'Designer atoms' for quantum metrology

Entanglement is recognized as a key resource for quantum computation and quantum cryptography. For quantum metrology, the use of entangled states has been discussed and demonstrated as a means of improving the signal-to-noise ratio. In addition, entangled states have been used in experiments for efficient quantum state detection and for the measurement of scattering lengths. In quantum information processing, manipulation of individual quantum bits allows for the tailored design of specific states that are insensitive to the detrimental influences of an environment. Such 'decoherence-free subspaces' (ref. 10) protect quantum information and yield significantly enhanced coherence times. Here we use a decoherence-free subspace with specifically designed entangled states to demonstrate precision spectroscopy of a pair of trapped Ca+ ions; we obtain the electric quadrupole moment, which is of use for frequency standard applications. We find that entangled states are not only useful for enhancing the signal-to-noise ratio in frequency measurements--a suitably designed pair of atoms also allows clock measurements in the presence of strong technical noise. Our technique makes explicit use of non-locality as an entanglement property and provides an approach for 'designed' quantum metrology.     

Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation

The eight catalytic subunits of the mammalian phosphoinositide-3-OH kinase (PI(3)K) family form the backbone of an evolutionarily conserved signalling pathway; however, the roles of most PI(3)K isoforms in organismal physiology and disease are unknown. To delineate the role of p110alpha, a ubiquitously expressed PI(3)K involved in tyrosine kinase and Ras signalling, here we generated mice carrying a knockin mutation (D933A) that abrogates p110alpha kinase activity. Homozygosity for this kinase-dead p110alpha led to embryonic lethality. Mice heterozygous for this mutation were viable and fertile, but displayed severely blunted signalling via insulin-receptor substrate (IRS) proteins, key mediators of insulin, insulin-like growth factor-1 and leptin action. Defective responsiveness to these hormones led to reduced somatic growth, hyperinsulinaemia, glucose intolerance, hyperphagia and increased adiposity in mice heterozygous for the D933A mutation. This signalling function of p110alpha derives from its highly selective recruitment and activation to IRS signalling complexes compared to p110beta, the other broadly expressed PI(3)K isoform, which did not contribute to IRS-associated PI(3)K activity. p110alpha was the principal IRS-associated PI(3)K in cancer cell lines. These findings demonstrate a critical role for p110alpha in growth factor and metabolic signalling and also suggest an explanation for selective mutation or overexpression of p110alpha in a variety of cancers.     

Pharmaco-metabonomic phenotyping and personalized drug treatment

There is a clear case for drug treatments to be selected according to the characteristics of an individual patient, in order to improve efficacy and reduce the number and severity of adverse drug reactions. However, such personalization of drug treatments requires the ability to predict how different individuals will respond to a particular drug/dose combination. After initial optimism, there is increasing recognition of the limitations of the pharmacogenomic approach, which does not take account of important environmental influences on drug absorption, distribution, metabolism and excretion. For instance, a major factor underlying inter-individual variation in drug effects is variation in metabolic phenotype, which is influenced not only by genotype but also by environmental factors such as nutritional status, the gut microbiota, age, disease and the co- or pre-administration of other drugs. Thus, although genetic variation is clearly important, it seems unlikely that personalized drug therapy will be enabled for a wide range of major diseases using genomic knowledge alone. Here we describe an alternative and conceptually new 'pharmaco-metabonomic' approach to personalizing drug treatment, which uses a combination of pre-dose metabolite profiling and chemometrics to model and predict the responses of individual subjects. We provide proof-of-principle for this new approach, which is sensitive to both genetic and environmental influences, with a study of paracetamol (acetaminophen) administered to rats. We show pre-dose prediction of an aspect of the urinary drug metabolite profile and an association between pre-dose urinary composition and the extent of liver damage sustained after paracetamol administration.     

Climate sensitivity constrained by temperature reconstructions over the past seven centuries

The magnitude and impact of future global warming depends on the sensitivity of the climate system to changes in greenhouse gas concentrations. The commonly accepted range for the equilibrium global mean temperature change in response to a doubling of the atmospheric carbon dioxide concentration, termed climate sensitivity, is 1.5-4.5 K (ref. 2). A number of observational studies, however, find a substantial probability of significantly higher sensitivities, yielding upper limits on climate sensitivity of 7.7 K to above 9 K (refs 3-8). Here we demonstrate that such observational estimates of climate sensitivity can be tightened if reconstructions of Northern Hemisphere temperature over the past several centuries are considered. We use large-ensemble energy balance modelling and simulate the temperature response to past solar, volcanic and greenhouse gas forcing to determine which climate sensitivities yield simulations that are in agreement with proxy reconstructions. After accounting for the uncertainty in reconstructions and estimates of past external forcing, we find an independent estimate of climate sensitivity that is very similar to those from instrumental data. If the latter are combined with the result from all proxy reconstructions, then the 5-95 per cent range shrinks to 1.5-6.2 K, thus substantially reducing the probability of very high climate sensitivity.     

