The earliest record of human activity in northern Europe

The colonization of Eurasia by early humans is a key event after their spread out of Africa, but the nature, timing and ecological context of the earliest human occupation of northwest Europe is uncertain and has been the subject of intense debate. The southern Caucasus was occupied about 1.8 million years (Myr) ago, whereas human remains from Atapuerca-TD6, Spain (more than 780 kyr ago) and Ceprano, Italy (about 800 kyr ago) show that early Homo had dispersed to the Mediterranean hinterland before the Brunhes-Matuyama magnetic polarity reversal (780 kyr ago). Until now, the earliest uncontested artefacts from northern Europe were much younger, suggesting that humans were unable to colonize northern latitudes until about 500 kyr ago. Here we report flint artefacts from the Cromer Forest-bed Formation at Pakefield (52 degrees N), Suffolk, UK, from an interglacial sequence yielding a diverse range of plant and animal fossils. Event and lithostratigraphy, palaeomagnetism, amino acid geochronology and biostratigraphy indicate that the artefacts date to the early part of the Brunhes Chron (about 700 kyr ago) and thus represent the earliest unequivocal evidence for human presence north of the Alps.     

Towards a proteome-scale map of the human protein-protein interaction network

Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.     

Non-equilibration of hydrostatic pressure in blebbing cells

Current models for protrusive motility in animal cells focus on cytoskeleton-based mechanisms, where localized protrusion is driven by local regulation of actin biochemistry. In plants and fungi, protrusion is driven primarily by hydrostatic pressure. For hydrostatic pressure to drive localized protrusion in animal cells, it would have to be locally regulated, but current models treating cytoplasm as an incompressible viscoelastic continuum or viscous liquid require that hydrostatic pressure equilibrates essentially instantaneously over the whole cell. Here, we use cell blebs as reporters of local pressure in the cytoplasm. When we locally perfuse blebbing cells with cortex-relaxing drugs to dissipate pressure on one side, blebbing continues on the untreated side, implying non-equilibration of pressure on scales of approximately 10 microm and 10 s. We can account for localization of pressure by considering the cytoplasm as a contractile, elastic network infiltrated by cytosol. Motion of the fluid relative to the network generates spatially heterogeneous transients in the pressure field, and can be described in the framework of poroelasticity.     

Spectroscopic evidence for a lava fountain driven by previously accumulated magmatic gas

Lava fountains are spectacular continuous gas jets, propelling lava fragments to heights of several hundred metres, which occasionally occur during eruptions of low-viscosity magmas. Whether they are generated by the effervescent disruption of fast-rising bubbly melt or by the separate ascent of a bubble foam layer accumulated at depth still remains a matter of debate. No field measurement has yet allowed firm discrimination between these two models. A key insight into the origin of lava fountains may be gained by measuring the chemical composition of the driving gas phase. This composition should differ markedly depending on whether the magma degassing occurs before or during eruption. Here we report the analysis of magmatic gas during a powerful (250-600 m high) lava fountain, measured with Fourier transform infrared spectroscopy on Mount Etna, Sicily. The abundances of volcanic gas species, determined from absorption spectra of lava radiation, reveal a fountain gas having higher CO2/S and S/Cl ratios than other etnean emissions, and which cannot derive from syn-eruptive bulk degassing of Etna basalt. Instead, its composition suggests violent emptying of a gas bubble layer previously accumulated at about 1.5 km depth below the erupting crater.     

A single-nucleotide polymorphism tagging set for human drug metabolism and transport

Interindividual variability in drug response, ranging from no therapeutic benefit to life-threatening adverse reactions, is influenced by variation in genes that control the absorption, distribution, metabolism and excretion of drugs. We genotyped 904 single-nucleotide polymorphisms (SNPs) from 55 such genes in two population samples (European and Japanese) and identified a set of tagging SNPs that represents the common variation in these genes, both known and unknown. Extensive empirical evaluations, including a direct assessment of association with candidate functional SNPs in a new, larger population sample, validated the performance of these tagging SNPs and confirmed their utility for linkage-disequilibrium mapping in pharmacogenetics. The analyses also suggest that rare variation is not amenable to tagging strategies.     

