Showing papers by "University of Cambridge published in 2011"
TL;DR: The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate.
Abstract: Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
22,227 citations
TL;DR: An overview of the CCP4 software suite for macromolecular crystallography is given.
Abstract: The CCP4 (Collaborative Computational Project, Number 4) software suite is a collection of programs and associated data and software libraries which can be used for macromolecular structure determination by X-ray crystallography. The suite is designed to be flexible, allowing users a number of methods of achieving their aims. The programs are from a wide variety of sources but are connected by a common infrastructure provided by standard file formats, data objects and graphical interfaces. Structure solution by macromolecular crystallography is becoming increasingly automated and the CCP4 suite includes several automation pipelines. After giving a brief description of the evolution of CCP4 over the last 30 years, an overview of the current suite is given. While detailed descriptions are given in the accompanying articles, here it is shown how the individual programs contribute to a complete software package.
11,023 citations
TL;DR: The principles of the method and how to impute categorical and quantitative variables, including skewed variables, are described and shown and the practical analysis of multiply imputed data is described, including model building and model checking.
Abstract: Multiple imputation by chained equations is a flexible and practical approach to handling missing data. We describe the principles of the method and show how to impute categorical and quantitative variables, including skewed variables. We give guidance on how to specify the imputation model and how many imputations are needed. We describe the practical analysis of multiply imputed data, including model building and model checking. We stress the limitations of the method and discuss the possible pitfalls. We illustrate the ideas using a data set in mental health, giving Stata code fragments. Copyright © 2010 John Wiley & Sons, Ltd.
6,349 citations
TL;DR: The known histone modifications are described, where they are found genomically and discussed and some of their functional consequences are discussed, concentrating mostly on transcription where the majority of characterisation has taken place.
Abstract: Chromatin is not an inert structure, but rather an instructive DNA scaffold that can respond to external cues to regulate the many uses of DNA. A principle component of chromatin that plays a key role in this regulation is the modification of histones. There is an ever-growing list of these modifications and the complexity of their action is only just beginning to be understood. However, it is clear that histone modifications play fundamental roles in most biological processes that are involved in the manipulation and expression of DNA. Here, we describe the known histone modifications, define where they are found genomically and discuss some of their functional consequences, concentrating mostly on transcription where the majority of characterisation has taken place.
4,536 citations
TL;DR: The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum, where they fold and assemble, and only properly assembled proteins advance from the ER to the cell surface.
Abstract: The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum (ER), where they fold and assemble. Only properly assembled proteins advance from the ER to the cell surface. To ascertain fidelity in protein folding, cells regulate the protein-folding capacity in the ER according to need. The ER responds to the burden of unfolded proteins in its lumen (ER stress) by activating intracellular signal transduction pathways, collectively termed the unfolded protein response (UPR). Together, at least three mechanistically distinct branches of the UPR regulate the expression of numerous genes that maintain homeostasis in the ER or induce apoptosis if ER stress remains unmitigated. Recent advances shed light on mechanistic complexities and on the role of the UPR in numerous diseases.
4,468 citations
University of California, San Francisco1, University of Trento2, Johns Hopkins University3, Northwestern University4, University of Western Ontario5, University of California, Los Angeles6, Vita-Salute San Raffaele University7, University College London8, University of Toronto9, Mayo Clinic10, University of California, Davis11, Katholieke Universiteit Leuven12, University of Cambridge13, University of New South Wales14, University of Pennsylvania15
TL;DR: This article provides a classification of primary progressive aphasia (PPA) and its 3 main variants to improve the uniformity of case reporting and the reliability of research results.
Abstract: This article provides a classification of primary progressive aphasia (PPA) and its 3 main variants to improve the uniformity of case reporting and the reliability of research results. Criteria for the 3 variants of PPA—nonfluent/agrammatic, semantic, and logopenic—were developed by an international group of PPA investigators who convened on 3 occasions to operationalize earlier published clinical descriptions for PPA subtypes. Patients are first diagnosed with PPA and are then divided into clinical variants based on specific speech and language features characteristic of each subtype. Classification can then be further specified as “imaging-supported” if the expected pattern of atrophy is found and “with definite pathology” if pathologic or genetic data are available. The working recommendations are presented in lists of features, and suggested assessment tasks are also provided. These recommendations have been widely agreed upon by a large group of experts and should be used to ensure consistency of PPA classification in future studies. Future collaborations will collect prospective data to identify relationships between each of these syndromes and specific biomarkers for a more detailed understanding of clinicopathologic correlations.
