445 research outputs found

    Simultaneous profiling of transcriptome and DNA methylome from a single cell.

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    BackgroundSingle-cell transcriptome and single-cell methylome technologies have become powerful tools to study RNA and DNA methylation profiles of single cells at a genome-wide scale. A major challenge has been to understand the direct correlation of DNA methylation and gene expression within single-cells. Due to large cell-to-cell variability and the lack of direct measurements of transcriptome and methylome of the same cell, the association is still unclear.ResultsHere, we describe a novel method (scMT-seq) that simultaneously profiles both DNA methylome and transcriptome from the same cell. In sensory neurons, we consistently identify transcriptome and methylome heterogeneity among single cells but the majority of the expression variance is not explained by proximal promoter methylation, with the exception of genes that do not contain CpG islands. By contrast, gene body methylation is positively associated with gene expression for only those genes that contain a CpG island promoter. Furthermore, using single nucleotide polymorphism patterns from our hybrid mouse model, we also find positive correlation of allelic gene body methylation with allelic expression.ConclusionsOur method can be used to detect transcriptome, methylome, and single nucleotide polymorphism information within single cells to dissect the mechanisms of epigenetic gene regulation

    The mechanical stimulation of myotubes counteracts the effects of tumor-derived factors through the modulation of the activin/follistatin ratio

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    Activin negatively affects muscle fibers and progenitor cells in aging (sarcopenia) and in chronic diseases characterized by severe muscle wasting (cachexia). High circulating activin levels predict poor survival in cancer patients. However, the relative impact of activin in mediating muscle atrophy and hampered homeostasis is still unknown. To directly assess the involvement of activin, and its physiological inhibitor follistatin, in cancer-induced muscle atrophy, we cultured C2C12 myotubes in the absence or in the presence of a mechanical stretching stimulus and in the absence or presence of C26 tumor-derived factors (CM), so as to mimic the mechanical stimulation of exercise and cancer cachexia, respectively. We found that CM induces activin release by myotubes, further exacerbating the negative effects of tumor-derived factors. In addition, mechanical stimulation is sufficient to counteract the adverse tumor-induced effects on muscle cells, in association with an increased follistatin/activin ratio in the cell culture medium, indicating that myotubes actively release follistatin upon stretching. Recombinant follistatin counteracts tumor effects on myotubes exclusively by rescuing fusion index, suggesting that it is only partially responsible for the stretch-mediated rescue. Therefore, besides activin, other tumor-derived factors may play a significant role in mediating muscle atrophy. In addition to increasing follistatin secretion mechanical stimulation induces additional beneficial responses in myotubes. We propose that in animal models of cancer cachexia and in cancer patients purely mechanical stimuli play an important role in mediating the rescue of the muscle homeostasis reported upon exercise

    Multi-objective integrated robust H∞ control for attitude tracking of a flexible spacecraft

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    This paper investigates the multi-objective attitude tracking problem of a flexible spacecraft in the presence of disturbances, parameter uncertainties and imprecise collocation of sensors and actuators. An integrated robust H∞ controller, including an output feedback component and a feedforward component, is proposed, and its gains are calculated by solving Linear Matrix Inequalities. The output feedback component stabilizes the integrated control system while the feedforward component can drive the attitude motion to track the desired angles. The system robustness against disturbances, parameter uncertainties and imprecise collocation is addressed by the H∞ approach and convex optimization. Numerical simulations are finally provided to assess the performance of the proposed controller

    Determination of the downwelling diffuse attenuation coefficient of lakewater with the sentinel-3A OLCI

