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The generalized Bilal (GB) distribution can be defined as the distribution of the median of three independent random variables drawn from the Weibull distribution. Its failure rate function can be monotonic (decreasing or increasing) or upside-down bathtub-shaped. In this study, we aim to reveal some important properties of the GB distribution that have not been considered before. The findings are both theoretical and practical. From the theoretical viewpoint, we present explicit expressions for both single and product moments of order statistics from the GB distribution. The L-moments are derived as well. From the practical viewpoint, the parameter estimations are accomplished using the maximum likelihood (ML) method, which is based on two different sampling schemes: simple random sampling (SRS) and ranked set sampling (RSS) schemes. Furthermore, the asymptotic confidence intervals for the SRS and RSS estimators are discussed. For the sake of comparison and illustration, a simulation study and a real data example are presented. Concluding remarks are given at the end.

We obtain explicit expressions for single and product moments of the order statistics of an omega distribution. We also discuss seven methods to estimate the omega parameters. Various simulation results are performed to compare the performance of the proposed estimators. Furthermore, the maximum likelihood method is adopted to estimate the omega parameters under the type II censoring scheme. The usefulness of the omega distribution is proven using a real data set.

In this paper probability density function of single concomitant and joint probability density function of two concomitants of dual generalized order statistics from bivariate Burr III distribution are obtained and expressions for single and product moments are derived. Further, results are deduced for the order statistics and lower record values.

We evaluated the compound imiquimod as a possible adjuvant for DNA immunization against human immunodeficiency virus (HIV). We found that gene-gun epidermal delivery of the DNA in combination with imiquimod resulted in the strongest HIV specific immune responses. The effect of imiquimod was further compared to that of recombinant granulocyte macrophage-colony stimulating factor (GM-CSF), a known DNA vaccine adjuvant. Both adjuvants were able to enhance the immune responses induced by the HIV-1 genes alone. The delivery of an adjuvant as a topical cream rather than through injections has a clear clinical benefit. We show for the first time that imiquimod can act as an adjuvant for DNA vaccination.

Drug resistance is becoming a problem in the treatment of the human immunodeficiency virus type one (HIV-1). To obtain therapeutic DNA vaccines that would target multiple drug-resistance (DR) mutations, we cloned genes for DR HIV-1 reverse transcriptase (RT) and codon-optimized synthetic genes encoding clusters of human CTL epitopes located at the sites of DR-mutations (RT minigenes) and antibody and CTL-epitope tags. Expression of RT genes/minigenes in eukaryotic cells was confirmed by Western blotting and immunofluoresence staining with RT- or tag-specific antibodies. Immunization of mice with DR-RT gene induced no RT-specific antibodies. Immunization of HLA-A(*)0201-transgenic mice with RT minigenes induced RT-specific cellular responses detected by interferon-gamma secretion. This documents first steps in creating therapeutic vaccine against drug-resistant HIV strains.

The fear of autoimmunity in DNA-vaccine recipients initiated screening for anti-DNA antibodies in rabbits immunized with genes of viral nucleic acid-binding and adapter proteins. Of 11 DNA/protein-immunized rabbits, seven had developed secondary antibodies against DNA detected at weeks 11-50 from the on-start of immunization. Two rabbits immunized with HIV-1 reverse transcriptase gene developed transient anti-double-stranded DNA antibodies of high avidity that recognized DNA in the kinetoplasts of Crithidia luciliae. Others developed antibodies reacting with DNA in ELISA and targeting nuclear-associated antigens in the immunofluoresence test. No anti-DNA antibodies were detected at these time-points in any of the controls (P=0.036). Induction of anti-DNA antibodies by epitope spreading from protein domains involved in nucleic acid-binding versus maturation of anti-protein antibodies to dual protein-DNA specificity is discussed. (126 words).

Mutations in reverse transcriptase (RT) confer high levels of HIV resistance to drugs. However, while conferring drug resistance, they can lower viral replication capacity (fitness). The molecular mechanisms behind remain largely unknown. The aim of the study was to characterize the effect of drug-resistance mutations on HIV RT expression. Genes encoding AZT-resistant RTs with single or combined mutations D67N, K70R, T215F, and K219Q, and RTs derived from drug-resistant HIV-1 strains were designed and expressed in a variety of eukaryotic cells. Expression in transiently transfected cells was assessed by Western blotting and immunofluorescent staining with RT-specific antibodies. To compare the levels of expression, mutated RT genes were microinjected into the nucleus of the oocytes of Xenopus laevis. Expression of RT was quantified by sandwich ELISA. Relative stability of RTs was assessed by pulse-chase experiments. Xenopus oocytes microinjected with the genes expressed 2-50 pg of RT mutants per cell. The level of RT expression decreased with accumulation of drug-resistance mutations. Pulse-chase experiments demonstrated that poor expression of DR-RTs was due to proteolytic instability. Instability could be attributed to additional cleavage sites predicted to appear in the vicinity of resistance mutations. Accumulation of drug-resistance mutations appears to affect the level of eukaryotic expression of HIV-1 RT by inducing proteolytic instability. Low RT levels might be one of the determinants of impaired replication fitness of drug-resistant HIV-1 strains.