Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+FoxP3+ regulatory T cells activation

Rationale: Loss of histone macroH2A1 induces appearance of cancer stem cells (CSCs)-like cells in hepatocellular carcinoma (HCC). How CSCs interact with the tumor microenvironment and the adaptive immune system is unclear. Methods: We screened aggressive human HCC for macroH2A1 and CD44 CSC marker expression. We also knocked down (KD) macroH2A1 in HCC cells, and performed integrated transcriptomic and secretomic analyses. Results: Human HCC showed low macroH2A1 and high CD44 expression compared to control tissues. MacroH2A1 KD CSC-like cells transferred paracrinally their chemoresistant properties to parental HCC cells. MacroH2A1 KD conditioned media transcriptionally reprogrammed parental HCC cells activated regulatory CD4+/CD25+/FoxP3+ T cells (Tregs). Conclusions: Loss of macroH2A1 in HCC cells drives cancer stem-cell propagation and evasion from immune surveillance

Asynchronous Training of Word Embeddings for Large Text Corpora

Word embeddings are a powerful approach for analyzing language and have been widely popular in numerous tasks in information retrieval and text mining. Training embeddings over huge corpora is computationally expensive because the input is typically sequentially processed and parameters are synchronously updated. Distributed architectures for asynchronous training that have been proposed either focus on scaling vocabulary sizes and dimensionality or suffer from expensive synchronization latencies. In this paper, we propose a scalable approach to train word embeddings by partitioning the input space instead in order to scale to massive text corpora while not sacrificing the performance of the embeddings. Our training procedure does not involve any parameter synchronization except a final sub-model merge phase that typically executes in a few minutes. Our distributed training scales seamlessly to large corpus sizes and we get comparable and sometimes even up to 45% performance improvement in a variety of NLP benchmarks using models trained by our distributed procedure which requires $1/10$ of the time taken by the baseline approach. Finally we also show that we are robust to missing words in sub-models and are able to effectively reconstruct word representations.Comment: This paper contains 9 pages and has been accepted in the WSDM201

The W43-MM1 mini-starburst ridge, a test for star formation efficiency models

Context: Star formation efficiency (SFE) theories are currently based on statistical distributions of turbulent cloud structures and a simple model of star formation from cores. They remain poorly tested, especially at the highest densities. Aims: We investigate the effects of gas density on the SFE through measurements of the core formation efficiency (CFE). With a total mass of $\sim2\times10^4$ M$_\odot$, the W43-MM1 ridge is one of the most convincing candidate precursor of starburst clusters and thus one of the best place to investigate star formation. Methods: We used high-angular resolution maps obtained at 3 mm and 1 mm within W43-MM1 with the IRAM Plateau de Bure Interferometer to reveal a cluster of 11 massive dense cores (MDCs), and, one of the most massive protostellar cores known. An Herschel column density image provided the mass distribution of the cloud gas. We then measured the 'instantaneous' CFE and estimated the SFE and the star formation rate (SFR) within subregions of the W43-MM1 ridge. Results: The high SFE found in the ridge ($\sim$6% enclosed in $\sim$8 pc$^3$) confirms its ability to form a starburst cluster. There is however a clear lack of dense cores in the northern part of the ridge, which may be currently assembling. The CFE and the SFE are observed to increase with volume gas density while the SFR steeply decreases with the virial parameter, $\alpha_{vir}$. Statistical models of the SFR may well describe the outskirts of the W43-MM1 ridge but struggle to reproduce its inner part, which corresponds to measurements at low $\alpha_{vir}$. It may be that ridges do not follow the log-normal density distribution, Larson relations, and stationary conditions forced in the statistical SFR models.Comment: 13 pages, 7 figures. Accepted by A&

ATLASGAL-selected massive clumps in the inner Galaxy: I. CO depletion and isotopic ratios

In the low-mass regime, it is found that the gas-phase abundances of C-bearing molecules in cold starless cores rapidly decrease with increasing density, as the molecules form mantles on dust grains. We study CO depletion in 102 massive clumps selected from the ATLASGAL 870 micron survey, and investigate its correlation with evolutionary stage and with the physical parameters of the sources. Moreover, we study the gradients in [12C]/[13C] and [18O]/[17O] isotopic ratios across the inner Galaxy, and the virial stability of the clumps. We use low-J emission lines of CO isotopologues and the dust continuum emission to infer the depletion factor fD. RATRAN one-dimensional models were also used to determine fD and to investigate the presence of depletion above a density threshold. The isotopic ratios and optical depth were derived with a Bayesian approach. We find a significant number of clumps with a large fD, up to ~20. Larger values are found for colder clumps, thus for earlier evolutionary phases. For massive clumps in the earliest stages of evolution we estimate the radius of the region where CO depletion is important to be a few tenths of a pc. Clumps are found with total masses derived from dust continuum emission up to ~20 times higher than the virial mass, especially among the less evolved sources. These large values may in part be explained by the presence of depletion: if the CO emission comes mainly from the low-density outer layers, the molecules may be subthermally excited, leading to an overestimate of the dust masses. CO depletion in high-mass clumps seems to behave as in the low-mass regime, with less evolved clumps showing larger values for the depletion than their more evolved counterparts, and increasing for denser sources. The C and O isotopic ratios are consistent with previous determinations, and show a large intrinsic scatter.Comment: 20 pages, 17 figures, 38 pages of online material (tables and figures

