We place firm upper limits on the global accretion history of massive black holes at z ≳ 5 from the recently measured unresolved fraction of the cosmic X-ray background. The maximum allowed ...unresolved intensity observed at 1.5 keV implies a maximum accreted-mass density onto massive black holes of ρacc ≲ 1.4 × 104 M⊙ Mpc-3 for z ≳ 5. Considering the contribution of lower-z AGNs, the value reduces to ρacc ≲ 0.66 × 104 M⊙ Mpc-3. The tension between the need for the efficient and rapid accretion required by the observation of massive black holes already in place at z ≳ 7 and the strict upper limit on the accreted mass derived from the X-ray background may indicate that black holes are rare in high redshift galaxies or that accretion is only efficient for the black holes hosted by rare galaxies.
We present a comprehensive statistical analysis of Swift X-ray light curves of gamma-ray bursts (GRBs) collecting data from more than 650 GRBs discovered by Swift and other facilities. The ...unprecedented sample size allows us to constrain the rest-frame
X-ray properties of GRBs from a statistical perspective, with particular reference to intrinsic time-scales and the energetics of the different light-curve phases in a common rest-frame 0.3-30 keV energy band. Temporal variability episodes are also studied and their properties constrained. Two fundamental questions drive this effort: (i) Does the X-ray emission retain any kind of 'memory' of the prompt γ-ray phase? (ii) Where is the dividing line between long and short GRB X-ray properties? We show that short GRBs decay faster, are less luminous and less energetic than long GRBs in the X-rays, but are interestingly characterized by similar intrinsic absorption. We furthermore reveal the existence of a number of statistically significant relations that link the X-ray to prompt γ-ray parameters in long GRBs; short GRBs are outliers of the majority of these two-parameter relations. However and more importantly, we report on the existence of a universal three-parameter scaling that links the X-ray and the γ-ray energy to the prompt spectral peak energy of both long and short GRBs: E
X, iso∝E
1.00 ± 0.06
γ, iso/E
0.60 ± 0.10
pk.
ABSTRACT
We present the space density evolution, from z = 1.5 up to z = 5.5, of the most massive ($M \ge 10^9\, \mathrm{M}_{\odot }$) black holes hosted in jetted active galactic nuclei (AGNs). The ...analysis is based on a sample of 380 luminosity-selected (λL1350 ≥ 1046 erg s−1 and $P_{5\, \text{GHz}}\ge 10^{27}$ W Hz−1) flat spectrum radio quasars (FSRQs) obtained from the Cosmic Lens All Sky Survey (CLASS). These sources are known to be face-on jetted AGNs (i.e. blazars) and can be exploited to infer the abundance of all the (misaligned) jetted AGNs, using a geometrical argument. We then compare the space density of the most massive supermassive black holes hosted in jetted AGNs with those present in the total population (mostly composed by non-jetted AGNs). We find that the space density has a peak at z ∼ 3, which is significantly larger than the value observed in the total AGN population with similar optical/UV luminosities (z ∼ 2.2), but not as extreme as the value previously inferred from X-ray-selected blazars (z ≳ 4). The jetted fraction (jetted AGNs/total AGNs) is overall consistent with the estimates in the local Universe (10–20 per cent) and at high redshift, assuming Lorentz bulk factors Γ ≈ 5. Finally, we find a marginal decrease in the jetted fraction at high redshifts (by a factor of ∼2). All these evidences point towards a different evolutionary path in the jetted AGNs compared to the total AGN population.
All estimates of cluster mass have some intrinsic scatter and perhaps some bias with true mass even in the absence of measurement errors for example caused by cluster triaxiality and large scale ...structure. Knowledge of the bias and scatter values is fundamental for both cluster cosmology and astrophysics. In this paper we show that the intrinsic scatter of a mass proxy can be constrained by measurements of the gas fraction because masses with higher values of intrinsic scatter with true mass produce more scattered gas fractions. Moreover, the relative bias of two mass estimates can be constrained by comparing the mean gas fraction at the same (nominal) cluster mass. Our observational study addresses the scatter between caustic (i.e., dynamically estimated) and true masses, and the relative bias of caustic and hydrostatic masses. For these purposes, we used the X-ray Unbiased Cluster Sample, a cluster sample selected independently from the intracluster medium content with reliable masses: 34 galaxy clusters in the nearby (0.050 < z < 0.135) Universe, mostly with 14 < log M500/M⊙ ≲ 14.5, and with caustic masses. We found a 35% scatter between caustic and true masses. Furthermore, we found that the relative bias between caustic and hydrostatic masses is small, 0.06 ± 0.05 dex, improving upon past measurements. The small scatter found confirms our previous measurements of a highly variable amount of feedback from cluster to cluster, which is the cause of the observed large variety of core-excised X-ray luminosities and gas masses.
