Showing papers by "Imperial College London published in 2010"
TL;DR: The Discriminant Analysis of Principal Components (DAPC) is introduced, a multivariate method designed to identify and describe clusters of genetically related individuals that performs generally better than STRUCTURE at characterizing population subdivision.
Abstract: The dramatic progress in sequencing technologies offers unprecedented prospects for deciphering the organization of natural populations in space and time. However, the size of the datasets generated also poses some daunting challenges. In particular, Bayesian clustering algorithms based on pre-defined population genetics models such as the STRUCTURE or BAPS software may not be able to cope with this unprecedented amount of data. Thus, there is a need for less computer-intensive approaches. Multivariate analyses seem particularly appealing as they are specifically devoted to extracting information from large datasets. Unfortunately, currently available multivariate methods still lack some essential features needed to study the genetic structure of natural populations. We introduce the Discriminant Analysis of Principal Components (DAPC), a multivariate method designed to identify and describe clusters of genetically related individuals. When group priors are lacking, DAPC uses sequential K-means and model selection to infer genetic clusters. Our approach allows extracting rich information from genetic data, providing assignment of individuals to groups, a visual assessment of between-population differentiation, and contribution of individual alleles to population structuring. We evaluate the performance of our method using simulated data, which were also analyzed using STRUCTURE as a benchmark. Additionally, we illustrate the method by analyzing microsatellite polymorphism in worldwide human populations and hemagglutinin gene sequence variation in seasonal influenza. Analysis of simulated data revealed that our approach performs generally better than STRUCTURE at characterizing population subdivision. The tools implemented in DAPC for the identification of clusters and graphical representation of between-group structures allow to unravel complex population structures. Our approach is also faster than Bayesian clustering algorithms by several orders of magnitude, and may be applicable to a wider range of datasets.
3,770 citations
TL;DR: The steep dispersion of the Fano resonance profile promises applications in sensors, lasing, switching, and nonlinear and slow-light devices.
Abstract: Since its discovery, the asymmetric Fano resonance has been a characteristic feature of interacting quantum systems. The shape of this resonance is distinctively different from that of conventional symmetric resonance curves. Recently, the Fano resonance has been found in plasmonic nanoparticles, photonic crystals, and electromagnetic metamaterials. The steep dispersion of the Fano resonance profile promises applications in sensors, lasing, switching, and nonlinear and slow-light devices.
3,536 citations
Tanya M. Teslovich1, Kiran Musunuru, Albert V. Smith2, Andrew C. Edmondson3 +215 more•Institutions (46)
TL;DR: The results identify several novel loci associated with plasma lipids that are also associated with CAD and provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
Abstract: Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
3,469 citations
TL;DR: This Review highlights the recent advances in optical properties of chemically derived GO, as well as new physical and biological applications that are attracting chemists for its own characteristics.
Abstract: Chemically derived graphene oxide (GO) is an atomically thin sheet of graphite that has traditionally served as a precursor for graphene, but is increasingly attracting chemists for its own characteristics. It is covalently decorated with oxygen-containing functional groups - either on the basal plane or at the edges - so that it contains a mixture of sp(2)- and sp(3)-hybridized carbon atoms. In particular, manipulation of the size, shape and relative fraction of the sp(2)-hybridized domains of GO by reduction chemistry provides opportunities for tailoring its optoelectronic properties. For example, as-synthesized GO is insulating but controlled deoxidation leads to an electrically and optically active material that is transparent and conducting. Furthermore, in contrast to pure graphene, GO is fluorescent over a broad range of wavelengths, owing to its heterogeneous electronic structure. In this Review, we highlight the recent advances in optical properties of chemically derived GO, as well as new physical and biological applications.
2,937 citations
TL;DR: This paper proposes generalizations that combine tie strength and node centrality, and illustrates the benefits of this approach by applying one of them to Freeman’s EIES dataset.
