Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and ...stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions. Exosomal miR-23a directly suppressed its target prolyl hydroxylase 1 and 2 (PHD1 and 2), leading to the accumulation of hypoxia-inducible factor-1 α (HIF-1 α) in endothelial cells. Consequently, hypoxic lung cancer cells enhanced angiogenesis by exosomes derived from hypoxic cancer under both normoxic and hypoxic conditions. In addition, exosomal miR-23a also inhibits tight junction protein ZO-1, thereby increasing vascular permeability and cancer transendothelial migration. Inhibition of miR-23a by inhibitor administration decreased angiogenesis and tumour growth in a mouse model. Furthermore, elevated levels of circulating miR-23a are found in the sera of lung cancer patients, and miR-23a levels are positively correlated with proangiogenic activities. Taken together, our study reveals the clinical relevance and prognostic value of cancer-derived exosomal miR-23a under hypoxic conditions, and investigates a unique intercellular communication, mediated by cancer-derived exosomes, which modulates tumour vasculature.
Summary
Background
Cirrhotic patients admitted to intensive care units (ICUs) have high mortality rates. The Chronic Liver Failure–Sequential Organ Failure Assessment (CLIF‐SOFA) score, a modified ...Sequential Organ Failure Assessment (SOFA) score, is a newly developed scoring system exclusively for patients with end‐stage liver disease.
Aim
To externally validate the efficacy of the CLIF‐SOFA score and evaluate other scoring systems for 6‐month mortality in critically ill cirrhotic patients.
Methods
This study prospectively recorded and analysed the data for 30 demographical parameters and some clinical characteristic variables on day 1 of 250 cirrhotic patients admitted to a 10‐bed specialised hepatogastroenterology ICU in a 2000‐bed tertiary care referral hospital during the period from September 2010 to August 2013.
Results
The overall in‐hospital and 6‐month mortality rate were 58.8% (147/250) and 78.0% (195/250), respectively. Liver diseases were mostly attributed to hepatitis B virus infection (32%). Multiple Cox logistic regression hazard analysis revealed that Glasgow coma scale, both the CLIF‐SOFA and Acute Physiology and Chronic Health Evaluation III (ACPACHE III) scores determined on the first day of ICU admission were independent predictors of 6‐month mortality. Analysis of the area under the receiver operating characteristic curve revealed that the CLIF‐SOFA score had the best discriminatory power (0.900 ± 0.020). Moreover, the cumulative 6‐month survival rates differed significantly for patients with a CLIF‐SOFA score ≤11 and those with a CLIF‐SOFA score >11 on the ICU admission day.
Conclusion
Both CLIF‐SOFA and APACHE III scores are excellent prognosis evaluation tools for critically ill cirrhotic patients.
On 17 August 2017, the Laser Interferometer Gravitational-Wave Observatory (LIGO) and the Virgo interferometer detected gravitational waves (GWs) emanating from a binary neutron star merger, ...GW170817. Nearly simultaneously, the Fermi and INTEGRAL (INTErnational Gamma-Ray Astrophysics Laboratory) telescopes detected a gamma-ray transient, GRB 170817A. At 10.9 hours after the GW trigger, we discovered a transient and fading optical source, Swope Supernova Survey 2017a (SSS17a), coincident with GW170817. SSS17a is located in NGC 4993, an S0 galaxy at a distance of 40 megaparsecs. The precise location of GW170817 provides an opportunity to probe the nature of these cataclysmic events by combining electromagnetic and GW observations.
Eleven hours after the detection of gravitational wave source GW170817 by the Laser Interferometer Gravitational-Wave Observatory and Virgo Interferometers, an associated optical transient, SSS17a, ...was identified in the galaxy NGC 4993. Although the gravitational wave data indicate that GW170817 is consistent with the merger of two compact objects, the electromagnetic observations provide independent constraints on the nature of that system. We synthesize the optical to near-infrared photometry and spectroscopy of SSS17a collected by the One-Meter Two-Hemisphere collaboration, finding that SSS17a is unlike other known transients. The source is best described by theoretical models of a kilonova consisting of radioactive elements produced by rapid neutron capture (the r-process). We conclude that SSS17a was the result of a binary neutron star merger, reinforcing the gravitational wave result.
