We present a new model for the distribution of free electrons in the Galaxy, the Magellanic Clouds, and the intergalactic medium (IGM) that can be used to estimate distances to real or simulated pulsars and fast radio bursts (FRBs) based on their dispersion measure (DM). The Galactic model has an extended thick disk representing the so-called warm interstellar medium, a thin disk representing the Galactic molecular ring, spiral arms based on a recent fit to Galactic H II regions, a Galactic Center disk, and seven local features including the Gum Nebula, Galactic Loop I, and the Local Bubble. An offset of the Sun from the Galactic plane and a warp of the outer Galactic disk are included in the model. Parameters of the Galactic model are determined by fitting to 189 pulsars with independently determined distances and DMs. Simple models are used for the Magellanic Clouds and the IGM. Galactic model distances are within the uncertainty range for 86 of the 189 independently determined distances and within 20% of the nearest limit for a further 38 pulsars. We estimate that 95% of predicted Galactic pulsar distances will have a relative error of less than a factor of 0.9. The predictions of YMW16 are compared to those of the TC93 and NE2001 models showing that YMW16 performs significantly better on all measures. Timescales for pulse broadening due to interstellar scattering are estimated for (real or simulated) Galactic and Magellanic Cloud pulsars and FRBs.

Stable ferroelectricity with high transition temperature in nanostructures is needed for miniaturizing ferroelectric devices. Here, we report the discovery of the stable in-plane spontaneous polarization in atomic-thick tin telluride (SnTe), down to a 1-unit cell (UC) limit. The ferroelectric transition temperature T(c) of 1-UC SnTe film is greatly enhanced from the bulk value of 98 kelvin and reaches as high as 270 kelvin. Moreover, 2- to 4-UC SnTe films show robust ferroelectricity at room temperature. The interplay between semiconducting properties and ferroelectricity in this two-dimensional material may enable a wide range of applications in nonvolatile high-density memories, nanosensors, and electronics.

Long-distance entanglement distribution is essential for both foundational tests of quantum physics and scalable quantum networks. Owing to channel loss, however, the previously achieved distance was limited to ~100 kilometers. Here we demonstrate satellite-based distribution of entangled photon pairs to two locations separated by 1203 kilometers on Earth, through two satellite-to-ground downlinks with a summed length varying from 1600 to 2400 kilometers. We observed a survival of two-photon entanglement and a violation of Bell inequality by 2.37 ± 0.09 under strict Einstein locality conditions. The obtained effective link efficiency is orders of magnitude higher than that of the direct bidirectional transmission of the two photons through telecommunication fibers.

National Center for Advancing Translational Sciences of the National Institutes of Health.

The existence of males and females, which are often strikingly different in morphology, reproductive strategies and behavior, is one of the most widespread phenomena in biology. However, the genetic mechanisms that generate this ubiquitous pattern are surprisingly diverse and do not follow a phylogenetic pattern. Sex-determination mechanisms can differ between even closely related species and arise frequently and independently. Fish provide a paradigmatic example, as their sex-determination mechanisms range from environmental to different modes of genetic determination. The evolutionary meaning of this remarkable plasticity is unknown. For genetic sex determination, where the trigger for female or male development comes from the genetic constitution of the individual, the evolution of sex-determination mechanisms is connected to a very peculiar genomic process, namely the formation of sex chromosomes [1][2][3][4] .To improve understanding of the function and evolution of sex chromosomes, their genetic organization must be deciphered.However, owing to their degenerate nature and high repetitive DNA content, sex chromosomes pose almost insurmountable problems in deciphering their gene content and organization. So far, only the human 5 , chimpanzee 6 and rhesus macaque Y chromosomes 7 and the male-specific region on the Y chromosome of one fish, the medaka 8 , have been sequenced. These analyses have nevertheless provided important insights into the evolution of Y chromosomes, their genomic organization and their degeneration processes, as well as predictions as to their likely evolutionary fate 9-12 .Much less genomic information exists on W chromosomes because, as with Y chromosomes, they are predominantly highly repetitive in nature. The prevailing theory of the evolution of sex chromosomes predicts that degeneration of the heterogametic sex chromosome is a stepwise process that occurs over an extended period of time. We therefore reasoned that an evolutionarily young W chromosome Whole-genome sequence of a flatfish provides insights into ZW sex chromosome evolution and adaptation to a benthic lifestyle Genetic sex determination by W and Z chromosomes has developed independently in different groups of organisms. To better understand the evolution of sex chromosomes and the plasticity of sex-determination mechanisms, we sequenced the whole genomes of a male (ZZ) and a female (ZW) half-smooth tongue sole (Cynoglossus semilaevis). In addition to insights into adaptation to a benthic lifestyle, we find that the sex chromosomes of these fish are derived from the same ancestral vertebrate protochromosome as the avian W and Z chromosomes. Notably, the same gene on the Z chromosome, dmrt1, which is the male-determining gene in birds, showed convergent evolution of features that are compatible with a similar function in tongue sole. Comparison of the relatively young tongue sole sex chromosomes with those of mammals and birds identified events that occurred during the early phase of sex-chromosome evolution. Pertinent to...

