Predictable Return Distributions

Using quantile regression this paper explores the predictability of the stock and bond return distributions as a function of economic state variables. The use of quantile regression allows us to examine specific parts of the return distribution such as the tails and the center, and for a sufficiently fine grid of quantiles we can trace out the entire distribution. A univariate quantile regression model is used to examine the marginal stock and bond return distributions, while a multivariate model is used to capture their joint distribution. An empirical analysis on US data shows that economic state variables predict the stock and bond return distributions in quite different ways in terms of, for example, location shifts, volatility and skewness. Comparing the different economic state variables in terms of their out‐of‐sample forecasting performance, the empirical analysis also shows that the relative accuracy of the state variables varies across the return distribution. Density forecasts based on an assumed normal distribution with forecasted mean and variance is compared to forecasts based on quantile estimates and, in general, the latter yields the best performance. Copyright © 2015 John Wiley & Sons, Ltd.     

Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants

Targeted capture combined with massively parallel exome sequencing is a promising approach to identify genetic variants implicated in human traits. We report exome sequencing of 200 individuals from Denmark with targeted capture of 18,654 coding genes and sequence coverage of each individual exome at an average depth of 12-fold. On average, about 95% of the target regions were covered by at least one read. We identified 121,870 SNPs in the sample population, including 53,081 coding SNPs (cSNPs). Using a statistical method for SNP calling and an estimation of allelic frequencies based on our population data, we derived the allele frequency spectrum of cSNPs with a minor allele frequency greater than 0.02. We identified a 1.8-fold excess of deleterious, non-syonomyous cSNPs over synonymous cSNPs in the low-frequency range (minor allele frequencies between 2% and 5%). This excess was more pronounced for X-linked SNPs, suggesting that deleterious substitutions are primarily recessive.     

Phase-contrast X-ray microtomography links Cretaceous seeds with Gnetales and Bennettitales

Over the past 25 years the discovery and study of Cretaceous plant mesofossils has yielded diverse and exquisitely preserved fossil flowers that have revolutionized our knowledge of early angiosperms, but remains of other seed plants in the same mesofossil assemblages have so far received little attention. These fossils, typically only a few millimetres long, have often been charred in natural fires and preserve both three-dimensional morphology and cellular detail. Here we use phase-contrast-enhanced synchrotron-radiation X-ray tomographic microscopy to clarify the structure of small charcoalified gymnosperm seeds from the Early Cretaceous of Portugal and North America. The new information links these seeds to Gnetales (including Erdtmanithecales, a putatively closely related fossil group), and to Bennettitales--important extinct Mesozoic seed plants with cycad-like leaves and flower-like reproductive structures. The results suggest that the distinctive seed architecture of Gnetales, Erdtmanithecales and Bennettitales defines a clade containing these taxa. This has significant consequences for hypotheses of seed plant phylogeny by providing support for key elements of the controversial anthophyte hypothesis, which links angiosperms, Bennettitales and Gnetales.     

Derivation of pluripotent epiblast stem cells from mammalian embryos

Although the first mouse embryonic stem (ES) cell lines were derived 25 years ago using feeder-layer-based blastocyst cultures, subsequent efforts to extend the approach to other mammals, including both laboratory and domestic species, have been relatively unsuccessful. The most notable exceptions were the derivation of non-human primate ES cell lines followed shortly thereafter by their derivation of human ES cells. Despite the apparent common origin and the similar pluripotency of mouse and human embryonic stem cells, recent studies have revealed that they use different signalling pathways to maintain their pluripotent status. Mouse ES cells depend on leukaemia inhibitory factor and bone morphogenetic protein, whereas their human counterparts rely on activin (INHBA)/nodal (NODAL) and fibroblast growth factor (FGF). Here we show that pluripotent stem cells can be derived from the late epiblast layer of post-implantation mouse and rat embryos using chemically defined, activin-containing culture medium that is sufficient for long-term maintenance of human embryonic stem cells. Our results demonstrate that activin/Nodal signalling has an evolutionarily conserved role in the derivation and the maintenance of pluripotency in these novel stem cells. Epiblast stem cells provide a valuable experimental system for determining whether distinctions between mouse and human embryonic stem cells reflect species differences or diverse temporal origins.     

