Abstract
The detection of black hole binary coalescence events by Advanced LIGO allows the science benefits of future detectors to be evaluated. In this paper, we report the science benefits of one ...or two 8 km arm length detectors based on the doubling of key parameters in an Advanced LIGO-type detector, combined with realizable enhancements. It is shown that the total detection rate for sources similar to those already detected would increase to ∼ 103–105 per year. Within 0.4 Gpc, we find that around 10 of these events would be localizable to within ∼10−1 deg2. This is sufficient to make unique associations or to rule out a direct association with the brightest galaxies in optical surveys (at r-band magnitudes of 17 or above) or for deeper limits (down to r-band magnitudes of 20) yield statistically significant associations. The combination of angular resolution and event rate would benefit precision testing of formation models, cosmic evolution, and cosmological studies.
Context. Long gamma-ray bursts (GRBs) are produced during the dramatic deaths of massive stars with very short lifetimes, meaning that they explode close to the birth place of their progenitors. Over ...a short period they become the most luminous objects observable in the Universe, being perfect beacons to study high-redshift star-forming regions. Aims. We aim to use the afterglow of GRB 161023A at a redshift z = 2.710 as a background source to study the environment of the explosion and the intervening systems along its line of sight. Methods. For the first time, we complement ultraviolet (UV), optical and near-infrared (NIR) spectroscopy with millimetre spectroscopy using the Atacama Large Millimeter Array (ALMA), which allows us to probe the molecular content of the host galaxy. The X-shooter spectrum shows a plethora of absorption features including fine-structure and metastable transitions of Fe, Ni, Si, C, and O. We present photometry ranging from 43 s to over 500 days after the burst. Results. We infer a host-galaxy metallicity of Zn/H = −1.11 ± 0.07, which, corrected for dust depletion, results in X/H = −0.94 ± 0.08. We do not detect molecular features in the ALMA data, but we derive limits on the molecular content of log(NCO/cm−2) < 15.7 and log(NHCO+/cm−-12, which are consistent with those that we obtain from the optical spectra, log(NH2/cm−2)< 15.2 and log(NCO/cm−2) < 14.5. Within the host galaxy, we detect three velocity systems through UV, optical and NIR absorption spectroscopy, all with levels that were excited by the GRB afterglow. We determine the distance from these systems to the GRB to be in the range between 0.7 and 1.0 kpc. The sight line to GRB 161023A shows nine independent intervening systems, most of them with multiple components. Conclusions. Although no molecular absorption was detected for GRB 161023A, we show that GRB millimetre spectroscopy is now feasible and is opening a new window on the study of molecular gas within star-forming galaxies at all redshifts. The most favoured lines of sight for this purpose will be those with high metallicity and dust.
To conduct a systematic review and meta-analysis that defines the worldwide incidence of celiac disease (CD) and examines temporal trends.
MEDLINE and EMBASE were searched for population-based ...studies reporting the incidence of CD in the overall population, children, or adults. No limits were placed on year or language of publication. Studies solely examining at-risk populations (e.g., patients with type 1 diabetes) were excluded. Random-effects models were performed to meta-analyze sex- and age-specific incidence in the 21st century. Temporal trend analyses assessed the average annual percent change in CD incidence over time.
Of 11,189 citations, 86 eligible studies were identified for inclusion, of which 50 were deemed suitable for analyses. In the 21st century, the pooled female incidence of CD was 17.4 (95% confidence interval CI: 13.7, 21.1) (I = 99.5%) per 100,000 person-years, compared with 7.8 (95% CI: 6.3, 9.2) (I = 98.6%) in males. Child-specific incidence was 21.3 per 100,000 person-years (95% CI: 15.9, 26.7) (I = 99.7%) compared with 12.9 (95% CI: 7.6, 18.2) (I = 99.9%) in adults. Pooling average annual percent changes showed the incidence of CD to be increasing by 7.5% (95% CI: 5.8, 9.3) (I = 79.6%) per year over the past several decades.
Incidence of CD is highest in females and children. Overall, the incidence has been significantly rising in the latter half of the 20th century and into the 21st century throughout the Western world. Population-based studies in Africa, Asia, and Latin America are needed to provide a comprehensive picture of the global incidence of CD.
