Activation of p53-regulated pro-apoptotic signaling pathways in PrP-mediated myopathy

<p>Abstract</p> <p>Background</p> <p>We have reported that doxycycline-induced over-expression of wild type prion protein (PrP) in skeletal muscles of Tg(HQK) mice is sufficient to cause a primary myopathy with no signs of peripheral neuropathy. The preferential accumulation of the truncated PrP C1 fragment was closely correlated with these myopathic changes. In this study we use gene expression profiling to explore the temporal program of molecular changes underlying the PrP-mediated myopathy.</p> <p>Results</p> <p>We used DNA microarrays, and confirmatory real-time PCR and Western blot analysis to demonstrate deregulation of a large number of genes in the course of the progressive myopathy in the skeletal muscles of doxycycline-treated Tg(HQK) mice. These include the down-regulation of genes coding for the myofibrillar proteins and transcription factor MEF2c, and up-regulation of genes for lysosomal proteins that is concomitant with increased lysosomal activity in the skeletal muscles. Significantly, there was prominent up-regulation of p53 and p53-regulated genes involved in cell cycle arrest and promotion of apoptosis that paralleled the initiation and progression of the muscle pathology.</p> <p>Conclusion</p> <p>The data provides the first <it>in vivo </it>evidence that directly links p53 to a wild type PrP-mediated disease. It is evident that several mechanistic features contribute to the myopathy observed in PrP over-expressing mice and that p53-related apoptotic pathways appear to play a major role.</p

MM-Fi: Multi-Modal Non-Intrusive 4D Human Dataset for Versatile Wireless Sensing

4D human perception plays an essential role in a myriad of applications, such as home automation and metaverse avatar simulation. However, existing solutions which mainly rely on cameras and wearable devices are either privacy intrusive or inconvenient to use. To address these issues, wireless sensing has emerged as a promising alternative, leveraging LiDAR, mmWave radar, and WiFi signals for device-free human sensing. In this paper, we propose MM-Fi, the first multi-modal non-intrusive 4D human dataset with 27 daily or rehabilitation action categories, to bridge the gap between wireless sensing and high-level human perception tasks. MM-Fi consists of over 320k synchronized frames of five modalities from 40 human subjects. Various annotations are provided to support potential sensing tasks, e.g., human pose estimation and action recognition. Extensive experiments have been conducted to compare the sensing capacity of each or several modalities in terms of multiple tasks. We envision that MM-Fi can contribute to wireless sensing research with respect to action recognition, human pose estimation, multi-modal learning, cross-modal supervision, and interdisciplinary healthcare research.Comment: The paper has been accepted by NeurIPS 2023 Datasets and Benchmarks Track. Project page: https://ntu-aiot-lab.github.io/mm-f

Optical coherence tomography biomarkers as predictors of transition to chronic central serous chorioretinopathy after retinal laser photocoagulation

Objectives: To explore the optical coherence tomography (OCT) biomarkers to predict the transition to chronic central serous chorioretinopathy (cCSC) after retinal laser photocoagulation. Methods: Patients enrolled in this study were from a 12-week clinical trial comparing the efficacy and safety of subthreshold micropulse laser (SML) with threshold conventional laser (TCL) for CSC and had extended follow-up for more than 1 year. They were divided into two groups, transited to cCSC group (cCSC group) and did not transited to cCSC group (non-cCSC group) according to fundus examination at the extended follow-up. Collect the best-corrected visual acuity (BCVA) and OCT characteristics of patients at baseline and 12 weeks after laser treatment. Results: Twenty-seven patients were enrolled (42.6 ± 7.7 years old), and duration of follow-up was 178.9 ± 88.8 (57.0–312.0) weeks. Nine patients (33.3%) were assigned to cCSC group, and the other 18 patients (66.7%) were assigned to the non-cCSC group. Twelve weeks after the laser treatment, subretinal fluid (SRF) of 15 patients (83.3%) in non-cCSC group and 5 patients (55.6%) in cCSC group absorbed completely; the height of SRF had statistical difference between two groups ( p  = 0.035); rough RPE was less common in cCSC group ( p  = 0.030); hyper reflective mass (HRM) was more common in cCSC group ( p  = 0.024); more number of hyper reflective foci (HRF) in outer segment of photoreceptor layer were detected in cCSC group ( p  = 0.035). From baseline to 12 weeks after laser treatment, the number of HRF in outer segment photoreceptor layer did not change significantly in cCSC group ( p  = 0.665) but decreased significantly in non-cCSC group ( p  = 0.000). A total of five patients suffered binocular CSC, three of them in the non-cCSC group occurred later than the other two in the cCSC group (129.9–278.3 weeks vs 96.1–114.9 weeks after baseline). Conclusion: SRF, rough RPE, HRM, and number of HRF in outer segment photoreceptor layer 12 weeks after laser treatment, and change in the number of HRF in outer segment photoreceptor layer from baseline to 12 weeks after laser treatment may predict the transition to cCSC

Label-free optical-resolution photoacoustic microscopy of superficial microvasculature using a compact visible laser diode excitation

We have developed laser-diode-based optical-resolution photoacoustic microscopy (LD-OR-PAM) of superficial microvasculature which has the desirable properties of being compact, low-cost, and label-free. A 300-mW visible pulsed laser diode was operated at a 405 ± 5 nm wavelength with a pulse energy as low as 52 nJ. By using a 3.6 MHz ultrasound transducer, the system was tested on carbon fibers with a lateral resolution of 0.95 µm and an SNR of 38 dB. The subcutaneous microvasculature on a mouse back was imaged without an exogenous contrast agent which demonstrates the potential of the proposed prototype for skin chromophores. Our eventual goal is to offer a practical and affordable multi-wavelength functional LD-OR-PAM instrument suitable for clinical applications

Numerical Study on the Yaw Control for Two Wind Turbines under Different Spacings

In this study, the large eddy simulation method and the actuator line model are used to investigate the wake redirection of two turbines. Different turbine spacings and yaw-based control of the upstream turbine are considered. The effects of yaw angle and turbine spacing on the output power of two turbines are comprehensively analyzed, and the physical mechanisms of the wake deficit, deflection and interaction are revealed from the distributions of the wake velocity, turbulence intensity and the structures of wake vortices. The results show that the overall power of two turbines is related to the yaw angle of the upstream turbine and the spacing between two turbines. We find yaw angle is the dominant factor in the total power improvement compared to turbine spacing. Still, a large yaw angle causes significant power fluctuations of the downstream turbine. The deficit of wake velocity and the change of output power are determined by the characteristics of the wake flow field, which the yaw control regulates