ray measurements of the accretion-powered pulsar 4U 1907+09

X-ray observations of the accreting X-ray pulsar 4U~1907+09, obtained during February 1996 with the Proportional Counter Array on the Rossi X-ray Timing Experiment (RXTE), have enabled the first measurement of the intrinsic pulse period Ppulse since 1984: Ppulse=440.341[+0.012,-0.017] s. 4U 1907+09 is in a binary system with a blue supergiant. The orbital parameters were solved and this enabled the correction for orbital delay effects of a measurement of Ppulse obtained in 1990 with Ginga. Thus, three spin down rates could be extracted from four pulse periods obtained in 1983, 1984, 1990, and 1996. These are within 8% equal to a value of dPpulse/dt=+0.225 s/yr. This suggest that the pulsar is perhaps in a monotonous spin down mode since its discovery in 1983. Furthermore, the RXTE observations show transient ~18 s oscillations during a flare that lasted about 1 hour. The oscillations may be interpreted as Keplerian motion of an accretion disk near the magnetospheric radius. This, and the notion that the co-rotation radius is much larger than any conceivable value for the magnetospheric radius (because of the long spin period), renders it unlikely that this pulsar spins near equilibrium like is suspected for other slowing accreting X-ray pulsars. We suggest as an alternative that perhaps the frequent occurrence of a retrograde transient accretion disk may be consistently slowing the pulsar down. Further observations of flares can provide more evidence of this.Comment: 26 pages, 11 figures, to be published in Astrophysical Journal part I on March 20, 199