3,635 citations
TL;DR: It is found that the ratio between the D and G peak intensities, for a given defect density, strongly depends on the laser excitation energy, and a simple equation for the determination of the point defect density in graphene via Raman spectroscopy is presented.
Abstract: We present a Raman study of Ar(+)-bombarded graphene samples with increasing ion doses. This allows us to have a controlled, increasing, amount of defects. We find that the ratio between the D and G peak intensities for a given defect density strongly depends on the laser excitation energy. We quantify this effect and present a simple equation for the determination of the point defect density in graphene via Raman spectroscopy for any visible excitation energy. We note that, for all excitations, the D to G intensity ratio reaches a maximum for an inter-defect distance ~3nm. Thus, a given ratio could correspond to two different defect densities, above or below the maximum. The analysis of the G peak width and its dispersion with excitation energy solves this ambiguity.
2,558 citations
Stephen Sawcer1, Garrett Hellenthal2, Matti Pirinen2, Chris C. A. Spencer2 +262 more•Institutions (67)
TL;DR: In this article, a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, they have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci.
Abstract: Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
2,511 citations
TL;DR: A mitogen-activated protein kinase–dependent mechanism regulates autophagy by controlling the biogenesis and partnership of two distinct cellular organelles during starvation.
Abstract: Autophagy is a cellular catabolic process that relies on the cooperation of autophagosomes and lysosomes. During starvation, the cell expands both compartments to enhance degradation processes. We found that starvation activates a transcriptional program that controls major steps of the autophagic pathway, including autophagosome formation, autophagosome-lysosome fusion, and substrate degradation. The transcription factor EB (TFEB), a master gene for lysosomal biogenesis, coordinated this program by driving expression of autophagy and lysosomal genes. Nuclear localization and activity of TFEB were regulated by serine phosphorylation mediated by the extracellular signal-regulated kinase 2, whose activity was tuned by the levels of extracellular nutrients. Thus, a mitogen-activated protein kinase-dependent mechanism regulates autophagy by controlling the biogenesis and partnership of two distinct cellular organelles.
2,409 citations
Daniel J. Eisenstein1, Daniel J. Eisenstein2, David H. Weinberg3, Eric Agol4 +260 more•Institutions (62)
TL;DR: SDSS-III as mentioned in this paper is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars.
Abstract: Building on the legacy of the Sloan Digital Sky Survey (SDSS-I and II), SDSS-III is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars. In keeping with SDSS tradition, SDSS-III will provide regular public releases of all its data, beginning with SDSS DR8 (which occurred in Jan 2011). This paper presents an overview of the four SDSS-III surveys. BOSS will measure redshifts of 1.5 million massive galaxies and Lya forest spectra of 150,000 quasars, using the BAO feature of large scale structure to obtain percent-level determinations of the distance scale and Hubble expansion rate at z 100 per resolution element), H-band (1.51-1.70 micron) spectra of 10^5 evolved, late-type stars, measuring separate abundances for ~15 elements per star and creating the first high-precision spectroscopic survey of all Galactic stellar populations (bulge, bar, disks, halo) with a uniform set of stellar tracers and spectral diagnostics. MARVELS will monitor radial velocities of more than 8000 FGK stars with the sensitivity and cadence (10-40 m/s, ~24 visits per star) needed to detect giant planets with periods up to two years, providing an unprecedented data set for understanding the formation and dynamical evolution of giant planet systems. (Abridged)
2,265 citations
TL;DR: The molecular mechanisms linking ER stress to apoptosis are the topic of this review, with emphases on relevance to pathophysiology and integration and complementation among the various apoptotic pathways induced by ER stress.
Abstract: The ability to respond to perturbations in endoplasmic reticulum (ER) function is a fundamentally important property of all cells, but ER stress can also lead to apoptosis. In settings of chronic ER stress, the associated apoptosis may contribute to pathophysiological processes involved in a number of prevalent diseases, including neurodegenerative diseases, diabetes, atherosclerosis and renal disease. The molecular mechanisms linking ER stress to apoptosis are the topic of this review, with emphases on relevance to pathophysiology and integration and complementation among the various apoptotic pathways induced by ER stress.