Abstract
A spectral-energy distribution (SED) model for Type Ia supernovae (SNe Ia) is a critical tool for measuring precise and accurate distances across a large redshift range and constraining ...cosmological parameters. We present an improved model framework, SALT3, which has several advantages over current models—including the leading SALT2 model (SALT2.4). While SALT3 has a similar philosophy, it differs from SALT2 by having improved estimation of uncertainties, better separation of color and light-curve stretch, and a publicly available training code. We present the application of our training method on a cross-calibrated compilation of 1083 SNe with 1207 spectra. Our compilation is 2.5× larger than the SALT2 training sample and has greatly reduced calibration uncertainties. The resulting trained SALT3.K21 model has an extended wavelength range 2000–11,000 Å (1800 Å redder) and reduced uncertainties compared to SALT2, enabling accurate use of low-
z I
and
iz
photometric bands. Including these previously discarded bands, SALT3.K21 reduces the Hubble scatter of the low-
z
Foundation and CfA3 samples by 15% and 10%, respectively. To check for potential systematic uncertainties, we compare distances of low (0.01 <
z
< 0.2) and high (0.4 <
z
< 0.6) redshift SNe in the training compilation, finding an insignificant 3 ± 14 mmag shift between SALT2.4 and SALT3.K21. While the SALT3.K21 model was trained on optical data, our method can be used to build a model for rest-frame NIR samples from the Roman Space Telescope. Our open-source training code, public training data, model, and documentation are available at
https://saltshaker.readthedocs.io/en/latest/
, and the model is integrated into the
sncosmo
and
SNANA
software packages.
The merging neutron star gravitational-wave event GW170817 has been observed throughout the entire electromagnetic spectrum from radio waves to γ-rays. The resulting energetics, variability, and ...light curves are shown to be consistent with GW170817 originating from the merger of two neutron stars, in all likelihood followed by the prompt gravitational collapse of the massive remnant. The available γ-ray, X-ray, and radio data provide a clear probe for the nature of the relativistic ejecta and the non-thermal processes occurring within, while the ultraviolet, optical, and infrared emission are shown to probe material torn during the merger and subsequently heated by the decay of freshly synthesized r-process material. The simplest hypothesis, that the non-thermal emission is due to a low-luminosity short γ-ray burst (sGRB), seems to agree with the present data. While low-luminosity sGRBs might be common, we show here that the collective prompt and multi-wavelength observations are also consistent with a typical, powerful sGRB seen off-axis. Detailed follow-up observations are thus essential before we can place stringent constraints on the nature of the relativistic ejecta in GW170817.
Machine learning, a branch of artificial intelligence, learns from previous experience to optimize performance, which is ubiquitous in various fields such as computer sciences, financial analysis, ...robotics, and bioinformatics. A challenge is that machine learning with the rapidly growing "big data" could become intractable for classical computers. Recently, quantum machine learning algorithms Lloyd, Mohseni, and Rebentrost, arXiv.1307.0411 were proposed which could offer an exponential speedup over classical algorithms. Here, we report the first experimental entanglement-based classification of two-, four-, and eight-dimensional vectors to different clusters using a small-scale photonic quantum computer, which are then used to implement supervised and unsupervised machine learning. The results demonstrate the working principle of using quantum computers to manipulate and classify high-dimensional vectors, the core mathematical routine in machine learning. The method can, in principle, be scaled to larger numbers of qubits, and may provide a new route to accelerate machine learning.
