Background
The aim of this study was to assess the immune profile within the microenvironment of pancreatic ductal adenocarcinoma (PDAC), and to investigate the prognostic value of intratumoral ...infiltrating immune/inflammatory cells (IICs) in patients after surgery.
Methods
Eighteen phenotypic markers representing 11 types of IIC and the protein products of genes TP53, CDKN2A/p16 and SMAD4/DPC4 were assessed by immunohistochemistry of specimens from patients with pancreatic cancer. The expression of IICs and the mutational status of the genes were correlated with tumour recurrence and survival, and results were validated in an independent cohort.
Results
CD15+ neutrophils, CD20+ B cells and CD206+ tumour‐associated macrophages were seen frequently in tumours, and their presence was associated with reduced survival in a cohort of 79 patients. Expression of CD4+ T helper cells, CD8+ cytotoxic T lymphocytes and CD117+ mast cells was associated with a favourable prognosis. A weighted Cox regression recurrence‐predictive model was constructed that showed good correlation of IICs and gene mutations. A combination of CD15, CD206, CD117 and Smad4 expression was independently associated with overall (hazard ratio (HR) 3·63, 95 per cent c.i. 2·18 to 6·04; P < 0·001) and recurrence‐free (HR 2·93, 1·81 to 4·75; P < 0·001) survival. These findings were validated in an independent cohort (151 patients) and in 54 tissue samples obtained by preoperative endoscopic ultrasound‐guided fine‐needle aspiration.
Conclusion
PDAC has a unique immunosuppressive phenotype that is associated with characteristic gene mutations, disease recurrence and survival after pancreatectomy.
Surgical relevance
The immune microenvironment plays a critical role in the development of pancreatic ductal adenocarcinoma (PDAC). PDAC is associated with mutations in major driver genes, including KRAS, TP53, CDKN2A/p16 and SMAD4/DPC4.
This study shows that the microenvironment of PDAC has a unique immunosuppressive phenotype, which may be driven by oncogene mutations. Patients with PDAC with a highly immunosuppressive profile tended to have poor postoperative survival. A model including three intratumoral infiltrating immune markers (CD15+, CD206+ and CD117+) and a SMAD4 mutation can be used to predict recurrence and survival in patients after surgery for PDAC.
Immunosuppressive phenotype has poor prognosis
In engineering applications, fluid-conveying pipes usually have geometric imperfections or initially curved configurations. Unlike the initially curved pipe supported at both ends, a slightly curved ...cantilevered pipe is capable of displaying some interesting behavior because it is a nonconservative system of fluid-structure interactions. In the present study, nonlinear static and dynamic behaviors of cantilevered pipes conveying fluid are explored, with four different initial shapes being considered. To this end, the strongly nonlinear governing equation is derived by employing the extended Lagrange equations written for dynamical systems containing non-material volumes. The static (steady) equilibrium configurations, stability, and nonlinear dynamics of the slightly curved cantilevered pipes are obtained with the aid of absolute nodal coordinate formulation (ANCF). Based on extensive numerical calculations, some interesting and sometimes unexpected results are displayed. The first unexpected feature in this dynamical system is that the flow-induced static deformation of the pipe can be extremely large even if the initial geometric imperfection of the pipe is quite small. The second unexpected result is that the critical flow velocity for flutter instability of the slightly curved pipe conveying fluid may be either lower or higher than that of a straight pipe, mainly depending on the static equilibrium configuration when the critical flow velocity is just reached. Moreover, it is demonstrated that the slightly curved pipe oscillates about the static equilibrium position instead of the initially curved centerline, and the preferred form of post-instability behavior is periodic motion within a wide range of system parameters considered.
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.
ABSTRACT
Recent studies show that a universal relation between black hole (BH) growth and stellar mass (M⋆) or star formation rate (SFR) is an oversimplification of BH–galaxy coevolution, and that ...morphological and structural properties of host galaxies must also be considered. Particularly, a possible connection between BH growth and host-galaxy compactness was identified among star-forming (SF) galaxies. Utilizing ≈6300 massive galaxies with I814W < 24 at z < 1.2 in the Cosmic Evolution Survey (COSMOS) field, we perform systematic partial correlation analyses to investigate how sample-averaged BH accretion rate ($\rm \overline{BHAR}$) depends on host-galaxy compactness among SF galaxies, when controlling for morphology and M⋆ (or SFR). The projected central surface mass density within 1 kpc, Σ1, is utilized to represent host-galaxy compactness in our study. We find that the $\rm \overline{BHAR}$–Σ1 relation is stronger than either the $\rm \overline{BHAR}$–M⋆ or $\rm \overline{BHAR}$–SFR relation among SF galaxies, and this $\rm \overline{BHAR}$–Σ1 relation applies to both bulge-dominated galaxies and galaxies that are not dominated by bulges. This $\rm \overline{BHAR}$–Σ1 relation among SF galaxies suggests a link between BH growth and the central gas density of host galaxies on the kpc scale, which may further imply a common origin of the gas in the vicinity of the BH and in the central ∼kpc of the galaxy. This $\rm \overline{BHAR}$–Σ1 relation can also be interpreted as the relation between BH growth and the central velocity dispersion of host galaxies at a given gas content (i.e. gas mass fraction), indicating the role of the host-galaxy potential well in regulating accretion on to the BH.
