Suppression of MAPK11 or HIPK3 reduces mutant Huntingtin levels in Huntington's disease models.

Most neurodegenerative disorders are associated with accumulation of disease-relevant proteins. Among them, Huntington disease (HD) is of particular interest because of its monogenetic nature. HD is mainly caused by cytotoxicity of the defective protein encoded by the mutant Huntingtin gene (HTT). Thus, lowering mutant HTT protein (mHTT) levels would be a promising treatment strategy for HD. Here we report two kinases HIPK3 and MAPK11 as positive modulators of mHTT levels both in cells and in vivo. Both kinases regulate mHTT via their kinase activities, suggesting that inhibiting these kinases may have therapeutic values. Interestingly, their effects on HTT levels are mHTT-dependent, providing a feedback mechanism in which mHTT enhances its own level thus contributing to mHTT accumulation and disease progression. Importantly, knockout of MAPK11 significantly rescues disease-relevant behavioral phenotypes in a knockin HD mouse model. Collectively, our data reveal new therapeutic entry points for HD and target-discovery approaches for similar diseases

Protection of Dietary Polyphenols against Oral Cancer

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An Improved and Privacy-Preserving Mutual Authentication Scheme with Forward Secrecy in VANETs

Vehicular ad hoc network (VANETs) plays a major part in intelligent transportation to enhance traffic efficiency and safety. Security and privacy are the essential matters needed to be tackled due to the open communication channel. Most of the existing schemes only provide message authentication without identity authentication, especially the inability to support forward secrecy which is a major security goal of authentication schemes. In this article, we propose a privacy-preserving mutual authentication scheme with batch verification for VANETs which support both message authentication and identity authentication. More importantly, the proposed scheme achieves forward secrecy, which means the exposure of the shared key will not compromise the previous interaction. The security proof shows that our scheme can withstand various known security attacks, such as the impersonation attack and forgery attack. The experiment analysis results based on communication and computation cost demonstrate that our scheme is more efficient compared with the related schemes

Crystal growth and spectral properties of Nd3+/Er3+: CaLaAl0.6Ga2.4O7 crystal for a 2.7 mu m laser

Nd3+/Er3+: CaLaAl0.6Ga2.4O7 (abbr. as Nd3+/Er3+: CLAGO) crystal was firstly grown by Czochralski method. The 2.7 mu m fluorescence emission properties and energy transfer mechanism of this crystal were investigated. Besides better absorption characteristic, the spectra of Nd3+/Er3+: CLAGO show much weaker near-infrared emission as well as superior mid-infrared emission in comparison to Er3+: CLGO. Furthermore, the self-termination bottleneck for Er-3(+) 2.7 mu m laser was greatly decreased in Nd3+/Er3+: CLAGO crystal and the energy transfer efficiencies of Nd3+: F-4(3/2) -> Er3+: I-4(11/2) and EP + : I-4(13/2) -> Nd3+: I-4(15/2) were determined. In the best case, the above four advantages indicate that the Nd3+/Er3+: CLAGO crystal might be suitable for pulsed operation and a promising 2.7 mu m laser medium

Rayleigh Lidar Signal Denoising Method Combined with WT, EEMD and LOWESS to Improve Retrieval Accuracy

Lidar is an active remote sensing technology that has many advantages, but the echo lidar signal is extremely susceptible to noise and complex atmospheric environment, which affects the effective detection range and retrieval accuracy. In this paper, a wavelet transform (WT) and locally weighted scatterplot smoothing (LOWESS) based on ensemble empirical mode decomposition (EEMD) for Rayleigh lidar signal denoising was proposed. The WT method was used to remove the noise in the signal with a signal-to-noise ratio (SNR) higher than 16 dB. The EEMD method was applied to decompose the remaining signal into a series of intrinsic modal functions (IMFs), and then detrended fluctuation analysis (DFA) was conducted to determine the threshold for distinguishing whether noise or signal was the main component of the IMFs. Moreover, the LOWESS method was adopted to remove the noise in the IMFs component containing the signal, and thus, finely extract the signal. The simulation results showed that the denoising effect of the proposed WT-EEMD-LOWESS method was superior to EEMD-WT, EEMD-SVD and VMD-WOA. Finally, the use of WT-EEMD-LOWESS on the measured lidar signal led to significant improvement in retrieval accuracy. The maximum error of density and temperature retrievals was decreased from 1.36% and 125.79 K to 1.1% and 13.84 K, respectively

Rayleigh Lidar Signal Denoising Method Combined with WT, EEMD and LOWESS to Improve Retrieval Accuracy

Lidar is an active remote sensing technology that has many advantages, but the echo lidar signal is extremely susceptible to noise and complex atmospheric environment, which affects the effective detection range and retrieval accuracy. In this paper, a wavelet transform (WT) and locally weighted scatterplot smoothing (LOWESS) based on ensemble empirical mode decomposition (EEMD) for Rayleigh lidar signal denoising was proposed. The WT method was used to remove the noise in the signal with a signal-to-noise ratio (SNR) higher than 16 dB. The EEMD method was applied to decompose the remaining signal into a series of intrinsic modal functions (IMFs), and then detrended fluctuation analysis (DFA) was conducted to determine the threshold for distinguishing whether noise or signal was the main component of the IMFs. Moreover, the LOWESS method was adopted to remove the noise in the IMFs component containing the signal, and thus, finely extract the signal. The simulation results showed that the denoising effect of the proposed WT-EEMD-LOWESS method was superior to EEMD-WT, EEMD-SVD and VMD-WOA. Finally, the use of WT-EEMD-LOWESS on the measured lidar signal led to significant improvement in retrieval accuracy. The maximum error of density and temperature retrievals was decreased from 1.36% and 125.79 K to 1.1% and 13.84 K, respectively