Quantitative analysis reveals increased histone modifications and a broad nucleosome-free region bound by histone acetylases in highly expressed genes in human CD4+ T cells

AbstractGenome-wide mapping of nucleosomes and histone modifications revealed meaningful patterns. Despite advances in resolving the associations between chromatin and transcription, quantitative chromatin dynamics have not been well defined. We quantitatively determined differences in histone modifications, nucleosome positions, DNA methylation, and transcription factor binding in highly expressed and repressed genes in human CD4+ T cells. We showed that the first (−1) nucleosome upstream of the transcription start site (TSS) is shifted to the 5′ direction, thus forming a broad nucleosome-free region (NFR) near the TSS in highly expressed genes in CD4+ T cells. Moreover, the transcription factor YY1 and histone acetyltransferases bind the NFR with high affinity. Most of histone acetylations drastically increase in transcription activation (>5 folds). We also suggested that single nucleotide polymorphisms (SNPs) occur at a much lower frequency in highly expressed genes than in repressed genes. Our analysis quantitatively revealed details of chromatin dynamics

Dynamic Gradient Reactivation for Backward Compatible Person Re-identification

We study the backward compatible problem for person re-identification (Re-ID), which aims to constrain the features of an updated new model to be comparable with the existing features from the old model in galleries. Most of the existing works adopt distillation-based methods, which focus on pushing new features to imitate the distribution of the old ones. However, the distillation-based methods are intrinsically sub-optimal since it forces the new feature space to imitate the inferior old feature space. To address this issue, we propose the Ranking-based Backward Compatible Learning (RBCL), which directly optimizes the ranking metric between new features and old features. Different from previous methods, RBCL only pushes the new features to find best-ranking positions in the old feature space instead of strictly alignment, and is in line with the ultimate goal of backward retrieval. However, the sharp sigmoid function used to make the ranking metric differentiable also incurs the gradient vanish issue, therefore stems the ranking refinement during the later period of training. To address this issue, we propose the Dynamic Gradient Reactivation (DGR), which can reactivate the suppressed gradients by adding dynamic computed constant during forward step. To further help targeting the best-ranking positions, we include the Neighbor Context Agents (NCAs) to approximate the entire old feature space during training. Unlike previous works which only test on the in-domain settings, we make the first attempt to introduce the cross-domain settings (including both supervised and unsupervised), which are more meaningful and difficult. The experimental results on all five settings show that the proposed RBCL outperforms previous state-of-the-art methods by large margins under all settings.Comment: Submitted to Pattern Recognition on Dec 06, 2021. Under Revie

Repurposing Niclosamide as a Novel Anti-SARS-CoV-2 Drug by Restricting Entry Protein CD147

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic, and the search for effective treatments has been limited. Furthermore, the rapid mutations of SARS-CoV-2 have posed challenges to existing vaccines and neutralizing antibodies, as they struggle to keep up with the increased viral transmissibility and immune evasion. However, there is hope in targeting the CD147-spike protein, which serves as an alternative point for the entry of SARS-CoV-2 into host cells. This protein has emerged as a promising therapeutic target for the development of drugs against COVID-19. Here, we demonstrate that the RNA-binding protein Human-antigen R (HuR) plays a crucial role in the post-transcriptional regulation of CD147 by directly binding to its 3′-untranslated region (UTR). We observed a decrease in CD147 levels across multiple cell lines upon HuR depletion. Furthermore, we identified that niclosamide can reduce CD147 by lowering the cytoplasmic translocation of HuR and reducing CD147 glycosylation. Moreover, our investigation revealed that SARS-CoV-2 infection induces an upregulation of CD147 in ACE2-expressing A549 cells, which can be effectively neutralized by niclosamide in a dose-dependent manner. Overall, our study unveils a novel regulatory mechanism of regulating CD147 through HuR and suggests niclosamide as a promising therapeutic option against COVID-19

Measurement of the Near Field Distribution of a Microwave Horn Using a Resonant Atomic Probe

We measure the near field distribution of a microwave horn with a resonant atomic probe. The microwave field emitted by a standard microwave horn is investigated utilizing Rydberg electromagnetically inducted transparency (EIT), an all-optical Rydberg detection, in a room temperature caesium vapor cell. The ground 6S1/2 , excited 6P3/2 , and Rydberg 56D5/2 states constitute a three-level system, used as an atomic probe to detect microwave electric fields by analyzing microwave dressed Autler–Townes (AT) splitting. We present a measurement of the electric field distribution of the microwave horn operating at 3.99 GHz in the near field, coupling the transition 56D5/2→57P3/2 . The microwave dressed AT spectrum reveals information on both the strength and polarization of the field emitted from the microwave horn simultaneously. The measurements are compared with field measurements obtained using a dipole metal probe, and with simulations of the electromagnetic simulated software (EMSS). The atomic probe measurement is in better agreement with the simulations than the metal probe. The deviation from the simulation of measurements taken with the atomic probe is smaller than the metal probe, improving by 1.6 dB. The symmetry of the amplitude distribution of the measured field is studied by comparing the measurements taken on either side of the field maxima