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Showing papers by "Massachusetts Institute of Technology published in 2012"


Journal ArticleDOI
TL;DR: Fiji is a distribution of the popular open-source software ImageJ focused on biological-image analysis that facilitates the transformation of new algorithms into ImageJ plugins that can be shared with end users through an integrated update system.
Abstract: Fiji is a distribution of the popular open-source software ImageJ focused on biological-image analysis. Fiji uses modern software engineering practices to combine powerful software libraries with a broad range of scripting languages to enable rapid prototyping of image-processing algorithms. Fiji facilitates the transformation of new algorithms into ImageJ plugins that can be shared with end users through an integrated update system. We propose Fiji as a platform for productive collaboration between computer science and biology research communities.

43,540 citations


Journal ArticleDOI
TL;DR: This work reviews the historical development of Transition metal dichalcogenides, methods for preparing atomically thin layers, their electronic and optical properties, and prospects for future advances in electronics and optoelectronics.
Abstract: Single-layer metal dichalcogenides are two-dimensional semiconductors that present strong potential for electronic and sensing applications complementary to that of graphene.

13,348 citations


Journal ArticleDOI
TL;DR: This protocol begins with raw sequencing reads and produces a transcriptome assembly, lists of differentially expressed and regulated genes and transcripts, and publication-quality visualizations of analysis results, which takes less than 1 d of computer time for typical experiments and ∼1 h of hands-on time.
Abstract: Recent advances in high-throughput cDNA sequencing (RNA-seq) can reveal new genes and splice variants and quantify expression genome-wide in a single assay. The volume and complexity of data from RNA-seq experiments necessitate scalable, fast and mathematically principled analysis software. TopHat and Cufflinks are free, open-source software tools for gene discovery and comprehensive expression analysis of high-throughput mRNA sequencing (RNA-seq) data. Together, they allow biologists to identify new genes and new splice variants of known ones, as well as compare gene and transcript expression under two or more conditions. This protocol describes in detail how to use TopHat and Cufflinks to perform such analyses. It also covers several accessory tools and utilities that aid in managing data, including CummeRbund, a tool for visualizing RNA-seq analysis results. Although the procedure assumes basic informatics skills, these tools assume little to no background with RNA-seq analysis and are meant for novices and experts alike. The protocol begins with raw sequencing reads and produces a transcriptome assembly, lists of differentially expressed and regulated genes and transcripts, and publication-quality visualizations of analysis results. The protocol's execution time depends on the volume of transcriptome sequencing data and available computing resources but takes less than 1 d of computer time for typical experiments and ∼1 h of hands-on time.

10,913 citations


Journal ArticleDOI
04 Oct 2012-Nature
TL;DR: The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
Abstract: We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.

9,355 citations


Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, Jalal Abdallah4  +2964 moreInstitutions (200)
TL;DR: In this article, a search for the Standard Model Higgs boson in proton-proton collisions with the ATLAS detector at the LHC is presented, which has a significance of 5.9 standard deviations, corresponding to a background fluctuation probability of 1.7×10−9.

9,282 citations


Journal ArticleDOI
TL;DR: In this paper, results from searches for the standard model Higgs boson in proton-proton collisions at 7 and 8 TeV in the CMS experiment at the LHC, using data samples corresponding to integrated luminosities of up to 5.8 standard deviations.

8,857 citations


Journal ArticleDOI
Curtis Huttenhower1, Curtis Huttenhower2, Dirk Gevers2, Rob Knight3  +250 moreInstitutions (42)
14 Jun 2012-Nature
TL;DR: The Human Microbiome Project Consortium reported the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome as discussed by the authors.
Abstract: The Human Microbiome Project Consortium reports the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome.

8,410 citations


Journal ArticleDOI
Donna M. Muzny1, Matthew N. Bainbridge1, Kyle Chang1, Huyen Dinh1  +317 moreInstitutions (24)
19 Jul 2012-Nature
TL;DR: Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.
Abstract: To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase e (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.

6,883 citations


01 Apr 2012
TL;DR: The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis as mentioned in this paper, and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration.
Abstract: The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis. The pathway regulates many major cellular processes and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration. Here, we review recent advances in our understanding of the mTOR pathway and its role in health, disease, and aging. We further discuss pharmacological approaches to treat human pathologies linked to mTOR deregulation.