Viruses that affect humans, animals and plants are often dispersed and transmitted through airborne routes of infection. Due to current technological deficiencies, accurate determination of the ...presence of airborne viruses is challenging. This shortcoming limits our ability to evaluate the actual threat arising from inhalation or other relevant contact with aerosolized viruses. To improve our understanding of the mechanisms of airborne transmission of viruses, air sampling technologies that can detect the presence of aerosolized viruses, effectively collect them and maintain their viability, and determine their distribution in aerosol particles, are needed. The latest developments in sampling and detection methodologies for airborne viruses, their limitations, factors that can affect their performance and current research needs, are discussed in this review. Much more work is needed on the establishment of standard air sampling methods and their performance requirements. Sampling devices that can collect a wide size range of virus‐containing aerosols and maintain the viability of the collected viruses are needed. Ideally, the devices would be portable and technology‐enabled for on‐the‐spot detection and rapid identification of the viruses. Broad understanding of the airborne transmission of viruses is of seminal importance for the establishment of better infection control strategies.
SN 2013dy is a Type Ia supernova (SN Ia) for which we have compiled an extraordinary data set spanning from 0.1 to ∼ 500 d after explosion. We present 10 epochs of ultraviolet (UV) through ...near-infrared (NIR) spectra with Hubble Space Telescope/Space Telescope Imaging Spectrograph, 47 epochs of optical spectra (15 of them having high resolution), and more than 500 photometric observations in the BVrRiIZYJH bands. SN 2013dy has a broad and slowly declining light curve (Δm
15(B) = 0.92 mag), shallow
$\mathrm{Si}\,\small {II}\,\lambda 6355$
absorption, and a low velocity gradient. We detect strong C ii in our earliest spectra, probing unburned progenitor material in the outermost layers of the SN ejecta, but this feature fades within a few days. The UV continuum of SN 2013dy, which is strongly affected by the metal abundance of the progenitor star, suggests that SN 2013dy had a relatively high-metallicity progenitor. Examining one of the largest single set of high-resolution spectra for an SN Ia, we find no evidence of variable absorption from circumstellar material. Combining our UV spectra, NIR photometry, and high-cadence optical photometry, we construct a bolometric light curve, showing that SN 2013dy had a maximum luminosity of
$10.0^{+4.8}_{-3.8} \times 10^{42}$
erg s−1. We compare the synthetic light curves and spectra of several models to SN 2013dy, finding that SN 2013dy is in good agreement with a solar-metallicity W7 model.
Measurements of the dark energy equation-of-state parameter, w, have been limited by uncertainty in the selection effects and photometric calibration of z < 0.1 Type Ia supernovae (SNe Ia). The ...Foundation Supernova Survey is designed to lower these uncertainties by creating a new sample of z < 0.1 SNe Ia observed on the Pan-STARRS system. Here we combine the Foundation sample with SNe from the Pan-STARRS Medium Deep Survey and measure cosmological parameters with 1338 SNe from a single telescope and a single, well-calibrated photometric system. For the first time, both the low-z and high-z data are predominantly discovered by surveys that do not target preselected galaxies, reducing selection bias uncertainties. The z > 0.1 data include 875 SNe without spectroscopic classifications, and we show that we can robustly marginalize over CC SN contamination. We measure Foundation Hubble residuals to be fainter than the preexisting low-z Hubble residuals by 0.046 0.027 mag (stat + sys). By combining the SN Ia data with cosmic microwave background constraints, we find w = −0.938 0.053, consistent with ΛCDM. With 463 spectroscopically classified SNe Ia alone, we measure w = −0.933 0.061. Using the more homogeneous and better-characterized Foundation sample gives a 55% reduction in the systematic uncertainty attributed to SN Ia sample selection biases. Although use of just a single photometric system at low and high redshift increases the impact of photometric calibration uncertainties in this analysis, previous low-z samples may have correlated calibration uncertainties that were neglected in past studies. The full Foundation sample will observe up to 800 SNe to anchor the LSST and WFIRST Hubble diagrams.
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