Cancer progression is characterized by rapidly proliferating cancer cells that are in need of increased protein synthesis. Therefore, enhanced endoplasmic reticulum (ER) activity is required to ...facilitate the folding, assembly and transportation of membrane and secretory proteins. These functions are carried out by ER chaperones. It is now becoming clear that the ER chaperones have critical functions outside of simply facilitating protein folding. For example, cancer progression requires glucose regulated protein (GRP) 78 for cancer cell survival and proliferation, as well as angiogenesis in the microenvironment. GRP78 can translocate to the cell surface acting as a receptor regulating oncogenic signaling and cell viability. Calreticulin, another ER chaperone, can translocate to the cell surface of apoptotic cancer cells and induce immunogenic cancer cell death and antitumor responses in vivo. Tumor-secreted GRP94 has been shown to elicit antitumor immune responses when used as antitumor vaccines. Protein disulfide isomerase is another ER chaperone that demonstrates pro-oncogenic and pro-survival functions. Because of intrinsic alterations of cellular metabolism and extrinsic factors in the tumor microenvironment, cancer cells are under ER stress, and they respond to this stress by activating the unfolded protein response (UPR). Depending on the severity and duration of ER stress, the signaling branches of the UPR can activate adaptive and pro-survival signals, or induce apoptotic cell death. The protein kinase RNA-like ER kinase signaling branch of the UPR has a dual role in cancer proliferation and survival, and is also required for ER stress-induced autophagy. The activation of the inositol-requiring kinase 1α branch promotes tumorigenesis, cancer cell survival and regulates tumor invasion. In summary, perturbance of ER homeostasis has critical roles in tumorigenesis, and therapeutic modulation of ER chaperones and/or UPR components presents potential antitumor treatments.
Large-scale, highly integrated and low-power-consuming hardware is becoming progressively more important for realizing optical neural networks (ONNs) capable of advanced optical computing. ...Traditional experimental implementations need N
units such as Mach-Zehnder interferometers (MZIs) for an input dimension N to realize typical computing operations (convolutions and matrix multiplication), resulting in limited scalability and consuming excessive power. Here, we propose the integrated diffractive optical network for implementing parallel Fourier transforms, convolution operations and application-specific optical computing using two ultracompact diffractive cells (Fourier transform operation) and only N MZIs. The footprint and energy consumption scales linearly with the input data dimension, instead of the quadratic scaling in the traditional ONN framework. A ~10-fold reduction in both footprint and energy consumption, as well as equal high accuracy with previous MZI-based ONNs was experimentally achieved for computations performed on the MNIST and Fashion-MNIST datasets. The integrated diffractive optical network (IDNN) chip demonstrates a promising avenue towards scalable and low-power-consumption optical computational chips for optical-artificial-intelligence.
In this study, we report nonmetal plasmonic MoS2@TiO2 heterostructures for highly efficient photocatalytic H2 generation. Large area laminated MoS2 in conjunction with TiO2 nanocavity arrays is ...achieved via carefully controlled anodization, physical vapor deposition, and chemical vapor deposition processes. The broad spectral response ranging from ultraviolet-visible (UV-vis) to near-infrared (NIR) wavelengths and finite element frequency-domain simulations suggest that this MoS2@TiO2 heterostructure enhances photocatalytic activity for H+ reduction. A high H2 yield rate of 181 μmol h−1 cm−2 (equal to 580 mmol h−1 g−1 based on the loading mass of MoS2) is achieved using a low catalyst loading mass. The spatially uniform heterostructure, correlated with plasmon-resonance through the conformal MoS2 coating that effectively regulates charge transfer pathways, is proven to be vitally important for the unique solar energy harvesting and photocatalytic H2 production. As an innovative exploration, our study demonstrates that the photocatalytic activities of nonmetal, earth-abundant materials can be enhanced with plasmonic effects, which may serve as an excellent catalytic agent for solar energy conversion to chemical fuels.
Mergers of neutron stars are known to be associated with short γ-ray bursts
. If the neutron-star equation of state is sufficiently stiff (that is, the pressure increases sharply as the density ...increases), at least some such mergers will leave behind a supramassive or even a stable neutron star that spins rapidly with a strong magnetic field
(that is, a magnetar). Such a magnetar signature may have been observed in the form of the X-ray plateau that follows up to half of observed short γ-ray bursts
. However, it has been expected that some X-ray transients powered by binary neutron-star mergers may not be associated with a short γ-ray burst
. A fast X-ray transient (CDF-S XT1) was recently found to be associated with a faint host galaxy, the redshift of which is unknown
. Its X-ray and host-galaxy properties allow several possible explanations including a short γ-ray burst seen off-axis, a low-luminosity γ-ray burst at high redshift, or a tidal disruption event involving an intermediate-mass black hole and a white dwarf
. Here we report a second X-ray transient, CDF-S XT2, that is associated with a galaxy at redshift z = 0.738 (ref.
