SCALE method for single-cell ATAC-seq analysis via latent feature extraction.

Single-cell ATAC-seq (scATAC-seq) profiles the chromatin accessibility landscape at single cell level, thus revealing cell-to-cell variability in gene regulation. However, the high dimensionality and sparsity of scATAC-seq data often complicate the analysis. Here, we introduce a method for analyzing scATAC-seq data, called Single-Cell ATAC-seq analysis via Latent feature Extraction (SCALE). SCALE combines a deep generative framework and a probabilistic Gaussian Mixture Model to learn latent features that accurately characterize scATAC-seq data. We validate SCALE on datasets generated on different platforms with different protocols, and having different overall data qualities. SCALE substantially outperforms the other tools in all aspects of scATAC-seq data analysis, including visualization, clustering, and denoising and imputation. Importantly, SCALE also generates interpretable features that directly link to cell populations, and can potentially reveal batch effects in scATAC-seq experiments

Detection of lymphangiogenesis in non-small cell lung cancer and its prognostic value

<p>Abstract</p> <p>Background</p> <p>Our aim was to detect lymphatic endothelial marker podoplanin, lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and vascular endothelial growth factor receptor-3 (VEGFR)-3 and study the prognostic relevance of lymphangiogenesis in non-small cell lung cancer (NSCLC).</p> <p>Materials</p> <p>82 paraffin-embedded tissues and 40 fresh frozen tissues from patients with NSCLC were studied. Tumor samples were immunostained for the lymphatic endothelial markers. Lymphangiogenesis was assessed by immunohistochemical double stains for Podoplanin and Ki-67. The prognostic relevance of lymphangiogenesis-related clinicopathological parameters in NSCLC was evaluated.</p> <p>Results</p> <p>We found that the number of podoplanin positive vessels was correlated positively with the number of LYVE-1 positive vessels. Most of VEGFR-3 positive, few of LYVE-1 positive and none of podoplanin positive vessels were blood vessels. Peritumoral lymphatic vessel density (ptLVD), pathologic stage, lymph node status, lymphatic vessel invasion (LVI), vascular endothelial growth factor-C (VEGF-C) expression and Ki-67 index of the endothelium cells of the micro lymphatic vessels (Ki67%) were associated significantly with a higher risk of tumor progress. ptLVD, pathologic stage, lymph-node metastasis and Ki67% were independent prognostic parameters for overall survival.</p> <p>Conclusion</p> <p>Podoplanin positive ptLVD might play important roles in the lymphangiogenesis and progression of NSCLC. Patients with high podoplanin+ ptLVD have a poor prognosis.</p

Black Holes as the source of the dark energy: a stringent test with the high-redshift JWST AGNs

It has been suggested that there is evidence for cosmological coupling of black holes (BHs) with an index of $k\approx 3$ and hence the BHs serve as the astrophysical source of the dark energy. The data sample however is limited for the redshifts $\leq 2.5$. Recently, the James Webb Space Telescope (JWST) has detected more than 180 high-redshift Active Galactic Nuclei (AGNs) and quasars. Among the JWST NIRSpec/NIRCam resolved AGNs, three are identified in early-type host galaxies with a redshift $z\sim 4.5-7$. Their $M_{\star}$ and $M_{\rm BH}$, however, are in tension with the prediction of the cosmological coupling of black holes with $k=3$ at a confidence level of $\sim 3\sigma$, which is not in support of the hypothesis that BHs serve as the origin of dark energy. The future observations of high-redshift AGNs by JWST will further test such a hypothesis by identifying more early-type host galaxies in the higher mass range.Comment: 9 pages, 3 figures, 1 table; Submitted to ApJL. Comments are welcome

Role of dimensional crossover on spin-orbit torque efficiency in magnetic insulator thin films