CIB1 (calcium and integrin binding protein 1) is a small intracellular protein with numerous interacting partners, and hence has been implicated in various cellular functions. Recent studies have ...revealed emerging roles of CIB1 in regulating cancer cell survival and angiogenesis, although the mechanisms involved have remained largely undefined. In investigating the oncogenic function of CIB1, we initially found that CIB1 is widely up-regulated across a diverse range of cancers, with this upregulation frequently correlating with oncogenic mutations of KRas. Consistent with this, we found that ectopic expression of oncogenic KRas and HRas in cells resulted in elevated CIB1 expression. We previously described the Ca
-myristoyl switch function of CIB1, and its ability to facilitate agonist-induced plasma membrane localisation of sphingosine kinase 1 (SK1), a location where SK1 is known to elicit oncogenic signalling. Thus, we examined the role this may play in oncogenesis. Consistent with these findings, we demonstrated here that over-expression of CIB1 by itself is sufficient to drive localisation of SK1 to the plasma membrane and enhance the membrane-associated enzymatic activity of SK1, as well as its oncogenic signalling. We subsequently demonstrated that elevated levels of CIB1 resulted in full neoplastic transformation, in a manner dependent on SK1. In agreement with our previous findings that SK1 is a downstream mediator of oncogenic signalling by Ras, we found that targeting CIB1 also inhibited neoplastic growth of cells induced by oncogenic Ras, suggesting an important pro-tumorigenic role for CIB1. Thus, we have demonstrated for the first time a role for CIB1 in neoplastic transformation, and revealed a novel mechanism facilitating oncogenic signalling by Ras and SK1.
We report on the direct observation of an extended X-ray jet in the
z
= 6.1 radio-loud active galactic nucleus PSO J030947.49+271757.31 from a deep
Chandra
X-ray observation (128 ksec). This ...detection represents the most distant kiloparsec-scale off-nuclear emission resolved in X-rays to date. The angular distance of the emission is ∼4″ (corresponding to ∼20 kpc at
z
= 6.1), along the same direction of the jet observed at parsec scales in previous VLBA high-resolution radio observations. Moreover, the 0.5–7.0 keV isophotes coincide with the extended radio emission as imaged by the VLA Sky Survey at 3 GHz. The rest-frame 2–10 keV luminosity of the extended component is
L
2 − 10
keV = 5.9 × 10
44
erg s
−1
, about 8% of the core: this makes it one of the most luminous jets resolved in X-rays so far. Through spectral energy distribution modelling we find that this emission can be explained by the inverse Compton interaction with the photons of the cosmic microwave background, assuming that the jet’s physical parameters are similar to those in the local Universe. At the same time, we find that the radiation produced by a putative population of high-energy electrons through the synchrotron process observed at low redshift is quenched at high redshift, hence becoming negligible.
Frameshift mutations in the DMD gene, encoding dystrophin, cause Duchenne muscular dystrophy (DMD), leading to terminal muscle and heart failure in patients. Somatic gene editing by sequence-specific ...nucleases offers new options for restoring the DMD reading frame, resulting in expression of a shortened but largely functional dystrophin protein. Here, we validated this approach in a pig model of DMD lacking exon 52 of DMD (DMDΔ52), as well as in a corresponding patient-derived induced pluripotent stem cell model. In DMDΔ52 pigs
, intramuscular injection of adeno-associated viral vectors of serotype 9 carrying an intein-split Cas9 (ref.