TL;DR: In this paper, a Raman study of Ar+-bombarded graphene samples with increasing ion doses was conducted and it was shown that the ratio between the D and G peak intensities strongly depends on the laser excitation energy.
Abstract: We present a Raman study of Ar+-bombarded graphene samples with increasing ion doses. This allows us to have a controlled, increasing, amount of defects. We find that the ratio between the D and G peak intensities, for a given defect density, strongly depends on the laser excitation energy. We quantify this effect and present a simple equation for the determination of the point defect density in graphene via Raman spectroscopy for any visible excitation energy. We note that, for all excitations, the D to G intensity ratio reaches a maximum for an interdefect distance ∼3 nm. Thus, a given ratio could correspond to two different defect densities, above or below the maximum. The analysis of the G peak width and its dispersion with excitation energy solves this ambiguity.
TL;DR: It is found that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis, which has important implications for the origins of genomic remodeling and temporal emergence of cancer.
Max Planck Society1, National University of Cordoba2, Centre national de la recherche scientifique3, Macquarie University4, University of Paris-Sud5, University of Western Sydney6, University of Minnesota7, VU University Amsterdam8, University of Arizona9, University of California, Berkeley10, University of Guelph11, Australian National University12, University of Innsbruck13, University of Leeds14, University of Groningen15, Universidade Federal do Rio Grande do Sul16, University of Cape Town17, University of Wollongong18, New Jersey Institute of Technology19, Centro Agronómico Tropical de Investigación y Enseñanza20, Lawrence Berkeley National Laboratory21, University of Alaska Fairbanks22, University of Cambridge23, Kansas State University24, Helmholtz Centre for Environmental Research - UFZ25, Arizona State University26, University of Giessen27, Autonomous University of Barcelona28, University of Maryland, College Park29, Universidad del Tolima30, University of São Paulo31, University of La Réunion32, University of York33, University of Sydney34, Harvard University35, Goethe University Frankfurt36, University of Sheffield37, University of Ulm38, State University of Campinas39, Kenyon College40, Royal Botanic Gardens41, University of Florida42, University of Oldenburg43, University of Nebraska–Lincoln44, Tohoku University45, Northern Arizona University46, University of Wisconsin–Eau Claire47, Naturalis48, James Cook University49, Institut national de la recherche agronomique50, Newcastle University51, University of New South Wales52, Leipzig University53, Columbia University54, Estonian University of Life Sciences55, Polish Academy of Sciences56, Moscow State University57, Kyushu University58, Wageningen University and Research Centre59, Spanish National Research Council60, University of Regensburg61, University of Rennes62, Université du Québec à Trois-Rivières63, Potsdam Institute for Climate Impact Research64, Technical University of Denmark65, University of California, Los Angeles66, Hokkaido University67, Université de Sherbrooke68, Syracuse University69, Empresa Brasileira de Pesquisa Agropecuária70, University of Aberdeen71, Michigan State University72, Oak Ridge National Laboratory73, University of Leicester74, Utah State University75, Smithsonian Institution76, University of Missouri77
TL;DR: TRY as discussed by the authors is a global database of plant traits, including morphological, anatomical, physiological, biochemical and phenological characteristics of plants and their organs, which can be used for a wide range of research from evolutionary biology, community and functional ecology to biogeography.
Abstract: Plant traits – the morphological, anatomical, physiological, biochemical and phenological characteristics of plants and their organs – determine how primary producers respond to environmental factors, affect other trophic levels, influence ecosystem processes and services and provide a link from species richness to ecosystem functional diversity. Trait data thus represent the raw material for a wide range of research from evolutionary biology, community and functional ecology to biogeography. Here we present the global database initiative named TRY, which has united a wide range of the plant trait research community worldwide and gained an unprecedented buy-in of trait data: so far 93 trait databases have been contributed. The data repository currently contains almost three million trait entries for 69 000 out of the world's 300 000 plant species, with a focus on 52 groups of traits characterizing the vegetative and regeneration stages of the plant life cycle, including growth, dispersal, establishment and persistence. A first data analysis shows that most plant traits are approximately log-normally distributed, with widely differing ranges of variation across traits. Most trait variation is between species (interspecific), but significant intraspecific variation is also documented, up to 40% of the overall variation. Plant functional types (PFTs), as commonly used in vegetation models, capture a substantial fraction of the observed variation – but for several traits most variation occurs within PFTs, up to 75% of the overall variation. In the context of vegetation models these traits would better be represented by state variables rather than fixed parameter values. The improved availability of plant trait data in the unified global database is expected to support a paradigm shift from species to trait-based ecology, offer new opportunities for synthetic plant trait research and enable a more realistic and empirically grounded representation of terrestrial vegetation in Earth system models.