2,713 citations
Elizabeth K. Speliotes1, Elizabeth K. Speliotes2, Cristen J. Willer3, Sonja I. Berndt +410 more•Institutions (86)
TL;DR: Genetic loci associated with body mass index map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor, which may provide new insights into human body weight regulation.
Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
2,632 citations
TL;DR: The Spectral and Photometric Imaging REceiver (SPIRE) is the Herschel Space Observatory's sub-millimetre camera and spectrometer as discussed by the authors, which is used for image and spectroscopic data acquisition.
Abstract: The Spectral and Photometric Imaging REceiver (SPIRE), is the Herschel Space Observatory`s submillimetre camera and spectrometer It contains a three-band imaging photometer operating at 250, 350 and 500 mu m, and an imaging Fourier-transform spectrometer (FTS) which covers simultaneously its whole operating range of 194-671 mu m (447-1550 GHz) The SPIRE detectors are arrays of feedhorn-coupled bolometers cooled to 03 K The photometer has a field of view of 4' x 8', observed simultaneously in the three spectral bands Its main operating mode is scan-mapping, whereby the field of view is scanned across the sky to achieve full spatial sampling and to cover large areas if desired The spectrometer has an approximately circular field of view with a diameter of 26' The spectral resolution can be adjusted between 12 and 25 GHz by changing the stroke length of the FTS scan mirror Its main operating mode involves a fixed telescope pointing with multiple scans of the FTS mirror to acquire spectral data For extended source measurements, multiple position offsets are implemented by means of an internal beam steering mirror to achieve the desired spatial sampling and by rastering of the telescope pointing to map areas larger than the field of view The SPIRE instrument consists of a cold focal plane unit located inside the Herschel cryostat and warm electronics units, located on the spacecraft Service Module, for instrument control and data handling Science data are transmitted to Earth with no on-board data compression, and processed by automatic pipelines to produce calibrated science products The in-flight performance of the instrument matches or exceeds predictions based on pre-launch testing and modelling: the photometer sensitivity is comparable to or slightly better than estimated pre-launch, and the spectrometer sensitivity is also better by a factor of 15-2
2,425 citations
TL;DR: In this paper, the current status of area laws in quantum many-body systems is reviewed and a significant proportion is devoted to the clear and quantitative connection between the entanglement content of states and the possibility of their efficient numerical simulation.
Abstract: Physical interactions in quantum many-body systems are typically local: Individual constituents interact mainly with their few nearest neighbors. This locality of interactions is inherited by a decay of correlation functions, but also reflected by scaling laws of a quite profound quantity: the entanglement entropy of ground states. This entropy of the reduced state of a subregion often merely grows like the boundary area of the subregion, and not like its volume, in sharp contrast with an expected extensive behavior. Such ``area laws'' for the entanglement entropy and related quantities have received considerable attention in recent years. They emerge in several seemingly unrelated fields, in the context of black hole physics, quantum information science, and quantum many-body physics where they have important implications on the numerical simulation of lattice models. In this Colloquium the current status of area laws in these fields is reviewed. Center stage is taken by rigorous results on lattice models in one and higher spatial dimensions. The differences and similarities between bosonic and fermionic models are stressed, area laws are related to the velocity of information propagation in quantum lattice models, and disordered systems, nonequilibrium situations, and topological entanglement entropies are discussed. These questions are considered in classical and quantum systems, in their ground and thermal states, for a variety of correlation measures. A significant proportion is devoted to the clear and quantitative connection between the entanglement content of states and the possibility of their efficient numerical simulation. Matrix-product states, higher-dimensional analogs, and variational sets from entanglement renormalization are also discussed and the paper is concluded by highlighting the implications of area laws on quantifying the effective degrees of freedom that need to be considered in simulations of quantum states.
2,282 citations
TL;DR: In this article, a review of the literature on open innovation is presented, focusing on two inbound processes: sourcing and acquiring, and two outbound processes, revealing and selling.
