An intelligent second-order sliding-mode control (I2OSMC) using a wavelet fuzzy neural network with an asymmetric membership function (WFNN-AMF) estimator is proposed in this study to control a ...six-phase permanent magnet synchronous motor (PMSM) for an electric power steering (EPS) system. First, the dynamics of the steer-by-wire (SBW) EPS system and six-phase PMSM drive system with a lumped uncertainty are described in detail. Then, to alleviate the chattering phenomena in a traditional sliding-mode control (SMC), a second-order sliding-mode control (2OSMC) is designed. Moreover, the I2OSMC is developed to improve the required control performance of the EPS system. In the I2OSMC, the WFNN-AMF estimator with accurate approximation capability is employed to estimate the lumped uncertainty. Furthermore, the adaptive learning algorithms for the online training of the WFNN-AMF are derived using the Lyapunov theorem to guarantee the asymptotical stability of the closed-loop system. In addition, a 32-bit floating-point digital signal processor (DSP), i.e., TMS320F28335, is adopted for the implementation of the proposed control approach. Finally, some experimental results are illustrated to demonstrate the validity of the proposed I2OSMC using the WFNN-AMF estimator for the EPS system.
Amyotrophic lateral sclerosis (ALS) is a devastating disorder in which motor neurons degenerate, the causes of which remain unclear. In particular, the basis for selective vulnerability of spinal ...motor neurons (sMNs) and resistance of ocular motor neurons to degeneration in ALS has yet to be elucidated. Here, we applied comparative multi-omics analysis of human induced pluripotent stem cell-derived sMNs and ocular motor neurons to identify shared metabolic perturbations in inherited and sporadic ALS sMNs, revealing dysregulation in lipid metabolism and its related genes. Targeted metabolomics studies confirmed such findings in sMNs of 17 ALS (SOD1, C9ORF72, TDP43 (TARDBP) and sporadic) human induced pluripotent stem cell lines, identifying elevated levels of arachidonic acid. Pharmacological reduction of arachidonic acid levels was sufficient to reverse ALS-related phenotypes in both human sMNs and in vivo in Drosophila and SOD1
mouse models. Collectively, these findings pinpoint a catalytic step of lipid metabolism as a potential therapeutic target for ALS.
A wavelet fuzzy neural network using asymmetric membership function (WFNN-AMF) with improved differential evolution (IDE) algorithm is proposed in this study to control a six-phase permanent magnet ...synchronous motor (PMSM) for an electric power steering (EPS) system. First, the dynamics of a steer-by-wire EPS system and a six-phase PMSM drive system are described in detail. Moreover, the WFNN-AMF controller, which combines the advantages of wavelet decomposition, fuzzy logic system, and asymmetric membership function (AMF), is developed to achieve the required control performance of the EPS system for the improvement of stability of the vehicle and the comfort of the driver. Furthermore, the online learning algorithm of WFNN-AMF is derived using back-propagation method. However, degenerated or diverged responses will be resulted due to the inappropriate selection of small or large learning rates of the WFNN-AMF. Therefore, an IDE algorithm is proposed to online adapt the learning rates of WFNN-AMF. In addition, a 32-bit floating-point digital signal processor, TMS320F28335, is adopted for the implementation of the proposed intelligent controlled EPS system. Finally, the feasibility of the proposed WFNN-AMF controller with IDE for the EPS system is verified through experimental results.
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•The extraction of multi-class components was performed using bio-derived solvents.•Ethyl lactate (24.7%) can efficiently extract both polysaccharides and phenolics.•Ethyl lactate ...based salt-responsive system possess tailorable enrichment effects.•Ethyl lactate based responsive ultrasound-assisted extraction method was developed.•These new findings holds substantial theoretical and practical implications.
The utilization of bio-derived solvents holds immense promise in the extraction of natural products. In the present study, a systematic evaluation was conducted to assess the performance of bio-derived solvents in simultaneously extracting polysaccharides and phenolic substances from Carthamus tinctorius L. flower. Among them, ethyl lactate (24.7%) exhibited superior efficacy. A comprehensive investigation was also conducted on the salt response behavior of ethyl lactate and its in-situ enrichment efficiency for polysaccharides and phenolics, demonstrating that the recovery yield, enrichment factor, and separation factor can be finely tuned by manipulating the system composition. Based on these findings, we have developed a highly efficient ultrasound-assisted method that is responsive to salt and enables simultaneous extraction and in situ enrichment of polysaccharides and phenolics. In comparison with the method in Chinese Pharmacopoeia (2020), the extraction yield of Carthamus tinctorius L. flower quality markers is increased by more than 1.14 times, while the extraction time is shortened by over 4 times. Additionally, the amount of solvent used is reduced by a factor of 5.73, eliminating the need for methanol and corrosive HCl that are harmful to the environment. The findings of this study will provide crucial theoretical guidance for the application of bio-derived solvents, demonstrating significant potential in terms of quality control and large-scale preparation of natural medicines.
