XMM-Newton spectroscopy of high redshift quasars

We present XMM-Newton X-ray spectra and optical photometry of four high redshift (z=2.96-3.77) quasars, [HB89] 0438-436, [HB89] 2000-330, [SP89] 1107+487 and RX J122135.6+280613; of these four objects the former two are radio-loud, the latter two radio-quiet. Model fits require only a power law with Galactic absorption in each case; additional intrinsic absorption is also needed for [HB89] 0438-436 and RX J122135.6+280613. The spectra are hard (Gamma \~1.7 for [HB89] 0438-436, [HB89] 2000-330 and ~1.4 for RX J122135.6+280613) with the exception of [SP89]~1107+487 which is softer (Gamma ~2.0); the combined Galactic and intrinsic absorption of lower energy X-rays in the latter source is much less significant than in the other three. The two intrinsically unabsorbed sources have greater optical fluxes relative to the X-ray contributions at the observed energies. While there is no need to include reflection or iron line components in the models, our derived upper limits (99% confidence) on these parameters are not stringent; the absence of these features, if confirmed, may be explained in terms of the high power law contribution and/or a potentially lower albedo due to the low disc temperature. However, we note that the power-law spectrum can be produced via mechanisms other than the Comptonization of accretion disc emission by a corona; given that all four of these quasars are radio sources at some level we should also consider the possibility that the X-ray emission originates, at least partially, in a jet.Comment: Accepted for publication in MNRA

Multiple episodes of ice loss from the Wilkes Subglacial Basin during the Last Interglacial

The Last Interglacial (LIG: 130,000-115,000 years ago) was a period of warmer global mean temperatures and higher and more variable sea levels than the Holocene (11,700-0 years ago). Therefore, a better understanding of Antarctic ice-sheet dynamics during this interval would provide valuable insights for projecting sea-level change in future warming scenarios. Here we present a high-resolution record constraining ice-sheet changes in the Wilkes Subglacial Basin (WSB) of East Antarctica during the LIG, based on analysis of sediment provenance and an ice melt proxy in a marine sediment core retrieved from the Wilkes Land margin. Our sedimentary records, together with existing ice-core records, reveal dynamic fluctuations of the ice sheet in the WSB, with thinning, melting, and potentially retreat leading to ice loss during both early and late stages of the LIG. We suggest that such changes along the East Antarctic Ice Sheet margin may have contributed to fluctuating global sea levels during the LIG

Effects of finite width of excited states on heavy-ion sub-barrier fusion reactions

We discuss the effects of coupling of the relative motion to nuclear collective excitations which have a finite lifetime on heavy-ion fusion reactions at energies near and below the Coulomb barrier. Both spreading and escape widths are explicitly taken into account in the exit doorway model. The coupled-channels equations are numerically solved to show that the finite resonance width always hinders fusion cross sections at subbarrier energies irrespective of the relative importance between the spreading and the escape widths. We also show that the structure of fusion barrier distribution is smeared due to the spreading of the strength of the doorway state.Comment: 13 pages, 3 figures, Submitted to Physical Review

Radio Frequency Spectra of 388 Bright 74 MHz Sources

As a service to the community, we have compiled radio frequency spectra from the literature for all sources within the VLA Low Frequency Sky Survey (VLSS) that are brighter than 15 Jy at 74 MHz. Over 160 references were used to maximize the amount of spectral data used in the compilation of the spectra, while also taking care to determine the corrections needed to put the flux densities from all reference on the same absolute flux density scale. With the new VLSS data, we are able to vastly improve upon previous efforts to compile spectra of bright radio sources to frequencies below 100 MHz because (1) the VLSS flux densities are more reliable than those from some previous low frequency surveys and (2) the VLSS covers a much larger area of the sky (declination >-30 deg.) than many other low frequency surveys (e.g., the 8C survey). In this paper, we discuss how the spectra were constructed and how parameters quantifying the shapes of the spectra were derived. Both the spectra and the shape parameters are made available here to assist in the calibration of observations made with current and future low frequency radio facilities.Comment: Accepted to ApJ

After DART: Using the First Full-scale Test of a Kinetic Impactor to Inform a Future Planetary Defense Mission

NASA’s Double Asteroid Redirection Test (DART) is the first full-scale test of an asteroid deflection technology. Results from the hypervelocity kinetic impact and Earth-based observations, coupled with LICIACube and the later Hera mission, will result in measurement of the momentum transfer efficiency accurate to ∼10% and characterization of the Didymos binary system. But DART is a single experiment; how could these results be used in a future planetary defense necessity involving a different asteroid? We examine what aspects of Dimorphos’s response to kinetic impact will be constrained by DART results; how these constraints will help refine knowledge of the physical properties of asteroidal materials and predictive power of impact simulations; what information about a potential Earth impactor could be acquired before a deflection effort; and how design of a deflection mission should be informed by this understanding. We generalize the momentum enhancement factor β, showing that a particular direction-specific β will be directly determined by the DART results, and that a related direction-specific β is a figure of merit for a kinetic impact mission. The DART β determination constrains the ejecta momentum vector, which, with hydrodynamic simulations, constrains the physical properties of Dimorphos’s near-surface. In a hypothetical planetary defense exigency, extrapolating these constraints to a newly discovered asteroid will require Earth-based observations and benefit from in situ reconnaissance. We show representative predictions for momentum transfer based on different levels of reconnaissance and discuss strategic targeting to optimize the deflection and reduce the risk of a counterproductive deflection in the wrong direction