2,278 citations
Grenoble Institute of Technology1, National University of Mar del Plata2, Case Western Reserve University3, University of Fribourg4, University of Nottingham5, Virginia Tech6, University of Natural Resources and Life Sciences, Vienna7, University of Leoben8, Kyoto University9, Oregon State University10, Portland State University11, Imperial College London12, Queen Mary University of London13
TL;DR: An overview of recent progress in the area of cellulose nanofibre-based nanocomposites is given in this article, with particular emphasis on applications, such as reinforced adhesives, to make optically transparent paper for electronic displays, to create DNA-hybrid materials, to generate hierarchical composites and for use in foams, aerogels and starch nanocom composites.
Abstract: This paper provides an overview of recent progress made in the area of cellulose nanofibre-based nanocomposites. An introduction into the methods used to isolate cellulose nanofibres (nanowhiskers, nanofibrils) is given, with details of their structure. Following this, the article is split into sections dealing with processing and characterisation of cellulose nanocomposites and new developments in the area, with particular emphasis on applications. The types of cellulose nanofibres covered are those extracted from plants by acid hydrolysis (nanowhiskers), mechanical treatment and those that occur naturally (tunicate nanowhiskers) or under culturing conditions (bacterial cellulose nanofibrils). Research highlighted in the article are the use of cellulose nanowhiskers for shape memory nanocomposites, analysis of the interfacial properties of cellulose nanowhisker and nanofibril-based composites using Raman spectroscopy, switchable interfaces that mimic sea cucumbers, polymerisation from the surface of cellulose nanowhiskers by atom transfer radical polymerisation and ring opening polymerisation, and methods to analyse the dispersion of nanowhiskers. The applications and new advances covered in this review are the use of cellulose nanofibres to reinforce adhesives, to make optically transparent paper for electronic displays, to create DNA-hybrid materials, to generate hierarchical composites and for use in foams, aerogels and starch nanocomposites and the use of all-cellulose nanocomposites for enhanced coupling between matrix and fibre. A comprehensive coverage of the literature is given and some suggestions on where the field is likely to advance in the future are discussed.
2,214 citations
TL;DR: The backbone of a π-conjugated polymer is comprised of a linear series of overlapping pz orbitals that have formed via sp2 hybridization, thereby creating a conjugated chain of delocalized electron density, which dictates the electronic characteristics of the polymer.
Abstract: In recent years, organic solar cells utilizing π-conjugated polymers have attracted widespread interest in both the academic and, increasingly, the commercial communities. These polymers are promising in terms of their electronic properties, low cost, versatility of functionalization, thin film flexibility, and ease of processing. These factors indicate that organic solar cells, although currently producing relatively low power conversion efficiencies (∼5-7%),1–3 compared to inorganic solar cells, have the potential to compete effectively with alternative solar cell technologies. However, in order for this to be feasible, the efficiencies of organic solar cells need further improvement. This is the focus of extensive studies worldwide. The backbone of a π-conjugated polymer is comprised of a linear series of overlapping pz orbitals that have formed via sp2 hybridization, thereby creating a conjugated chain of delocalized electron density. It is the interaction of these π electrons that dictates the electronic characteristics of the polymer. The energy levels become closely spaced as the delocalization length increases, resulting in a ‘band’ structure somewhat similar to that observed in inorganic solid-state semiconductors. In contrast to the latter, however, the primary photoexcitations in conjugated polymers are bound electron-hole pairs (excitons) rather than free charge carriers; this is largely due to their low dielectric constant and the presence of significant electron-lattice interactions and electron correlation effects.4 In the absence of a mechanism to dissociate the excitons into free charge carriers, the exciton will undergo radiative and nonradiative decay, with a typical exciton lifetime in the range from 100 ps to 1 ns. Achieving efficient charge photogeneration has long been recognized as a vital challenge for molecular-based solar cells. For example, the first organic solar cells were simple single-layer devices based on the pristine polymer and two electrodes of different work function. These devices, based on a Schottky diode structure, resulted in poor photocurrent efficiency.5–7 Relatively efficient photocurrent generation in an organic device was first reported by Tang in 1986,8 employing a vacuum-deposited CuPc/ perylene derivative donor/acceptor bilayer device. The differing electron affinities (and/or ionization potentials) between these two materials created an energy offset at their interface, thereby driving exciton dissociation. However, the efficiency of such bilayer devices is limited by the requirement of exciton diffusion to the donor/acceptor interface, typically requiring film thicknesses less than the optical absorption depth. Organic materials usually exhibit exciton diffusion lengths of ∼10 nm and optical absorption depths of 100 nm, although we note significant progress is now being made with organic materials with exciton diffusion lengths comparable to or exceeding their optical absorption depth.9–12 The observation of ultrafast photoinduced electron transfer13,14 from a conjugated polymer to C60 and the * To whom correspondence should be addressed. E-mail: j.durrant@ imperial.ac.uk. Chem. Rev. 2010, 110, 6736–6767 6736
TL;DR: It is demonstrated that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
Abstract: Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
TL;DR: The fundamental structure and properties of GO-based thin films are discussed in relation to their potential applications in electronics and optoelectronics.
