Enhancement of electroporation facilitated immunogene therapy via T-reg depletion

Regulatory T cells (T-regs) can negatively impact tumor antigen-specific immune responses after infiltration into tumor tissue. However, depletion of T-regs can facilitate enhanced anti-tumor responses, thus augmenting the potential for immunotherapies. Here we focus on treating a highly aggressive form of cancer using a murine melanoma model with a poor prognosis. We utilize a combination of T-reg depletion and immunotherapy plasmid DNA delivered into the B16F10 melanoma tumor model via electroporation. Plasmids encoding murine granulocyte macrophage colony-stimulating factor and human B71 were transfected with electroporation into the tumor and transient elimination of T-regs was achieved with CD25-depleting antibodies (PC61). The combinational treatment effectively depleted T-regs compared to the untreated tumor and significantly reduced lung metastases. The combination treatment was not effective in increasing the survival, but only effective in suppression of metastases. These results indicate the potential for combining T-reg depletion with immunotherapy-based gene electrotransfer to decrease systemic metastasis and potentially enhance survival

Time-Series Photometry of M67: W UMa Systems, Blue Stragglers, and Related Systems

We present an analysis of over 2200 V images taken on 14 nights at the Mt. Laguna 1 m telescope of the open cluster M67. Our observations overlap but extend beyond the field analyzed by Gilliland et al. (1991), and complement data recently published by van den Berg et al. (2002) and Stassun et al. (2002). We show variability in the light curves of all 4 of the known W UMa variables on timescales ranging from a day to decades (for AH Cnc). We have modeled the light curve of AH Cnc, and the total eclipses allow us to determine q = 0.16 +0.03/-0.02 and i = 86 +4/-8 degrees. The position of this system near the turnoff of M67 makes it useful for constraining the turnoff mass for the cluster. We have also detected two unusual features in the light curve of AH Cnc that may be caused by prominences. We have also monitored cluster blue stragglers for variability, and we present evidence hinting at low level variations in the stragglers S752, S968, and S1263, and we place limits on the variability of a number of other cluster blue stragglers. Finally, we provide photometry of the sub-subgiant branch star S1063 showing variability on timescales similar to the orbital period, while the ``red straggler'' S1040 shows evidence of an unexplained drop in brightness at phases corresponding to the passage of the white dwarf in front of the giant.Comment: 44 pages, 16 figures, AASTeX, accepted for A

A fast stroboscopic spectral method for rotating systems in numerical relativity

We present a numerical technique for solving evolution equations, as the wave equation, in the description of rotating astrophysical compact objects in comoving coordinates, which avoids the problems associated with the light cylinder. The technique implements a fast spectral matching between two domains in relative rotation: an inner spherical domain, comoving with the sources and lying strictly inside the light cylinder, and an outer inertial spherical shell. Even though the emphasis is placed on spectral techniques, the matching is independent of the specific manner in which equations are solved inside each domain, and can be adapted to different schemes. We illustrate the strategy with some simple but representative examples.Comment: 16 pages, 15 figure

Australian encephalitis: sentinel chicken surveillance programme

Sentinel chicken flocks are used to monitor flavivirus activity in Australia. The main viruses of concern are Murray Valley encephalitis (MVE) and Kunjin which cause the potentially fatal disease encephalitis, in humans. Currently 30 flocks are maintained in the north of Western Australia, 9 in the Northern Territory, 12 in New South Wales and 10 in Victoria. The flocks in Western Australia and the Northern Territory are tested year round but those in New South Wales and Victoria are tested only from November to March, during the main risk season. Results are coordinated by the Arbovirus Laboratory in Perth and reported bimonthly

Stochastic Background Search Correlating ALLEGRO with LIGO Engineering Data

We describe the role of correlation measurements between the LIGO interferometer in Livingston, LA, and the ALLEGRO resonant bar detector in Baton Rouge, LA, in searches for a stochastic background of gravitational waves. Such measurements provide a valuable complement to correlations between interferometers at the two LIGO sites, since they are sensitive in a different, higher, frequency band. Additionally, the variable orientation of the ALLEGRO detector provides a means to distinguish gravitational wave correlations from correlated environmental noise. We describe the analysis underway to set a limit on the strength of a stochastic background at frequencies near 900 Hz using ALLEGRO data and data from LIGO's E7 Engineering Run.Comment: 8 pages, 2 encapsulated PostScript figures, uses IOP class files, submitted to the proceedings of the 7th Gravitational Wave Data Analysis Workshop (which will be published in Classical and Quantum Gravity

