The origins of the stellar-mass black hole mergers discovered by LIGO/Virgo are still unknown. Here we show that if migration traps develop in the accretion disks of active galactic nuclei (AGNs) and ...promote the mergers of their captive black holes, the majority of black holes within disks will undergo hierarchical mergers-with one of the black holes being the remnant of a previous merger. 40% of AGN-assisted mergers detected by LIGO/Virgo will include a black hole with mass ≳50M⊙, the mass limit from stellar core collapse. Hierarchical mergers at traps in AGNs will exhibit black hole spins (anti)aligned with the binary's orbital axis, a distinct property from other hierarchical channels. Our results suggest, although not definitively (with odds ratio of ∼1), that LIGO's heaviest merger so far, GW170729, could have originated from this channel.
According to current dogma, chondrocytes and osteoblasts are considered independent lineages derived from a common osteochondroprogenitor. In endochondral bone formation, chondrocytes undergo a ...series of differentiation steps to form the growth plate, and it generally is accepted that death is the ultimate fate of terminally differentiated hypertrophic chondrocytes (HCs). Osteoblasts, accompanying vascular invasion, lay down endochondral bone to replace cartilage. However, whether an HC can become an osteoblast and contribute to the full osteogenic lineage has been the subject of a century-long debate. Here we use a cell-specific tamoxifen-inducible genetic recombination approach to track the fate of murine HCs and show that they can survive the cartilage-to-bone transition and become osteogenic cells in fetal and postnatal endochondral bones and persist into adulthood. This discovery of a chondrocyte-to-osteoblast lineage continuum revises concepts of the ontogeny of osteoblasts, with implications for the control of bone homeostasis and the interpretation of the underlying pathological bases of bone disorders.
Large peridotite massifs are scattered along the 1500km length of the Yarlung-Zangbo Suture Zone (southern Tibet, China), the major suture between Asia and Greater India. Diamonds occur in the ...peridotites and chromitites of several massifs, together with an extensive suite of trace phases that indicate extremely low fO sub(2) (SiC, nitrides, carbides, native elements) and/or ultrahigh pressures (UHP) (diamond, TiO sub(2) II, coesite, possible stishovite). New physical and isotopic (C, N) studies of the diamonds indicate that they are natural, crystallized in a disequilibrium, high-T environment, and spent only a short time at mantle temperatures before exhumation and cooling. These constraints are difficult to reconcile with previous models for the history of the diamond-bearing rocks. Possible evidence for metamorphism in or near the upper part of the Transition Zone includes the following: (1) chromite (in disseminated, nodular and massive chromitites) containing exsolved pyroxenes and coesite, suggesting inversion from a high-P polymorph of chromite; (2) microstructural studies suggesting that the chromitites recrystallized from fine-grained, highly deformed mixtures of wadsleyite and an octahedral polymorph of chromite; (3) a new cubic Mg-silicate, with the space group of ringwoodite but an inverse-spinel structure (all Si in octahedral coordination); (4) harzburgites with coarsely vermicular symplectites of opx + Cr-Al spinel plus or minus cpx; reconstructions suggest that these are the breakdown products of majoritic garnets, with estimated minimum pressures to>13GPa. Evidence for a shallow pre-metamorphic origin for the chromitites and peridotites includes the following: (1) trace-element data showing that the chromitites are typical of suprasubduction-zone (SSZ) chromitites formed by magma mixing or mingling, consistent with Hf-isotope data from magmatic (375Ma) zircons in the chromitites; (2) the composition of the new cubic Mg-silicate, which suggests a low-P origin as antigorite, subsequently dehydrated; (3) the peridotites themselves, which carry the trace element signature of metasomatism in an SSZ environment, a signature that must have been imposed before the incorporation of the UHP and low-fO sub(2) phases. A proposed P-T-t path involves the original formation of chromitites in mantle-wedge harzburgites, subduction of these harzburgites at c. 375Ma, residence in the upper Transition Zone for >200 Myr, and rapid exhumation at c. 170-150Ma or 130-120Ma. Os-isotope data suggest that the subducted mantle consisted of previously depleted subcontinental lithosphere, dragged down by a subducting oceanic slab. Thermomechanical modeling shows that roll-back of a (much later) subducting slab would produce a high-velocity channelized upwelling that could exhume the buoyant harzburgites (and their chromitites) from the Transition Zone in<10 Myr. This rapid upwelling, which may explain some characteristics of the diamonds, appears to have brought some massifs to the surface in forearc or back-arc basins, where they provided a basement for oceanic crust. This model can reconcile many apparently contradictory petrological and geological datasets. It also defines an important, previously unrecognized geodynamic process that may have operated along other large suture zones such as the Urals.