ABSTRACT
Possible connections between central black hole (BH) growth and host-galaxy compactness have been found observationally, which may provide insight into BH–galaxy coevolution: compact ...galaxies might have large amounts of gas in their centres due to their high mass-to-size ratios, and simulations predict that high central gas density can boost BH accretion. However, it is not yet clear if BH growth is fundamentally related to the compactness of the host galaxy, due to observational degeneracies between compactness, stellar mass (M⋆) and star formation rate (SFR). To break these degeneracies, we carry out systematic partial-correlation studies to investigate the dependence of sample-averaged BH accretion rate ($\rm \overline{BHAR}$) on the compactness of host galaxies, represented by the surface-mass density, Σe, or the projected central surface-mass density within 1 kpc, Σ1. We utilize 8842 galaxies with H < 24.5 in the five CANDELS fields at z = 0.5–3. We find that $\rm \overline{BHAR}$ does not significantly depend on compactness when controlling for SFR or M⋆ among bulge-dominated galaxies and galaxies that are not dominated by bulges, respectively. However, when testing is confined to star-forming galaxies at z = 0.5–1.5, we find that the $\rm \overline{BHAR}$–Σ1 relation is not simply a secondary manifestation of a primary $\rm \overline{BHAR}$–M⋆ relation, which may indicate a link between BH growth and the gas density within the central 1 kpc of galaxies.
In this paper, the vortex-induced vibrations of a hinged–hinged pipe conveying fluid are examined, by considering the internal fluid velocities ranging from the subcritical to the supercritical ...regions. The nonlinear coupled equations of motion are discretized by employing a four-mode Galerkin method. Based on numerical simulations, diagrams of the displacement amplitude versus the external fluid reduced velocity are constructed for pipes transporting subcritical and supercritical fluid flows. It is shown that when the internal fluid velocity is in the subcritical region, the pipe is always vibrating periodically around the pre-buckling configuration and that with increasing external fluid reduced velocity the peak amplitude of the pipe increases first and then decreases, with jumping phenomenon between the upper and lower response branches. When the internal fluid velocity is in the supercritical region, however, the pipe displays various dynamical behaviors around the post-buckling configuration such as inverse period-doubling bifurcations, periodic and chaotic motions. Moreover, the bifurcation diagrams for vibration amplitude of the pipe with varying internal fluid velocities are constructed for each of the lowest four modes of the pipe in the lock-in conditions. The results show that there is a significant difference between the vibrations of the pipe around the pre-buckling configuration and those around the post-buckling configuration.
A fatigue reliability model which integrates the probability distribution of hot spot stress range with a continuous probabilistic formulation of Miner’s damage cumulative rule is developed for ...fatigue life and reliability evaluation of steel bridges with long-term monitoring data. By considering both the nominal stress obtained by measurements and the corresponding stress concentration factor (SCF) as random variables, a probabilistic model of the hot spot stress is formulated with the use of the
S-N
curve and the Miner’s rule, which is then used to evaluate the fatigue life and failure probability with the aid of structural reliability theory. The proposed method is illustrated using the long-term strain monitoring data from the instrumented Tsing Ma Bridge. A standard daily stress spectrum accounting for highway traffic, railway traffic, and typhoon effects is derived by use of the monitoring data. Then global and local finite element models (FEMs) of the bridge are developed for numerically calculating the SCFs at fatigue-susceptible locations, while the stochastic characteristics of SCF for a typical welded T-joint are obtained by full-scale model experiments of a railway beam section of the bridge. A multimodal probability density function (PDF) of the stress range is derived from the monitoring data using the finite mixed Weibull distributions in conjunction with a hybrid parameter estimation algorithm. The failure probability and reliability index versus fatigue life are achieved from the obtained joint PDF of the hot spot stress in terms of the nominal stress and SCF random variables.