Giant Spin Seebeck Effect through an Interface Organic Semiconductor

Interfacing an organic semiconductor C60 with a non-magnetic metallic thin film (Cu or Pt) has created a novel heterostructure that is ferromagnetic at ambient temperature, while its interface with a magnetic metal (Fe or Co) can tune the anisotropic magnetic surface property of the material. Here, we demonstrate that sandwiching C60 in between a magnetic insulator (Y3Fe5O12: YIG) and a non-magnetic, strong spin-orbit metal (Pt) promotes highly efficient spin current transport via the thermally driven spin Seebeck effect (SSE). Experiments and first principles calculations consistently show that the presence of C60 reduces significantly the conductivity mismatch between YIG and Pt and the surface perpendicular magnetic anisotropy of YIG, giving rise to enhanced spin mixing conductance across YIG/C60/Pt interfaces. As a result, a 600% increase in the SSE voltage (VLSSE) has been realized in YIG/C60/Pt relative to YIG/Pt. Temperature-dependent SSE voltage measurements on YIG/C60/Pt with varying C60 layer thicknesses also show an exponential increase in VLSSE at low temperatures below 200 K, resembling the temperature evolution of spin diffusion length of C60. Our study emphasizes the important roles of the magnetic anisotropy and the spin diffusion length of the intermediate layer in the SSE in YIG/C60/Pt structures, providing a new pathway for developing novel spin-caloric materials

Environmental contamination with clostridioides (Clostridium) difficile in Vietnam

AIMS: To investigate the prevalence, molecular type, and antimicrobial susceptibility of Clostridioides difficile in the environment in Vietnam, where little is known about C. difficile. METHODS AND RESULTS: Samples of pig faeces, soils from pig farms, potatoes, and the hospital environment were cultured for C. difficile. Isolates were identified and typed by polymerase chain reaction (PCR) ribotyping. The overall prevalence of C. difficile contamination was 24.5% (68/278). Clostridioides difficile was detected mainly in soils from pig farms and hospital soils, with 70%-100% prevalence. Clostridioides difficile was isolated from 3.4% of pig faecal samples and 5% of potato surfaces. The four most prevalent ribotypes (RTs) were RTs 001, 009, 038, and QX574. All isolates were susceptible to metronidazole, fidaxomicin, vancomycin, and amoxicillin/clavulanate, while resistance to erythromycin, tetracycline, and moxifloxacin was common in toxigenic strains. Clostridioides difficile RTs 001A+B+CDT- and 038A-B-CDT- were predominantly multidrug resistant. CONCLUSIONS: Environmental sources of C. difficile are important to consider in the epidemiology of C. difficile infection in Vietnam, however, contaminated soils are likely to be the most important source of C. difficile. This poses additional challenges to controlling infections in healthcare settings

Transaminase abnormalities and adaptations of the liver lobule manifest at specific cut-offs of steatosis

There is little documented evidence suggesting that liver fat is responsible for liver injury in the absence of other disease processes. We investigated the relationships between liver fat, aminotransferases and hepatic architecture in liver biopsies with simple steatosis. We identified 136 biopsies with simple steatosis from the Royal Free Hospital Archives with both clinical data and sufficient material. Digital image analysis was employed to measure fat proportionate area (mFPA). Hepatocyte area (HA) and lobule radius (LR) were also measured. There were significant increases in ALT (p < 0.001) and AST (p = 0.013) with increased fat content and evidence to suggest both 5% and 20% mFPA as a cut-off for raised ALT. In liver with increased fat content there were significant increases in HA (p < 0.001). LR also increased as mFPA increased to 10% (p < 0.001), at which point the lobule ceased to expand further and was counterbalanced with a decrease in the number of hepatocytes per lobule (p = 0.029). Consequently there are mechanisms of adaption in the liver architecture to accommodate the accumulation of fat and these are accompanied by significant increases in transaminases. These results support the generally accepted cut-off of 5% fat for steatosis and indicate 20% as a threshold of more severe liver injury

Required flows for aquatic ecosystems in Ma River, Vietnam

Ecological flow requirements for the Ma River in dry season were assessed in three reaches of Ma – Buoi, Ma – Len and Ma – Chu. 5 indictor fish species was chosen based on biodiversity survey and roles of those species in aquatic ecosystem as well as local communities. Biological and hydrological data (dry season of 2016- 2017) and 35 year recorded hydrological data were collected and analyzed as input data for a physical habitat model River HYdraulic and HABitat SImulation Model – RHYHABSIM. Model results shown that the optimal flows of the reaches were very much higher compare with the minimum annual low flow - MALF. In this study, MALF7day were applied to calculate the recommended minimum flows of the three reaches. The recommended required minimum flows for Ma – Buoi, Ma – Len and Ma – Chu reaches were 51 m3/s, 49 m3/s and 61 m3/s, respectively. It must be stressed that this study only assessed whether or not there is enough habitat available for the river to sustain a healthy ecosystem