Selective Constraints on Amino Acids Estimated by a Mechanistic Codon Substitution Model with Multiple Nucleotide Changes

Empirical substitution matrices represent the average tendencies of substitutions over various protein families by sacrificing gene-level resolution. We develop a codon-based model, in which mutational tendencies of codon, a genetic code, and the strength of selective constraints against amino acid replacements can be tailored to a given gene. First, selective constraints averaged over proteins are estimated by maximizing the likelihood of each 1-PAM matrix of empirical amino acid (JTT, WAG, and LG) and codon (KHG) substitution matrices. Then, selective constraints specific to given proteins are approximated as a linear function of those estimated from the empirical substitution matrices. Akaike information criterion (AIC) values indicate that a model allowing multiple nucleotide changes fits the empirical substitution matrices significantly better. Also, the ML estimates of transition-transversion bias obtained from these empirical matrices are not so large as previously estimated. The selective constraints are characteristic of proteins rather than species. However, their relative strengths among amino acid pairs can be approximated not to depend very much on protein families but amino acid pairs, because the present model, in which selective constraints are approximated to be a linear function of those estimated from the JTT/WAG/LG/KHG matrices, can provide a good fit to other empirical substitution matrices including cpREV for chloroplast proteins and mtREV for vertebrate mitochondrial proteins. The present codon-based model with the ML estimates of selective constraints and with adjustable mutation rates of nucleotide would be useful as a simple substitution model in ML and Bayesian inferences of molecular phylogenetic trees, and enables us to obtain biologically meaningful information at both nucleotide and amino acid levels from codon and protein sequences.Comment: Table 9 in this article includes corrections for errata in the Table 9 published in 10.1371/journal.pone.0017244. Supporting information is attached at the end of the article, and a computer-readable dataset of the ML estimates of selective constraints is available from 10.1371/journal.pone.001724

Evolution of Hard X-Ray Spectra Along the Branches in Cir X-1

Using the data from the PCA and HEXTE on board the RXTE satellite, we investigate the evolution of the 3-200 keV spectra of the peculiar low mass X-ray binary (LMXB) Cir X-1 along the branches on its hardness-intensity diagram (HID) from the vertical horizontal branch (VHB), through the horizontal horizontal branch (HHB) and normal branch (NB), to the flaring branch (FB). We detect a power-law hard component in the spectra. It is found that the derived photon indices ($\Gamma$) of the power-law hard component are correlated with the position on the HID. The power-law component dominates the X-ray emission of Cir X-1 in the energy band higher than $\sim 20$ keV. The fluxes of the power-law component are compared with those of the bremsstrahlung component in the spectra. A possible origin of the power-law hard component is discussed.Comment: 14 pages, 5 figures, ApJ Letter accepte

Surface Enhanced Second Harmonic Generation from Macrocycle, Catenane, and Rotaxane Thin Films: Experiments and Theory

Surface enhanced second harmonic generation (SE SHG) experiments on molecular structures, macrocycles, catenanes, and rotaxanes, deposited as monolayers and multilayers by vacuum sublimation on silver, are reported. The measurements show that the molecules form ordered thin films, where the highest degree of order is observed in the case of macrocycle monolayers and the lowest in the case of rotaxane multilayers. The second harmonic generation activity is interpreted in terms of electric field induced second harmonic (EFISH) generation where the electric field is created by the substrate silver atoms. The measured second order nonlinear optical susceptibility for a rotaxane thin film is compared with that obtained by considering only EFISH contribution to SHG intensity. The electric field on the surface of a silver layer is calculated by using the Delphi4 program for structures obtained with TINKER molecular mechanics/dynamics simulations. An excellent agreement is observed between the calculated and the measured SHG susceptibilities.