Vascular endothelial growth factor signaling requires glycine to promote angiogenesis

Peripheral vascular occlusive disease (PVOD) is a common manifestation of atherosclerosis, and it has a high rate of morbidity. Therapeutic angiogenesis would re-establish blood perfusion and rescue ischemic tissue. Vascular endothelial growth factor (VEGF) induces angiogenesis and can potentially be used to treat ischemic diseases, yet in clinical trials VEGF has not fulfilled its full potential with side effects. Whether amino acids promote angiogenesis and the molecular mechanisms are largely unknown. Here we showed that (1) Glycine significantly promoted angiogenesis both in vitro and in vivo and effectively protected mitochondrial function. (2) Activation of glycine transporter 1(GlyT1) induced by VEGF led to an increase in intracellular glycine. (3) Glycine directly bounded to voltage dependent anion channel 1 (VDAC1) on the mitochondrial outer membrane and inhibited its opening. These original results highlight glycine as a necessary mediator in VEGF signalling via the GlyT1-glycine-mTOR-VDAC1 axis pathway. Therefore, the findings in this study are of significance providing new mechanistic insights into angiogenesis and providing better understanding of glycine function in angiogenesis, which may provide valuable information for development of novel therapeutic targets for the treatment of angiogenic vascular disorders

Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents

GermlineGATA2 mutations cause cellular deficiencieswith high propensity for myeloid disease. We investigated 426 children and adolescents with primary myelodysplastic syndrome (MDS) and 82 cases with secondary MDS enrolled in 2 consecutive prospective studies of the European Working Group of MDS in Childhood (EWOGMDS) conducted in Germany over a period of 15 years. Germline GATA2 mutations accounted for 15% of advanced and 7% of all primary MDS cases, but were absent in children with MDS secondary to therapy or acquired aplastic anemia. Mutation carriers were older at diagnosis and more likely to present with monosomy 7 and advanced disease compared with wild-type cases. For stratified analysis according to karyotype, 108 additional primary MDS patients registered with EWOG-MDS were studied. Overall, we identified 57 MDS patients with germline GATA2mutations. GATA2 mutations were highly prevalent among patients with monosomy 7 (37%, all ages) reaching its peak in adolescence (72%of adolescents withmonosomy 7).Unexpectedly, monocytosis was more frequent in GATA2-mutated patients. However, when adjusted for the selection bias from monosomy 7, mutational status had no effect on the hematologic phenotype. Finally, overall survival and outcome of hematopoietic stem cell transplantation (HSCT) were not influenced by mutational status. This study identifies GATA2 mutations as the most common germline defect predisposing to pediatric MDS with a very high prevalence in adolescents with monosomy 7. GATA2 mutations do not confer poor prognosis in childhood MDS. However, the high risk for progression to advanced diseasemust guide decision-making toward timely HSCT

Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency

Deficiency of the transcription factor GATA2 is a highly penetrant genetic disorder predisposing to myelodysplastic syndromes (MDS) and immunodeficiency. It has been recognized as the most common cause underlying primary MDS in children. Triggered by the discovery of a recurrent synonymousGATA2variant, we systematically investigated 911 patients with phenotype of pediatric MDS or cellular deficiencies for the presence of synonymous alterations inGATA2. In total, we identified nine individuals with five heterozygous synonymous mutations: c.351C>G, p.T117T (N = 4); c.649C>T, p.L217L; c.981G>A, p.G327G; c.1023C>T, p.A341A; and c.1416G>A, p.P472P (N = 2). They accounted for 8.2% (9/110) of cases with GATA2 deficiency in our cohort and resulted in selective loss of mutant RNA. While for the hotspot mutation (c.351C>G) a splicing error leading to RNA and protein reduction was identified, severe, likely late stage RNA loss without splicing disruption was found for other mutations. Finally, the synonymous mutations did not alter protein function or stability. In summary, synonymousGATA2substitutions are a new common cause of GATA2 deficiency. These findings have broad implications for genetic counseling and pathogenic variant discovery in Mendelian disorders

DNA-Methylation Profiling of Fetal Tissues Reveals Marked Epigenetic Differences between Chorionic and Amniotic Samples

Epigenetic mechanisms including DNA methylation are supposed to play a key role in fetal development. Here we have investigated fetal DNA-methylation levels of 27,578 CpG loci in 47 chorionic villi (CVS) and 16 amniotic cell (AC) samples. Methylation levels differed significantly between karyotypically normal AC and CVS for 2,014 genes. AC showed more extreme DNA-methylation levels of these genes than CVS and the differentially methylated genes are significantly enriched for processes characteristic for the different cell types sampled. Furthermore, we identified 404 genes differentially methylated in CVS with trisomy 21. These genes were significantly enriched for high CG dinucleotid (CpG) content and developmental processes associated with Down syndrome. Our study points to major tissue-specific differences of fetal DNA-methylation and gives rise to the hypothesis that part of the Down syndrome phenotype is epigenetically programmed in the first trimester of pregnancy