Showing papers by "Trinity College, Dublin published in 2009"
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TL;DR: An Explanation and Elaboration of the PRISMA Statement is presented and updated guidelines for the reporting of systematic reviews and meta-analyses are presented.
Abstract: Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users.
Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions.
The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
25,711 citations
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TL;DR: This Explanation and Elaboration document explains the meaning and rationale for each checklist item and includes an example of good reporting and, where possible, references to relevant empirical studies and methodological literature.
8,021 citations
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Broad Institute1, Harvard University2, QIMR Berghofer Medical Research Institute3, Cardiff University4, North Carolina State University5, Trinity College, Dublin6, University of Edinburgh7, Karolinska Institutet8, Uppsala University9, University of Southern California10, University of North Carolina at Chapel Hill11, University College London12, National Health Service13, University of Oxford14, University of Aberdeen15, Strathclyde Institute of Pharmacy and Biomedical Sciences16, State University of New York Upstate Medical University17, University of Coimbra18
TL;DR: The extent to which common genetic variation underlies the risk of schizophrenia is shown, using two analytic approaches, and the major histocompatibility complex is implicate, which is shown to involve thousands of common alleles of very small effect.
Abstract: Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%(1,2). We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.
4,573 citations
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Cardiff University1, Medical Research Council2, University of Bristol3, National Institute for Health Research4, King's College5, Trinity College, Dublin6, University of Cambridge7, University of Nottingham8, Queen's University Belfast9, University of Southampton10, University of Manchester11, John Radcliffe Hospital12, UCL Institute of Neurology13, University of Bonn14, University of Hamburg15, Charité16, University of Erlangen-Nuremberg17, University of Duisburg-Essen18, Ludwig Maximilian University of Munich19, Heidelberg University20, University College Dublin21, University of Freiburg22, Washington University in St. Louis23, Brigham Young University24, University of Antwerp25, University College London26, Wellcome Trust Sanger Institute27, King's College London28, Aristotle University of Thessaloniki29, National Institutes of Health30, Mayo Clinic31
TL;DR: A two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals, the most powerful AD GWAS to date, produced compelling evidence for association with Alzheimer's Disease in the combined dataset.
Abstract: We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 10-157) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 10-9) and 5' to the PICALM gene (rs3851179, P = 1.9 10-8). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 10-10, odds ratio = 0.86; rs3851179, P = 1.3 10-9, odds ratio = 0.86).
2,956 citations
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Institut Gustave Roussy1, University of Paris-Sud2, French Institute of Health and Medical Research3, Icahn School of Medicine at Mount Sinai4, University of Texas Southwestern Medical Center5, Thomas Jefferson University6, McMaster University7, University of Massachusetts Medical School8, LSU Health Sciences Center New Orleans9, Roswell Park Cancer Institute10, Boston Children's Hospital11, University of Gothenburg12, University of Freiburg13, Buck Institute for Research on Aging14, University of California, San Francisco15, Centre national de la recherche scientifique16, National Institutes of Health17, Technion – Israel Institute of Technology18, University of Leicester19, University of Chieti-Pescara20, Istituto Superiore di Sanità21, University of North Carolina at Chapel Hill22, New York University23, University of Pennsylvania24, Yale University25, Howard Hughes Medical Institute26, University of Ulm27, University of Burgundy28, Aix-Marseille University29, Pasteur Institute30, University of Strasbourg31, Johns Hopkins University32, University of Zurich33, University of Tokyo34, Weizmann Institute of Science35, University of Michigan36, University College London37, Duke University38, University of Graz39, Ghent University40, Trinity College, Dublin41, University of Amsterdam42, University of Lyon43, University of Rome Tor Vergata44, Stony Brook University45, University of Göttingen46, Kyoto University47, Merck & Co.48, Austrian Academy of Sciences49, National University of Singapore50, University of Chicago51, Royal College of Surgeons in Ireland52, La Trobe University53, University of Buenos Aires54, University of Padua55, University of Lisbon56, University of Cambridge57, University of Würzburg58, University of Geneva59, University of Bern60, Rockefeller University61, University of Lausanne62, Osaka University63, University of California, San Diego64, University of Glasgow65, Harvard University66, Karolinska Institutet67
TL;DR: A nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls is provided and the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells is emphasized.
