ABSTRACT We report the detection of coherent pulsations from the ultraluminous X-ray source (ULX) NGC 7793 P13. The 0.42 s nearly sinusoidal pulsations were initially discovered in broadband X-ray ...observations using XMM-Newton and NuSTAR taken in 2016. We subsequently also found pulsations in archival XMM-Newton data taken in 2013 and 2014. The significant (>5 ) detection of coherent pulsations demonstrates that the compact object in P13 is a neutron star, and given the observed peak luminosity of 1040 erg s − 1 (assuming isotropy), it is well above the Eddington limit for a 1.4 M accretor. This makes P13 the second ULX known to be powered by an accreting neutron star. The pulse period varies between epochs, with a slow but persistent spin-up over the 2013-2016 period. This spin-up indicates a magnetic field of B 1.5 × 1012 G, typical of many Galactic accreting pulsars. The most likely explanation for the extreme luminosity is a high degree of beaming; however, this is difficult to reconcile with the sinusoidal pulse profile.
Secretory vesicles in endocrine cells store hormones such as growth hormone (GH) and insulin before their release into the bloodstream. The molecular mechanisms governing budding of immature ...secretory vesicles from the trans-Golgi network (TGN) and their subsequent maturation remain unclear. Here, we identify the lipid binding BAR (Bin/amphiphysin/Rvs) domain protein PICK1 (protein interacting with C kinase 1) as a key component early in the biogenesis of secretory vesicles in GH-producing cells. Both PICK1-deficient Drosophila and mice displayed somatic growth retardation. Growth retardation was rescued in flies by reintroducing PICK1 in neurosecretory cells producing somatotropic peptides. PICK1-deficient mice were characterized by decreased body weight and length, increased fat accumulation, impaired GH secretion, and decreased storage of GH in the pituitary. Decreased GH storage was supported by electron microscopy showing prominent reduction in secretory vesicle number. Evidence was also obtained for impaired insulin secretion associated with decreased glucose tolerance. PICK1 localized in cells to immature secretory vesicles, and the PICK1 BAR domain was shown by live imaging to associate with vesicles budding from the TGN and to possess membrane-sculpting properties in vitro. In mouse pituitary, PICK1 co-localized with the BAR domain protein ICA69, and PICK1 deficiency abolished ICA69 protein expression. In the Drosophila brain, PICK1 and ICA69 co-immunoprecipitated and showed mutually dependent expression. Finally, both in a Drosophila model of type 2 diabetes and in high-fat-diet-induced obese mice, we observed up-regulation of PICK1 mRNA expression. Our findings suggest that PICK1, together with ICA69, is critical during budding of immature secretory vesicles from the TGN and thus for vesicular storage of GH and possibly other hormones. The data link two BAR domain proteins to membrane remodeling processes in the secretory pathway of peptidergic endocrine cells and support an important role of PICK1/ICA69 in maintenance of metabolic homeostasis.
Adipocyte differentiation is driven by waves of transcriptional regulators that reprogram the enhancer landscape and change the wiring of the promoter interactome. Here, we use high-throughput ...chromosome conformation enhancer capture to interrogate the role of enhancer-to-enhancer interactions during differentiation of human mesenchymal stem cells. We find that enhancers form an elaborate network that is dynamic during differentiation and coupled with changes in enhancer activity. Transcription factors (TFs) at baited enhancers amplify TF binding at target enhancers, a phenomenon we term cross-interaction stabilization of TFs. Moreover, highly interconnected enhancers (HICE) act as integration hubs orchestrating differentiation by the formation of three-dimensional enhancer communities, inside which, HICE, and other enhancers, converge on phenotypically important gene promoters. Collectively, these results indicate that enhancer interactions play a key role in the regulation of enhancer function, and that HICE are important for both signal integration and compartmentalization of the genome.