Summary
Background
Asthma in the elderly (aged ≥ 65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late‐onset asthma. Recent studies ...suggest staphylococcal enterotoxin IgE (SE‐IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late‐onset elderly asthma.
Objective
We aimed to examine the associations of SE‐IgE sensitization with late‐onset asthma in the elderly, using a database of elderly asthma cohort study.
Methods
A total of 249 elderly patients with asthma and 98 controls were analysed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE‐IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12‐month follow‐up period.
Results
At baseline, serum SE‐IgE concentrations were significantly higher in patients with asthma than in controls median 0.16 (interquartile range 0.04–0.53) vs. 0.10 (0.01–0.19), P < 0.001. Elderly asthma patients with high SE‐IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE‐IgE levels. In multivariate logistic regression analyses, the associations between serum SE‐IgE concentrations and severe asthma were significant, independently of covariables SE‐IgE‐high (≥ 0.35 kU/L) vs. negative (< 0.10 kU/L) group: odds ratio 7.47, 95% confidence interval 1.86–30.03, P = 0.005. Multiple correspondence analyses also showed that high serum SE‐IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together.
Conclusions and Clinical Relevance
This is the first report on the significant associations of SE‐IgE sensitization with late‐onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma and suggest clues to the pathogenesis of severe late‐onset eosinophilic asthma in the elderly.
Accretion disks around supermassive black holes (SMBHs) are promising sites for stellar mass black hole (BH) mergers due to mass segregation and merger acceleration by disk gas torques. Here we show ...that a gravitational-wave (GW) kick at BH merger causes ram-pressure stripping of gas within the BH Hill sphere. If RH ≥ H, the disk height, an off-center UV flare at aBH ∼ 103rg, emerges within tUV ∼ O(2 days)(aBH/103rg)(MSMBH/108M )(vkick/102 km s−1) postmerger and lasts O(RH/vkick) ∼ O(5tUV). The flare emerges with luminosity O(1042erg s−1)(tUV/2days)−1(MHill/1M )(vkick/102 km s−1)2. Active galactic nucleus optical/UV photometry is altered and asymmetric broad emission line profiles can develop after weeks. If RH < H, detectability depends on disk optical depth. Follow-up by large optical sky surveys is optimized for small GW error volumes and for Laser Interferometer Gravitational-Wave Observatory/Virgo triggers >50M .
Summary
The present study aimed to identify the factors associated with osteoporosis in patients with chronic obstructive pulmonary disease in Taiwan. The study found that female sex, old age, and ...use of a high dose of oral corticosteroids were significantly associated with osteoporosis in these patients.
Introduction
Chronic obstructive pulmonary disease (COPD) is becoming an increasingly serious and prevalent issue worldwide. The treatment of COPD with long-term steroid use may cause osteoporosis and have significant influences on disability and mortality. However, few studies have evaluated the association between steroid use and osteoporosis in patients with COPD. The present study aimed to identify the factors, including demographic characteristics and steroid use (oral corticosteroids OCSs, inhaled corticosteroids, and injected steroids), associated with osteoporosis in patients with COPD in Taiwan.
Methods
This was a retrospective case-control study. Data were obtained from the National Health Insurance Research Database from 1997 to 2009. Cox proportional hazard regression models were used to identify the factors associated with osteoporosis.
Results
The incidence of osteoporosis in the patients with COPD was 1343.0 per 100,000 person-years, the majority of patients were women (63.6 %), and the mean age of the patients was 72.5 years. In multivariate regression analysis, female sex, old age, and use of a high OCS dose with a defined daily dose (DDD) >56 (hazard ratio 1.85, 95 % confidence interval 1.52–2.26,
P
< .0001) exhibited significant independent associations with osteoporosis.
