Blocking HSV-1 glycoprotein K binding to signal peptide peptidase reduces virus infectivity in vitro and in vivo

HSV glycoprotein K (gK) is an essential herpes protein that contributes to enhancement of eye disease. We previously reported that gK binds to signal peptide peptidase (SPP) and that depletion of SPP reduces HSV-1 infectivity in vivo. To determine the therapeutic potential of blocking gK binding to SPP on virus infectivity and pathogenicity, we mapped the gK binding site for SPP to a 15mer peptide within the amino-terminus of gK. This 15mer peptide reduced infectivity of three different virus strains in vitro as determined by plaque assay, FACS, and RT-PCR. Similarly, the 15mer peptide reduced ocular virus replication in both BALB/c and C57BL/6 mice and also reduced levels of latency and exhaustion markers in infected mice when compared with control treated mice. Addition of the gK-15mer peptide also increased the survival of infected mice when compared with control mice. These results suggest that blocking gK binding to SPP using gK peptide may have therapeutic potential in treating HSV-1-associated infection.     

Complete sequence of bluetongue virus L2 RNA that codes for the antigen recognized by neutralizing antibodies.

The complete sequence of the RNA which encodes the major outer-shell-neutralizing antigen (VP2) of bluetongue virus serotype 10 was determined from overlapping cDNA clones inserted into pBR322. The segment L2 RNA was 2,926 base pairs long (1.87 X 10(6) daltons) and had, in one strand, an open reading frame capable of coding for a protein that had a calculated size of 111,122 daltons (956 amino acids) and a +11.5 net charge. The coding strands of both the L2 gene and the group-specific L3 gene of bluetongue virus serotype 17 (M. Purdy, J. Petre, and P. Roy, J. Virol. 51:754-759, 1984) had common sequences of some six nucleotides at their 5' termini (namely, GUUAAA...) and eight nucleotides (namely, ...ACACUUAC) at their 3' termini. Both had short 5' noncoding regions with AUG codons at residues 20 to 22 (L2) and 18 to 20 (L3). The sequences flanking these AUG codons were similar (A/GCCAUGG). The 3' noncoding regions were longer (36 nucleotides for L2, 49 nucleotides for L3). The predicted amino acid sequence of the L2, compared with the similarly sized L3 gene product, was rich in cysteine residues and charged amino acids.     

Safe bunker designing for the 18?MV Varian 2100 Clinac: a comparison between Monte Carlo simulation based upon data and new protocol recommendations

Aim

The aim of this study was to compare two bunkers designed by only protocols recommendations and Monte Carlo (MC) based upon data derived for an 18 MV Varian 2100Clinac accelerator.

Background

High energy radiation therapy is associated with fast and thermal photoneutrons. Adequate shielding against the contaminant neutron has been recommended by IAEA and NCRP new protocols.

Materials and methods

The latest protocols released by the IAEA (safety report No. 47) and NCRP report No. 151 were used for the bunker designing calculations. MC method based upon data was also derived. Two bunkers using protocols and MC upon data were designed and discussed.

Results

From designed door''s thickness, the door designed by the MC simulation and Wu–McGinley analytical method was closer in both BPE and lead thickness. In the case of the primary and secondary barriers, MC simulation resulted in 440.11 mm for the ordinary concrete, total concrete thickness of 1709 mm was required. Calculating the same parameters value with the recommended analytical methods resulted in 1762 mm for the required thickness using 445 mm as recommended by TVL for the concrete. Additionally, for the secondary barrier the thickness of 752.05 mm was obtained.

Conclusion

Our results showed MC simulation and the followed protocols recommendations in dose calculation are in good agreement in the radiation contamination dose calculation. Difference between the two analytical and MC simulation methods revealed that the application of only one method for the bunker design may lead to underestimation or overestimation in dose and shielding calculations.