6,268 citations


Journal ArticleDOI
13 Apr 2012-Cell
TL;DR: Recent advances in understanding of the mTOR pathway are reviewed and pharmacological approaches to treat human pathologies linked to mTOR deregulation are discussed.

5,792 citations


Journal ArticleDOI
Kaoru Hagiwara, Ken Ichi Hikasa1, Koji Nakamura, Masaharu Tanabashi1, M. Aguilar-Benitez, Claude Amsler2, R. M. Barnett3, P. R. Burchat4, C. D. Carone5, C. Caso6, G. Conforto7, Olav Dahl3, Michael Doser8, Semen Eidelman9, Jonathan L. Feng10, L. K. Gibbons11, M. C. Goodman12, Christoph Grab13, D. E. Groom3, Atul Gurtu8, Atul Gurtu14, K. G. Hayes15, J.J. Hernández-Rey16, K. Honscheid17, Christopher Kolda18, Michelangelo L. Mangano8, D. M. Manley19, Aneesh V. Manohar20, John March-Russell8, Alberto Masoni, Ramon Miquel3, Klaus Mönig, Hitoshi Murayama21, Hitoshi Murayama3, S. Sánchez Navas13, Keith A. Olive22, Luc Pape8, C. Patrignani6, A. Piepke23, Matts Roos24, John Terning25, Nils A. Tornqvist24, T. G. Trippe3, Petr Vogel26, C. G. Wohl3, Ron L. Workman27, W-M. Yao3, B. Armstrong3, P. S. Gee3, K. S. Lugovsky, S. B. Lugovsky, V. S. Lugovsky, Marina Artuso28, D. Asner29, K. S. Babu30, E. L. Barberio8, Marco Battaglia8, H. Bichsel31, O. Biebel32, P. Bloch8, Robert N. Cahn3, Ariella Cattai8, R.S. Chivukula33, R. Cousins34, G. A. Cowan35, Thibault Damour36, K. Desler, R. J. Donahue3, D. A. Edwards, Victor Daniel Elvira37, Jens Erler38, V. V. Ezhela, A Fassò8, W. Fetscher13, Brian D. Fields39, B. Foster40, Daniel Froidevaux8, Masataka Fukugita41, Thomas K. Gaisser42, L. A. Garren37, H J Gerber13, Frederick J. Gilman43, Howard E. Haber44, C. A. Hagmann29, J.L. Hewett4, Ian Hinchliffe3, Craig J. Hogan31, G. Höhler45, P. Igo-Kemenes46, John David Jackson3, Kurtis F Johnson47, D. Karlen48, B. Kayser37, S. R. Klein3, Konrad Kleinknecht49, I.G. Knowles50, P. Kreitz4, Yu V. Kuyanov, R. Landua8, Paul Langacker38, L. S. Littenberg51, Alan D. Martin52, Tatsuya Nakada53, Tatsuya Nakada8, Meenakshi Narain33, Paolo Nason, John A. Peacock54, H. R. Quinn55, Stuart Raby17, Georg G. Raffelt32, E. A. Razuvaev, B. Renk49, L. Rolandi8, Michael T Ronan3, L.J. Rosenberg54, C.T. Sachrajda55, A. I. Sanda56, Subir Sarkar57, Michael Schmitt58, O. Schneider53, Douglas Scott59, W. G. Seligman60, M. H. Shaevitz60, Torbjörn Sjöstrand61, George F. Smoot3, Stefan M Spanier4, H. Spieler3, N. J. C. Spooner62, Mark Srednicki63, Achim Stahl, Todor Stanev42, M. Suzuki3, N. P. Tkachenko, German Valencia64, K. van Bibber29, Manuella Vincter65, D. R. Ward66, Bryan R. Webber66, M R Whalley52, Lincoln Wolfenstein43, J. Womersley37, C. L. Woody51, Oleg Zenin 
Tohoku University1, University of Zurich2, Lawrence Berkeley National Laboratory3, Stanford University4, College of William & Mary5, University of Genoa6, University of Urbino7, CERN8, Budker Institute of Nuclear Physics9, University of California, Irvine10, Cornell University11, Argonne National Laboratory12, ETH Zurich13, Tata Institute of Fundamental Research14, Hillsdale College15, Spanish National Research Council16, Ohio State University17, University of Notre Dame18, Kent State University19, University of California, San Diego20, University of California, Berkeley21, University of Minnesota22, University of Alabama23, University of Helsinki24, Los Alamos National Laboratory25, California Institute of Technology26, George Washington University27, Syracuse University28, Lawrence Livermore National Laboratory29, Oklahoma State University–Stillwater30, University of Washington31, Max Planck Society32, Boston University33, University of California, Los Angeles34, Royal Holloway, University of London35, Université Paris-Saclay36, Fermilab37, University of Pennsylvania38, University of Illinois at Urbana–Champaign39, University of Bristol40, University of Tokyo41, University of Delaware42, Carnegie Mellon University43, University of California, Santa Cruz44, Karlsruhe Institute of Technology45, Heidelberg University46, Florida State University47, Carleton University48, University of Mainz49, University of Edinburgh50, Brookhaven National Laboratory51, Durham University52, University of Lausanne53, Massachusetts Institute of Technology54, University of Southampton55, Nagoya University56, University of Oxford57, Northwestern University58, University of British Columbia59, Columbia University60, Lund University61, University of Sheffield62, University of California, Santa Barbara63, Iowa State University64, University of Alberta65, University of Cambridge66
TL;DR: The Particle Data Group's biennial review as mentioned in this paper summarizes much of particle physics, using data from previous editions, plus 2658 new measurements from 644 papers, and lists, evaluates, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons.
Abstract: This biennial Review summarizes much of particle physics. Using data from previous editions, plus 2658 new measurements from 644 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. Among the 112 reviews are many that are new or heavily revised including those on Heavy-Quark and Soft-Collinear Effective Theory, Neutrino Cross Section Measurements, Monte Carlo Event Generators, Lattice QCD, Heavy Quarkonium Spectroscopy, Top Quark, Dark Matter, V-cb & V-ub, Quantum Chromodynamics, High-Energy Collider Parameters, Astrophysical Constants, Cosmological Parameters, and Dark Matter. A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review. All tables, listings, and reviews (and errata) are also available on the Particle Data Group website: http://pdg.lbl.gov.

