We report the design and characterization of a CMOS pixel direct charge sensor, Topmetal-II -, fabricated in a standard 0.35 µm CMOS Integrated Circuit process. The sensor utilizes exposed metal patches on top of each pixel to directly collect charge. Each pixel contains a low-noise charge-sensitive preamplifier to establish the analog signal and a discriminator with tunable threshold to generate hits. The analog signal from each pixel is accessible through time-shared multiplexing over the entire array. Hits are read out digitally through a column-based priority logic structure. Tests show that the sensor achieved a < 15 e − analog noise and a 200 e − minimum threshold for digital readout per pixel. The sensor is capable of detecting both electrons and ions drifting in gas. These characteristics enable its use as the charge readout device in future Time Projection Chambers without gaseous gain mechanism, which has unique advantages in low background and low rate-density experiments.
Researches show that chronic viral infection and persistent antigen and/or inflammatory signal exposure in cancer causes the functional status of T cells to be altered, mainly by major changes in the epigenetic and metabolic environment, which then leads to T cell exhaustion. The discovery of the immune checkpoint pathway is an important milestone in understanding and reversing T cell exhaustion. Antibodies targeting these pathways have shown superior ability to reverse T cell exhaustion. However, there are still some limitations in immune checkpoint blocking therapy, such as the short-term nature of therapeutic effects and high individual heterogeneity. Assay for transposase-accessible chromatin with sequencing(ATAC-seq) is a method used to analyze the accessibility of whole-genome chromatin. It uses hyperactive Tn5 transposase to assess chromatin accessibility. Recently, a growing number of studies have reported that ATAC-seq can be used to characterize the dynamic changes of epigenetics in the process of T cell exhaustion. It has been determined that immune checkpoint blocking can only temporarily restore the function of exhausted T cells because of an irreversible change in the epigenetics of exhausted T cells. In this study, we review the latest developments, which provide a clearer molecular understanding of T cell exhaustion, reveal potential new therapeutic targets for persistent viral infection and cancer, and provide new insights for designing effective immunotherapy for treating cancer and chronic infection.
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