ABSTRACT We report the first hard X-ray observations with NuSTAR of the BL Lac-type blazar PKS 2155-304, augmented with soft X-ray data from XMM-Newton and γ-ray data from the Fermi Large Area ...Telescope, obtained in 2013 April when the source was in a very low flux state. A joint NuSTAR and XMM spectrum, covering the energy range 0.5-60 keV, is best described by a model consisting of a log-parabola component with curvature and a (local) photon index 3.04 0.15 at photon energy of 2 keV, and a hard power-law tail with photon index 2.2 0.4. The hard X-ray tail can be smoothly joined to the quasi-simultaneous γ-ray spectrum by a synchrotron self-Compton component produced by an electron distribution with index p = 2.2. Assuming that the power-law electron distribution extends down to γmin = 1 and that there is one proton per electron, an unrealistically high total jet power of Lp ∼ 1047 erg s−1 is inferred. This can be reduced by two orders of magnitude either by considering a significant presence of electron-positron pairs with lepton-to-proton ratio , or by introducing an additional, low-energy break in the electron energy distribution at the electron Lorentz factor γbr1 ∼ 100. In either case, the jet composition is expected to be strongly matter-dominated.
The interest in improving the thermoelectric response of bulk materials has received a boost after it has been recognized that layered materials, in particular SnSe, show a very large thermoelectric ...figure of merit. This result has received great attention while it is now possible to conceive other similar materials or experimental methods to improve this value. Before we can now think of engineering this material it is important we understand the basic mechanism that explains this unusual behavior, where very low thermal conductivity and a high thermopower result from a delicate balance between the crystal and electronic structure. In this Letter, we present a complete temperature evolution of the Seebeck coefficient as the material undergoes a soft crystal transformation and its consequences on other properties within SnSe by means of first-principles calculations. Our results are able to explain the full range of considered experimental temperatures.
Mesenchymal (stromal) stem cells (MSCs) constitute populations of mesodermal multipotent cells involved in tissue regeneration and homeostasis in many different organs. Here we performed ...comprehensive characterization of the transcriptional and epigenomic changes associated with osteoblast and adipocyte differentiation of human MSCs. We demonstrate that adipogenesis is driven by considerable remodeling of the chromatin landscape and de novo activation of enhancers, whereas osteogenesis involves activation of preestablished enhancers. Using machine learning algorithms for in silico modeling of transcriptional regulation, we identify a large and diverse transcriptional network of pro-osteogenic and antiadipogenic transcription factors. Intriguingly, binding motifs for these factors overlap with SNPs related to bone and fat formation in humans, and knockdown of single members of this network is sufficient to modulate differentiation in both directions, thus indicating that lineage determination is a delicate balance between the activities of many different transcription factors.
Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia ...chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, P<0.001), KMT2A rearrangements (6%/5%/3%, P<0.001) and higher day 29 residual leukemia for B-lineage (P<0.001), but not T-ALL (P=0.53). Event-free survival rates (pEFS
) were 89±1% (A), 80±3% (B) and 74±4% (C) with significant differences only for non-high risk groups. Except for thrombosis, pancreatitis and osteonecrosis, the risk of 19 specified toxicities was not enhanced by age above 10 years. In conclusion, a pediatric-based protocol is tolerable and effective for young adults, despite their increased frequency of higher risk features.
We use ab initio calculations to predict the thermal conductivity of cubic SiC with different types of defects. An excellent quantitative agreement with previous experimental measurements is found. ...The results unveil that B_{C} substitution has a much stronger effect than any of the other defect types in 3C-SiC, including vacancies. This finding contradicts the prediction of the classical mass-difference model of impurity scattering, according to which the effects of B_{C} and N_{C} would be similar and much smaller than that of the C vacancy. The strikingly different behavior of the B_{C} defect arises from a unique pattern of resonant phonon scattering caused by the broken structural symmetry around the B impurity.
An automated band structure calculation based on the inorganic crystal structure database and the augmented plane wave method for electronic structure calculations is presented. Using a rigid band ...approach and semiclassic Boltzmann theory the band structures are analyzed and a large number of compounds are screened for potential interesting thermoelectric properties. We thereby propose LiZnSb as a potential new thermoelectric material. The k-space structure of the lowest conduction band of LiZnSb is analyzed in detail, and excellent thermoelectric properties are expected for this material. Furthermore the lattice dynamics are calculated, and anisotropic lattice thermal conduction is predicted.
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