Abstract: Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios Thus far, dozens of methods have been proposed to quantify cell death-related parameters However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells
2,218 citations
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TL;DR: A method to disperse and exfoliate graphite to give graphene suspended in water-surfactant solutions and suggests the flakes to be largely free of defects and oxides, although X-ray photoelectron spectroscopy shows evidence of a small oxide population.
Abstract: We have demonstrated a method to disperse and exfoliate graphite to give graphene suspended in water−surfactant solutions. Optical characterization of these suspensions allowed the partial optimization of the dispersion process. Transmission electron microscopy showed the dispersed phase to consist of small graphitic flakes. More than 40% of these flakes had <5 layers with ∼3% of flakes consisting of monolayers. Atomic resolution transmission electron microscopy shows the monolayers to be generally free of defects. The dispersed graphitic flakes are stabilized against reaggregation by Coulomb repulsion due to the adsorbed surfactant. We use DLVO and Hamaker theory to describe this stabilization. However, the larger flakes tend to sediment out over ∼6 weeks, leaving only small flakes dispersed. It is possible to form thin films by vacuum filtration of these dispersions. Raman and IR spectroscopic analysis of these films suggests the flakes to be largely free of defects and oxides, although X-ray photoelect...
2,086 citations
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TL;DR: These nanowire films are electromechanically very robust, with all but the thinnest films showing no change in sheet resistance when flexed over >1000 cycles, which makes these films ideal as replacements for indium tin oxide as transparent electrodes.
Abstract: We have used aqueous dispersions of silver nanowires to prepare thin, flexible, transparent, conducting films. The nanowires are of length and diameter close to 6.5 μm and 85 nm, respectively. At low thickness, the films consist of networks but appear to become bulk-like for mean film thicknesses above ∼160 nm. These films can be very transparent with optical transmittance reaching as high as 92% for low thickness. The transmittance (550 nm) decreases with increasing thickness, consistent with an optical conductivity of 6472 S/m. The films are also very uniform; the transmittance varies spatially by typically <2%. The sheet resistance decreases with increasing thickness, falling below 1 Ω/◻ for thicknesses above 300 nm. The DC conductivity increases from 2 × 105 S/m for very thin films before saturating at 5 × 106 S/m for thicker films. Similarly, the ratio of DC to optical conductivity increases with increasing thickness from 25 for the thinnest films, saturating at ∼500 for thicknesses above ∼160 nm. We...
1,530 citations
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TL;DR: It is shown that gammadelta T cells express IL-23R and the transcription factor RORgammat and produce IL-17, IL-21, and IL-22 in response to IL-1beta andIL-23, without T cell receptor engagement.
1,410 citations
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TL;DR: In this paper, the authors investigated the relationship between stocks, bonds and gold and found that gold is a hedge against stocks on average and a safe haven in extreme stock market conditions.
Abstract: Is gold a hedge against sudden changes in stock and bond returns, or does it instead have a subtly different property, that of being a safe haven? This paper addresses these two interlinked questions. A safe haven is defined as a security that is uncorrelated with stocks and bonds in case of a market crash. This is counterpoised against a hedge, defined as a security that is uncorrelated with stocks or bonds on average. We study constant and time-varying relationships between stocks, bonds and gold in order to investigate the existence of a hedge and a safe haven. The empirical analysis examines US, UK and German stock and bond returns and their relationship with gold returns. We find that gold is a hedge against stocks on average and a safe haven in extreme stock market conditions. This finding suggests that the existence of a safe haven enhances the stability and resiliency of financial markets since it reduces investors' losses at times when a reduction is needed the most. A portfolio analysis further shows that the safe haven property is extremely short-lived so that an investor buying gold one day after a shock loses money.