Abstract: Chemically derived graphene oxide (GO) possesses a unique set of properties arising from oxygen functional groups that are introduced during chemical exfoliation of graphite. Large-area thin-film deposition of GO, enabled by its solubility in a variety of solvents, offers a route towards GO-based thin-film electronics and optoelectronics. The electrical and optical properties of GO are strongly dependent on its chemical and atomic structure and are tunable over a wide range via chemical engineering. In this Review, the fundamental structure and properties of GO-based thin films are discussed in relation to their potential applications in electronics and optoelectronics.
Benjamin F. Voight1, Benjamin F. Voight2, Laura J. Scott3, Valgerdur Steinthorsdottir4 +180 more•Institutions (53)
TL;DR: By combining genome-wide association data from 8,130 individuals with type 2 diabetes and 38,987 controls of European descent and following up previously unidentified meta-analysis signals, 12 new T2D association signals are identified with combined P < 5 × 10−8.
Abstract: By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
TL;DR: It is shown that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait, and indicates that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
University of Lisbon1, University of Paris-Sud2, Netherlands Environmental Assessment Agency3, United Nations Environment Programme4, Spanish National Research Council5, University of Évora6, National Autonomous University of Mexico7, Stockholm University8, University of East Anglia9, University of Maryland, College Park10, Hawaii Pacific University11, University of British Columbia12, Joint Global Change Research Institute13, Imperial College London14, The Nature Conservancy15, Virginia Tech College of Natural Resources and Environment16
TL;DR: Scenarios consistently indicate that biodiversity will continue to decline over the 21st century, however, the range of projected changes is much broader than most studies suggest, partly because there are major opportunities to intervene through better policies, but also because of large uncertainties in projections.
Abstract: Quantitative scenarios are coming of age as a tool for evaluating the impact of future socioeconomic development pathways on biodiversity and ecosystem services. We analyze global terrestrial, freshwater, and marine biodiversity scenarios using a range of measures including extinctions, changes in species abundance, habitat loss, and distribution shifts, as well as comparing model projections to observations. Scenarios consistently indicate that biodiversity will continue to decline over the 21st century. However, the range of projected changes is much broader than most studies suggest, partly because there are major opportunities to intervene through better policies, but also because of large uncertainties in projections.
TL;DR: This work implemented standard bone measurements in a novel ImageJ plugin, BoneJ, with which it analysed trabecular bone, whole bones and osteocyte lacunae and found that available software solutions were expensive, inflexible or methodologically opaque.