Journal ArticleDOI
TL;DR: These guidelines are presented for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Journal ArticleDOI
TL;DR: This work has examined the completeness of the transcript annotation and found that 35% of transcriptional start sites are supported by CAGE clusters and 62% of protein-coding genes have annotated polyA sites, and over one-third of GENCODE protein-Coding genes aresupported by peptide hits derived from mass spectrometry spectra submitted to Peptide Atlas.
Abstract: The GENCODE Consortium aims to identify all gene features in the human genome using a combination of computational analysis, manual annotation, and experimental validation. Since the first public release of this annotation data set, few new protein-coding loci have been added, yet the number of alternative splicing transcripts annotated has steadily increased. The GENCODE 7 release contains 20,687 protein-coding and 9640 long noncoding RNA loci and has 33,977 coding transcripts not represented in UCSC genes and RefSeq. It also has the most comprehensive annotation of long noncoding RNA (lncRNA) loci publicly available with the predominant transcript form consisting of two exons. We have examined the completeness of the transcript annotation and found that 35% of transcriptional start sites are supported by CAGE clusters and 62% of protein-coding genes have annotated polyA sites. Over one-third of GENCODE protein-coding genes are supported by peptide hits derived from mass spectrometry spectra submitted to Peptide Atlas. New models derived from the Illumina Body Map 2.0 RNA-seq data identify 3689 new loci not currently in GENCODE, of which 3127 consist of two exon models indicating that they are possibly unannotated long noncoding loci. GENCODE 7 is publicly available from gencodegenes.org and via the Ensembl and UCSC Genome Browsers.