1,255 citations
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Christine G. Elsik1, Christine G. Elsik2, Christine G. Elsik3, Ross L. Tellam3 +325 more•Institutions (65)
TL;DR: To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage and provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
Abstract: To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
1,144 citations
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TL;DR: Electric field–dependent studies show that a tetragonal-like phase can be reversibly converted into a rhombohedral- like phase, accompanied by measurable displacements of the surface, making this new lead-free system of interest for probe-based data storage and actuator applications.
Abstract: Piezoelectric materials, which convert mechanical to electrical energy and vice versa, are typically characterized by the intimate coexistence of two phases across a morphotropic phase boundary. Electrically switching one to the other yields large electromechanical coupling coefficients. Driven by global environmental concerns, there is currently a strong push to discover practical lead-free piezoelectrics for device engineering. Using a combination of epitaxial growth techniques in conjunction with theoretical approaches, we show the formation of a morphotropic phase boundary through epitaxial constraint in lead-free piezoelectric bismuth ferrite (BiFeO3) films. Electric field-dependent studies show that a tetragonal-like phase can be reversibly converted into a rhombohedral-like phase, accompanied by measurable displacements of the surface, making this new lead-free system of interest for probe-based data storage and actuator applications.
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TL;DR: In this article, the authors prove that the nonlinear dispersive partial differential equations (NPDPDE) and Korteweg-de Vries (KDE) arise in the modeling of the propagation of shallow water waves over a flat bed.
Abstract: In recent years two nonlinear dispersive partial differential equations have attracted a lot of attention due to their integrable structure. We prove that both equations arise in the modeling of the propagation of shallow water waves over a flat bed. The equations capture stronger nonlinear effects than the classical nonlinear dispersive Benjamin-Bona-Mahoney and Korteweg-de Vries equations. In particular, they accomodate wave breaking phenomena.
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TL;DR: The contribution of cognitive neuroscience, molecular genetics and clinical investigations to understanding how response inhibition is mediated in the human brain is reviewed.
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Baylor College of Medicine1, University of Missouri2, United States Department of Agriculture3, University of New England (United States)4, Commonwealth Scientific and Industrial Research Organisation5, Texas A&M University6, Norwegian University of Life Sciences7, George Mason University8, AgResearch9, Catholic University of the Sacred Heart10, International Atomic Energy Agency11, Empresa Brasileira de Pesquisa Agropecuária12, Sao Paulo State University13, International Livestock Research Institute14, Parco Tecnologico Padano15, University of Edinburgh16, Ethiopian Institute of Agricultural Research17, Livestock Improvement Corporation18, Cornell University19, University of Alberta20, Tuscia University21, Wellcome Trust Sanger Institute22, University of Melbourne23, Government of Victoria24, Trinity College, Dublin25, Simon Fraser University26
TL;DR: Data show that cattle have undergone a rapid recent decrease in effective population size from a very large ancestral population, possibly due to bottlenecks associated with domestication, selection, and breed formation.
Abstract: The imprints of domestication and breed development on the genomes of livestock likely differ from those of companion animals. A deep draft sequence assembly of shotgun reads from a single Hereford female and comparative sequences sampled from six additional breeds were used to develop probes to interrogate 37,470 single-nucleotide polymorphisms (SNPs) in 497 cattle from 19 geographically and biologically diverse breeds. These data show that cattle have undergone a rapid recent decrease in effective population size from a very large ancestral population, possibly due to bottlenecks associated with domestication, selection, and breed formation. Domestication and artificial selection appear to have left detectable signatures of selection within the cattle genome, yet the current levels of diversity within breeds are at least as great as exists within humans.
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TL;DR: This work provides a mechanism for the coordinate repression of let-7 miRNAs observed in a subset of human cancers, and associates activation of LIN28 and LIN28B with poor clinical prognosis.
