Eosinophils play a homeostatic role in the body’s immune responses. These cells are involved in combating some parasitic, bacterial, and viral infections and certain cancers and have pathologic roles ...in diseases including asthma, chronic rhinosinusitis with nasal polyps, eosinophilic gastrointestinal disorders, and hypereosinophilic syndromes. Treatment of eosinophilic diseases has traditionally been through nonspecific eosinophil attenuation by use of glucocorticoids. However, several novel biologic therapies targeting eosinophil maturation factors, such as interleukin (IL)-5 and the IL-5 receptor or IL-4/IL-13, have recently been approved for clinical use. Despite the success of biologic therapies, some patients with eosinophilic inflammatory disease may not achieve adequate symptom control, underlining the need to further investigate the contribution of patient characteristics, such as comorbidities and other processes, in driving ongoing disease activity. New research has shown that eosinophils are also involved in several homeostatic processes, including metabolism, tissue remodeling and development, neuronal regulation, epithelial and microbiome regulation, and immunoregulation, indicating that these cells may play a crucial role in metabolic regulation and organ function in healthy humans. Consequently, further investigation is needed into the homeostatic roles of eosinophils and eosinophil-mediated processes across different tissues and their varied microenvironments. Such work may provide important insights into the role of eosinophils not only under disease conditions but also in health. This narrative review synthesizes relevant publications retrieved from PubMed informed by author expertise to provide new insights into the diverse roles of eosinophils in health and disease, with particular emphasis on the implications for current and future development of eosinophil-targeted therapies.
Changing-look quasars are a recently identified class of active galaxies in which the strong UV continuum and/or broad optical hydrogen emission lines associated with unobscured quasars either appear ...or disappear on time-scales of months to years. The physical processes responsible for this behaviour are still debated, but changes in the black hole accretion rate or accretion disc structure appear more likely than changes in obscuration. Here, we report on four epochs of spectroscopy of SDSS J110057.70-005304.5, a quasar at a redshift of z = 0.378 whose UV continuum and broad hydrogen emission lines have faded, and then returned over the past ≈20 yr. The change in this quasar was initially identified in the infrared, and an archival spectrum from 2010 shows an intermediate phase of the transition during which the flux below rest frame ≈3400 Å has decreased by close to an order of magnitude. This combination is unique compared to previously published examples of changing-look quasars, and is best explained by dramatic changes in the innermost regions of the accretion disc. The optical continuum has been rising since mid-2016, leading to a prediction of a rise in hydrogen emission-line flux in the next year. Increases in the infrared flux are beginning to follow, delayed by a ~3 yr observed time-scale. If our model is confirmed, the physics of changing-look quasars are governed by processes at the innermost stable circular orbit around the black hole, and the structure of the innermost disc. The easily identifiable and monitored changing-look quasars would then provide a new probe and laboratory of the nuclear central engine.
Spectroscopic detection of narrow emission lines traces the presence of circumstellar mass distributions around massive stars exploding as core-collapse supernovae. Transient emission lines ...disappearing shortly after the supernova explosion suggest that the material spatial extent is compact and implies an increased mass loss shortly prior to explosion. Here, we present a systematic survey for such transient emission lines (Flash Spectroscopy) among Type II supernovae detected in the first year of the Zwicky Transient Facility survey. We find that at least six out of ten events for which a spectrum was obtained within two days of the estimated explosion time show evidence for such transient flash lines. Our measured flash event fraction (>30% at 95% confidence level) indicates that elevated mass loss is a common process occurring in massive stars that are about to explode as supernovae.
ABSTRACT
We present the results of a systematic search for quasars in the Catalina Real-time Transient Survey exhibiting both strong photometric variability and spectroscopic variability over a ...decadal baseline. We identify 111 sources with specific patterns of optical and mid-infrared photometric behaviour and a defined spectroscopic change. These ‘changing-state’ quasars (CSQs) form a higher luminosity sample to complement existing sets of ‘changing-look’ AGNs and quasars in the literature. The CSQs (by selection) exhibit larger photometric variability than the changing-look quasars (CLQs). The spectroscopic variability is marginally stronger in the CSQs than CLQs as defined by the change in H β/$\rm {O \,\rm {\small {III}}}$ ratio. We find 48 sources with declining H β flux and 63 sources with increasing H β flux, and discover 8 sources with $z$ > 0.8, further extending the redshift arm. Our CSQ sample compares to the literature CLQ objects in similar distributions of H β flux ratios and differential Eddington ratios between high (bright) and low (dim) states. Taken as a whole, we find that this population of extreme varying quasars is associated with changes in the Eddington ratio and the time-scales imply cooling/heating fronts propagating through the disc.