Journal Article
TL;DR: Big data, the authors write, is far more powerful than the analytics of the past, and executives can measure and therefore manage more precisely than ever before, and make better predictions and smarter decisions.
Abstract: Big data, the authors write, is far more powerful than the analytics of the past. Executives can measure and therefore manage more precisely than ever before. They can make better predictions and smarter decisions. They can target more-effective interventions in areas that so far have been dominated by gut and intuition rather than by data and rigor. The differences between big data and analytics are a matter of volume, velocity, and variety: More data now cross the internet every second than were stored in the entire internet 20 years ago. Nearly real-time information makes it possible for a company to be much more agile than its competitors. And that information can come from social networks, images, sensors, the web, or other unstructured sources. The managerial challenges, however, are very real. Senior decision makers have to learn to ask the right questions and embrace evidence-based decision making. Organizations must hire scientists who can find patterns in very large data sets and translate them into useful business information. IT departments have to work hard to integrate all the relevant internal and external sources of data. The authors offer two success stories to illustrate how companies are using big data: PASSUR Aerospace enables airlines to match their actual and estimated arrival times. Sears Holdings directly analyzes its incoming store data to make promotions much more precise and faster.

Journal ArticleDOI
TL;DR: It is shown that respondents recruited in this manner are often more representative of the U.S. population than in-person convenience samples but less representative than subjects in Internet-based panels or national probability samples.
Abstract: We examine the trade-offs associated with using Amazon.com’s Mechanical Turk (MTurk) interface for subject recruitment. We first describe MTurk and its promise as a vehicle for performing low-cost and easy-to-field experiments. We then assess the internal and external validity of experiments performed using MTurk, employing a framework that can be used to evaluate other subject pools. We first investigate the characteristics of samples drawn from the MTurk population. We show that respondents recruited in this manner are often more representative of the U.S. population than in-person convenience samples—the modal sample in published experimental political science—but less representative than subjects in Internet-based panels or national probability samples. Finally, we replicate important published experimental work using MTurk samples.

Journal ArticleDOI
Peter S. Hammerman1, Doug Voet1, Michael S. Lawrence1, Douglas Voet1  +342 moreInstitutions (32)
27 Sep 2012-Nature
TL;DR: It is shown that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour.
Abstract: Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers.

Journal ArticleDOI
TL;DR: In this paper, both negative and positive electrode materials in NIB are briefly reviewed, and it is concluded that cost-effective NIB can partially replace Li-ion batteries, but requires further investigation and improvement.
Abstract: Lithium (Li)-ion batteries (LIB) have governed the current worldwide rechargeable battery market due to their outstanding energy and power capability. In particular, the LIB's role in enabling electric vehicles (EVs) has been highlighted to replace the current oil-driven vehicles in order to reduce the usage of oil resources and generation of CO2 gases. Unlike Li, sodium is one of the more abundant elements on Earth and exhibits similar chemical properties to Li, indicating that Na chemistry could be applied to a similar battery system. In the 1970s-80s, both Na-ion and Li-ion electrodes were investigated, but the higher energy density of Li-ion cells made them more applicable to small, portable electronic devices, and research efforts for rechargeable batteries have been mainly concentrated on LIB since then. Recently, research interest in Na-ion batteries (NIB) has been resurrected, driven by new applications with requirements different from those in portable electronics, and to address the concern on Li abundance. In this article, both negative and positive electrode materials in NIB are briefly reviewed. While the voltage is generally lower and the volume change upon Na removal or insertion is larger for Na-intercalation electrodes, compared to their Li equivalents, the power capability can vary depending on the crystal structures. It is concluded that cost-effective NIB can partially replace LIB, but requires further investigation and improvement.

Journal ArticleDOI
TL;DR: This review focuses on continuous-variable quantum information processes that rely on any combination of Gaussian states, Gaussian operations, and Gaussian measurements, including quantum communication, quantum cryptography, quantum computation, quantum teleportation, and quantum state and channel discrimination.
Abstract: The science of quantum information has arisen over the last two decades centered on the manipulation of individual quanta of information, known as quantum bits or qubits. Quantum computers, quantum cryptography, and quantum teleportation are among the most celebrated ideas that have emerged from this new field. It was realized later on that using continuous-variable quantum information carriers, instead of qubits, constitutes an extremely powerful alternative approach to quantum information processing. This review focuses on continuous-variable quantum information processes that rely on any combination of Gaussian states, Gaussian operations, and Gaussian measurements. Interestingly, such a restriction to the Gaussian realm comes with various benefits, since on the theoretical side, simple analytical tools are available and, on the experimental side, optical components effecting Gaussian processes are readily available in the laboratory. Yet, Gaussian quantum information processing opens the way to a wide variety of tasks and applications, including quantum communication, quantum cryptography, quantum computation, quantum teleportation, and quantum state and channel discrimination. This review reports on the state of the art in this field, ranging from the basic theoretical tools and landmark experimental realizations to the most recent successful developments.