) and a pair of guide RNAs targeting sequences flanking exon 51 (AAV9-Cas9-gE51) induced expression of a shortened dystrophin (DMDΔ51-52) and improved skeletal muscle function. Moreover, systemic application of AAV9-Cas9-gE51 led to widespread dystrophin expression in muscle, including diaphragm and heart, prolonging survival and reducing arrhythmogenic vulnerability. Similarly, in induced pluripotent stem cell-derived myoblasts and cardiomyocytes of a patient lacking DMDΔ52, AAV6-Cas9-g51-mediated excision of exon 51 restored dystrophin expression and amelioreate skeletal myotube formation as well as abnormal cardiomyocyte Ca
handling and arrhythmogenic susceptibility. The ability of Cas9-mediated exon excision to improve DMD pathology in these translational models paves the way for new treatment approaches in patients with this devastating disease.
Context. The fraction of binary stars is an important ingredient to interpret globular cluster dynamical evolution and their stellar population. Aims. We investigate the properties of main-sequence ...binaries measured in a uniform photometric sample of 59 Galactic globular clusters that were observed by HST WFC/ACS as a part of the Globular Cluster Treasury project. Methods. We measured the fraction of binaries and the distribution of mass-ratio as a function of radial location within the cluster, from the central core to beyond the half-mass radius. We studied the radial distribution of binary stars, and the distribution of stellar mass ratios. We investigated monovariate relations between the fraction of binaries and the main parameters of their host clusters. Results. We found that in nearly all the clusters, the total fraction of binaries is significantly smaller than the fraction of binaries in the field, with a few exceptions only. Binary stars are significantly more centrally concentrated than single MS stars in most of the clusters studied in this paper. The distribution of the mass ratio is generally flat (for mass-ratio parameter q > 0.5). We found a significant anti-correlation between the binary fraction in a cluster and its absolute luminosity (mass). Some, less significant correlation with the collisional parameter, the central stellar density, and the central velocity dispersion are present. There is no statistically significant relation between the binary fraction and other cluster parameters. We confirm the correlation between the binary fraction and the fraction of blue stragglers in the cluster.
Inducing cell death by the sphingolipid ceramide is a potential anti-cancer strategy, but the underlying mechanisms remain poorly defined. Here, we show that triggering accumulation of ceramide in ...acute myeloid leukaemia (AML) cells by inhibition of sphingosine kinase induces an apoptotic integrated stress response (ISR) through protein kinase R-mediated activation of the master transcription factor ATF4. This leads to transcription of the BH3-only protein, Noxa, and degradation of the pro-survival Mcl-1 protein on which AML cells are highly dependent on for survival. Targeting this novel ISR pathway in combination with the Bcl-2 inhibitor venetoclax synergistically killed primary AML blasts, including those with venetoclax-resistant mutations, as well as immunophenotypic leukemic stem cells, and reduced leukemic engraftment in patient-derived AML xenografts. Collectively, these findings provide mechanistic insight into the anti-cancer effects of ceramide and pre-clinical evidence for new approaches to augment Bcl-2 inhibition in the therapy of AML and other cancers with high Mcl-1 dependency.
We analyse the star formation history (SFH) of galaxies as a function of present-day environment, galaxy stellar mass and morphology. The SFH is derived by means of a non-parametric ...spectrophotometric model applied to individual galaxies at z ∼ 0.04–0.1 in the WIde-field Nearby Galaxy-cluster Survey (WINGS) clusters and the Padova Millennium Galaxy and Group Catalogue (PM2GC) field. The field reconstructed evolution of the star formation rate density (SFRD) follows the values observed at each redshift, except at z > 2, where our estimate is ∼1.7 × higher than the high-z observed value. The slope of the SFRD decline with time gets progressively steeper going from low-mass to high-mass haloes. The decrease of the SFRD since z = 2 is due to (1) quenching – 50 per cent of the SFRD in the field and 75 per cent in clusters at z > 2 originated in galaxies that are passive today – and (2) the fact that the average SFR of today's star-forming galaxies has decreased with time. We quantify the contribution to the SFRD(z) of galaxies of today's different masses and morphologies. The current morphology correlates with the current star formation activity but is irrelevant for the past stellar history. The average SFH depends on galaxy mass, but galaxies of a given mass have different histories depending on their environment. We conclude that the variation of the SFRD(z) with environment is not driven by different distributions of galaxy masses and morphologies in clusters and field, and must be due to an accelerated formation in high-mass haloes compared to low-mass ones even for galaxies that will end up having the same galaxy mass today.
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