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Natural selection operating at the amino acid sequence level can be detected by comparing the rates of synonymous (r(S)) and nonsynonymous (r(N)) nucleotide substitutions, where r(N)/r(S) (omega) > 1 and omega < 1 suggest positive and negative selection, respectively. The branch-site test has been developed for detecting positive selection operating at a group of amino acid sites for a pre-specified (foreground) branch of a phylogenetic tree by taking into account the heterogeneity of omega among sites and branches. Here the performance of the branch-site test was examined by computer simulation, with special reference to the false-positive rate when the divergence of the sequences analyzed was small. The false-positive rate was found to inflate when the assumptions made on the omega values for the foreground and other (background) branches in the branch-site test were violated. In addition, under a similar condition, false-positive results were often obtained even when Bonferroni correction was conducted and the false-discovery rate was controlled in a large-scale analysis. False-positive results were also obtained even when the number of nonsynonymous substitutions for the foreground branch was smaller than the minimum value required for detecting positive selection. The existence of a codon site with a possibility of occurrence of multiple nonsynonymous substitutions for the foreground branch often caused the branch-site test to falsely identify positive selection. In the re-analysis of orthologous trios of protein-coding genes from humans, chimpanzees, and macaques, most of the genes previously identified to be positively selected for the human or chimpanzee branch by the branch-site test contained such a codon site, suggesting a possibility that a significant fraction of these genes are false-positives.  相似文献   

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Enzyme immunoassay (EIA) with the use of test systems based on recombinant HIV antigens has yielded positive results much more often than that with the test systems based on HIV lysate. In comparison with the use of protein A-peroxidase conjugate, the use of antiglobulin conjugates decreased the specificity of EIA, thus ruling out the false positive results. The tested sera containing antibodies to antigens of enteric bacilli could yield false positive EIA results with test systems prepared from recombinant antigens due to the interaction of these antibodies with antigens of enteric bacilli. A conclusion on the usefulness of the control for the presence of the components of enteric bacilli, producers of HIV antigen, and their elimination from recombinant preparations is made.  相似文献   

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Objective:  To determine the spectrum of disease, diagnostic accuracy and adequacy of fine needle aspirates (FNA) in human immunodeficiency virus (HIV) positive children who present with mass lesions.
Methods:  Between January 1997 and December 2002, 95 FNAs were performed in 91 children aged 15 years and younger who were known to be infected with the human immunodeficiency virus (HIV).
Results:  Head and neck masses including salivary gland swellings were the most common presentation (58.9%) followed by axillary masses (25.3%). Groin masses were aspirated in six children, flank and abdominal masses in four children, buttock masses in three children, a chest wall mass in one child and a sonar guided FNA of a lung mass in one child. Eight FNAs (8.4%) proved inadequate. Reactive lymphadenopathy was diagnosed in 42 cases, mycobacterial infection in 22, four children were diagnosed with abscess, one child had a fungal infection and five were found to have non-Hodgkin's lymphoma. There were four cases each of lymphoepithelial lesion and Kaposi sarcoma. There was one case each of nephroblastoma, rhabdomyosarcoma, myeloma, melanotic progonoma and spindle cells, not otherwise specified.
Conclusion:  Fine needle aspiration in HIV positive children is a worthwhile procedure and in most instances allows a rapid diagnosis obviating the need for surgery and enabling swift treatment to be undertaken where necessary. Ancillary studies form an important diagnostic component. Universal safety precautions must be strictly adhered to.  相似文献   

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The ability of human immunodeficiency virus type 1 (HIV-1) to develop high levels of genetic diversity, and thereby acquire mutations to escape immune pressures, contributes to the difficulties in producing a vaccine. Possibly no single HIV-1 sequence can induce sufficiently broad immunity to protect against a wide variety of infectious strains, or block mutational escape pathways available to the virus after infection. The authors describe the generation of HIV-1 immunogens that minimizes the phylogenetic distance of viral strains throughout the known viral population (the center of tree [COT]) and then extend the COT immunogen by addition of a composite sequence that includes high-frequency variable sites preserved in their native contexts. The resulting COT+ antigens compress the variation found in many independent HIV-1 isolates into lengths suitable for vaccine immunogens. It is possible to capture 62% of the variation found in the Nef protein and 82% of the variation in the Gag protein into immunogens of three gene lengths. The authors put forward immunogen designs that maximize representation of the diverse antigenic features present in a spectrum of HIV-1 strains. These immunogens should elicit immune responses against high-frequency viral strains as well as against most mutant forms of the virus.  相似文献   

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Second-generation sequencing is a powerful method for identifying and quantifying small-RNA components of cells. However, little attention has been paid to the effects of the choice of sequencing platform and library preparation protocol on the results obtained. We present a thorough comparison of small-RNA sequencing libraries generated from the same embryonic stem cell lines, using different sequencing platforms, which represent the three major second-generation sequencing technologies, and protocols. We have analysed and compared the expression of microRNAs, as well as populations of small RNAs derived from repetitive elements. Despite the fact that different libraries display a good correlation between sequencing platforms, qualitative and quantitative variations in the results were found, depending on the protocol used. Thus, when comparing libraries from different biological samples, it is strongly recommended to use the same sequencing platform and protocol in order to ensure the biological relevance of the comparisons.  相似文献   

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A weeping pulsed radar reflectometer designed for measuring the spatial electron density distribution in the Globus-M spherical tokamak with a minor plasma radius of a=24 cm, a major radius of R=36 cm, a toroidal field of B T=0.5 T, a plasma current of I p=200 kA, and an average density of n=(3–10)×1013 cm?3 is described. The reflectometer operation is based on the reflection of microwaves with a carrier frequency f from a plasma layer with the critical density n=(0.0111f)2, where n is the electron density in units of 1014 cm?3 and f is the microwave frequency in GHz. By simultaneously probing the plasma at different frequencies, it is possible to recover the electron density profile. Microwave pulses with different frequencies are obtained by frequency sweeping. To increase the range of measured densities, channels with fixed frequencies are also used; as a result, the instrument has eleven frequency channels: a 19.5-GHz channel, eight channels in the 26-to 40-GHz frequency range, a 51.5-GHz channel, and a 60-GHz channel, which corresponds to eleven points in the density profile: 0.47×1013 cm?3, eight points in the (0.8–1.95)×1013-cm?3 range, 3.27×1013 cm?3, and 4.5×1013 cm?3. The reflectometer allows detailed measurements of the density profile with a time resolution of several tens of microseconds, which can be useful, in particular, in studying the processes related to the formation of an internal transport barrier in plasma. The first results obtained using this reflectometer in the Globus-M tokamak under various operating conditions are discussed.  相似文献   

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Development of a prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine is a leading priority in biomedical research. Much of this work has been done with the nonhuman primate model of AIDS. In a historical context, vaccine studies, which use this model, are summarized and discussed.  相似文献   

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