Intrasexual competition and sexual selection in cooperative mammals

In most animals, the sex that invests least in its offspring competes more intensely for access to the opposite sex and shows greater development of secondary sexual characters than the sex that invests most. However, in some mammals where females are the primary care-givers, females compete more frequently or intensely with each other than males. A possible explanation is that, in these species, the resources necessary for successful female reproduction are heavily concentrated and intrasexual competition for breeding opportunities is more intense among females than among males. Intrasexual competition between females is likely to be particularly intense in cooperative breeders where a single female monopolizes reproduction in each group. Here, we use data from a twelve-year study of wild meerkats (Suricata suricatta), where females show high levels of reproductive skew, to show that females gain greater benefits from acquiring dominant status than males and traits that increase competitive ability exert a stronger influence on their breeding success. Females that acquire dominant status also develop a suite of morphological, physiological and behavioural characteristics that help them to control other group members. Our results show that sex differences in parental investment are not the only mechanism capable of generating sex differences in reproductive competition and emphasize the extent to which competition for breeding opportunities between females can affect the evolution of sex differences and the operation of sexual selection.     

A new gamma-ray burst classification scheme from GRB 060614

Gamma-ray bursts (GRBs) are known to come in two duration classes, separated at approximately 2 s. Long-duration bursts originate from star-forming regions in galaxies, have accompanying supernovae when these are near enough to observe and are probably caused by massive-star collapsars. Recent observations show that short-duration bursts originate in regions within their host galaxies that have lower star-formation rates, consistent with binary neutron star or neutron star-black hole mergers. Moreover, although their hosts are predominantly nearby galaxies, no supernovae have been so far associated with short-duration GRBs. Here we report that the bright, nearby GRB 060614 does not fit into either class. Its approximately 102-s duration groups it with long-duration GRBs, while its temporal lag and peak luminosity fall entirely within the short-duration GRB subclass. Moreover, very deep optical observations exclude an accompanying supernova, similar to short-duration GRBs. This combination of a long-duration event without an accompanying supernova poses a challenge to both the collapsar and the merging-neutron-star interpretations and opens the door to a new GRB classification scheme that straddles both long- and short-duration bursts.     

Active terahertz metamaterial devices

The development of artificially structured electromagnetic materials, termed metamaterials, has led to the realization of phenomena that cannot be obtained with natural materials. This is especially important for the technologically relevant terahertz (1 THz = 10(12) Hz) frequency regime; many materials inherently do not respond to THz radiation, and the tools that are necessary to construct devices operating within this range-sources, lenses, switches, modulators and detectors-largely do not exist. Considerable efforts are underway to fill this 'THz gap' in view of the useful potential applications of THz radiation. Moderate progress has been made in THz generation and detection; THz quantum cascade lasers are a recent example. However, techniques to control and manipulate THz waves are lagging behind. Here we demonstrate an active metamaterial device capable of efficient real-time control and manipulation of THz radiation. The device consists of an array of gold electric resonator elements (the metamaterial) fabricated on a semiconductor substrate. The metamaterial array and substrate together effectively form a Schottky diode, which enables modulation of THz transmission by 50 per cent, an order of magnitude improvement over existing devices.     

Climate-driven trends in contemporary ocean productivity

Contributing roughly half of the biosphere's net primary production (NPP), photosynthesis by oceanic phytoplankton is a vital link in the cycling of carbon between living and inorganic stocks. Each day, more than a hundred million tons of carbon in the form of CO2 are fixed into organic material by these ubiquitous, microscopic plants of the upper ocean, and each day a similar amount of organic carbon is transferred into marine ecosystems by sinking and grazing. The distribution of phytoplankton biomass and NPP is defined by the availability of light and nutrients (nitrogen, phosphate, iron). These growth-limiting factors are in turn regulated by physical processes of ocean circulation, mixed-layer dynamics, upwelling, atmospheric dust deposition, and the solar cycle. Satellite measurements of ocean colour provide a means of quantifying ocean productivity on a global scale and linking its variability to environmental factors. Here we describe global ocean NPP changes detected from space over the past decade. The period is dominated by an initial increase in NPP of 1,930 teragrams of carbon a year (Tg C yr(-1)), followed by a prolonged decrease averaging 190 Tg C yr(-1). These trends are driven by changes occurring in the expansive stratified low-latitude oceans and are tightly coupled to coincident climate variability. This link between the physical environment and ocean biology functions through changes in upper-ocean temperature and stratification, which influence the availability of nutrients for phytoplankton growth. The observed reductions in ocean productivity during the recent post-1999 warming period provide insight on how future climate change can alter marine food webs.     

The ABC protein turned chloride channel whose failure causes cystic fibrosis

CFTR chloride channels are encoded by the gene mutated in patients with cystic fibrosis. These channels belong to the superfamily of ABC transporter ATPases. ATP-driven conformational changes, which in other ABC proteins fuel uphill substrate transport across cellular membranes, in CFTR open and close a gate to allow transmembrane flow of anions down their electrochemical gradient. New structural and biochemical information from prokaryotic ABC proteins and functional information from CFTR channels has led to a unifying mechanism explaining those ATP-driven conformational changes.