A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets

Proneural genes such as Ascl1 are known to promote cell cycle exit and neuronal differentiation when expressed in neural progenitor cells. The mechanisms by which proneural genes activate neurogenesis--and, in particular, the genes that they regulate--however, are mostly unknown. We performed a genome-wide characterization of the transcriptional targets of Ascl1 in the embryonic brain and in neural stem cell cultures by location analysis and expression profiling of embryos overexpressing or mutant for Ascl1. The wide range of molecular and cellular functions represented among these targets suggests that Ascl1 directly controls the specification of neural progenitors as well as the later steps of neuronal differentiation and neurite outgrowth. Surprisingly, Ascl1 also regulates the expression of a large number of genes involved in cell cycle progression, including canonical cell cycle regulators and oncogenic transcription factors. Mutational analysis in the embryonic brain and manipulation of Ascl1 activity in neural stem cell cultures revealed that Ascl1 is indeed required for normal proliferation of neural progenitors. This study identified a novel and unexpected activity of the proneural gene Ascl1, and revealed a direct molecular link between the phase of expansion of neural progenitors and the subsequent phases of cell cycle exit and neuronal differentiation.

Synthesis, structural characterisation and thermoelectric properties of Bi1−xPbxOCuSe

The effect of Pb2+ doping on the structure and thermoelectric properties of BiOCuSe (also known as BiCuSeO or BiCuOSe) is described. With increasing Pb2+ content, the expansion of the unit cell results in a weakening of the bonding between the [Bi2(1-x) Pb2xO2]2(1-x)+ and the [Cu2Se2]2(1-x)- layers. The electrical resistivity and Seebeck coefficient decrease in a systematic way with growing Pb2+ levels. The thermal conductivity rises due to the increase of the electronic contribution with doping. The power factor of materials with a 4-5% Pb2+ content takes values of ca. 8 W cm-1 K-2 over a wide temperature range. ZT at 673 K is enhanced by ca. 50% when compared to values found for other dopants, such as Sr2+ or Mg2+.

A time-series method to identify and correct range sidelobes in meteorological radar data

The use of pulse compression techniques to improve the sensitivity of meteorological radars has become increasingly common in recent years. An unavoidable side-effect of such techniques is the formation of ‘range sidelobes’ which lead to spreading of information across several range gates. These artefacts are particularly troublesome in regions where there is a sharp gradient in the power backscattered to the antenna as a function of range. In this article we present a simple method for identifying and correcting range sidelobe artefacts. We make use of the fact that meteorological targets produce an echo which fluctuates at random, and that this echo, like a fingerprint, is unique to each range gate. By cross-correlating the echo time series from pairs of gates therefore we can identify whether information from one gate has spread into another, and hence flag regions of contamination. In addition we show that the correlation coefficients contain quantitative information about the fraction of power leaked from one range gate to another, and we propose a simple algorithm to correct the corrupted reflectivity profile.

Evaluation of ECMWF medium-range ensemble forecasts of precipitation for river basins

Providing probabilistic forecasts using Ensemble Prediction Systems has become increasingly popular in both the meteorological and hydrological communities. Compared to conventional deterministic forecasts, probabilistic forecasts may provide more reliable forecasts of a few hours to a number of days ahead, and hence are regarded as better tools for taking uncertainties into consideration and hedging against weather risks. It is essential to evaluate performance of raw ensemble forecasts and their potential values in forecasting extreme hydro-meteorological events. This study evaluates ECMWF’s medium-range ensemble forecasts of precipitation over the period 2008/01/01-2012/09/30 on a selected mid-latitude large scale river basin, the Huai river basin (ca. 270,000 km2) in central-east China. The evaluation unit is sub-basin in order to consider forecast performance in a hydrologically relevant way. The study finds that forecast performance varies with sub-basin properties, between flooding and non-flooding seasons, and with the forecast properties of aggregated time steps and lead times. Although the study does not evaluate any hydrological applications of the ensemble precipitation forecasts, its results have direct implications in hydrological forecasts should these ensemble precipitation forecasts be employed in hydrology.

Pollen-based reconstructions of biome distributions for Australia, Southeast Asia and the Pacific (SEAPAC region) at 0,6000 and 18,000 14C yr B.P.