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TL;DR: The probable cause and effect relationship between perturbed autophagy and aging is discussed, as well as possible molecular mechanisms that may mediate the anti-aging effects of Autophagy.
TL;DR: A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function, and these findings suggest potential novel therapeutic pathways for cardiovascular disease prevention.
Abstract: Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
TL;DR: Meta-analyses of all data provided compelling evidence that ABCA7 and the MS4A gene cluster are new Alzheimer's disease susceptibility loci and independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance.
Abstract: We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10).
TL;DR: The Alzheimer Disease Genetics Consortium performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1), two replication stages (stages 2 and 3), and both joint analysis and meta-analysis approaches were used.
Abstract: The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.
TL;DR: This review will look at key preclinical stages of the drug discovery process, from initial target identification and validation, through assay development, high throughput screening, hit identification, lead optimization and finally the selection of a candidate molecule for clinical development.
Abstract: Developing a new drug from original idea to the launch of a finished product is a complex process which can take 12-15 years and cost in excess of $1 billion. The idea for a target can come from a variety of sources including academic and clinical research and from the commercial sector. It may take many years to build up a body of supporting evidence before selecting a target for a costly drug discovery programme. Once a target has been chosen, the pharmaceutical industry and more recently some academic centres have streamlined a number of early processes to identify molecules which possess suitable characteristics to make acceptable drugs. This review will look at key preclinical stages of the drug discovery process, from initial target identification and validation, through assay development, high throughput screening, hit identification, lead optimization and finally the selection of a candidate molecule for clinical development.
Wellcome Trust1, University of London2, Dana Corporation3, University of Toronto4, Federal University of São Paulo5, Duke University6, University of Wisconsin-Madison7, University of Oxford8, John E. Fogarty International Center9, University of Queensland10, Chinese Center for Disease Control and Prevention11, Harvard University12, Johns Hopkins University13, Muhimbili University of Health and Allied Sciences14, King's College London15, University of Ibadan16, Cayetano Heredia University17, University of California, Berkeley18, Indian Institute of Science19, University of Cambridge20, World Health Organization21, Health Canada22, University of Cape Town23, National Health and Medical Research Council24, Medical Research Council25, Canadian Institutes of Health Research26, National Institutes of Health27
TL;DR: A consortium of researchers, advocates and clinicians announces here research priorities for improving the lives of people with mental illness around the world, and calls for urgent action and investment.
Abstract: A consortium of researchers, advocates and clinicians announces here research priorities for improving the lives of people with mental illness around the world, and calls for urgent action and investment.
Heribert Schunkert1, Inke R. König1, Sekar Kathiresan2, Muredach P. Reilly3 +163 more•Institutions (59)
TL;DR: This paper performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals.
Abstract: We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 - 10'8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
TL;DR: In this paper, the Tait equation of state (TEOS) was used to model the temperature dependence of both the thermal expansion and bulk modulus in a consistent way, which has led to improved fitting of the phase equilibrium experiments.
Abstract: The thermodynamic properties of 254 end-members, including 210 mineral end-members, 18 silicate liquid end-members and 26 aqueous fluid species are presented in a revised and updated internally consistent thermodynamic data set. The PVT properties of the data set phases are now based on a modified Tait equation of state (EOS) for the solids and the Pitzer & Sterner (1995) equation for gaseous components. Thermal expansion and compressibility are linked within the modified Tait EOS (TEOS) by a thermal pressure formulation using an Einstein temperature to model the temperature dependence of both the thermal expansion and bulk modulus in a consistent way. The new EOS has led to improved fitting of the phase equilibrium experiments. Many new end-members have been added, including several deep mantle phases and, for the first time, sulphur-bearing minerals. Silicate liquid end-members are in good agreement with both phase equilibrium experiments and measured heat of melting. The new dataset considerably enhances the capabilities for thermodynamic calculation on rocks, melts and aqueous fluids under crustal to deep mantle conditions. Implementations are already available in thermocalc to take advantage of the new data set and its methodologies, as illustrated by example calculations on sapphirine-bearing equilibria, sulphur-bearing equilibria and calculations to 300 kbar and 2000 °C to extend to lower mantle conditions.
