Physics

8 typically slower than ϳ1 km s −1 ) might differ significantly from what is assumed by current modelling efforts 27 . The expected equation-of-state differences among small bodies (ice versus rock, for instance) presents another dimension of study; having recently adapted our code for massively parallel architectures (K. M. Olson and E.A, manuscript in preparation), we are now ready to perform a more comprehensive analysis.

We assess various approximate forms for the correlation energy per particle of the spin-polarized homogeneous electron gas that have frequently been used in applications of the local spin density approximation to the exchange-correlation energy functional. By accurately recalculating the RPA correlation energy as a function of electron density and spin polarization we demonstrate the inadequacies of the usual approximation for interpolating between the para- and ferro-magnetic states and present an accurate new interpolation formula. A Padé approximant technique is used to accurately interpolate the recent Monte Carlo results (para and ferro) of Ceperley and Alder into the important range of densities for atoms, molecules, and metals. These results can be combined with the RPA spin-dependence so as to produce a correlation energy for a spin-polarized homogeneous electron gas with an estimated maximum error of 1 mRy and thus should reliably determine the magnitude of non-local correc...

Graphene sheets-one-atom-thick two-dimensional layers of sp 2 -bonded carbon-are predicted to have a range of unusual properties. Their thermal conductivity and mechanical stiffness may rival the remarkable in-plane values for graphite (,3,000 Wm 21 K 21 and 1,060 GPa, respectively); their fracture strength should be comparable to that of carbon nanotubes for similar types of defects 1-3 ; and recent studies have shown that individual graphene sheets have extraordinary electronic transport properties 4-8 . One possible route to harnessing these properties for applications would be to incorporate graphene sheets in a composite material. The manufacturing of such composites requires not only that graphene sheets be produced on a sufficient scale but that they also be incorporated, and homogeneously distributed, into various matrices. Graphite, inexpensive and available in large quantity, unfortunately does not readily exfoliate to yield individual graphene sheets. Here we present a general approach for the preparation of graphene-polymer composites via complete exfoliation of graphite 9 and molecular-level dispersion of individual, chemically modified graphene sheets within polymer hosts. A polystyrene-graphene composite formed by this route exhibits a percolation threshold 10 of ,0.1 volume per cent for room-temperature electrical conductivity, the lowest reported value for any carbon-based composite except for those involving carbon nanotubes 11 ; at only 1 volume per cent, this composite has a conductivity of ,0.1 S m 21 , sufficient for many electrical applications 12 . Our bottom-up chemical approach of tuning the graphene sheet properties provides a path to a broad new class of graphenebased materials and their use in a variety of applications.

Causal attribution of recent biological trends to climate change is complicated because non-climatic influences dominate local, short-term biological changes. Any underlying signal from climate change is likely to be revealed by analyses that seek systematic trends across diverse species and geographic regions; however, debates within the Intergovernmental Panel on Climate Change (IPCC) reveal several definitions of a 'systematic trend'. Here, we explore these differences, apply diverse analyses to more than 1,700 species, and show that recent biological trends match climate change predictions. Global meta-analyses documented significant range shifts averaging 6.1 km per decade towards the poles (or metres per decade upward), and significant mean advancement of spring events by 2.3 days per decade. We define a diagnostic fingerprint of temporal and spatial 'sign-switching' responses uniquely predicted by twentieth century climate trends. Among appropriate long-term/large-scale/multi-species data sets, this diagnostic fingerprint was found for 279 species. This suite of analyses generates 'very high confidence' (as laid down by the IPCC) that climate change is already affecting living systems.

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic ...

The long-standing challenge of designing and constructing new crystalline solid-state materials from molecular building blocks is just beginning to be addressed with success. A conceptual approach that requires the use of secondary building units to direct the assembly of ordered frameworks epitomizes this process: we call this approach reticular synthesis. This chemistry has yielded materials designed to have predetermined structures, compositions and properties. In particular, highly porous frameworks held together by strong metal-oxygen-carbon bonds and with exceptionally large surface area and capacity for gas storage have been prepared and their pore metrics systematically varied and functionalized. The deconstruction of diamond and lonsdaleite. a, diamond; b, lonsdaleite ('hexagonal diamond'). The units outlined in red are the natural tiles for these structures.

