81,594 research outputs found
In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1.
Although antiretroviral drug resistance is common in treated HIV infected individuals, it is not a consistent indicator of HIV morbidity and mortality. To the contrary, HIV resistance-associated mutations may lead to changes in viral fitness that are beneficial to infected individuals. Using a bioinformatics-based model to assess the effects of numerous drug resistance mutations, we determined that the D30N mutation in HIV-1 protease had the largest decrease in replication capacity among known protease resistance mutations. To test this in silico result in an in vivo environment, we constructed several drug-resistant mutant HIV-1 strains and compared their relative fitness utilizing the SCID-hu mouse model. We found HIV-1 containing the D30N mutation had a significant defect in vivo, showing impaired replication kinetics and a decreased ability to deplete CD4+ thymocytes, compared to the wild-type or virus without the D30N mutation. In comparison, virus containing the M184V mutation in reverse transcriptase, which shows decreased replication capacity in vitro, did not have an effect on viral fitness in vivo. Thus, in this study we have verified an in silico bioinformatics result with a biological assessment to identify a unique mutation in HIV-1 that has a significant fitness defect in vivo
Pemilihan kerjaya di kalangan pelajar aliran perdagangan sekolah menengah teknik : satu kajian kes
This research is a survey to determine the career chosen of form four student
in commerce streams. The important aspect of the career chosen has been divided
into three, first is information about career, type of career and factor that most
influence students in choosing a career. The study was conducted at Sekolah
Menengah Teknik Kajang, Selangor Darul Ehsan. Thirty six form four students was
chosen by using non-random sampling purpose method as respondent. All
information was gather by using questionnaire. Data collected has been analyzed in
form of frequency, percentage and mean. Results are performed in table and graph.
The finding show that information about career have been improved in students
career chosen and mass media is the main factor influencing students in choosing
their career
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Genomic Alteration Burden in Advanced Prostate Cancer and Therapeutic Implications.
The increasing number of patients with sequenced prostate cancer genomes enables us to study not only individual oncogenic mutations, but also capture the global burden of genomic alterations. Here we review the extent of tumor genome mutations and chromosomal structural variants in various clinical states of prostate cancer, and the related prognostic information. Next, we discuss the underlying mutational processes that give rise to these various alterations, and their relationship to the various molecular subtypes of prostate cancer. Finally, we examine the relationships between the tumor mutation burden of castration-resistant prostate cancer, DNA repair defects, and response to immune checkpoint inhibitor therapy
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