National University of Singapore1, University of California, San Diego2, Yale University3, ETH Zurich4, University of Adelaide5, University of Cambridge6, Lancaster University7, University of East Anglia8, South Australian Research and Development Institute9, James Cook University10, National Institute of Amazonian Research11
TL;DR: It is found that biodiversity values were substantially lower in degraded forests, but that this varied considerably by geographic region, taxonomic group, ecological metric and disturbance type.
Abstract: Human-driven land-use changes increasingly threaten biodiversity, particularly in tropical forests where both species diversity and human pressures on natural environments are high. The rapid conversion of tropical forests for agriculture, timber production and other uses has generated vast, human-dominated landscapes with potentially dire consequences for tropical biodiversity. Today, few truly undisturbed tropical forests exist, whereas those degraded by repeated logging and fires, as well as secondary and plantation forests, are rapidly expanding. Here we provide a global assessment of the impact of disturbance and land conversion on biodiversity in tropical forests using a meta-analysis of 138 studies. We analysed 2,220 pairwise comparisons of biodiversity values in primary forests (with little or no human disturbance) and disturbed forests. We found that biodiversity values were substantially lower in degraded forests, but that this varied considerably by geographic region, taxonomic group, ecological metric and disturbance type. Even after partly accounting for confounding colonization and succession effects due to the composition of surrounding habitats, isolation and time since disturbance, we find that most forms of forest degradation have an overwhelmingly detrimental effect on tropical biodiversity. Our results clearly indicate that when it comes to maintaining tropical biodiversity, there is no substitute for primary forests.
TL;DR: This paper reviewed the literature describing and quantifying time lags in the health research translation process and concluded that the current state of knowledge of time lag is of limited use to those responsible for R&D and knowledge transfer who face difficulties in knowing what they should or can do to reduce time lag.
Abstract: This study aimed to review the literature describing and quantifying time lags in the health research translation process. Papers were included in the review if they quantified time lags in the development of health interventions. The study identified 23 papers. Few were comparable as different studies use different measures, of different things, at different time points. We concluded that the current state of knowledge of time lags is of limited use to those responsible for R&D and knowledge transfer who face difficulties in knowing what they should or can do to reduce time lags. This effectively ‘blindfolds’ investment decisions and risks wasting effort. The study concludes that understanding lags first requires agreeing models, definitions and measures, which can be applied in practice. A second task would be to develop a process by which to gather these data.
TL;DR: On the bicentenary of the publication of Poisson's Traité de Mécanique, the continuing relevance of Poissons's ratio in the understanding of the mechanical characteristics of modern materials is reviewed.
Abstract: In comparing a material's resistance to distort under mechanical load rather than to alter in volume, Poisson's ratio offers the fundamental metric by which to compare the performance of any material when strained elastically. The numerical limits are set by ½ and -1, between which all stable isotropic materials are found. With new experiments, computational methods and routes to materials synthesis, we assess what Poisson's ratio means in the contemporary understanding of the mechanical characteristics of modern materials. Central to these recent advances, we emphasize the significance of relationships outside the elastic limit between Poisson's ratio and densification, connectivity, ductility and the toughness of solids; and their association with the dynamic properties of the liquids from which they were condensed and into which they melt.
Hiroaki Aihara1, Carlos Allende Prieto2, Carlos Allende Prieto3, Deokkeun An4 +191 more•Institutions (58)
TL;DR: The first data release of SDSS-III is described in this article, which includes five-band imaging of roughly 5200 deg2 in the southern Galactic cap, bringing the total footprint of the Sloan Digital Sky Survey imaging to 14,555 deg2, or over a third of the Celestial Sphere.
Abstract: The Sloan Digital Sky Survey (SDSS) started a new phase in 2008 August, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Lyα forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg2 in the southern Galactic cap, bringing the total footprint of the SDSS imaging to 14,555 deg2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Exploration (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameter pipeline, which has better determination of metallicity for high-metallicity stars.