We have developed and implemented a self-consistent density functional method using standard norm-conserving pseudopotentials and a flexible, numerical LCAO basis set, which includes multiplezeta and polarization orbitals. Exchange and correlation are treated with the local spin density or generalized gradient approximations. The basis functions and the electron density are projected on a real-space grid, in order to calculate the Hartree and exchange-correlation potentials and matrix elements, with a number of operations that scales linearly with the size of the system. We use a modified energy functional, whose minimization produces orthogonal wavefunctions and the same energy and density as the Kohn-Sham energy functional, without the need of an explicit orthogonalization. Additionally, using localized Wannier-like electron wavefunctions allows the computation time and memory, required to minimize the energy, to also scale linearly with the size of the system. Forces and stresses are also calculated efficiently and accurately, thus allowing structural relaxation and molecular dynamics simulations.

ERA-40 is a re-analysis of meteorological observations from September 1957 to August 2002 produced by the European Centre for Medium-Range Weather Forecasts (ECMWF) in collaboration with many institutions. The observing system changed considerably over this re-analysis period, with assimilable data provided by a succession of satellite-borne instruments from the 1970s onwards, supplemented by increasing numbers of observations from aircraft, ocean-buoys and other surface platforms, but with a declining number of radiosonde ascents since the late 1980s. The observations used in ERA-40 were accumulated from many sources. The first part of this paper describes the data acquisition and the principal changes in data type and coverage over the period. It also describes the data assimilation system used for ERA-40. This benefited from many of the changes introduced into operational forecasting since the mid-1990s, when the systems used for the 15-year ECMWF re-analysis (ERA-15) and the National Centers for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) re-analysis were implemented. Several of the improvements are discussed. General aspects of the production of the analyses are also summarized.A number of results indicative of the overall performance of the data assimilation system, and implicitly of the observing system, are presented and discussed. The comparison of background (short-range) forecasts and analyses with observations, the consistency of the global mass budget, the magnitude of differences between analysis and background fields and the accuracy of medium-range forecasts run from the ERA-40 analyses are illustrated. Several results demonstrate the marked improvement that was made to the observing system for the southern hemisphere in the 1970s, particularly towards the end of the decade. In contrast, the synoptic quality of the analysis for the northern hemisphere is sufficient to provide forecasts that remain skilful well into the medium range for all years. Two particular problems are also examined: excessive precipitation over tropical oceans and a too strong Brewer-Dobson circulation, both of which are pronounced in later years. Several other aspects of the quality of the re-analyses revealed by monitoring and validation studies are summarized. Expectations that the ‘second-generation’ ERA-40 re-analysis would provide products that are better than those from the firstgeneration ERA-15 and NCEP/NCAR re-analyses are found to have been met in most cases. © Royal Meteorological Society, 2005. The contributions of N. A. Rayner and R. W. Saunders are Crown copyright.

We report re-optimization of a recently proposed long-range corrected (LC) hybrid density functional [J.-D. Chai and M. Head-Gordon, J. Chem. Phys., 2008, 128, 084106] to include empirical atom-atom dispersion corrections. The resulting functional, oB97X-D yields satisfactory accuracy for thermochemistry, kinetics, and non-covalent interactions. Tests show that for non-covalent systems, oB97X-D shows slight improvement over other empirical dispersion-corrected density functionals, while for covalent systems and kinetics it performs noticeably better. Relative to our previous functionals, such as oB97X, the new functional is significantly superior for non-bonded interactions, and very similar in performance for bonded interactions.