Journal ArticleDOI
TL;DR: This study shows that these r-RuO2 and r-IrO2 NPs can serve as a benchmark in the development of active OER catalysts for electrolyzers, metal-air batteries, and photoelectrochemical water splitting applications.
Abstract: The activities of the oxygen evolution reaction (OER) on iridium-oxide- and ruthenium-oxide-based catalysts are among the highest known to date. However, the OER activities of thermodynamically stable rutile iridium oxide (r-IrO2) and rutile iridium oxide (r-RuO2), normalized to catalyst mass or true surface area are not well-defined. Here we report a synthesis of r-IrO2 and r-RuO2 nanoparticles (NPs) of ∼6 nm, and examine their OER activities in acid and alkaline solutions. Both r-IrO2 and r-RuO2 NPs were highly active for OER, with r-RuO2 exhibiting up to 10 A/goxide at 1.48 V versus reversible hydrogen electrode. When comparing the two, r-RuO2 NPs were found to have slightly higher intrinsic and mass OER activities than r-IrO2 in both acid and basic solutions. Interestingly, these oxide NPs showed higher stability under OER conditions than commercial Ru/C and Ir/C catalysts. Our study shows that these r-RuO2 and r-IrO2 NPs can serve as a benchmark in the development of active OER catalysts for electrol...

Journal ArticleDOI
TL;DR: Entropy balancing, a data preprocessing method to achieve covariate balance in observational studies with binary treatments, obviates the need for continual balance checking and iterative searching over propensity score models that may stochastically balance the covariate moments.
Abstract: This paper proposes entropy balancing, a data preprocessing method to achieve covariate balance in observational studies with binary treatments. Entropy balancing relies on a maximum entropy reweighting scheme that calibrates unit weights so that the reweighted treatment and control group satisfy a potentially large set of prespecified balance conditions that incorporate information about known sample moments. Entropy balancing thereby exactly adjusts inequalities in representation with respect to the first, second, and possibly higher moments of the covariate distributions. These balance improvements can reduce model dependence for the subsequent estimation of treatment effects. The method assures that balance improves on all covariate moments included in the reweighting. It also obviates the need for continual balance checking and iterative searching over propensity score models that may stochastically balance the covariate moments. We demonstrate the use of entropy balancing with Monte Carlo simulations and empirical applications.


Journal ArticleDOI
TL;DR: Head motion was associated with decreased functional coupling in the default and frontoparietal control networks--two networks characterized by coupling among distributed regions of association cortex and other network measures increased with motion including estimates of local functional coupling and coupling between left and right motor regions.

Journal ArticleDOI
TL;DR: The microbiome of ileal Crohn's disease was notable for increases in virulence and secretion pathways, and the first insights into community-wide microbial processes and pathways that underpin IBD pathogenesis are provided.
Abstract: Background: The inflammatory bowel diseases (IBD) Crohn’s disease and ulcerative colitis result from alterations in intestinal microbes and the immune system. However, the precise dysfunctions of microbial metabolism in the gastrointestinal microbiome during IBD remain unclear. We analyzed the microbiota of intestinal biopsies and stool samples from 231 IBD and healthy subjects by 16S gene pyrosequencing and followed up a subset using shotgun metagenomics. Gene and pathway composition were assessed, based on 16S data from phylogenetically-related reference genomes, and associated using sparse multivariate linear modeling with medications, environmental factors, and IBD status. Results: Firmicutes and Enterobacteriaceae abundances were associated with disease status as expected, but also with treatment and subject characteristics. Microbial function, though, was more consistently perturbed than composition, with 12% of analyzed pathways changed compared with 2% of genera. We identified major shifts in oxidative stress pathways, as well as decreased carbohydrate metabolism and amino acid biosynthesis in favor of nutrient transport and uptake. The microbiome of ileal Crohn’s disease was notable for increases in virulence and secretion pathways.