Revealing forecaster's preferences: A Bayesian multivariate loss function approach

Revealing the underlying preferences of a forecaster has always been at the core of much controversy. Herein, we build on the multivariate loss function concept and propose a flexible and multivariate family of likelihoods. This allows examining whether a vector of forecast errors, along with control variables, shapes a forecaster's preferences and, therefore, the underlying multivariate, nonseparable, loss function. We estimate the likelihood function using Bayesian exponentially tilted empirical likelihood, which reveals the shape of the parameter and the power of the multivariate loss function. In the empirical section, the reported evidence reveals that the EU Commission forecasts are predominantly asymmetric, leaning towards optimism in the year ahead, while a correction towards pessimism occurs in the current year forecast. There is some variability of this asymmetry across member states, with forecasts, i.e. gross domestic product growth, for large Member States exhibiting more optimism     

Stochastic Multivariate Mixture Covariance Model

Stochastic covariance models have been explored in recent research to model the interdependence of assets in financial time series. The approach uses a single stochastic model to capture such interdependence. However, it may be inappropriate to assume a single coherence structure at all time t. In this paper, we propose the use of a mixture of stochastic covariance models to generalize the approach and offer greater flexibility in real data applications. Parameter estimation is performed by Bayesian analysis with Markov chain Monte Carlo sampling schemes. We conduct a simulation study on three different model setups and evaluate the performance of estimation and model selection. We also apply our modeling methods to high‐frequency stock data from Hong Kong. Model selection favors a mixture rather than non‐mixture model. In a real data study, we demonstrate that the mixture model is able to identify structural changes in market risk, as evidenced by a drastic change in mixture proportions over time. Copyright © 2016 John Wiley & Sons, Ltd.     

Idea Networking: Constructing a Pragmatic Conceptual Frame for Action Research Interventions

Action research interventions require use of some form of conceptual frame to guide and evaluate the intervention. Pragmatism offers an explanation of ideas that enables this conceptual frame to be constructed inductively from diverse participants’ ideas. They define ideas as experienced patterns of activity. The purpose of this paper is to explain why and how this pragmatic explanation of ideas can be used to induce an action research conceptual frame. As a demonstration, the paper inducts (emerges) a conceptual frame using idea networking for service providers in an emerging cultural accommodation industry. 50 h of interviews and site visits provided 117 individual idea statements which were networked. The conceptual frame that emerged had five elements: sufficient-legitimation, selected-market, inclusive-boomi, appropriately-financial, and collaboratively-empowered. This provides a coordinated, multi-part, way of evaluating any possible future changes.     

A luminous quasar at a redshift of z = 7.085

The intergalactic medium was not completely reionized until approximately a billion years after the Big Bang, as revealed by observations of quasars with redshifts of less than 6.5. It has been difficult to probe to higher redshifts, however, because quasars have historically been identified in optical surveys, which are insensitive to sources at redshifts exceeding 6.5. Here we report observations of a quasar (ULAS?J112001.48+064124.3) at a redshift of 7.085, which is 0.77 billion years after the Big Bang. ULAS?J1120+0641 has a luminosity of 6.3 × 10(13)L(⊙) and hosts a black hole with a mass of 2 × 10(9)M(⊙) (where L(⊙) and M(⊙) are the luminosity and mass of the Sun). The measured radius of the ionized near zone around ULAS?J1120+0641 is 1.9?megaparsecs, a factor of three smaller than is typical for quasars at redshifts between 6.0 and 6.4. The near-zone transmission profile is consistent with a Lyα damping wing, suggesting that the neutral fraction of the intergalactic medium in front of ULAS?J1120+0641 exceeded 0.1.