On activation, T cells undergo distinct developmental pathways, attaining specialized properties and effector functions. T-helper (T H ) cells are traditionally thought to differentiate into T H 1 and T H 2 cell subsets. T H 1 cells are necessary to clear intracellular pathogens and T H 2 cells are important for clearing extracellular organisms 1,2 . Recently, a subset of interleukin (IL)-17-producing T (T H 17) cells distinct from T H 1 or T H 2 cells has been described and shown to have a crucial role in the induction of autoimmune tissue injury 3-5 . In contrast, CD4 1 CD25 1 Foxp3 1 regulatory T (T reg ) cells inhibit autoimmunity and protect against tissue injury 6 . Transforming growth factor-b (TGF-b) is a critical differentiation factor for the generation of T reg cells 7 . Here we show, using mice with a reporter introduced into the endogenous Foxp3 locus, that IL-6, an acute phase protein induced during inflammation 8,9 , completely inhibits the generation of Foxp3 1 T reg cells induced by TGF-b. We also demonstrate that IL-23 is not the differentiation factor for the generation of T H 17 cells. Instead, IL-6 and TGF-b together induce the differentiation of pathogenic T H 17 cells from naive T cells. Our data demonstrate a dichotomy in the generation of pathogenic (T H 17) T cells that induce autoimmunity and regulatory (Foxp3 1 ) T cells that inhibit autoimmune tissue injury.

insight review articles NATURE | VOL 414 | 15 NOVEMBER 2001 | www.nature.com 353 E nergy can be stored in different forms: as mechanical energy (for example, potential energy or rotation energy of a flywheel); in an electric or magnetic field (capacitors and coils, respectively); as chemical energy of reactants and fuels (batteries, petrol or hydrogen); or as nuclear fuel (uranium or deuterium). Chemical and electric energy can be transmitted easily because they both involve electronic Coulomb interaction. Chemical energy is based on the energy of unpaired outer electrons (valence electrons) eager to be stabilized by electrons from other atoms. The hydrogen atom is most attractive because its electron (for charge neutrality) is accompanied by only one proton. Hydrogen thus has the best ratio of valence electrons to protons (and neutrons) of all the periodic table, and the energy gain per electron is very high.

We have achieved mobilities in excess of 200,000 cm 2 V −1 s −1 at electron densities of ∼2×10 11 cm −2 by suspending single layer graphene. Suspension ∼150 nm above a Si/SiO2 gate electrode and electrical contacts to the graphene was achieved by a combination of electron beam lithography and etching. The specimens were cleaned in situ by employing current-induced heating, directly resulting in a significant improvement of electrical transport. Concomitant with large mobility enhancement, the widths of the characteristic Dirac peaks are reduced by a factor of 10 compared to traditional, non-suspended devices. This advance should allow for accessing the intrinsic transport properties of graphene.

CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecular simulation program. It has been developed over the last three decades with a primary focus on molecules of biological interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estimators, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. The CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numerous platforms in both serial and parallel architectures. This article provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM article

Advances in the science and observation of climate change are providing a clearer understanding of the inherent variability of Earth's climate system and its likely response to human and natural influences. The implications of climate change for the environment and society will depend not only on the response of the Earth system to changes in radiative forcings, but also on how humankind responds through changes in technology, economies, lifestyle and policy. Extensive uncertainties exist in future forcings of and responses to climate change, necessitating the use of scenarios of the future to explore the potential consequences of different response options. To date, such scenarios have not adequately examined crucial possibilities, such as climate change mitigation and adaptation, and have relied on research processes that slowed the exchange of information among physical, biological and social scientists. Here we describe a new process for creating plausible scenarios to investigate some of the most challenging and important questions about climate change confronting the global community.

Oxidative stress and low-grade inflammation are the hallmarks of the aging process and are even more enhanced in many age-related degenerative diseases. Mitochondrial dysfunction and oxidative stress can provoke and potentiate inflammatory responses, but the mechanism has remained elusive. Recent studies indicate that oxidative stress can induce the assembly of multiprotein inflammatory complexes called the inflammasomes. Nod-like receptor protein 3 (NLRP3) is the major immune sensor for cellular stress signals, e.g., reactive oxygen species, ceramides, and cathepsin B. NLRP3 activation triggers the caspase-1-mediated maturation of the precursors of IL-1b and IL-18 cytokines. During aging, the autophagic clearance of mitochondria declines and dysfunctional mitochondria provoke chronic oxidative stress, which disturbs the cellular redox balance. Moreover, increased NF-jB signaling observed during aging could potentiate the expression of NLRP3 and cytokine proforms enhancing the priming of NLRP3 inflammasomes. Recent studies have demonstrated that NLRP3 activation is associated with several age-related diseases, e.g., the metabolic syndrome. We will review here the emerging field of inflammasomes in the appearance of the proinflammatory phenotype during the aging process and in age-related diseases.