Aim  This paper documents reconstructions of the vegetation patterns in Australia, Southeast Asia and the Pacific (SEAPAC region) in the mid-Holocene and at the last glacial maximum (LGM). Methods  Vegetation patterns were reconstructed from pollen data using an objective biomization scheme based on plant functional types. The biomization scheme was first tested using 535 modern pollen samples from 377 sites, and then applied unchanged to fossil pollen samples dating to 6000 ± 500 or 18,000 ± 1000 14C yr bp. Results  1. Tests using surface pollen sample sites showed that the biomization scheme is capable of reproducing the modern broad-scale patterns of vegetation distribution. The north–south gradient in temperature, reflected in transitions from cool evergreen needleleaf forest in the extreme south through temperate rain forest or wet sclerophyll forest (WSFW) and into tropical forests, is well reconstructed. The transitions from xerophytic through sclerophyll woodlands and open forests to closed-canopy forests, which reflect the gradient in plant available moisture from the continental interior towards the coast, are reconstructed with less geographical precision but nevertheless the broad-scale pattern emerges. 2. Differences between the modern and mid-Holocene vegetation patterns in mainland Australia are comparatively small and reflect changes in moisture availability rather than temperature. In south-eastern Australia some sites show a shift towards more moisture-stressed vegetation in the mid-Holocene with xerophytic woods/scrub and temperate sclerophyll woodland and shrubland at sites characterized today by WSFW or warm-temperate rain forest (WTRF). However, sites in the Snowy Mountains, on the Southern Tablelands and east of the Great Dividing Range have more moisture-demanding vegetation in the mid-Holocene than today. South-western Australia was slightly drier than today. The single site in north-western Australia also shows conditions drier than today in the mid-Holocene. Changes in the tropics are also comparatively small, but the presence of WTRF and tropical deciduous broadleaf forest and woodland in the mid-Holocene, in sites occupied today by cool-temperate rain forest, indicate warmer conditions. 3. Expansion of xerophytic vegetation in the south and tropical deciduous broadleaf forest and woodland in the north indicate drier conditions across mainland Australia at the LGM. None of these changes are informative about the degree of cooling. However the evidence from the tropics, showing lowering of the treeline and forest belts, indicates that conditions were between 1 and 9 °C (depending on elevation) colder. The encroachment of tropical deciduous broadleaf forest and woodland into lowland evergreen broadleaf forest implies greater aridity. Main conclusions  This study provides the first continental-scale reconstruction of mid-Holocene and LGM vegetation patterns from Australia, Southeast Asia and the Pacific (SEAPAC region) using an objective biomization scheme. These data will provide a benchmark for evaluation of palaeoclimate simulations within the framework of the Palaeoclimate Modelling Intercomparison Project.

Automated determination of auroral breakup during the substorm expansion phase using all sky imager data

This technique paper describes a novel method for quantitatively and routinely identifying auroral breakup following substorm onset using the Time History of Events and Macroscale Interactions During Substorms (THEMIS) all-sky imagers (ASIs). Substorm onset is characterised by a brightening of the aurora that is followed by auroral poleward expansion and auroral breakup. This breakup can be identified by a sharp increase in the auroral intensity i(t) and the time derivative of auroral intensity i'(t). Utilising both i(t) and i'(t) we have developed an algorithm for identifying the time interval and spatial location of auroral breakup during the substorm expansion phase within the field of view of ASI data based solely on quantifiable characteristics of the optical auroral emissions. We compare the time interval determined by the algorithm to independently identified auroral onset times from three previously published studies. In each case the time interval determined by the algorithm is within error of the onset independently identified by the prior studies. We further show the utility of the algorithm by comparing the breakup intervals determined using the automated algorithm to an independent list of substorm onset times. We demonstrate that up to 50% of the breakup intervals characterised by the algorithm are within the uncertainty of the times identified in the independent list. The quantitative description and routine identification of an interval of auroral brightening during the substorm expansion phase provides a foundation for unbiased statistical analysis of the aurora to probe the physics of the auroral substorm as a new scientific tool for aiding the identification of the processes leading to auroral substorm onset.

Pollen-based reconstructions of Japanese biomes at 0, 6000 and 18,000 14C yr bp

A biomization method, which objectively assigns individual pollen assemblages to biomes ( Prentice et al., 1996 ), was tested using modern pollen data from Japan and applied to fossil pollen data to reconstruct palaeovegetation patterns 6000 and 18,000 14C yr bp Biomization started with the assignment of 135 pollen taxa to plant functional types (PFTs), and nine possible biomes were defined by specific combinations of PFTs. Biomes were correctly assigned to 54% of the 94 modern sites. Incorrect assignments occur near the altitudinal limits of individual biomes, where pollen transport from lower altitudes blurs the local pollen signals or continuous changes in species composition characterizes the range limits of biomes. As a result, the reconstructed changes in the altitudinal limits of biomes at 6000 and 18,000 14C yr bp are likely to be conservative estimates of the actual changes. The biome distribution at 6000 14C yr bp was rather similar to today, suggesting that changes in the bioclimate of Japan have been small since the mid-Holocene. At 18,000 14C yr bp the Japanese lowlands were covered by taiga and cool mixed forests. The southward expansion of these forests and the absence of broadleaved evergreen/warm mixed forests reflect a pronounced year-round cooling.