Abstract: Multiple members of the let-7 family of miRNAs are often repressed in human cancers, thereby promoting oncogenesis by derepressing targets such as HMGA2, K-Ras and c-Myc. However, the mechanism by which let-7 miRNAs are coordinately repressed is unclear. The RNA-binding proteins LIN28 and LIN28B block let-7 precursors from being processed to mature miRNAs, suggesting that their overexpression might promote malignancy through repression of let-7. Here we show that LIN28 and LIN28B are overexpressed in primary human tumors and human cancer cell lines (overall frequency approximately 15%), and that overexpression is linked to repression of let-7 family miRNAs and derepression of let-7 targets. LIN28 and LIN28b facilitate cellular transformation in vitro, and overexpression is associated with advanced disease across multiple tumor types. Our work provides a mechanism for the coordinate repression of let-7 miRNAs observed in a subset of human cancers, and associates activation of LIN28 and LIN28B with poor clinical prognosis.
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TL;DR: Recent human genetic studies strongly suggest that perturbation of skin barrier function as a result of reduction or complete loss of filaggrin expression leads to enhanced percutaneous transfer of allergens.
Abstract: Recently, loss-of-function mutations in FLG, the human gene encoding profilaggrin and filaggrin, have been identified as the cause of the common skin condition ichthyosis vulgaris (which is characterised by dry, scaly skin). These mutations, which are carried by up to 10% of people, also represent a strong genetic predisposing factor for atopic eczema, asthma and allergies. Profilaggrin is the major component of the keratohyalin granules within epidermal granular cells. During epidermal terminal differentiation, the ∼400 kDa profilaggrin polyprotein is dephosphorylated and rapidly cleaved by serine proteases to form monomeric filaggrin (37 kDa), which binds to and condenses the keratin cytoskeleton and thereby contributes to the cell compaction process that is required for squame biogenesis. Within the squames, filaggrin is citrullinated, which promotes its unfolding and further degradation into hygroscopic amino acids, which constitute one element of natural moisturising factor. Loss of profilaggrin or filaggrin leads to a poorly formed stratum corneum (ichthyosis), which is also prone to water loss (xerosis). Recent human genetic studies strongly suggest that perturbation of skin barrier function as a result of reduction or complete loss of filaggrin expression leads to enhanced percutaneous transfer of allergens. Filaggrin is therefore in the frontline of defence, and protects the body from the entry of foreign environmental substances that can otherwise trigger aberrant immune responses.
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Juntendo University1, Rockefeller University2, University of Calgary3, University of Copenhagen4, Curtin University5, Trinity College, Dublin6, CEPHEID7, University of Chicago8, Statens Serum Institut9, Imperial College London10, Public Health Research Institute11, Sungkyunkwan University12, Public Health England13, Health Protection Agency14, Veterans Health Administration15, Örebro University16
TL;DR: Classification of staphylococcal cassette chromosome mec (S CCmec) : guidelines for reporting novel SCCmec elements.
Abstract: Classification of staphylococcal cassette chromosome mec (SCCmec) : guidelines for reporting novel SCCmec elements.
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Cold Spring Harbor Laboratory1, Medical Research Council2, National Institutes of Health3, University of Washington4, University of North Carolina at Chapel Hill5, State University of New York System6, Harvard University7, University of Chicago8, University of Pennsylvania9, Ontario Institute for Cancer Research10, Rockefeller University11, Warneford Hospital12, Columbia University13, Johns Hopkins University14, Heidelberg University15, University of Bonn16, Vanderbilt University17, University College London18, Trinity College, Dublin19, Stony Brook University20, Veterans Health Administration21, University of Massachusetts Medical School22
TL;DR: A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia, bipolar disorder, and autism, while the reciprocal microdeletion was associated only with autism and developmental disorders.
Abstract: Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders1, 2, 3. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 10-5, OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 10-7), bipolar disorder (P = 0.017) and autism (P = 1.9 10-7). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 10-13). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).
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01 Jan 2009TL;DR: In this article, the effects of stochastic wind and load on the unit commitment and dispatch of power systems with high levels of wind power are examined, by comparing the costs, planned operation and performance of the schedules produced.