). The measured light curve is fully consistent with the X-ray transient being powered by a millisecond magnetar. More intriguingly, CDF-S XT2 lies in the outskirts of its star-forming host galaxy with a moderate offset from the galaxy centre, as short γ-ray bursts often do
. The estimated event-rate density of similar X-ray transients, when corrected to the local value, is consistent with the event-rate density of binary neutron-star mergers that is robustly inferred from the detection of the gravitational-wave event GW170817.
ABSTRACT We present improved point-source catalogs for the 2 Ms Chandra Deep Field-North (CDF-N) and the 250 ks Extended Chandra Deep Field-South (E-CDF-S) Surveys, implementing a number of recent ...improvements in Chandra source-cataloging methodology. For CDF-N/E-CDF-S, we provide a main catalog that contains 683/1003 X-ray sources detected with wavdetect at a false-positive probability threshold of 10−5 that also satisfy a binomial-probability source-selection criterion of /P < 0.002. Such an approach maximizes the number of reliable sources detected: a total of 196/275 main-catalog sources are new compared to the Alexander et al. CDF-N/Lehmer et al. E-CDF-S main catalogs. We also provide CDF-N/E-CDF-S supplementary catalogs that consist of 72/56 sources detected at the same wavdetect threshold and having P of 0.004-0.1/0.002-0.1 and mag counterparts. For all CDF-N and E-CDF-S sources, including the newly detected ones (these being generally fainter and more obscured), we determine X-ray source positions utilizing centroid and matched-filter techniques; we also provide multiwavelength identifications, apparent magnitudes of counterparts, spectroscopic and/or photometric redshifts, basic source classifications, and estimates of observed active galactic nucleus and galaxy source densities around respective field centers. Simulations show that both the CDF-N and E-CDF-S main catalogs are highly reliable and reasonably complete. Background and sensitivity analyses indicate that the on-axis mean flux limits reached represent a factor of -2.0 improvement over the previous CDF-N and E-CDF-S limits. We make our data products publicly available.
ABSTRACT We present X-ray source catalogs for the 7 Ms exposure of the Chandra Deep Field-South (CDF-S), which covers a total area of 484.2 arcmin2. Utilizing wavdetect for initial source detection ...and ACIS Extract for photometric extraction and significance assessment, we create a main source catalog containing 1008 sources that are detected in up to three X-ray bands: 0.5-7.0 keV, 0.5-2.0 keV, and 2-7 keV. A supplementary source catalog is also provided, including 47 lower-significance sources that have bright ( ) near-infrared counterparts. We identify multiwavelength counterparts for 992 (98.4%) of the main-catalog sources, and we collect redshifts for 986 of these sources, including 653 spectroscopic redshifts and 333 photometric redshifts. Based on the X-ray and multiwavelength properties, we identify 711 active galactic nuclei (AGNs) from the main-catalog sources. Compared to the previous 4 Ms CDF-S catalogs, 291 of the main-catalog sources are new detections. We have achieved unprecedented X-ray sensitivity with average flux limits over the central 1 arcmin2 region of 1.9 × 10−17, 6.4 × 10−18, and 2.7 × 10−17 erg cm−2 s−1 in the three X-ray bands, respectively. We provide cumulative number-count measurements observing, for the first time, that normal galaxies start to dominate the X-ray source population at the faintest 0.5-2.0 keV flux levels. The highest X-ray source density reaches 50,500 deg−2, and 47% 4% of these sources are AGNs ( 23,900 deg−2).
ABSTRACT We present measurements of the evolution of normal-galaxy X-ray emission from 0-7 using local galaxies and galaxy samples in the 6 Ms Chandra Deep Field-South (CDF-S) survey. The majority of ...the CDF-S galaxies are observed at rest-frame energies above 2 keV, where the emission is expected to be dominated by X-ray binary (XRB) populations; however, hot gas is expected to provide small contributions to the observed-frame 1 keV emission at z 1. We show that a single scaling relation between X-ray luminosity ( ) and star-formation rate (SFR) literature, is insufficient for characterizing the average X-ray emission at all redshifts. We establish that scaling relations involving not only SFR, but also stellar mass ( ) and redshift, provide significantly improved characterizations of the average X-ray emission from normal galaxy populations at 0-7. We further provide the first empirical constraints on the redshift evolution of X-ray emission from both low-mass XRB (LMXB) and high-mass XRB (HMXB) populations and their scalings with and SFR, respectively. We find (LMXB)/ and (HMXB)/SFR , and show that these relations are consistent with XRB population-synthesis model predictions, which attribute the increase in LMXB and HMXB scaling relations with redshift as being due to declining host galaxy stellar ages and metallicities, respectively. We discuss how emission from XRBs could provide an important source of heating to the intergalactic medium in the early universe, exceeding that of active galactic nuclei.