We are developing a system to control G protein signaling in vivo to regulate a broad range of physiologic responses. Our system utilizes G protein-coupled peptide receptors engineered to respond ...exclusively to synthetic small molecule ligands and not to their natural ligand(s). These engineered receptors are designated RASSLs (receptor activated solely by a synthetic ligand). We have made two prototype RASSLs that are based on the human κ opioid receptor. Small molecule drugs that activate the κ receptor are nonaddictive and safe to administer in vivo. Binding and signaling assays reveal 200-2000-fold reductions in the ability of our RASSLs to bind or be activated by dynorphin, an endogenous peptide ligand of the κ opioid receptor. In a high-throughput signaling assay, these prototype RASSLs expressed in Chinese hamster ovary K1 cells showed little or no response to a panel of 21 opioid peptides but still signaled normally in response to small molecule drugs such as spiradoline. Activation of a RASSL by spiradoline also caused proliferation of rat-1a tissue culture cells. These data provide evidence that G protein-coupled receptors can be made into RASSLs. The potential in vivo applications for RASSLs include the positive enrichment of transfected cells and the development of new animal models of disease.
Context.
Long gamma-ray bursts (GRBs) are produced during the dramatic deaths of massive stars with very short lifetimes, meaning that they explode close to the birth place of their progenitors. Over ...a short period they become the most luminous objects observable in the Universe, being perfect beacons to study high-redshift star-forming regions.
Aims.
We aim to use the afterglow of GRB 161023A at a redshift
z
= 2.710 as a background source to study the environment of the explosion and the intervening systems along its line of sight.
Methods.
For the first time, we complement ultraviolet (UV), optical and near-infrared (NIR) spectroscopy with millimetre spectroscopy using the Atacama Large Millimeter Array (ALMA), which allows us to probe the molecular content of the host galaxy. The X-shooter spectrum shows a plethora of absorption features including fine-structure and metastable transitions of Fe, Ni, Si, C, and O. We present photometry ranging from 43 s to over 500 days after the burst.
Results.
We infer a host-galaxy metallicity of Zn/H = −1.11 ± 0.07, which, corrected for dust depletion, results in X/H = −0.94 ± 0.08. We do not detect molecular features in the ALMA data, but we derive limits on the molecular content of log(
N
CO
/cm
−2
) < 15.7 and log(
N
HCO
+
/cm
−-12
, which are consistent with those that we obtain from the optical spectra, log(
N
H
2
/cm
−2
)< 15.2 and log(
N
CO
/cm
−2
) < 14.5. Within the host galaxy, we detect three velocity systems through UV, optical and NIR absorption spectroscopy, all with levels that were excited by the GRB afterglow. We determine the distance from these systems to the GRB to be in the range between 0.7 and 1.0 kpc. The sight line to GRB 161023A shows nine independent intervening systems, most of them with multiple components.
Conclusions.
Although no molecular absorption was detected for GRB 161023A, we show that GRB millimetre spectroscopy is now feasible and is opening a new window on the study of molecular gas within star-forming galaxies at all redshifts. The most favoured lines of sight for this purpose will be those with high metallicity and dust.
Stimulation of cultured epithelial cells with scatter factor/hepatocyte growth factor (HGF) results in the detachment of cell-cell junctions and initiation of cell migration. Instead of coordinating ...collective cell behavior within a tissue, cells become solitary and have few cell-cell interactions. Since epithelial scattering is recapitulated in cancer progression and since HGF signaling drives cancer metastasis in many cases, inhibitors of HGF signaling have been proposed to act as anticancer agents. We previously sought to better understand critical components required for HGF-induced epithelial scattering by performing a forward chemical genetics screen, which resulted in the identification of compounds with no previously reported biological activity that we report here. In efforts to determine the mechanism of these compounds, we find that many compounds have broad antiproliferative effects on cancer cell lines by arrest of cell division in G2/M with minimal induction of apoptosis. This effect is reminiscent of microtubule-targeting agents, and we find that several of these scaffolds directly inhibit microtubule polymerization. Compounds are assessed for their toxicity and pharmacokinetics in vivo. The identification of novel small-molecule inhibitors of microtubule polymerization highlights the role of the microtubule cytoskeleton in HGF-induced epithelial scattering.
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