TL;DR: In this paper, blue photoluminescence from chemically derived graphene oxide Goki Eda, Yun-Yue Lin, Cecilia Mattevi, Hisato Yamaguchi, Hsin-An Chen, I-Sheng Chen, Chun-Wei Chen, and Manish Chhowalla
Abstract: Blue photoluminescence from chemically derived graphene oxide Goki Eda, Yun-Yue Lin, Cecilia Mattevi, Hisato Yamaguchi, Hsin-An Chen, I-Sheng Chen, Chun-Wei Chen, and Manish Chhowalla 1 Department of Materials, Imperial College, Exhibition Road, London SW7 2AZ, UK. 2 Department of Materials Science and Engineering, Rutgers University 607 Taylor Road, Piscataway, NJ 08854, USA. 3 Department of Materials Science and Engineering, National Taiwan University No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan.
TL;DR: The chemical changes of oxygen-containing functional groups on the annealing of graphene oxide are elucidated and the simulations reveal the formation of highly stable carbonyl and ether groups that hinder its complete reduction to graphene.
Abstract: The excellent electrical, optical and mechanical properties of graphene have driven the search to find methods for its large-scale production, but established procedures (such as mechanical exfoliation or chemical vapour deposition) are not ideal for the manufacture of processable graphene sheets. An alternative method is the reduction of graphene oxide, a material that shares the same atomically thin structural framework as graphene, but bears oxygen-containing functional groups. Here we use molecular dynamics simulations to study the atomistic structure of progressively reduced graphene oxide. The chemical changes of oxygen-containing functional groups on the annealing of graphene oxide are elucidated and the simulations reveal the formation of highly stable carbonyl and ether groups that hinder its complete reduction to graphene. The calculations are supported by infrared and X-ray photoelectron spectroscopy measurements. Finally, more effective reduction treatments to improve the reduction of graphene oxide are proposed.
TL;DR: This work focuses on Organic Electronics Materials, which consist of Organic Transistors, Polymer Semiconductors, and Poly(3,2-b)thiophenes, and investigates the role of bias stress in these materials.
Abstract: 2.3. Medical Devices and Sensors 9 2.4. Radio Frequency Applications 10 3. Materials 12 3.1. Organic Electronics Materials 12 3.2. Semiconducting Polymer Design 13 3.3. Poly(3-alkylthiophenes) 14 3.4. Poly(thieno(3,2-b)thiophenes 15 3.5. Benchmark Polymer Semiconductors 15 3.6. High Performance Polymer Semiconductors 15 4. Device Stability 16 4.1. Bias Stress in Organic Transistors 17 4.1.1. Bias Stress Characterization 17 4.1.2. Bias Stress Mechanism 18 4.2. Short Channel Effects in Organic Transistors 19 5. Materials Patterning and Integration 20 6. Conclusions 22 7. Acknowledgments 22 8. References 22
TL;DR: A hitherto underappreciated role of type I IFN-αβ signalling in the pathogenesis of TB is demonstrated, which has implications for vaccine and therapeutic development and a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic are provided.
Abstract: Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis, is a major cause of morbidity and mortality worldwide. Efforts to control it are hampered by difficulties with diagnosis, prevention and treatment. Most people infected with M. tuberculosis remain asymptomatic, termed latent TB, with a 10% lifetime risk of developing active TB disease. Current tests, however, cannot identify which individuals will develop disease. The immune response to M. tuberculosis is complex and incompletely characterized, hindering development of new diagnostics, therapies and vaccines. Here we identify a whole-blood 393 transcript signature for active TB in intermediate and high-burden settings, correlating with radiological extent of disease and reverting to that of healthy controls after treatment. A subset of patients with latent TB had signatures similar to those in patients with active TB. We also identify a specific 86-transcript signature that discriminates active TB from other inflammatory and infectious diseases. Modular and pathway analysis revealed that the TB signature was dominated by a neutrophil-driven interferon (IFN)-inducible gene profile, consisting of both IFN-gamma and type I IFN-alphabeta signalling. Comparison with transcriptional signatures in purified cells and flow cytometric analysis suggest that this TB signature reflects changes in cellular composition and altered gene expression. Although an IFN-inducible signature was also observed in whole blood of patients with systemic lupus erythematosus (SLE), their complete modular signature differed from TB, with increased abundance of plasma cell transcripts. Our studies demonstrate a hitherto underappreciated role of type I IFN-alphabeta signalling in the pathogenesis of TB, which has implications for vaccine and therapeutic development. Our study also provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic.