Nanostructures in the terahertz range

With advances in technology, terahertz imaging and spectroscopy are beginning to move out of the laboratory and find applications in areas as diverse as security screening, medicine, art conservation and field archaeology. Nevertheless, there is still a need to improve upon the performance of existing terahertz systems to achieve greater compactness and robustness, enhanced spatial resolution, more rapid data acquisition times and operation at greater standoff distances. This chapter will review recent technological developments in this direction that make use of nanostructures in the generation, detection and manipulation of terahertz radiation. The chapter will also explain how terahertz spectroscopy can be used as a tool to characterize the ultrafast carrier dynamics of nanomaterials.

Survival at the frontier of Holy War: political expansion, crusading, commerce and the medieval colonizing settlement at Biała Gora, North Poland

Between the eleventh and thirteenth centuries AD, the Lower Vistula valley represented a permeable and shifting frontier between Pomerelia (eastern Pomerania), which had been incorporated into the Polish Christian state by the end of the tenth century, and the territories of western Prussian tribes, who had resisted attempts at Christianization. Pomeranian colonization eventually began to falter in the latter decades of the twelfth and early thirteenth centuries, most likely as a result of Prussian incursions, which saw the abandonment of sites across the borderland. Subsequently, the Teutonic Order and its allies led a protracted holy war against the Prussian tribes, which resulted in the conquest of the region and its incorporation into a theocratic state by the end of the thirteenth century. This was accompanied by a second wave of colonization, which resulted in the settlement pattern that is still visible in the landscape of north-central Poland today. However, not all colonies were destroyed or abandoned in between the two phases of colonization. The recently excavated site of Biała Góra, situated on the western side of the Forest of Sztum overlooking the River Nogat, represents a unique example of a transitional settlement that included both Pomeranian and Teutonic Order phases. The aim of this paper is to situate the site within its broader landscape context which can be characterized as a militarized frontier, where, from the later twelfth century and throughout much of the thirteenth century, political and economic expansion was combined with the ideology of Christian holy war and missionary activity. This paper considers how the colonists provisioned and sustained themselves in comparison to other sites within the region, and how Biała Góra may be tentatively linked to a documented but otherwise lost outpost in this volatile borderland.

Flight of Meligethes aeneus at a range of altitudes

The pollen beetle, Meligethes aeneus, is a significant pest of oilseed rape crops and there is considerable research effort focused on developing novel, sustainable methods of integrated control. These insects rely on flight for all dispersal movements and we have investigated their flight patterns using a novel combination of data from suction traps, vertical-looking radar and field counts. Analysis of these preliminary data will help determine the best timing for different control measures within an integrated pest management strategy.

Farmers' interest in growing GM crops in the UK, in the context of a range of on-farm coexistence issues

Although no GM crops currently are licensed for commercial production in the UK, as opposition to GM crops by consumers softens, this could change quickly. Although past studies have examined attitudes of UK farmers toward GM technologies in general, there has been little work on the impact of possible coexistence measures on their attitudes toward GM crop production. This could be because the UK Government has not engaged in any public dialogue on the coexistence measures that might be applied on farms. Based on a farm survey, this article examines farmers’ attitudes toward GM technologies and planting intentions for three crops (maize, oilseed rape, and sugar beet) based on a GM availability scenario. The article then nuances this analysis with a review of farmer perceptions of the level of constraint associated with a suite of notional farm-level coexistence measures and issues, based on current European Commission guidelines and practice in other EU Member States.

