A chalcone derivative reactivates latent HIV-1 transcription through activating P-TEFb and promoting Tat-SEC interaction on viral promoter.

The principal barrier to the eradication of HIV/AIDS is the existence of latent viral reservoirs. One strategy to overcome this barrier is to use latency-reversing agents (LRAs) to reactivate the latent proviruses, which can then be eliminated by effective anti-retroviral therapy. Although a number of LRAs have been found to reactivate latent HIV, they have not been used clinically due to high toxicity and poor efficacy. In this study, we report the identification of a chalcone analogue called Amt-87 that can significantly reactivate the transcription of latent HIV provirses and act synergistically with known LRAs such as prostratin and JQ1 to reverse latency. Amt-87 works by activating the human transcriptional elongation factor P-TEFb, a CDK9-cyclin T1 heterodimer that is part of the super elongation complex (SEC) used by the viral encoded Tat protein to activate HIV transcription. Amt-87 does so by promoting the phosphorylation of CDK9 at the T-loop, liberating P-TEFb from the inactive 7SK snRNP, and inducing the formation of the Tat-SEC complex at the viral promoter. Together, our data reveal chalcones as a promising category of compounds that should be further explored to identify effective LRAs for targeted reversal of HIV latency

Neural Volumetric Mesh Generator

Deep generative models have shown success in generating 3D shapes with different representations. In this work, we propose Neural Volumetric Mesh Generator(NVMG) which can generate novel and high-quality volumetric meshes. Unlike the previous 3D generative model for point cloud, voxel, and implicit surface, the volumetric mesh representation is a ready-to-use representation in industry with details on both the surface and interior. Generating this such highly-structured data thus brings a significant challenge. We first propose a diffusion-based generative model to tackle this problem by generating voxelized shapes with close-to-reality outlines and structures. We can simply obtain a tetrahedral mesh as a template with the voxelized shape. Further, we use a voxel-conditional neural network to predict the smooth implicit surface conditioned on the voxels, and progressively project the tetrahedral mesh to the predicted surface under regularizations. The regularization terms are carefully designed so that they can (1) get rid of the defects like flipping and high distortion; (2) force the regularity of the interior and surface structure during the deformation procedure for a high-quality final mesh. As shown in the experiments, our pipeline can generate high-quality artifact-free volumetric and surface meshes from random noise or a reference image without any post-processing. Compared with the state-of-the-art voxel-to-mesh deformation method, we show more robustness and better performance when taking generated voxels as input

Psychological Stress Induces Temporary Masticatory Muscle Mechanical Sensitivity in Rats

To explore the relationship between psychological stress and masticatory muscle pain, we created a communication stress animal model to determine whether psychological stress could induce increased mechanical sensitivity in masticatory muscles and to study the changes of mechanical nociceptive thresholds after stress removal. Forty-eight male Sprague-Dawley rats were divided into a control group (CON), a foot-shocked group (FS, including 3 subgroups recorded as FS-1, FS-2, and FS-3), a psychological stress group (PS), and a drug treatment group (DT). PS and DT rats were confined in a communication box for one hour a day to observe the psychological responses of neighboring FS rats.Measurements of the mechanical nociceptive thresholds of the bilateral temporal and masseter muscles showed a stimulus-response relationship between psychological stress and muscle mechanical sensitivity. The DT rats, who received a diazepam injection, showed almost the same mechanical sensitivity of the masticatory muscles to that of the control in response to psychological stress. Fourteen days after the psychological stressor was removed, the mechanical nociceptive thresholds returned to normal. These findings suggest that psychological stress is directly related to masticatory muscle pain. Removal of the stressor could be a useful method for relieving mechanical sensitivity increase induced by psychological stress

5 GHz TMRT observations of 71 pulsars

We present integrated pulse profiles at 5~GHz for 71 pulsars, including eight millisecond pulsars (MSPs), obtained using the Shanghai Tian Ma Radio Telescope (TMRT). Mean flux densities and pulse widths are measured. For 19 normal pulsars and one MSP, these are the first detections at 5~GHz and for a further 19, including five MPSs, the profiles have a better signal-to-noise ratio than previous observations. Mean flux density spectra between 400~MHz and 9~GHz are presented for 27 pulsars and correlations of power-law spectral index are found with characteristic age, radio pseudo-luminosity and spin-down luminosity. Mode changing was detected in five pulsars. The separation between the main pulse and interpulse is shown to be frequency independent for six pulsars but a frequency dependence of the relative intensity of the main pulse and interpulse is found. The frequency dependence of component separations is investigated for 20 pulsars and three groups are found: in seven cases the separation between the outmost leading and trailing components decreases with frequency, roughly in agreement with radius-to-frequency mapping; in eleven cases the separation is nearly constant; in the remain two cases the separation between the outmost components increases with frequency. We obtain the correlations of pulse widths with pulsar period and estimate the core widths of 23 multi-component profiles and conal widths of 17 multi-component profiles at 5.0~GHz using Gaussian fitting and discuss the width-period relationship at 5~GHz compared with the results at at 1.0~GHz and 8.6~GHz.Comment: 46 pages, 14 figures, 8 Tables, accepted by Ap

Experimental Decoy Quantum Key Distribution Up To 130KM Fiber

Decoy State Quantum Key Distribution (QKD), being capable of beating PNS attack and uncon- ditionally secure, have become an attractive one recently. But, in many QKD systems, disturbances of transmission channel make quantum bit error rate (QBER) increase which limits both security distance and key bit rate of real-life decoy state QKD systems. We demonstrate the two-intensity decoy QKD with one-way Faraday-Michelson phase modulation system, which is free of channel dis- turbance and keeps interference fringe visibility (99%) long period, near 130KM single mode optical fiber in telecom (1550 nm) wavelength. This is longest distance fiber decoy state QKD system based on two intensity protocol.Comment: 4 pages, 2figure