Conclusions
Female sex, old age, and use of a high OCS dose with a cumulative DDD >56 are associated with osteoporosis in patients with COPD. Additionally, female patients >50 years old and male patients >70 years old have a higher risk of osteoporosis. Medical personnel should actively provide health education for the prevention of osteoporosis in these patients.
The mouse organ of Corti, housed inside the cochlea, contains hair cells and supporting cells that transduce sound into electrical signals. These cells develop in two main steps: progenitor ...specification followed by differentiation. Fibroblast Growth Factor (FGF) signaling is important in this developmental pathway, as deletion of FGF receptor 1 (Fgfr1) or its ligand, Fgf20, leads to the loss of hair cells and supporting cells from the organ of Corti. However, whether FGF20-FGFR1 signaling is required during specification or differentiation, and how it interacts with the transcription factor Sox2, also important for hair cell and supporting cell development, has been a topic of debate. Here, we show that while FGF20-FGFR1 signaling functions during progenitor differentiation, FGFR1 has an FGF20-independent, Sox2-dependent role in specification. We also show that a combination of reduction in Sox2 expression and Fgf20 deletion recapitulates the Fgfr1-deletion phenotype. Furthermore, we uncovered a strong genetic interaction between Sox2 and Fgf20, especially in regulating the development of hair cells and supporting cells towards the basal end and the outer compartment of the cochlea. To explain this genetic interaction and its effects on the basal end of the cochlea, we provide evidence that decreased Sox2 expression delays specification, which begins at the apex of the cochlea and progresses towards the base, while Fgf20-deletion results in premature onset of differentiation, which begins near the base of the cochlea and progresses towards the apex. Thereby, Sox2 and Fgf20 interact to ensure that specification occurs before differentiation towards the cochlear base. These findings reveal an intricate developmental program regulating organ of Corti development along the basal-apical axis of the cochlea.
We report an experiment to test quantum interference, entanglement, and nonlocality using two dissimilar photon sources, the Sun and a semiconductor quantum dot on the Earth, which are separated by ...∼150 million kilometers. By making the otherwise vastly distinct photons indistinguishable in all degrees of freedom, we observe time-resolved two-photon quantum interference with a raw visibility of 0.796(17), well above the 0.5 classical limit, providing unambiguous evidence of the quantum nature of thermal light. Further, using the photons with no common history, we demonstrate postselected two-photon entanglement with a state fidelity of 0.826(24) and a violation of Bell inequality by 2.20(6). The experiment can be further extended to a larger scale using photons from distant stars and open a new route to quantum optics experiments at an astronomical scale.
A polarisation diversity antenna for an ultra-high-frequency RFID tag is presented. The antenna consists of two dual-planar inverted-F antennas arranged in a cross-configuration, and mountable on a ...metallic object. The antenna can work together with a linearly polarised reader antenna that has an arbitrary polarisation direction. The proposed tag antenna has a nearly uniform read range between 9.1 and 10.2 m, regardless of the polarisation direction of the reader's transmit field.
We performed a genomewide association study (GWAS) of primary erythrocyte thiopurine S‐methyltransferase (TPMT) activity in children with leukemia (n = 1,026). Adjusting for age and ancestry, TPMT ...was the only gene that reached genomewide significance (top hit rs1142345 or 719A>G; P = 8.6 × 10‐61). Additional genetic variants (in addition to the three single‐nucleotide polymorphisms SNPs, rs1800462, rs1800460, and rs1142345, defining TPMT clinical genotype) did not significantly improve classification accuracy for TPMT phenotype. Clinical mercaptopurine tolerability in 839 patients was related to TPMT clinical genotype (P = 2.4 × 10‐11). Using 177 lymphoblastoid cell lines (LCLs), there were 251 SNPs ranked higher than the top TPMT SNP (rs1142345; P = 6.8 × 10‐5), revealing a limitation of LCLs for pharmacogenomic discovery. In a GWAS, TPMT activity in patients behaves as a monogenic trait, further bolstering the utility of TPMT genetic testing in the clinic.
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