Landscape change in central Latvia since the Iron Age: multi-proxy analysis of the vegetation impact of conflict, colonization and economic expansion during the last 2000 years

This study represents the first detailed multi-proxy palaeoenvironmental investigation associated with a Late Iron Age lake-dwelling site in the eastern Baltic. The main objective was to reconstruct the environmental and vegetation dynamics associated with the establishment of the lake-dwelling and land-use during the last 2,000 years. A lacustrine sediment core located adjacent to a Late Iron Age lake-dwelling, medieval castle and Post-medieval manor was sampled in Lake Āraiši. The core was dated using spheroidal fly-ash particles and radiocarbon dating, and analysed in terms of pollen, non-pollen palynomorphs, diatoms, loss-on-ignition, magnetic susceptibility and element geochemistry. Associations between pollen and other proxies were statistically tested. During ad 1–700, the vicinity of Lake Āraiši was covered by forests and human activities were only small-scale with the first appearance of cereal pollen (Triticum and Secale cereale) after ad 400. The most significant changes in vegetation and environment occurred with the establishment of the lake-dwelling around ad 780 when the immediate surroundings of the lake were cleared for agriculture, and within the lake there were increased nutrient levels. The highest accumulation rates of coprophilous fungi coincide with the occupation of the lake-dwelling from ad 780–1050, indicating that parts of the dwelling functioned as byres for livestock. The conquest of tribal lands during the crusades resulted in changes to the ownership, administration and organisation of the land, but our results indicate that the form and type of agriculture and land-use continued much as it had during the preceding Late Iron Age.

Expansion quality of epidemic protocols

Epidemic protocols are a bio-inspired communication and computation paradigm for large and extreme-scale networked systems. This work investigates the expansion property of the network overlay topologies induced by epidemic protocols. An expansion quality index for overlay topologies is proposed and adopted for the design of epidemic membership protocols. A novel protocol is proposed, which explicitly aims at improving the expansion quality of the overlay topologies. The proposed protocol is tested with a global aggregation task and compared to other membership protocols. The analysis by means of simulations indicates that the expansion quality directly relates to the speed of dissemination and convergence of epidemic protocols and can be effectively used to design better protocols.

Clonal expansion of early to mid-life mitochondrial DNA point mutations drives mitochondrial dysfunction during human ageing

Age-related decline in the integrity of mitochondria is an important contributor to the human ageing process. In a number of ageing stem cell populations, this decline in mitochondrial function is due to clonal expansion of individual mitochondrial DNA (mtDNA) point mutations within single cells. However the dynamics of this process and when these mtDNA mutations occur initially are poorly understood. Using human colorectal epithelium as an exemplar tissue with a well-defined stem cell population, we analysed samples from 207 healthy participants aged 17-78 years using a combination of techniques (Random Mutation Capture, Next Generation Sequencing and mitochondrial enzyme histochemistry), and show that: 1) non-pathogenic mtDNA mutations are present from early embryogenesis or may be transmitted through the germline, whereas pathogenic mtDNA mutations are detected in the somatic cells, providing evidence for purifying selection in humans, 2) pathogenic mtDNA mutations are present from early adulthood (<20 years of age), at both low levels and as clonal expansions, 3) low level mtDNA mutation frequency does not change significantly with age, suggesting that mtDNA mutation rate does not increase significantly with age, and 4) clonally expanded mtDNA mutations increase dramatically with age. These data confirm that clonal expansion of mtDNA mutations, some of which are generated very early in life, is the major driving force behind the mitochondrial dysfunction associated with ageing of the human colorectal epithelium.

Broad range of 2050 warming from an observationally constrained large climate model ensemble

Incomplete understanding of three aspects of the climate system—equilibrium climate sensitivity, rate of ocean heat uptake and historical aerosol forcing—and the physical processes underlying them lead to uncertainties in our assessment of the global-mean temperature evolution in the twenty-first century1,2. Explorations of these uncertainties have so far relied on scaling approaches3,4, large ensembles of simplified climate models1,2, or small ensembles of complex coupled atmosphere–ocean general circulation models5,6 which under-represent uncertainties in key climate system properties derived from independent sources7–9. Here we present results from a multi-thousand-member perturbed-physics ensemble of transient coupled atmosphere–ocean general circulation model simulations. We find that model versions that reproduce observed surface temperature changes over the past 50 years show global-mean temperature increases of 1.4–3 K by 2050, relative to 1961–1990, under a mid-range forcing scenario. This range of warming is broadly consistent with the expert assessment provided by the Intergovernmental Panel on Climate Change Fourth Assessment Report10, but extends towards larger warming than observed in ensemblesof-opportunity5 typically used for climate impact assessments. From our simulations, we conclude that warming by the middle of the twenty-first century that is stronger than earlier estimates is consistent with recent observed temperature changes and a mid-range ‘no mitigation’ scenario for greenhouse-gas emissions.