Abstract
We present a systematic X-ray and multiwavelength study of a sample of 47 active galactic nuclei (AGNs) with reverberation mapping measurements. This sample includes 21 super-Eddington ...accreting AGNs and 26 sub-Eddington accreting AGNs. Using high-state observations with simultaneous X-ray and UV/optical measurements, we investigate whether super-Eddington accreting AGNs exhibit different accretion disk–corona connections compared to sub-Eddington accreting AGNs. We find tight correlations between the X-ray-to-UV/optical spectral slope parameter (
α
OX
) and the monochromatic luminosity at 2500 Å (
L
2500Å
) for both the super- and sub-Eddington subsamples. The best-fit
α
OX
–
L
2500Å
relations are consistent overall, indicating that super-Eddington accreting AGNs are not particularly X-ray weak in general compared to sub-Eddington accreting AGNs. We find dependences of
α
OX
on both the Eddington ratio (
L
Bol
/
L
Edd
) and black hole mass (
M
BH
) parameters for our full sample. A multivariate linear regression analysis yields
, with a scatter similar to that of the
α
OX
–
L
2500Å
relation. The hard (rest-frame >2 keV) X-ray photon index (Γ) is strongly correlated with
L
Bol
/
L
Edd
for the full sample and the super-Eddington subsample, but these two parameters are not significantly correlated for the sub-Eddington subsample. A fraction of super-Eddington accreting AGNs show strong X-ray variability, probably due to small-scale gas absorption, and we highlight the importance of employing high-state (intrinsic) X-ray radiation to study the accretion disk–corona connections in AGNs.
We investigate the dependence of black hole accretion rate (BHAR) on host-galaxy star formation rate (SFR) and stellar mass (M*) in the CANDELS/GOODS-South field in the redshift range of . Our sample ...consists of galaxies, allowing us to probe galaxies with and/or . We use sample-mean BHAR to approximate long-term average BHAR. Our sample-mean BHARs are derived from the Chandra Deep Field-South 7 Ms observations, while the SFRs and M* have been estimated by the CANDELS team through spectral energy distribution fitting. The average BHAR is correlated positively with both SFR and M*, and the BHAR-SFR and BHAR-M* relations can both be described acceptably by linear models with a slope of unity. However, BHAR appears to be correlated more strongly with M* than SFR. This result indicates that M* is the primary host-galaxy property related to supermassive black hole (SMBH) growth, and the apparent BHAR-SFR relation is largely a secondary effect due to the star-forming main sequence. Among our sources, massive galaxies ( ) have significantly higher BHAR/SFR ratios than less massive galaxies, indicating that the former have higher SMBH fueling efficiency and/or higher SMBH occupation fraction than the latter. Our results can naturally explain the observed proportionality between and M* for local giant ellipticals and suggest that their is higher than that of local star-forming galaxies. Among local star-forming galaxies, massive systems might have higher compared to dwarfs.
Evidence suggests that periodontitis contributes to the pathogenesis of inflammatory bowel disease, including Crohn’s disease and ulcerative colitis. However, few studies have examined the role of ...swallowing and saliva in the pathogenesis of gastrointestinal diseases. Saliva contains an enormous number of oral bacteria and is swallowed directly into the intestine. Here, we explored the influence of periodontitis salivary microbiota on colonic inflammation and possible mechanisms in dextran sulfate sodium (DSS)–induced colitis. The salivary microbiota was collected from healthy individuals and those with periodontitis and gavaged to C57BL/6 mice. Periodontitis colitis was induced by DSS for 5 d and ligature for 1 wk. The degree of colon inflammation was evaluated through hematoxylin and eosin staining, ELISA, and quantitative real-time polymerase chain reaction. Immune parameters were measured with quantitative real-time polymerase chain reaction, flow cytometry, and immunofluorescence. The gut microbiota and metabolome analyses were performed via 16S rRNA gene sequencing and liquid chromatography–mass spectrometry. Although no significant colitis-associated phenotypic changes were found under physiologic conditions, periodontitis salivary microbiota exacerbated colitis in a periodontitis colitis model after DSS induction. The immune response more closely resembled the pathology of ulcerative colitis, including aggravated macrophage M2 polarization and Th2 cell induction (T helper 2). Inflammatory bowel disease–associated microbiota, such as Blautia, Helicobacter, and Ruminococcus, were changed in DSS-induced colitis after periodontitis salivary microbiota gavage. Periodontitis salivary microbiota decreased unsaturated fatty acid levels and increased arachidonic acid metabolism in DSS-induced colitis, which was positively correlated with Aerococcus and Ruminococcus, suggesting the key role of these metabolic events and microbes in the exacerbating effect of periodontitis salivary microbiota on experimental colitis. Our study demonstrated that periodontitis contributes to the pathogenesis of colitis through the swallowing of salivary microbiota, confirming the role of periodontitis in systemic disease and providing new insights into the etiology of gastrointestinal inflammatory diseases.
PDF