Journal ArticleDOI
Barbara A. Methé1, Karen E. Nelson1, Mihai Pop2, Heather Huot Creasy3  +250 moreInstitutions (42)
14 Jun 2012-Nature
TL;DR: The Human Microbiome Project (HMP) Consortium has established a population-scale framework which catalyzed significant development of metagenomic protocols resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomics data available to the scientific community as mentioned in this paper.
Abstract: A variety of microbial communities and their genes (microbiome) exist throughout the human body, playing fundamental roles in human health and disease. The NIH funded Human Microbiome Project (HMP) Consortium has established a population-scale framework which catalyzed significant development of metagenomic protocols resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 to 18 body sites up to three times, which to date, have generated 5,177 microbial taxonomic profiles from 16S rRNA genes and over 3.5 Tb of metagenomic sequence. In parallel, approximately 800 human-associated reference genomes have been sequenced. Collectively, these data represent the largest resource to date describing the abundance and variety of the human microbiome, while providing a platform for current and future studies.

Journal ArticleDOI
TL;DR: The Model of Emissions of Gases and Aerosols from Nature version 2.1 (MEGAN2.1) as discussed by the authors is an update from the previous versions including MEGAN1.0, which was described for isoprene emissions by Guenther et al. (2006) and MEGan2.02, which were described for monoterpene and sesquiterpene emissions by Sakulyanontvittaya et al (2008).
Abstract: . The Model of Emissions of Gases and Aerosols from Nature version 2.1 (MEGAN2.1) is a modeling framework for estimating fluxes of biogenic compounds between terrestrial ecosystems and the atmosphere using simple mechanistic algorithms to account for the major known processes controlling biogenic emissions. It is available as an offline code and has also been coupled into land surface and atmospheric chemistry models. MEGAN2.1 is an update from the previous versions including MEGAN2.0, which was described for isoprene emissions by Guenther et al. (2006) and MEGAN2.02, which was described for monoterpene and sesquiterpene emissions by Sakulyanontvittaya et al. (2008). Isoprene comprises about half of the total global biogenic volatile organic compound (BVOC) emission of 1 Pg (1000 Tg or 1015 g) estimated using MEGAN2.1. Methanol, ethanol, acetaldehyde, acetone, α-pinene, β-pinene, t-β-ocimene, limonene, ethene, and propene together contribute another 30% of the MEGAN2.1 estimated emission. An additional 20 compounds (mostly terpenoids) are associated with the MEGAN2.1 estimates of another 17% of the total emission with the remaining 3% distributed among >100 compounds. Emissions of 41 monoterpenes and 32 sesquiterpenes together comprise about 15% and 3%, respectively, of the estimated total global BVOC emission. Tropical trees cover about 18% of the global land surface and are estimated to be responsible for ~80% of terpenoid emissions and ~50% of other VOC emissions. Other trees cover about the same area but are estimated to contribute only about 10% of total emissions. The magnitude of the emissions estimated with MEGAN2.1 are within the range of estimates reported using other approaches and much of the differences between reported values can be attributed to land cover and meteorological driving variables. The offline version of MEGAN2.1 source code and driving variables is available from http://bai.acd.ucar.edu/MEGAN/ and the version integrated into the Community Land Model version 4 (CLM4) can be downloaded from http://www.cesm.ucar.edu/ .