The realization of conservation goals requires strategies for managing whole landscapes including areas allocated to both production and protection. Reserves alone are not adequate for nature conservation but they are the cornerstone on which regional strategies are built. Reserves have two main roles. They should sample or represent the biodiversity of each region and they should separate this biodiversity from processes that threaten its persistence. Existing reserve systems throughout the world contain a biased sample of biodiversity, usually that of remote places and other areas that are unsuitable for commercial activities. A more systematic approach to locating and designing reserves has been evolving and this approach will need to be implemented if a large proportion of today's biodiversity is to exist in a future of increasing numbers of people and their demands on natural resources.

The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. It is currently believed that four to six crypt stem cells reside at the 14 position immediately above the Paneth cells in the small intestine; colon stem cells remain undefined. Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5, also known as Gpr49) was selected from a panel of intestinal Wnt target genes for its restricted crypt expression. Here, using two knock-in alleles, we reveal exclusive expression of Lgr5 in cycling columnar cells at the crypt base. In addition, Lgr5 was expressed in rare cells in several other tissues. Using an inducible Cre knock-in allele and the Rosa26-lacZ reporter strain, lineage-tracing experiments were performed in adult mice. The Lgr5-positive crypt base columnar cell generated all epithelial lineages over a 60-day period, suggesting that it represents the stem cell of the small intestine and colon. The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers.

| In response to stress, the brain activates several neuropeptide-secreting systems. This eventually leads to the release of adrenal corticosteroid hormones, which subsequently feed back on the brain and bind to two types of nuclear receptor that act as transcriptional regulators. By targeting many genes, corticosteroids function in a binary fashion, and serve as a master switch in the control of neuronal and network responses that underlie behavioural adaptation. In genetically predisposed individuals, an imbalance in this binary control mechanism can introduce a bias towards stress-related brain disease after adverse experiences. New candidate susceptibility genes that serve as markers for the prediction of vulnerable phenotypes are now being identified.

Human alteration of the global environment has triggered the sixth major extinction event in the history of life and caused widespread changes in the global distribution of organisms. These changes in biodiversity alter ecosystem processes and change the resilience of ecosystems to environmental change. This has profound consequences for services that humans derive from ecosystems. The large ecological and societal consequences of changing biodiversity should be minimized to preserve options for future solutions to global environmental problems.