TL;DR: The authors analyze developmental, genetic, and demographic mechanisms by which populations tolerate changing environments and discuss empirical methods for determining the critical rate of sustained environmental change that causes population extinction.
Abstract: Many species are experiencing sustained environmental change mainly due to human activities. The unusual rate and extent of anthropogenic alterations of the environment may exceed the capacity of developmental, genetic, and demographic mechanisms that populations have evolved to deal with environmental change. To begin to understand the limits to population persistence, we present a simple evolutionary model for the critical rate of environmental change beyond which a population must decline and go extinct. We use this model to highlight the major determinants of extinction risk in a changing environment, and identify research needs for improved predictions based on projected changes in environmental variables. Two key parameters relating the environment to population biology have not yet received sufficient attention. Phenotypic plasticity, the direct influence of environment on the development of individual phenotypes, is increasingly considered an important component of phenotypic change in the wild and should be incorporated in models of population persistence. Environmental sensitivity of selection, the change in the optimum phenotype with the environment, still crucially needs empirical assessment. We use environmental tolerance curves and other examples of ecological and evolutionary responses to climate change to illustrate how these mechanistic approaches can be developed for predictive purposes.
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TL;DR: In this paper, a parsimonious measure of brand attachment was developed and validated, and the convergent and discriminant validity of this measure in relation to brand attitude strength was demonstrated.
Abstract: Research has not verified the theoretical or practical value of the brand attachment construct in relation to alternative constructs, particularly brand attitude strength. The authors make conceptual, measurement, and managerial contributions to this research issue. Conceptually, they define brand attachment, articulate its defining properties, and differentiate it from brand attitude strength. From a measurement perspective, they develop and validate a parsimonious measure of brand attachment, test the assumptions that underlie it, and demonstrate that it indicates the concept of attachment. They also demonstrate the convergent and discriminant validity of this measure in relation to brand attitude strength. Managerially, they demonstrate that brand attachment offers value over brand attitude strength in predicting (a) consumers’ intentions to perform difficult behaviors (those they regard as utilizing consumer resources), (b) actual purchase behaviors, (c) brand purchase share (the share of a brand among directly competing brands), and (d) need share (the extent to which consumers rely on a brand to address relevant needs including those brands in substitutable product categories).
TL;DR: Flexible sigmoidoscopy is a safe and practical test and, when offered only once between ages 55 and 64 years, confers a substantial and longlasting benefit.
TL;DR: Visit-to-visit variability in systolic blood pressure (SBP) and maximum SBP are strong predictors of stroke, independent of mean SBP.
TL;DR: In this article, a parsimonious measure of brand attachment was developed and validated from a measurement perspective, test the assumptions that underlie it, and demonstrate that it indicates the concept of attachment.
Abstract: Research has not verified the theoretical or practical value of the brand attachment construct in relation to alternative constructs, particularly brand attitude strength. The authors make conceptual, measurement, and managerial contributions to this research issue. Conceptually, they define brand attachment, articulate its defining properties, and differentiate it from brand attitude strength. From a measurement perspective, they develop and validate a parsimonious measure of brand attachment, test the assumptions that underlie it, and demonstrate that it indicates the concept of attachment. They also demonstrate the convergent and discriminant validity of this measure in relation to brand attitude strength. Managerially, they demonstrate that brand attachment offers value over brand attitude strength in predicting (1) consumers' intentions to perform difficult behaviors (those they regard as using consumer resources), (2) actual purchase behaviors, (3) brand purchase share (the share of a brand...
University of East Anglia1, University of Giessen2, King's College London3, Imperial College London4, University College London5, Met Office6, University of Birmingham7, University of Bonn8, Deutscher Wetterdienst9, Centre national de la recherche scientifique10, RWTH Aachen University11, University of Graz12
TL;DR: In this paper, the authors integrate perspectives from meteorologists, climatologists, statisticians, and hydrologists to identify generic end user (in particular, impact modeler) needs and to discuss downscaling capabilities and gaps.