Quasars have long been known to be variable sources at all wavelengths. Their optical variability is stochastic and can be due to a variety of physical mechanisms; it is also well-described ...statistically in terms of a damped random walk model. The recent availability of large collections of astronomical time series of flux measurements (light curves) offers new data sets for a systematic exploration of quasar variability. Here we report the detection of a strong, smooth periodic signal in the optical variability of the quasar PG 1302-102 with a mean observed period of 1,884 ± 88 days. It was identified in a search for periodic variability in a data set of light curves for 247,000 known, spectroscopically confirmed quasars with a temporal baseline of about 9 years. Although the interpretation of this phenomenon is still uncertain, the most plausible mechanisms involve a binary system of two supermassive black holes with a subparsec separation. Such systems are an expected consequence of galaxy mergers and can provide important constraints on models of galaxy formation and evolution.
Abstract
We present a public catalog of transients from the Zwicky Transient Facility (ZTF) Bright Transient Survey, a magnitude-limited (
m
< 19 mag in either the
g
or
r
filter) survey for ...extragalactic transients in the ZTF public stream. We introduce cuts on survey coverage, sky visibility around peak light, and other properties unconnected to the nature of the transient, and show that the resulting statistical sample is spectroscopically 97% complete at <18 mag, 93% complete at <18.5 mag, and 75% complete at <19 mag. We summarize the fundamental properties of this population, identifying distinct duration–luminosity correlations in a variety of supernova (SN) classes and associating the majority of fast optical transients with well-established spectroscopic SN types (primarily SN Ibn and II/IIb). We measure the Type Ia SN and core-collapse (CC) SN rates and luminosity functions, which show good consistency with recent work. About 7% of CC SNe explode in very low-luminosity galaxies (
M
i
> −16 mag), 10% in red-sequence galaxies, and 1% in massive ellipticals. We find no significant difference in the luminosity or color distributions between the host galaxies of SNe Type II and SNe Type Ib/c, suggesting that line-driven wind stripping does not play a major role in the loss of the hydrogen envelope from their progenitors. Future large-scale classification efforts with ZTF and other wide-area surveys will provide high-quality measurements of the rates, properties, and environments of all known types of optical transients and limits on the existence of theoretically predicted but as yet unobserved explosions.
Abstract
We present a search for extragalactic fast blue optical transients (FBOTs) during Phase I of the Zwicky Transient Facility (ZTF). We identify 38 candidates with durations above half-maximum ...light 1 day <
t
1/2
< 12 days, of which 28 have blue (
g
−
r
≲ −0.2 mag) colors at peak light. Of the 38 transients (28 FBOTs), 19 (13) can be spectroscopically classified as core-collapse supernovae (SNe): 11 (8) H- or He-rich (Type II/IIb/Ib) SNe, 6 (4) interacting (Type IIn/Ibn) SNe, and 2 (1) H&He-poor (Type Ic/Ic-BL) SNe. Two FBOTs (published previously) had predominantly featureless spectra and luminous radio emission: AT2018lug (The Koala) and AT2020xnd (The Camel). Seven (five) did not have a definitive classification: AT 2020bdh showed tentative broad H
α
in emission, and AT 2020bot showed unidentified broad features and was 10 kpc offset from the center of an early-type galaxy. Ten (eight) have no spectroscopic observations or redshift measurements. We present multiwavelength (radio, millimeter, and/or X-ray) observations for five FBOTs (three Type Ibn, one Type IIn/Ibn, one Type IIb). Additionally, we search radio-survey (VLA and ASKAP) data to set limits on the presence of radio emission for 24 of the transients. All X-ray and radio observations resulted in nondetections; we rule out AT2018cow-like X-ray and radio behavior for five FBOTs and more luminous emission (such as that seen in the Camel) for four additional FBOTs. We conclude that exotic transients similar to AT2018cow, the Koala, and the Camel represent a rare subset of FBOTs and use ZTF’s SN classification experiments to measure the rate to be at most 0.1% of the local core-collapse SN rate.