Journal ArticleDOI
TL;DR: ChromHMM as mentioned in this paper is an automated computational system for learning chromatin states, characterizing their biological functions and correlations with large-scale functional datasets, and visualizing the resulting genome-wide maps of chromatin state annotations.
Abstract: Chromatin state annotation using combinations of chromatin modification patterns has emerged as a powerful approach for discovering regulatory regions and their cell type specific activity patterns, and for interpreting disease-association studies1-5 However, the computational challenge of learning chromatin state models from large numbers of chromatin modification datasets in multiple cell types still requires extensive bioinformatics expertise making it inaccessible to the wider scientific community To address this challenge, we have developed ChromHMM, an automated computational system for learning chromatin states, characterizing their biological functions and correlations with large-scale functional datasets, and visualizing the resulting genome-wide maps of chromatin state annotations

Journal ArticleDOI
TL;DR: HaploReg is presented, a tool for exploring annotations of the non-coding genome among the results of published GWAS or novel sets of variants, and will be useful to researchers developing mechanistic hypotheses of the impact of non-Coding variants on clinical phenotypes and normal variation.
Abstract: The resolution of genome-wide association studies (GWAS) is limited by the linkage disequilibrium (LD) structure of the population being studied. Selecting the most likely causal variants within an LD block is relatively straightforward within coding sequence, but is more difficult when all variants are intergenic. Predicting functional non-coding sequence has been recently facilitated by the availability of conservation and epigenomic information. We present HaploReg, a tool for exploring annotations of the non-coding genome among the results of published GWAS or novel sets of variants. Using LD information from the 1000 Genomes Project, linked SNPs and small indels can be visualized along with their predicted chromatin state in nine cell types, conservation across mammals and their effect on regulatory motifs. Sets of SNPs, such as those resulting from GWAS, are analyzed for an enrichment of cell type-specific enhancers. HaploReg will be useful to researchers developing mechanistic hypotheses of the impact of non-coding variants on clinical phenotypes and normal variation. The HaploReg database is available at http://compbio.mit.edu/HaploReg.

01 Nov 2012
TL;DR: The Model of Emissions of Gases and Aerosols from Nature version 2.1 (MEGAN2.1) as mentioned in this paper is an update from the previous versions including MEGAN1.0, which was described for isoprene emissions by Guenther et al. (2006) and MEGan2.02, which were described for monoterpene and sesquiterpene emissions by Sakulyanontvittaya et al (2008).
Abstract: . The Model of Emissions of Gases and Aerosols from Nature version 2.1 (MEGAN2.1) is a modeling framework for estimating fluxes of biogenic compounds between terrestrial ecosystems and the atmosphere using simple mechanistic algorithms to account for the major known processes controlling biogenic emissions. It is available as an offline code and has also been coupled into land surface and atmospheric chemistry models. MEGAN2.1 is an update from the previous versions including MEGAN2.0, which was described for isoprene emissions by Guenther et al. (2006) and MEGAN2.02, which was described for monoterpene and sesquiterpene emissions by Sakulyanontvittaya et al. (2008). Isoprene comprises about half of the total global biogenic volatile organic compound (BVOC) emission of 1 Pg (1000 Tg or 1015 g) estimated using MEGAN2.1. Methanol, ethanol, acetaldehyde, acetone, α-pinene, β-pinene, t-β-ocimene, limonene, ethene, and propene together contribute another 30% of the MEGAN2.1 estimated emission. An additional 20 compounds (mostly terpenoids) are associated with the MEGAN2.1 estimates of another 17% of the total emission with the remaining 3% distributed among >100 compounds. Emissions of 41 monoterpenes and 32 sesquiterpenes together comprise about 15% and 3%, respectively, of the estimated total global BVOC emission. Tropical trees cover about 18% of the global land surface and are estimated to be responsible for ~80% of terpenoid emissions and ~50% of other VOC emissions. Other trees cover about the same area but are estimated to contribute only about 10% of total emissions. The magnitude of the emissions estimated with MEGAN2.1 are within the range of estimates reported using other approaches and much of the differences between reported values can be attributed to land cover and meteorological driving variables. The offline version of MEGAN2.1 source code and driving variables is available from http://bai.acd.ucar.edu/MEGAN/ and the version integrated into the Community Land Model version 4 (CLM4) can be downloaded from http://www.cesm.ucar.edu/ .

Journal ArticleDOI
TL;DR: This paper introduces a novel longitudinal image processing framework, based on unbiased, robust, within-subject template creation, for automatic surface reconstruction and segmentation of brain MRI of arbitrarily many time points and successfully reduces variability and avoids over-regularization.

Journal ArticleDOI
TL;DR: This article conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent, and identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association.
Abstract: To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.