Carbon dioxide release from the North Pacific abyss during the last deglaciation

Atmospheric carbon dioxide concentrations were significantly lower during glacial periods than during intervening interglacial periods, but the mechanisms responsible for this difference remain uncertain. Many recent explanations call on greater carbon storage in a poorly ventilated deep ocean during glacial periods, but direct evidence regarding the ventilation and respired carbon content of the glacial deep ocean is sparse and often equivocal. Here we present sedimentary geochemical records from sites spanning the deep subarctic Pacific that--together with previously published results--show that a poorly ventilated water mass containing a high concentration of respired carbon dioxide occupied the North Pacific abyss during the Last Glacial Maximum. Despite an inferred increase in deep Southern Ocean ventilation during the first step of the deglaciation (18,000-15,000 years ago), we find no evidence for improved ventilation in the abyssal subarctic Pacific until a rapid transition approximately 14,600 years ago: this change was accompanied by an acceleration of export production from the surface waters above but only a small increase in atmospheric carbon dioxide concentration. We speculate that these changes were mechanistically linked to a roughly coeval increase in deep water formation in the North Atlantic, which flushed respired carbon dioxide from northern abyssal waters, but also increased the supply of nutrients to the upper ocean, leading to greater carbon dioxide sequestration at mid-depths and stalling the rise of atmospheric carbon dioxide concentrations. Our findings are qualitatively consistent with hypotheses invoking a deglacial flushing of respired carbon dioxide from an isolated, deep ocean reservoir, but suggest that the reservoir may have been released in stages, as vigorous deep water ventilation switched between North Atlantic and Southern Ocean source regions.     

Interferon modulation of cellular microRNAs as an antiviral mechanism

RNA interference through non-coding microRNAs (miRNAs) represents a vital component of the innate antiviral immune response in plants and invertebrate animals; however, a role for cellular miRNAs in the defence against viral infection in mammalian organisms has thus far remained elusive. Here we show that interferon beta (IFNbeta) rapidly modulates the expression of numerous cellular miRNAs, and that eight of these IFNbeta-induced miRNAs have sequence-predicted targets within the hepatitis C virus (HCV) genomic RNA. The introduction of synthetic miRNA-mimics corresponding to these IFNbeta-induced miRNAs reproduces the antiviral effects of IFNbeta on HCV replication and infection, whereas neutralization of these antiviral miRNAs with anti-miRNAs reduces the antiviral effects of IFNbeta against HCV. In addition, we demonstrate that IFNbeta treatment leads to a significant reduction in the expression of the liver-specific miR-122, an miRNA that has been previously shown to be essential for HCV replication. Therefore, our findings strongly support the notion that mammalian organisms too, through the interferon system, use cellular miRNAs to combat viral infections.     

A very energetic supernova associated with the gamma-ray burst of 29 March 2003

Over the past five years evidence has mounted that long-duration (>2 s) gamma-ray bursts (GRBs)-the most luminous of all astronomical explosions-signal the collapse of massive stars in our Universe. This evidence was originally based on the probable association of one unusual GRB with a supernova, but now includes the association of GRBs with regions of massive star formation in distant galaxies, the appearance of supernova-like 'bumps' in the optical afterglow light curves of several bursts and lines of freshly synthesized elements in the spectra of a few X-ray afterglows. These observations support, but do not yet conclusively demonstrate, the idea that long-duration GRBs are associated with the deaths of massive stars, presumably arising from core collapse. Here we report evidence that a very energetic supernova (a hypernova) was temporally and spatially coincident with a GRB at redshift z = 0.1685. The timing of the supernova indicates that it exploded within a few days of the GRB, strongly suggesting that core-collapse events can give rise to GRBs, thereby favouring the 'collapsar' model.