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    The Ocean and Land Color Imager (OLCI) on the Sentinel-3A satellite, which was launched by the European Space Agency in 2016, is a new-generation water color sensor with a spatial resolution of 300 m and 21 bands in the range of 400-1020 nm. The OLCI is important to the expansion of remote sensing monitoring of inland waters using water color satellite data. In this study, we developed a dual band ratio algorithm for the downwelling diffuse attenuation coefficient at 490 nm (Kd(490)) for the waters of Lake Taihu, a large shallow lake in China, based on data measured during seven surveys conducted between 2008 and 2017 in combination with Sentinel-3A-OLCI data. The results show that: (1) Compared to the available Kd(490) estimation algorithms, the dual band ratio (681 nm/560 nm and 754 nm/560 nm) algorithm developed in this study had a higher estimation accuracy (N = 26, coefficient of determination (R2) = 0.81, root-mean-square error (RMSE) = 0.99m-1and mean absolute percentage error (MAPE) = 19.55%) and validation accuracy (N = 14, R2= 0.83, RMSE = 1.06 m-1and MAPE = 27.30%), making it more suitable for turbid inland waters; (2) A comparison of the OLCI Kd(490) product and a similar Moderate Resolution Imaging Spectroradiometer (MODIS) product reveals a high consistency between the OLCI and MODIS products in terms of the spatial distribution of Kd(490). However, the OLCI product has a smoother spatial distribution and finer textural characteristics than the MODIS product and contains notably higher-quality data; (3) The Kd(490) values for Lake Taihu exhibit notable spatial and temporal variations. Kd(490) is higher in seasons with relatively high wind speeds and in open waters that are prone to wind- and wave-induced sediment resuspension. Finally, the Sentinel-3A-OLCI has a higher spatial resolution and is equipped with a relatively wide dynamic range of spectral bands suitable for inland waters. The Sentinel-3B satellite will be launched soon and, together with the Sentinel-3A satellite, will form a two-satellite network with the ability to make observations twice every three days. This satellite network will have a wider range of application and play an important role in the monitoring of inland waters with complex optical properties

    Transfer Learning for Motor Imagery Based Brain-Computer Interfaces: A Complete Pipeline

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    Transfer learning (TL) has been widely used in motor imagery (MI) based brain-computer interfaces (BCIs) to reduce the calibration effort for a new subject, and demonstrated promising performance. While a closed-loop MI-based BCI system, after electroencephalogram (EEG) signal acquisition and temporal filtering, includes spatial filtering, feature engineering, and classification blocks before sending out the control signal to an external device, previous approaches only considered TL in one or two such components. This paper proposes that TL could be considered in all three components (spatial filtering, feature engineering, and classification) of MI-based BCIs. Furthermore, it is also very important to specifically add a data alignment component before spatial filtering to make the data from different subjects more consistent, and hence to facilitate subsequential TL. Offline calibration experiments on two MI datasets verified our proposal. Especially, integrating data alignment and sophisticated TL approaches can significantly improve the classification performance, and hence greatly reduces the calibration effort

    Inversion of inherent optical properties in optically complex waters using sentinel-3A/OLCI images: A case study using China\u27s three largest freshwater lakes

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    Inherent optical properties (IOPs) play an important role in underwater light field, and are difficult to estimate accurately using satellite data in optically complex waters. To study water quality in appropriate temporal and spatial scales, it is necessary to develop methods to obtain IOPs form space-based observation with quantified uncertainties. Field-measured IOP data (N = 405) were collected from 17 surveys between 2011 and 2017 in the three major largest freshwater lakes of China (Lake Chaohu, Lake Taihu, and Lake Hongze) in the lower reaches of the Yangtze River and Huai River (LYHR). Here we provide a case-study on how to use in-situ observation of IOPs to devise an improved algorithm for retrieval of IOPs. We then apply this algorithm to observation with Sentinel-3A OLCI (Ocean and Land Colour Instrument, corrected with our improved AC scheme), and use in-situ data to show that the algorithm performs better than the standard OLCI IOP product. We use the satellite derived products to study the spatial and seasonal distributions of IOPs and concentrations of optically active constituents in these three lakes, including chlorophyll-a (Chla) and suspended particulate matter (SPM), using all cloud-free OLCI images (115 scenes) over the lakes in the LYHR basin in 2017. Our study provides a strategy for using local and remote observations to obtain important water quality parameters necessary to manage resources such as reservoirs, lakes and coastal waters

    Flexible Control Strategy for Grid-Connected Inverter under Unbalanced Grid Faults without PLL

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