分类: 生物学 >> 生物物理学 提交时间: 2016-05-11
摘要: Enfuvirtide (T20), is the first HIV fusion inhibitor approved for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, its clinical application is limited because of short half-life, drug resistance and cross-reactivity with the preexisting antibodies in HIV-infected patients. Using an artificial peptide strategy, we designed a peptide with non-native protein sequence, AP3, which exhibited potent antiviral activity against a broad spectrum of HIV-1 strains, including those resistant to T20, and had remarkably longer in vivo half-life than T20. While the preexisting antibodies in HIV-infected patients significantly suppressed T20's antiviral activity, these antibodies neither recognized AP3, nor attenuated its anti-HIV-1 activity. Structurally different from T20, AP3 could fold into single-helix and interact with gp41 NHR. The two residues, Met and Thr, at the N-terminus of AP3 form a hook-like structure to stabilize interaction between AP3 and NHR helices. Therefore, AP3 has potential for further development as a new HIV fusion inhibitor with improved antiviral efficacy, resistance profile and pharmacological properties over enfuvirtide. Meanwhile, this study highlighted the advantages of artificially designed peptides, and confirmed that this strategy could be used in developing artificial peptide-based viral fusion inhibitors against HIV and other enveloped viruses.
分类: 天文学 >> 天文学 提交时间: 2024-03-29 合作期刊: 《Research in Astronomy and Astrophysics》
摘要: Ground-based arrays of imaging atmospheric Cherenkov telescopes (IACTs) are the most sensitive γ-ray detectors for energies of approximately 100 GeV and above. One such IACT is the High Altitude Detection of Astronomical Radiation (HADAR) experiment, which uses a large aperture refractive water lens system to capture atmospheric Cherenkov photons (i.e., the imaging atmospheric Cherenkov technique). The telescope array has a low threshold energy and large field of view, and can continuously scan the area of the sky being observed, which is conducive to monitoring and promptly responding to transient phenomena. The process of γ-hadron separation is essential in very-high-energy (>30 GeV) γ-ray astronomy and is a key factor for the successful utilization of IACTs. In this study, Monte Carlo simulations were carried out to model the response of cosmic rays within the HADAR detectors. By analyzing the Hillas parameters and the distance between the event core and the telescope, the distinction between air showers initiated by γ-rays and those initiated by cosmic rays was determined. Additionally, a Quality Factor was introduced to assess the telescope's ability to suppress the background and to provide a more effective characterization of its performance.