A single fast radio burst localized to a massive galaxy at cosmological distance

Fast radio bursts (FRBs) are brief radio emissions from distant astronomical sources. Some are known to repeat, but most are single bursts. Nonrepeating FRB observations have had insufficient positional accuracy to localize them to an individual host galaxy. We report the interferometric localization of the single-pulse FRB 180924 to a position 4 kiloparsecs from the center of a luminous galaxy at redshift 0.3214. The burst has not been observed to repeat. The properties of the burst and its host are markedly different from those of the only other accurately localized FRB source. The integrated electron column density along the line of sight closely matches models of the intergalactic medium, indicating that some FRBs are clean probes of the baryonic component of the cosmic web

Abnormalities in the ultradian oscillations of insulin secretion and glucose levels in Type 2 (non-insulin-dependent) diabetic patients

To investigate the temporal organization of insulin secretion and glucose concentration during fasting in Type 2 (non-insulin-dependent) diabetes mellitus, we studied seven patients with Type 2 diabetes, eight obese non-diabetic control subjects and eight normal weight non-diabetic subjects. Blood sampling for glucose, insulin and C-peptide was performed at 15-min intervals during a 24-h period of fasting for the diabetic and the obese control subjects and during an 8-h fasting period for the normal subjects. Insulin secretion rates were calculated from the peripheral C-peptide concentration profiles. Ultradian oscillations of glucose levels and insulin secretion rates were evident during fasting in all subjects. An additional study with blood sampling at 2-min intervals for 8 h further indicated that this ultradian periodicity is expressed independently of rapid 10-15 min insulin oscillations. There were no differences between diabetic and non-diabetic subjects in the frequency of the ultradian oscillations of insulin secretion (which averaged 12-15 oscillations per 24 h) and in the rate of concomitancy of oscillations of insulin secretion with oscillations in glucose levels, which averaged 63-65%. The relative amplitudes of both the insulin and glucose oscillations were also similar in diabetic and non-diabetic subjects. The major abnormality in patients with Type 2 diabetes was evidenced by spectral analysis, and confirmed by calculations of the distributions of inter-pulse intervals. It consisted of a slowing of the glucose oscillations, without a similar slowing of the oscillations in insulin secretion. This slowing of the glucose oscillations in fasting Type 2 diabetic patients is consistent with our previous observations of sluggish and irregular glucose oscillations in diabetic subjects receiving mixed meals. This partial dissociation between the oscillatory patterns of insulin secretion and glucose levels could represent a sensitive quantitative marker of the breakdown of the insulin-glucose feedback loop in diabetes.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Differential effects of glucose stimulation upon rapid pulses and ultradian oscillations of insulin secretion

To determine the effect of glucose stimulation on the rapid 8- to 15-min pulses and the ultradian 80- to 170-min oscillations of insulin secretion, peripheral concentrations of glucose, insulin, and C-peptide were measured at 2-min intervals over 2 h (i.e. rapid experiments), at 15-min intervals over 8-20 h (i.e. ultradian experiments) in 17 normal subjects during saline infusion, or during constant glucose infusion at a rate of 3 mg/(kg.min) (i.e. low dose) or 6 mg/(kg.min) (i.e. high dose). In the ultradian experiments, insulin secretory rates (ISR) were calculated by deconvolution of the plasma C-peptide concentrations. Significant oscillations with 125- to 166-min periods were detected in all glucose and ISR profiles. The numbers of ISR oscillations per 24 h were similar during saline infusion and low and high dose glucose infusion. In contrast, the amplitude of the ISR peaks increased progressively from 14 ± 1 pmol/min during saline infusion to 50 ± 7 pmol/min and further to 97 ± 9 pmol/min during low and high dose glucose infusions, respectively. When expressed as percent increment, the amplitude of the ISR oscillations increased significantly from 31 ± 5% during saline infusion to 41 ± 4% during low dose glucose infusion and 44 ± 3% during high dose glucose infusion (P < 0.05). In all profiles obtained from the 2-min sampling experiments, rapid pulses of glucose, insulin, and C-peptide were apparent. The number of insulin pulses during saline and glucose infusions corresponded to a mean periodicity of 10 min. The amplitude of these rapid insulin pulses increased from 17.3 ± 2.9 to 39.8 ± 11.8 pmol/L (P < 0.01) in response to glucose. In contrast to the ultradian oscillations, the relative amplitude of the rapid insulin pulses decreased significantly from 28.8 ± 3.4% during saline infusion to 13.6 ± 1.6% during high dose glucose infusion (P < 0.01). Our findings demonstrate that the pancreatic response to glucose stimulation is different for the rapid pulses and the ultradian oscillations. When the rate of glucose stimulation is increased, the absolute amplitude of both the rapid pulses and the ultradian oscillations increases. However, when expressed as percent increment, the amplitude of the rapid pulses decreases during glucose stimulation, whereas the amplitude of the ultradian oscillations increases. These findings suggest that the two oscillatory modes have a different origin and physiological significance. © 1993 by The Endocrine Society.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation; analyses timings and patterns of tumour evolution; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity; and evaluates a range of more-specialized features of cancer genomes