Magnetic insulators (MIs) attract tremendous interest for spintronic applications due to low Gilbert damping and absence of Ohmic loss. Magnetic order of MIs can be manipulated and even switched by spin-orbit torques (SOTs) generated through spin Hall effect and Rashba-Edelstein effect in heavy metal/MI bilayers. SOTs on MIs are more intriguing than magnetic metals since SOTs cannot be transferred to MIs through direct injection of electron spins. Understanding of SOTs on MIs remains elusive, especially how SOTs scale with the film thickness. Here, we observe the critical role of dimensionality on the SOT efficiency by systematically studying the MI layer thickness dependent SOT efficiency in tungsten/thulium iron garnet (W/TmIG) bilayers. We first show that the TmIG thin film evolves from two-dimensional to three-dimensional magnetic phase transitions as the thickness increases, due to the suppression of long-wavelength thermal fluctuation. Then, we report the significant enhancement of the measured SOT efficiency as the thickness increases. We attribute this effect to the increase of the magnetic moment density in concert with the suppression of thermal fluctuations. At last, we demonstrate the current-induced SOT switching in the W/TmIG bilayers with a TmIG thickness up to 15 nm. The switching current density is comparable with those of heavy metal/ferromagnetic metal cases. Our findings shed light on the understanding of SOTs in MIs, which is important for the future development of ultrathin MI-based low-power spintronics

Modeling mammalian gastrulation with embryonic stem cells

Understanding cell fate patterning and morphogenesis in the mammalian embryo remains a formidable challenge. Recently, in vivo models based on embryonic stem cells (ESCs) have emerged as complementary methods to quantitatively dissect the physical and molecular processes that shape the embryo. Here we review recent developments in using embryonic stem cells to create both two and three-dimensional culture models that shed light on mammalian gastrulation.Comment: 18 pages, 1 figur

Middle Holocene marine flooding and human response in the south Yangtze coastal plain, East China

Coastal flooding catastrophes have affected human societies on coastal plains around the world on several occasions in the past, and are threatening 21st century societies under global warming and sea-level rise. However, the role of coastal flooding in the interruption of the Neolithic Liangzhu culture in the lower Yangtze valley, East China coast has been long contested. In this study, we used a well-dated Neolithic site (the Yushan site) close to the present coastline to demonstrate a marine drowning event at the terminal stage of the Liangzhu culture and discuss its linkage to relative sea-level rise. We analysed sedimentology, chronology, organic elemental composition, diatoms and dinoflagellate cysts for several typical profiles at the Yushan site. The field and sedimentary data provided clear evidence of a palaeo-typhoon event that overwhelmed the Yushan site at ∼2560 BCE, which heralded a period of marine inundation and ecological deterioration at the site. We also infer an acceleration in sea-level rise at 2560–2440 BCE from the sedimentary records at Yushan, which explains the widespread signatures of coastal flooding across the south Yangtze coastal plain at that time. The timing of this mid-Holocene coastal flooding coincided with the sudden disappearance of the advanced and widespread Liangzhu culture along the lower Yangtze valley. We infer that extreme events and flooding accompanying accelerated sea-level rise were major causes of vulnerability for prehistoric coastal societies

Extensive beam test study of prototype MRPCs for the T0 detector at the CSR external-target experiment

The CSR External-target Experiment (CEE) will be the first large-scale nuclear physics experiment device at the Cooling Storage Ring (CSR) of the Heavy-Ion Research Facility in Lanzhou (HIRFL) in China. A new T0 detector has been proposed to measure the multiplicity, angular distribution and timing information of charged particles produced in heavy-ion collisions at the target region. Multi-gap resistive plate chamber (MRPC) technology was chosen as part of the construction of the T0 detector, which provides precision event collision times (T0) and collision geometry information. The prototype was tested with hadron and heavy-ion beams to study its performance. By comparing the experimental results with a Monte Carlo simulation, the time resolution of the MRPCs are found to be $\sim$ 50 ps or better. The timing performance of the T0 detector, including both detector and readout electronics, we found to fulfil the requirements of the CEE.Comment: 12 pages, 36 figure