TL;DR: In the aftermath of the English Civil War, as people were groping for new forms of political order, Robert Boyle built an air-pump to do experiments and argued that facts should be manufactured by machines like the airpump so that gentlemen could witness the experiments and produce knowledge that everyone agreed on as mentioned in this paper.
Abstract: In the aftermath of the English Civil War, as people were groping for new forms of political order, Robert Boyle built an air-pump to do experiments. Does the story of Roundheads and Restoration have something to do with the origins of experimental science? Schaffer and Shapin believed it does. Focusing on the debates between Boyle and his archcritic Thomas Hobbes over the air-pump, the authors proposed that 'solutions to the problem of knowledge are solutions to the problem of social order. Both Boyle and Hobbes were looking for ways of establishing knowledge that did not decay into ad hominem attacks and political division. Boyle proposed the experiment as cure. He argued that facts should be manufactured by machines like the air-pump so that gentlemen could witness the experiments and produce knowledge that everyone agreed on. Hobbes, by contrast, looked for natural law and viewed experiments as the artificial, unreliable products of an exclusive guild. The new approaches taken in "Leviathan and the Air-Pump" have been enormously influential on historical studies of science. Shapin and Schaffer found a moment of scientific revolution and showed how key scientific givens - facts, interpretations, experiment, truth - were fundamental to a new political order. Shapin and Schaffer were also innovative in their ethnographic approach. Attempting to understand the work habits, rituals, and social structures of a remote, unfamiliar group, they argued that politics were tied up in what scientists did, rather than what they said.
TL;DR: Observations of a quasar at a redshift of 7.3 are reported, suggesting that the neutral fraction of the intergalactic medium in front of ULAS J1120+0641 exceeded 0.1.
Abstract: Quasars have historically been identified in optical surveys, which are insensitive to sources at z > 6.5. Infrared deep-sky survey data now make it possible to explore higher redshifts, with the result that a luminous quasar (ULAS J1120+0641) with a redshift z = 7.085, beyond the previous high of z = 6.44, has now been identified. Further observations of this and other distant quasars should reveal the ionization state of the Universe as it was only about 0.75 billion years after the Big Bang. The intergalactic medium was not completely reionized until approximately a billion years after the Big Bang, as revealed1 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 identified2,3,4 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 × 1013L⊙ and hosts a black hole with a mass of 2 × 109M⊙ (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 wing5, suggesting that the neutral fraction of the intergalactic medium in front of ULAS J1120+0641 exceeded 0.1.
TL;DR: An overview of the criteria used in the diagnosis of Alzheimer disease is provided, highlighting how this disease is related to, but distinct from, normal aging.
Abstract: The global prevalence of dementia is estimated to be as high as 24 million, and is predicted to double every 20 years through to 2040, leading to a costly burden of disease. Alzheimer disease (AD) is the leading cause of dementia and is characterized by a progressive decline in cognitive function, which typically begins with deterioration in memory. Before death, individuals with this disorder have usually become dependent on caregivers. The neuropathological hallmarks of the AD brain are diffuse and neuritic extracellular amyloid plaques-which are frequently surrounded by dystrophic neurites-and intracellular neurofibrillary tangles. These hallmark pathologies are often accompanied by the presence of reactive microgliosis and the loss of neurons, white matter and synapses. The etiological mechanisms underlying the neuropathological changes in AD remain unclear, but are probably affected by both environmental and genetic factors. Here, we provide an overview of the criteria used in the diagnosis of AD, highlighting how this disease is related to, but distinct from, normal aging. We also summarize current information relating to AD prevalence, incidence and risk factors, and review the biomarkers that may be used for risk assessment and in diagnosis.
TL;DR: It is found that purified osteocytes express a much higher amount of receptor activator of nuclear factor-κB ligand (RANKL) and have a greater capacity to support osteoclastogenesis in vitro than osteoblasts and bone marrow stromal cells.
Abstract: Osteocytes embedded in bone have been postulated to orchestrate bone homeostasis by regulating both bone-forming osteoblasts and bone-resorbing osteoclasts. We find here that purified osteocytes express a much higher amount of receptor activator of nuclear factor-κB ligand (RANKL) and have a greater capacity to support osteoclastogenesis in vitro than osteoblasts and bone marrow stromal cells. Furthermore, the severe osteopetrotic phenotype that we observe in mice lacking RANKL specifically in osteocytes indicates that osteocytes are the major source of RANKL in bone remodeling in vivo.