We investigate systematically the X-ray emission from type 1 quasars using a sample of 1825 Sloan Digital Sky Survey non-broad absorption line (non-BAL) quasars with Chandra archival observations. A ...significant correlation is found between the X-ray-to-optical power-law slope parameter ( OX) and the 2500 monochromatic luminosity (L2500 ), and the X-ray weakness of a quasar is assessed via the deviation of its OX value from that expected from this relation. We demonstrate the existence of a population of non-BAL X-ray-weak quasars, and the fractions of quasars that are X-ray weak by factors of ≥6 and ≥10 are 5.8% 0.7% and 2.7% 0.5%, respectively. We classify X-ray-weak quasars (X-ray weak by factors of ≥6) into three categories based on their optical spectral features: weak emission-line quasars (WLQs; C iv rest-frame equivalent width < 16 ), red quasars (Δ(g − i) > 0.2), and unclassified X-ray-weak quasars. The X-ray-weak fraction of within the WLQ population is significantly higher than that within non-WLQs, confirming previous findings that WLQs represent one population of X-ray-weak quasars. The X-ray-weak fraction of within the red quasar population is also considerably higher than that within the normal quasar population. The unclassified X-ray-weak quasars do not have unusual optical spectral features, and their X-ray weakness may be mainly related to quasar X-ray variability.
ABSTRACT
We present Chandra observations of 2106 radio-quiet quasars in the redshift range 1.7 ≤ z ≤ 2.7 from the Sloan Digital Sky Survey (SDSS), through data release 14 (DR14), that do not contain ...broad absorption lines in their rest-frame ultraviolet (UV) spectra. This sample adds over a decade worth of SDSS and Chandra observations to our previously published sample of 139 quasars from SDSS DR5 that is still used to correlate X-ray and optical/UV emission in typical quasars. We fit the SDSS spectra for 753 of the quasars in our sample that have high-quality (exposure time ≥ 10 ks and off-axis observation angle ≤ 10 arcmin) X-ray observations, and analyse their X-ray-to-optical spectral energy distribution properties (αox and Δαox) with respect to the measured C iv and Mg ii emission-line rest-frame equivalent width (EW) and the C iv emission-line blueshift. We find significant correlations (at the ≥99.99 per cent level) between αox and these emission-line parameters, as well as between Δαox and $\rm{C \, \small{IV}}$ EW. Slight correlations are found between Δαox and $\rm{C \, \small{IV}}$ blueshift, $\rm{Mg \, \small{II}}$ EW, and the $\rm{C \, \small{IV}}$ EW to $\rm{Mg \, \small{II}}$ EW ratio. The best-fitting trend in each parameter space is used to compare the X-ray weakness (Δαox) and optical/UV emission properties of typical quasars and weak-line quasars (WLQs). The WLQs typically exhibit weaker X-ray emission than predicted by the typical quasar relationships. The best-fitting relationships for our typical quasars are consistent with predictions from the disc–wind quasar model. The behaviour of the WLQs compared to our typical quasars can be explained by an X-ray ‘shielding’ model.
ABSTRACT
Observations in the local universe show a tight correlation between the masses of supermassive black holes (SMBHs; MBH) and host-galaxy bulges (Mbulge), suggesting a strong connection ...between SMBH and bulge growth. However, direct evidence for such a connection in the distant universe remains elusive. We have studied sample-averaged SMBH accretion rate ($\overline{\rm BHAR}$) for bulge-dominated galaxies at z = 0.5–3. While previous observations found $\overline{\rm BHAR}$ is strongly related to host-galaxy stellar mass (M⋆) for the overall galaxy population, our analyses show that, for the bulge-dominated population, $\overline{\rm BHAR}$ is mainly related to SFR rather than M⋆. This ${\overline{\rm BHAR}}$–SFR relation is highly significant, e.g. 9.0σ (Pearson statistic) at z = 0.5–1.5. Such a $\overline{\rm BHAR}$–SFR connection does not exist among our comparison sample of galaxies that are not bulge dominated, for which M⋆ appears to be the main determinant of SMBH accretion. This difference between the bulge-dominated and comparison samples indicates that SMBHs only coevolve with bulges rather than the entire galaxies, explaining the tightness of the local MBH−Mbulge correlation. Our best-fitting ${\overline{\rm BHAR}}$–SFR relation for the bulge-dominated sample is ${\log \overline{\rm BHAR}= \log \mathrm{SFR} - (2.48\pm 0.05)}$ (solar units). The best-fitting $\overline{\rm BHAR}/\mathrm{SFR}$ ratio (10−2.48) for bulge-dominated galaxies is similar to the observed MBH/Mbulge values in the local universe. Our results reveal that SMBH and bulge growth are in lockstep, and thus non-causal scenarios of merger averaging are unlikely the origin of the MBH−Mbulge correlation. This lockstep growth also predicts that the MBH−Mbulge relation should not have strong redshift dependence.
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