Abstract: The stochastic nature of wind alters the unit commitment and dispatch problem. By accounting for this uncertainty when scheduling the system, more robust schedules are produced, which should, on average, reduce expected costs. In this paper, the effects of stochastic wind and load on the unit commitment and dispatch of power systems with high levels of wind power are examined. By comparing the costs, planned operation and performance of the schedules produced, it is shown that stochastic optimization results in less costly, of the order of 0.25%, and better performing schedules than deterministic optimization. The impact of planning the system more frequently to account for updated wind and load forecasts is then examined. More frequent planning means more up to date forecasts are used, which reduces the need for reserve and increases performance of the schedules. It is shown that mid merit and peaking units and the interconnection are the most affected parts of the system where uncertainty of wind is concerned
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TL;DR: It is shown that extensive training on a free‐operant task reduces the sensitivity of participants’ behavior to a reduction in outcome value, and suggested that cue‐driven activation in a specific region of dorsolateral posterior putamen may contribute to the habitual control of behavior in humans.
Abstract: Habits are characterized by an insensitivity to their consequences and, as such, can be distinguished from goal-directed actions. The neural basis of the development of demonstrably outcome-insensitive habitual actions in humans has not been previously characterized. In this experiment, we show that extensive training on a free-operant task reduces the sensitivity of participants' behavior to a reduction in outcome value. Analysis of functional magnetic resonance imaging data acquired during training revealed a significant increase in task-related cue sensitivity in a right posterior putamen-globus pallidus region as training progressed. These results provide evidence for a shift from goal-directed to habit-based control of instrumental actions in humans, and suggest that cue-driven activation in a specific region of dorsolateral posterior putamen may contribute to the habitual control of behavior in humans.
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TL;DR: In this paper, the effects of stochastic wind and load on the unit commitment and dispatch of power systems with high levels of wind power are examined, by comparing the costs, planned operation and performance of the schedules produced.
Abstract: The stochastic nature of wind alters the unit commitment and dispatch problem. By accounting for this uncertainty when scheduling the system, more robust schedules are produced, which should, on average, reduce expected costs. In this paper, the effects of stochastic wind and load on the unit commitment and dispatch of power systems with high levels of wind power are examined. By comparing the costs, planned operation and performance of the schedules produced, it is shown that stochastic optimization results in less costly, of the order of 0.25%, and better performing schedules than deterministic optimization. The impact of planning the system more frequently to account for updated wind and load forecasts is then examined. More frequent planning means more up to date forecasts are used, which reduces the need for reserve and increases performance of the schedules. It is shown that mid-merit and peaking units and the interconnection are the most affected parts of the system where uncertainty of wind is concerned.
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TL;DR: It is shown that IL-33 was processed by caspases activated during apoptosis but was not a physiological substrate for caspasing associated with inflammation, and caspase-mediated proteolysis acts as a switch to dampen the proinflammatory properties of IL- 33.
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TL;DR: In this paper, a review of recent work in this area is presented, focusing on results from the author's group, and it is concluded that functionalized nanotubes can be exfoliated to the greatest degree.
Abstract: Many applications of carbon nanotubes require the exfoliation of the nanotubes to give individual tubes in the liquid phase. This requires the dispersion, exfoliation, and stabilization of nanotubes in a variety of liquids. In this paper recent work in this area is reviewed, focusing on results from the author's group. It begins by reviewing stabilization mechanisms before exploring research into the exfoliation of nanotubes in solvents, by using surfactants or biomolecules and by covalent attachment of molecules. The concentration dependence of the degree of exfoliation in each case will be highlighted. In addition research into the dispersion mechanism for each dispersant type is discussed. Most importantly, dispersion quality metrics for all dispersants are compared. From this analysis, it is concluded that functionalized nanotubes can be exfoliated to the greatest degree. Finally, the extension of this work to the liquid phase exfoliation of graphite to give graphene is reviewed.
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TL;DR: A linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms in a common set of 1,031 multiplex autism families, implicating SEMA5A as an autism susceptibility gene.
Abstract: Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 x 10(-7)). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.