Background: Accumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation. Objective: This study evaluated the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, for coronavirus disease 2019. Methods: We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe coronavirus disease 2019. Results: Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus standard-of-care treatment (22 patients) or placebo based on standard-of-care treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study. Treatment with ruxolitinib plus standard-of-care was not associated with significantly accelerated clinical improvement in severe patients with coronavirus disease 2019, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed computed tomography improvement at day 14 compared with 13 (61.9%) patients from the control group (P 5 .0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at day 28; no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines were significantly decreased in the ruxolitinib group in comparison to the control group. Conclusions: Although no statistical difference was observed, ruxolitinib recipients had a numerically faster clinical improvement. Significant chest computed tomography improvement, a faster recovery from lymphopenia, and favorable side-effect profile in the ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population. (

With its relatively long observation time per pointing, the Parkes multibeam survey was effective in detecting nulling pulsars. We have made 2‐h observations of 23 pulsars which showed evidence for pulse nulling or mode changing in the survey data. Because of the low flux density of these pulsars, in most cases averaging times of between 10 and 60 s were necessary and so this analysis is insensitive to very short nulls. Seven of the pulsars had null fractions of more than 40 per cent with the largest having a lower limit of 95 per cent. Mode changes were observed in six pulsars with clear relationships between nulling and mode changing in some cases. Combined with earlier results, the data suggest that large null fractions are more related to large characteristic age than to long pulse period. The observations suggest that nulling and mode changing are different manifestations of the same phenomenon.

BackgroundSeveral of the thousands of human long noncoding RNAs (lncRNAs) have been functionally characterized, yet their potential involvement in hepatocellular carcinoma (HCC) remains poorly understood.MethodsLncRNA-HOXD-AS1 was identified by microarray and validated by real-time PCR. The clinicopathological significance of HOXD-AS1 was analyzed by Kaplan-Meier method. Chromatin immunoprecipitation was conducted to examine the mechanism of HOXD-AS1 upregulation. The role of HOXD-AS1 in HCC cells was assessed both in vitro and in vivo. ceRNA function of HOXD-AS1 was evaluated by RNA immunoprecipitation and biotin-coupled miRNA pull down assays.ResultsIn this study, we found that HOXD-AS1 was significantly upregulated in HCC tissues. Clinical investigation demonstrated high expression level of HOXD-AS1 was associated with poor prognosis and high tumor node metastasis stage of HCC patients, and was an independent risk factor for survival. Moreover, our results revealed that STAT3 could specifically interact with the promoter of HOXD-AS1 and activate HOXD-AS1 transcription. Knockdown of HOXD-AS1 significantly inhibited migration and invasion of HCC cells in vitro and distant lung metastasis in vivo. Additionally, HOXD-AS1 was enriched in the cytoplasm, and shared miRNA response elements with SOX4. Overexpression of HOXD-AS1 competitively bound to miR-130a-3p that prevented SOX4 from miRNA-mediated degradation, thus activated the expression of EZH2 and MMP2 and facilitated HCC metastasis.ConclusionsIn summary, HOXD-AS1 is a prognostic marker for HCC patients and it may play a pro-metastatic role in hepatocarcinogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0680-1) contains supplementary material, which is available to authorized users.