分类: 物理学 >> 核物理学 分类: 天文学 >> 天文仪器与技术 提交时间: 2023-08-29
摘要: In the future, the Very Large Area gamma-ray Space Telescope (VLAST) is expected to observe high-energy electrons and gamma rays in the MeV to TeV range with unprecedented acceptance. As part of the detector suite, a high-energy imaging calorimeter (HEIC) is currently being developed as a homogeneous calorimeter that utilizes long bismuth germanate (BGO) scintillation crystals as both absorbers and detectors. To accurately measure the energy deposition in the BGO bar of HEIC, a high-dynamic-range readout method using a silicon photoMultiplier (SiPM) and multiphotodiode (PD) with different active areas has been proposed. A prototype readout system that adopts multichannel charge measurement ASICs was also developed to read out the combined system of SiPMs and PDs. Preliminary tests confirmed the feasibility of the readout scheme, which is expected to have a dynamic range close to 106.
分类: 生物学 >> 生物物理学 提交时间: 2016-05-12
摘要: The best way to increase patient survival rate is to identify patients who are likely to progress to muscle-invasive or metastatic disease upfront and treat them more aggressively. The human cell lines HCV29 (normal bladder epithelia), KK47 (low grade nonmuscle invasive bladder cancer, NMIBC), and YTS1 (metastatic bladder cancer) have been widely used in studies of molecular mechanisms and cell signaling during bladder cancer (BC) progression. However, little attention has been paid to global quantitative proteome analysis of these three cell lines. We labeled HCV29, KK47, and YTS1 cells by the SILAC method using three stable isotopes each of arginine and lysine. Labeled proteins were analyzed by 2D ultrahigh-resolution liquid chromatography LTQ Orbitrap mass spectrometry. Among 3721 unique identified and annotated proteins in KK47 and YTS1 cells, 36 were significantly upregulated and 74 were significantly downregulated with >95% confidence. Differential expression of these proteins was confirmed by western blotting, quantitative RT-PCR, and cell staining with specific antibodies. Gene ontology (GO) term and pathway analysis indicated that the differentially regulated proteins were involved in DNA replication and molecular transport, cell growth and proliferation, cellular movement, immune cell trafficking, and cell death and survival. These proteins and the advanced proteome techniques described here will be useful for further elucidation of molecular mechanisms in BC and other types of cancer.
分类: 生物学 >> 生物物理学 >> 免疫学 提交时间: 2016-05-05
摘要: Background: Programmed cell death ligand-1 (PD-L1) with its receptor PD-1 pathway is overactivated in many tumors. Inhibiting the interaction of PD-L1 and PD-1 is an attractive strategy to restore tumor-specific T cell immunity for tumor therapy. Methods: A fully human anti-PD-L1 monoclonal antibody (mAb) B60-55 was identified by yeast surface display. The affinity, specificity, activity, and efficacy of mAb B60-55 were investigated in vitro or in vivo. Results: mAb B60-55 (purity >99%) could bind to PD-L1 that is expressed on HEK293 cells with a dissociation constant of 02 nM, and specifically bind to human or cynomolgus macaque PD-L1 without a cross-reaction with murine PD-L1. Moreover, mAb B60-55 is an antagonistic antibody, which can block PD-L1 binding to its receptors, including PD-1 (PDCD1) and B7.1 (CD80). In vitro assays demonstrated the ability of mAb B60-55 to enhance T cell responses and cytokine production in the mixed lymphocyte reaction. In vivo studies showed that administration of mAb B60-55 exhibited a potent antitumor activity toward tumor cell carcinoma xenograft, with a mean half-life of 177.9 h in cynomolgus monkeys. Conclusion: mAb B60-55 is a potential candidate for clinical development in cancer treatment. (C) 2016 Elsevier B.V. All rights reserved.