Abstract: Precipitation downscaling improves the coarse resolution and poor representation of precipitation in global climate models and helps end users to assess the likely hydrological impacts of climate change. This paper integrates perspectives from meteorologists, climatologists, statisticians, and hydrologists to identify generic end user (in particular, impact modeler) needs and to discuss downscaling capabilities and gaps. End users need a reliable representation of precipitation intensities and temporal and spatial variability, as well as physical consistency, independent of region and season. In addition to presenting dynamical downscaling, we review perfect prognosis statistical downscaling, model output statistics, and weather generators, focusing on recent developments to improve the representation of space-time variability. Furthermore, evaluation techniques to assess downscaling skill are presented. Downscaling adds considerable value to projections from global climate models. Remaining gaps are uncertainties arising from sparse data; representation of extreme summer precipitation, subdaily precipitation, and full precipitation fields on fine scales; capturing changes in small-scale processes and their feedback on large scales; and errors inherited from the driving global climate model.
Harvard University1, McGill University2, University of Washington3, Erasmus University Rotterdam4, UCL Institute of Child Health5, University of Helsinki6, University of Cambridge7, Indiana University – Purdue University Indianapolis8, Wellcome Trust Sanger Institute9, National Institutes of Health10, Imperial College London11, Wake Forest University12, University of Oxford13, Wellcome Trust Centre for Human Genetics14, Churchill Hospital15, Tufts University16, Cedars-Sinai Medical Center17, Agency for Science, Technology and Research18, University of Miami19, Health Canada20, Public Health Agency of Canada21, University College London22, University of Aberdeen23, Broad Institute24, University of Pittsburgh25, Boston University26, King's College London27, University of Oulu28, Finnish Institute of Occupational Health29
TL;DR: In this article, a genome-wide association study of 25-hydroxyvitamin D concentrations in 33,996 individuals of European descent from 15 cohorts was conducted to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency.
TL;DR: Heteronuclear NMR Studies, NMR and EPR Spectroscopies, and Vibrational Spectra of POSS Compounds 2136 3.9.1.
Abstract: 3.6.3. T8R7R′ Compounds (R ) i-Bu) 2127 3.6.4. T8R7R′ Compounds (R ) Et, c-C5H9, or Cy) 2128 3.7. Mass Spectra of POSS Compounds 2128 3.8. Electronic Spectra of POSS Compounds 2130 3.9. NMR and EPR Spectroscopies 2131 3.9.1. Solution 29Si NMR Studies 2131 3.9.2. Other Heteronuclear NMR Studies 2134 3.9.3. EPR Spectra 2134 3.10. Vibrational Spectra of POSS Compounds 2136 3.11. X-ray Photoelectron Spectra of POSS Compounds 2139
TL;DR: Three of the leading options for large scale CO2 capture are reviewed from a technical perspective, including solvent-based chemisorption techniques, carbonate looping technology, and the so-called oxyfuel process.
Abstract: In this paper, three of the leading options for large scale CO2 capture are reviewed from a technical perspective. We consider solvent-based chemisorption techniques, carbonate looping technology, and the so-called oxyfuel process. For each technology option, we give an overview of the technology, listing advantages and disadvantages. Subsequently, a discussion of the level of technological maturity is presented, and we conclude by identifying current gaps in knowledge and suggest areas with significant scope for future work. We then discuss the suitability of using ionic liquids as novel, environmentally benign solvents with which to capture CO2. In addition, we consider alternatives to simply sequestering CO2—we present a discussion on the possibility of recycling captured CO2 and exploiting it as a C1 building block for the sustainable manufacture of polymers, fine chemicals, and liquid fuels. Finally, we present a discussion of relevant systems engineering methodologies in carbon capture system design.