Numerical assessments of global air quality and potential changes in atmospheric chemical constituents require estimates of the surface fluxes of a variety of trace gas species. We have developed a global model to estimate emissions of volatile organic compounds from natural sources (NVOC). Methane is not considered here and has been reviewed in detail elsewhere. The model has a highly resolved spatial grid (0.5øx 0.5 ølatitude/longitude) and generates hourly average emission estimates. Chemical species are grouped into four categories: isoprene, monoterpenes, other reactive VOC (ORVOC), and other VOC (OVOC). NVOC emissions from oceans are estimated as a function of geophysical variables from a general circulation model and ocean color satellite data. Emissions from plant foliage are estimated from ecosystem specific biomass and emission factors and algorithms describing light and temperature dependence of NVOC emissions. Foliar density estimates are based on climatic variables and satellite data. Temporal variations in the model are driven by monthly estimates of biomass and temperature and hourly light estimates. The annual global VOC flux is estimated to be 1150 Tg C, composed of 44% isoprene, 11% monoterpenes, 22.5% other reactive VOC, and 22.5% other VOC. Large uncertainties exist for each of these estimates and particularly for compounds other than isoprene and monoterpenes. Tropical woodlands (rain forest, seasonal, drought-deciduous, and savanna) contribute about half of all global natural VOC emissions. Croplands, shrublands and other woodlands contribute 10-20% apiece. Isoprene emissions calculated for temperate regions are as much as a factor of 5 higher than previous estimates. 1. Introduction Volatile organic compounds (VOC) are emitted into the atmosphere from natural sources in marine and terrestrial environments. Surface fluxes of these compounds are of interest because of their role in tropospheric chemistry and the global carbon cycle [see Fehsenfeld et al., 1992]. The development of three-dimensional (3-D) computer models of global climate, chemistry, surface emissions, and ecology is progressing to the point where these models can be coupled and used to investigate interactions between the processes simulated by each model. Three-dimensional climate models respond to forcings such as sea surface temperatures, planetary orientation with the sun, and the concentration of chemical species such as CO 2, C H 4, and sulfur compounds. Since VOC emission rates are critical in controlling the OH concentration of much of the troposphere, VOC emissions may play a major role in determining the growth rate of atmospheric CH 4 and CO concentrations. Since 1National Center for Atmospheric Research, Boulder, Colorado. compounds such as CH 4 influence the radiative balance of the 2Institute of Environmental and Biological Sciences, Lancaster, atmosphere, which in turn is related to global temperature and

There is now ample evidence of the ecological impacts of recent climate change, from polar terrestrial to tropical marine environments. The responses of both¯ora and fauna span an array of ecosystems and organizational hierarchies, from the species to the community levels. Despite continued uncertainty as to community and ecosystem trajectories under global change, our review exposes a coherent pattern of ecological change across systems. Although we are only at an early stage in the projected trends of global warming, ecological responses to recent climate change are already clearly visible.

A recent explosion in newly discovered vascular growth factors has coincided with exploitation of powerful new genetic approaches for studying vascular development. An emerging rule is that all of these factors must be used in perfect harmony to form functional vessels. These new findings also demand re-evaluation of therapeutic efforts aimed at regulating blood vessel growth in ischaemia, cancer and other pathological settings.

Helicobacter pylori, strain 26695, has a circular genome of 1,667,867 base pairs and 1,590 predicted coding sequences. Sequence analysis indicates that H. pylori has well-developed systems for motility, for scavenging iron, and for DNA restriction and modification. Many putative adhesins, lipoproteins and other outer membrane proteins were identified, underscoring the potential complexity of host-pathogen interaction. Based on the large number of sequence-related genes encoding outer membrane proteins and the presence of homopolymeric tracts and dinucleotide repeats in coding sequences, H. pylori, like several other mucosal pathogens, probably uses recombination and slipped-strand mispairing within repeats as mechanisms for antigenic variation and adaptive evolution. Consistent with its restricted niche, H. pylori has a few regulatory networks, and a limited metabolic repertoire and biosynthetic capacity. Its survival in acid conditions depends, in part, on its ability to establish a positive inside-membrane potential in low pH. grant from the National Center for Research Resources. We thank N. S. Akopyants for preparing high quality chromosomal DNA from H. pylori strain 26695; M. Heaney, J. Scott, A. Saeed and R. Shirley for software and database support; and V. Sapiro, B. Vincent, J. Meehan and D. Mass for computer system support.

The tumour-necrosis-factor-family molecule osteoprotegerin ligand (OPGL; also known as TRANCE, RANKL and ODF) has been identi®ed as a potential osteoclast differentiation factor and regulator of interactions between T cells and dendritic cells in vitro. Mice with a disrupted opgl gene show severe osteopetrosis and a defect in tooth eruption, and completely lack osteoclasts as a result of an inability of osteoblasts to support osteoclastogenesis. Although dendritic cells appear normal, opgl-de®cient mice exhibit defects in early differentiation of T and B lymphocytes. Surprisingly, opgl-de®cient mice lack all lymph nodes but have normal splenic structure and Peyer's patches. Thus OPGL is a new regulator of lymph-node organogenesis and lymphocyte development and is an essential osteoclast differentiation factor in vivo.