The relationship between the cells that initiate cancer and the cancer stem-like cells that propagate tumors has been poorly defined. In a human prostate tissue transformation model, basal cells ...expressing the oncogenes Myc and myristoylated AKT can initiate heterogeneous tumors. Tumors contain features of acinar-type adenocarcinoma with elevated eIF4E-driven protein translation and squamous cell carcinoma marked by activated beta-catenin. Lentiviral integration site analysis revealed that alternative histological phenotypes can be clonally derived from a common cell of origin. In advanced disease, adenocarcinoma can be propagated by self-renewing tumor cells with an androgen receptor-low immature luminal phenotype in the absence of basal-like cells. These data indicate that advanced prostate adenocarcinoma initiated in basal cells can be maintained by luminal-like tumor-propagating cells. Determining the cells that maintain human prostate adenocarcinoma and the signaling pathways characterizing these tumor-propagating cells is critical for developing effective therapeutic strategies against this population.
Deep Modeling of Quasar Variability Tachibana, Yutaro; Graham, Matthew J.; Kawai, Nobuyuki ...
The Astrophysical journal,
11/2020, Volume:
903, Issue:
1
Journal Article
Peer reviewed
Open access
Quasars have long been known as intrinsically variable sources, but the physical mechanism underlying the temporal optical/UV variability is still not well understood. We propose a novel ...nonparametric method for modeling and forecasting the optical variability of quasars utilizing an AE neural network to gain insight into the underlying processes. The AE is trained with ∼15,000 decade-long quasar light curves obtained by the Catalina Real-time Transient Survey selected with negligible flux contamination from the host galaxy. The AE's performance in forecasting the temporal flux variation of quasars is superior to that of the damped random walk process. We find a temporal asymmetry in the optical variability and a novel relation-the amplitude of the variability asymmetry decreases as luminosity and/or black hole mass increases-is suggested with the help of autoencoded features. The characteristics of the variability asymmetry are in agreement with those from the self-organized disk instability model, which predicts that the magnitude of the variability asymmetry decreases as the ratio of the diffusion mass to inflow mass in the accretion disk increases.
Background:
Cushing's syndrome (CS) is a severe condition with excess mortality and significant morbidity necessitating control of hypercortisolemia. There are few data documenting use of the ...steroidogenesis inhibitor metyrapone for this purpose.
Objective:
The objective was to assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with CS.
Design:
This was designed as a retrospective, multicenter study.
Setting:
Thirteen University hospitals were studied.
Patients:
We studied a total of 195 patients with proven CS: 115 Cushing's disease, 37 ectopic ACTH syndrome, 43 ACTH-independent disease (adrenocortical carcinoma 10, adrenal adenoma 30, and ACTH-independent adrenal hyperplasia 3).
Measurements:
Measurements included biochemical parameters of activity of CS: mean serum cortisol “day-curve” (CDC) (target 150–300 nmol/L); 9 am serum cortisol; 24-hour urinary free cortisol (UFC).
Results:
A total of 164/195 received metyrapone monotherapy. Mean age was 49.6 ± 15.7 years; mean duration of therapy 8 months (median 3 mo, range 3 d to 11.6 y). There were significant improvements on metyrapone, first evaluation to last review: CDC (91 patients, 722.9 nmol/L 26.2 μg/dL vs 348.6 nmol/L 12.6 μg/dL; P < .0001); 9 am cortisol (123 patients, 882.9 nmol/L 32.0 μg/dL vs 491.1 nmol/L 17.8 μg/dL; P < .0001); and UFC (37 patients, 1483 nmol/24 h 537 μg/24 h vs 452.6 nmol/24 h 164 μg/24 h; P = .003). Overall, control at last review: 55%, 43%, 46%, and 76% of patients who had CDCs, UFCs, 9 am cortisol less than 331 nmol/L (12.0 μg/dL), and 9 am cortisol less than upper limit of normal/600 nmol/L (21.7 μg/dL). Median final dose: Cushing's disease 1375 mg; ectopic ACTH syndrome 1500 mg; benign adrenal disease 750 mg; and adrenocortical carcinoma 1250 mg. Adverse events occurred in 25% of patients, mostly mild gastrointestinal upset and dizziness, usually within 2 weeks of initiation or dose increase, all reversible.
Conclusions:
Metyrapone is effective therapy for short- and long-term control of hypercortisolemia in CS.
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