Gravesenguthrie8199

In this work, pattern recognition and characterization of the neuromuscular dynamics of driver upper limb during naturalistic driving were studied. During the human-in-the-loop experiments, two steering tasks, namely, the passive and active steering tasks, were instructed to be completed by the subjects. Furthermore, subjects manipulated the steering wheel with two distinct postures and six different hand positions. GSK-3484862 research buy The neuromuscular dynamics of subjects' upper limb were measured using electromyogram signals, and the behavioral data, including the steering torque and steering angle, were also collected. Based on the experimental data, patterns of muscle activities during naturalistic driving were investigated. The correlations, amplitudes, and responsiveness of the electromyogram signals, as well as the smoothness and regularity of the steering torque were discussed. The results reveal the mechanisms of neuromuscular dynamics of driver upper limb and provide a theoretical foundation for the design of the future human-machine interface for automated vehicles.Enhancer RNAs (eRNAs) are a subset of long noncoding RNA generated from genomic enhancers they are thought to act as potent promoters of the expression of nearby genes through interaction with the transcriptional and epigenomic machineries. In the present work, we describe two eRNAs transcribed from the enhancer of Nkx2-5-a gene specifying a master cardiomyogenic lineage transcription factor (TF)-which we call Intergenic Regulatory Element Nkx2-5 Enhancers (IRENEs). The IRENEs are encoded, respectively, on the same strand (SS) and in the divergent direction (div) respect to the nearby gene. Of note, these two eRNAs have opposing roles in the regulation of Nkx2-5 IRENE-SS acts as a canonical promoter of transcription, whereas IRENE-div represses the activity of the enhancer through recruitment of the histone deacetylase sirtuin 1. Thus, we have identified an autoregulatory loop controlling expression of the master cardiac TF NKX2-5, in which one eRNA represses transcription.The Chinese ginseng Panax notoginseng is a domesticated herb with significant medicinal and economic value. Here we report a chromosome-level P. notoginseng genome assembly with a high (∼79%) repetitive sequence content. The juxtaposition with the widely distributed, closely related Korean ginseng (Panax ginseng) genome revealed contraction of plant defense genes (in particular R-genes) in the P. notoginseng genome. We also investigated the reasons for the larger genome size of Panax species, revealing contributions from two Panax-specific whole-genome duplication events and transposable element expansion. Transcriptome data and comparative genome analysis revealed the candidate genes involved in the ginsenoside synthesis pathway. We also performed a genome-wide association study on 240 cultivated P. notoginseng individuals and identified the associated genes with dry root weight (63 genes) and stem thickness (168 genes). The P. notoginseng genome represents a critical step toward harnessing the full potential of an economically important and enigmatic plant.A major hurdle in the treatment of cancer is chemoresistance induced under hypoxia that is characteristic of tumor microenvironment. Triptolide, a potent inhibitor of eukaryotic transcription, possesses potent antitumor activity. However, its clinical potential has been limited by toxicity and water solubility. To address those limitations of triptolide, we designed and synthesized glucose-triptolide conjugates (glutriptolides) and demonstrated their antitumor activity in vitro and in vivo. Herein, we identified a lead, glutriptolide-2 with an altered linker structure. Glutriptolide-2 possessed improved stability in human serum, greater selectivity toward cancer over normal cells, and increased potency against cancer cells. Glutriptolide-2 exhibits sustained antitumor activity, prolonging survival in a prostate cancer metastasis animal model. Importantly, we found that glutriptolide-2 was more potent against cancer cells under hypoxia than normoxia. Together, this work provides an attractive glutriptolide drug lead and suggests a viable strategy to overcome chemoresistance through conjugation of cytotoxic agents to glucose.The role of lipid metabolism in human pluripotent stem cells (hPSCs) is poorly understood. We have used large-scale targeted proteomics to demonstrate that undifferentiated hPSCs express different fatty acid (FA) biosynthesis-related enzymes, including ATP citrate lyase and FA synthase (FASN), than those expressed in hPSC-derived cardiomyocytes (hPSC-CMs). Detailed lipid profiling revealed that inhibition of FASN resulted in significant reduction of sphingolipids and phosphatidylcholine (PC); moreover, we found that PC was the key metabolite for cell survival in hPSCs. Inhibition of FASN induced cell death in undifferentiated hPSCs via mitochondria-mediated apoptosis; however, it did not affect cell survival in hPSC-CMs, neurons, or hepatocytes as there was no significant reduction of PC. Furthermore, we did not observe tumor formation following transplantation of FASN inhibitor-treated cells. Our findings demonstrate the importance of de novo FA synthesis in the survival of undifferentiated hPSCs and suggest applications for FASN inhibition in regenerative medicine.Geological flows-from mudslides to volcanic eruptions-are often opaque and consist of multiple interacting phases. Scaled laboratory geological experiments using analog materials have often been limited to optical imaging of flow exteriors or ex situ measurements. Geological flows often include internal phase transitions and chemical reactions that are difficult to image externally. Thus, many physical mechanisms underlying geological flows remain unknown, hindering model development. We propose using magnetic resonance imaging (MRI) to enhance geosciences via non-invasive, in situ measurements of 3D flows. MRI is currently used to characterize the interior dynamics of multiphase flows, distinguishing between different chemical species as well as gas, liquid, and solid phases, while quantitatively measuring concentration, velocity, and diffusion fields. This perspective describes the potential of MRI techniques to image dynamics within scaled geological flow experiments and the potential of technique development for geological samples to be transferred to other disciplines utilizing MRI.