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TL;DR: The emerging roles of long non-coding RNAs and a subset of transcription factors in the regulation of PcG association with target genes are discussed and how their deregulation contributes to tumorigenesis is speculated about.
Abstract: The Polycomb group (PcG) proteins are transcriptional repressors that regulate lineage choices during development and differentiation. Recent studies have advanced our understanding of how the PcG proteins regulate cell fate decisions and how their deregulation potentially contributes to cancer. In this Review we discuss the emerging roles of long non-coding RNAs (ncRNAs) and a subset of transcription factors, which we call cell fate transcription factors, in the regulation of PcG association with target genes. We also speculate about how their deregulation contributes to tumorigenesis.
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TL;DR: Activity in a key brain region previously implicated in encoding goal-values: the ventromedial prefrontal cortex (vmPFC) was correlated with the subjects' value for each category of good, providing evidence that the brain encodes a “common currency” that allows for a shared valuation for different categories of goods.
Abstract: To make economic choices between goods, the brain needs to compute representations of their values. A great deal of research has been performed to determine the neural correlates of value representations in the human brain. However, it is still unknown whether there exists a region of the brain that commonly encodes decision values for different types of goods, or if, in contrast, the values of different types of goods are represented in distinct brain regions. We addressed this question by scanning subjects with functional magnetic resonance imaging while they made real purchasing decisions among different categories of goods (food, nonfood consumables, and monetary gambles). We found activity in a key brain region previously implicated in encoding goal-values: the ventromedial prefrontal cortex (vmPFC) was correlated with the subjects' value for each category of good. Moreover, we found a single area in vmPFC to be correlated with the subjects' valuations for all categories of goods. Our results provide evidence that the brain encodes a "common currency" that allows for a shared valuation for different categories of goods.
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TL;DR: This work examines the similarities and differences between RNAi and small-molecule screens, highlighting particular characteristics of RNAi screen data that must be addressed during analysis and provides guidance on selection of analysis techniques in the context of a sample workflow.
Abstract: RNA interference (RNAi) has become a powerful technique for reverse genetics and drug discovery, and in both of these areas large-scale high-throughput RNAi screens are commonly performed. The statistical techniques used to analyze these screens are frequently borrowed directly from small-molecule screening; however, small-molecule and RNAi data characteristics differ in meaningful ways. We examine the similarities and differences between RNAi and small-molecule screens, highlighting particular characteristics of RNAi screen data that must be addressed during analysis. Additionally, we provide guidance on selection of analysis techniques in the context of a sample workflow.
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TL;DR: This perspective with the role of the insula in interoception, self-awareness and drug craving, the anterior cingulate in behavioral monitoring and response selection and drug-related stimuli that predict emotional behavior in addicted individuals are integrated.
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University of Bern1, Cochrane Collaboration2, University Medical Center Freiburg3, American Society of Clinical Oncology4, Trinity College, Dublin5, National Institute for Health Research6, Mayo Clinic7, University of South Florida8, Thomas Jefferson University Hospital9, Gynecologic Oncology Group10
TL;DR: Treatment with erythropoiesis-stimulating agents in patients with cancer increased mortality during active study periods and worsened overall survival, and the increased risk of death associated with treatment with these drugs should be balanced against their benefits.
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TL;DR: This tutorial review surveys the covalent modification of SWCNTs with organic moieties, and illustrates the major analytical techniques routinely used to characterise the functionalised materials.
Abstract: Since carbon nanotubes (CNTs) display unique structures and remarkable physical properties, a variety of applications have emerged in both materials and life sciences. In terms of applications, the functionalisation of nanotubes is extremely important, as it increases their solubility and processability, and combines the unique properties of single-walled carbon nanotubes (SWCNTs) with those of other classes of materials. A number of methods have been developed, which can be divided into two major approaches: (1) non-covalent supramolecular modifications, and (2) covalent functionalisation. In this tutorial review, we survey the covalent modification of SWCNTs with organic moieties, and illustrate the major analytical techniques routinely used to characterise the functionalised materials.