Gliomas are highly malignant brain tumors with poor prognosis and short survival. NAD
has been shown to impact multiple processes that are dysregulated in cancer; however, anti-cancer therapies ...targeting NAD
synthesis have had limited success due to insufficient mechanistic understanding. Here, we adapted a
glial neoplasia model and discovered the genetic requirement for NAD
synthase nicotinamide mononucleotide adenylyltransferase (NMNAT) in glioma progression in vivo and in human glioma cells. Overexpressing enzymatically active NMNAT significantly promotes glial neoplasia growth and reduces animal viability. Mechanistic analysis suggests that NMNAT interferes with DNA damage-p53-caspase-3 apoptosis signaling pathway by enhancing NAD
-dependent posttranslational modifications (PTMs) poly(ADP-ribosyl)ation (PARylation) and deacetylation of p53. Since PARylation and deacetylation reduce p53 pro-apoptotic activity, modulating p53 PTMs could be a key mechanism by which NMNAT promotes glioma growth. Our findings reveal a novel tumorigenic mechanism involving protein complex formation of p53 with NAD
synthetic enzyme NMNAT and NAD
-dependent PTM enzymes that regulates glioma growth.
Traffic light control plays a crucial role in intelligent transportation systems. This paper introduces Temporal Difference-Aware Graph Convolutional Reinforcement Learning (TeDA-GCRL), a ...decentralized RL-based method for efficient multi-intersection traffic signal control. Specifically, we put forward a new graph architecture using each lane as a node for considering intersection relations. Additionally, we propose two new rewards by considering temporal information, namely Temporal-Aware Pressure on Incoming Lanes (TAPIL) and Temporal-Aware Action Consistency (TAAC), which enhance learning efficiency and time-interval sensitivity. Experimental results on five datasets show the superiority of TeDA-GCRL over state-of-the-art methods by at least 9.5% in average travel time.
Recently, facial expression recognition techniques have made significant progress on high-resolution web images. However, in real-world applications, the obtained images are often with low resolution ...since they are mostly captured in a wide range of public spaces. As a result, the ambiguity of the expression labels hinders recognition performance due to not only subjective emotion annotations but also ambiguous images. Existing approaches tend to perform poorly when the resolution of face images decreases. In this work, we aim to model the aleatoric uncertainty induced by low-image-resolution and label ambiguity for robust facial expression recognition. We propose probabilistic data uncertainty learning to capture the ambiguity induced by poor image resolution. Additionally, we introduce the emotion wheel to learn the label-uncertainty-aware embedding. Moreover, we exploit the ambiguous nature of neutrality and propose a neutral expression constraint to learn more robust features for facial expression recognition. To the best of our knowledge, this is the first work utilizing the intrinsic nature of neutrality as a regularization to benefit model training. Extensive experimental results show the effectiveness and robustness of our approach. Under low-resolution conditions, our proposed method outperforms the state-of-the-art approaches by 3.02% and 3.16% in terms of accuracy on RAF-DB and FERPlus, respectively.
Tauopathies, including Alzheimer's disease, are a group of neurodegenerative diseases characterized by abnormal tau hyperphosphorylation that leads to formation of neurofibrillary tangles. Drosophila ...models of tauopathy display prominent features of the human disease including compromised lifespan, impairments of learning, memory and locomotor functions and age-dependent neurodegeneration visible as vacuolization. Here, we use a Drosophila model of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), in order to study the neuroprotective capacity of a recently identified neuronal maintenance factor, nicotinamide mononucleotide (NAD) adenylyl transferase (NMNAT), a protein that has both NAD synthase and chaperone function. NMNAT is essential for maintaining neuronal integrity under normal conditions and has been shown to protect against several neurodegenerative conditions. However, its protective role in tauopathy has not been examined. Here, we show that overexpression of NMNAT significantly suppresses both behavioral and morphological deficits associated with tauopathy by means of reducing the levels of hyperphosphorylated tau oligomers. Importantly, the protective activity of NMNAT protein is independent of its NAD synthesis activity, indicating a role for direct protein-protein interaction. Next, we show that NMNAT interacts with phosphorylated tau in vivo and promotes the ubiquitination and clearance of toxic tau species. Consequently, apoptosis activation was significantly reduced in brains overexpressing NMNAT, and neurodegeneration was suppressed. Our report on the molecular basis of NMNAT-mediated neuroprotection in tauopathies opens future investigation of this factor in other protein foldopathies.
Nicotinamide mononucleotide adenylyltransferase (NMNAT) is a conserved enzyme in the NAD synthetic pathway. It has also been identified as an effective and versatile neuroprotective factor. However, ...it remains unclear how healthy neurons regulate the dual functions of NMNAT and achieve self-protection under stress. Here we show that Drosophila Nmnat (DmNmnat) is alternatively spliced into two mRNA variants, RA and RB, which translate to protein isoforms with divergent neuroprotective capacities against spinocerebellar ataxia 1-induced neurodegeneration. Isoform PA/PC translated from RA is nuclear-localized with minimal neuroprotective ability, and isoform PB/PD translated from RB is cytoplasmic and has robust neuroprotective capacity. Under stress, RB is preferably spliced in neurons to produce the neuroprotective PB/PD isoforms. Our results indicate that alternative splicing functions as a switch that regulates the expression of functionally distinct DmNmnat variants. Neurons respond to stress by driving the splicing switch to produce the neuroprotective variant and therefore achieve self-protection.
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