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Showing papers in "Science in 2015"


Journal ArticleDOI
23 Jan 2015-Science
TL;DR: In this paper, a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level.
Abstract: Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.

9,745 citations


Journal ArticleDOI
13 Feb 2015-Science
TL;DR: An updated and extended analysis of the planetary boundary (PB) framework and identifies levels of anthropogenic perturbations below which the risk of destabilization of the Earth system (ES) is likely to remain low—a “safe operating space” for global societal development.
Abstract: The planetary boundaries framework defines a safe operating space for humanity based on the intrinsic biophysical processes that regulate the stability of the Earth system. Here, we revise and update the planetary boundary framework, with a focus on the underpinning biophysical science, based on targeted input from expert research communities and on more general scientific advances over the past 5 years. Several of the boundaries now have a two-tier approach, reflecting the importance of cross-scale interactions and the regional-level heterogeneity of the processes that underpin the boundaries. Two core boundaries—climate change and biosphere integrity—have been identified, each of which has the potential on its own to drive the Earth system into a new state should they be substantially and persistently transgressed.

7,169 citations


Journal ArticleDOI
13 Feb 2015-Science
TL;DR: This work combines available data on solid waste with a model that uses population density and economic status to estimate the amount of land-based plastic waste entering the ocean, which is estimated to be 275 million metric tons.
Abstract: Plastic debris in the marine environment is widely documented, but the quantity of plastic entering the ocean from waste generated on land is unknown. By linking worldwide data on solid waste, population density, and economic status, we estimated the mass of land-based plastic waste entering the ocean. We calculate that 275 million metric tons (MT) of plastic waste was generated in 192 coastal countries in 2010, with 4.8 to 12.7 million MT entering the ocean. Population size and the quality of waste management systems largely determine which countries contribute the greatest mass of uncaptured waste available to become plastic marine debris. Without waste management infrastructure improvements, the cumulative quantity of plastic waste available to enter the ocean from land is predicted to increase by an order of magnitude by 2025.

6,689 citations


Journal ArticleDOI
03 Apr 2015-Science
TL;DR: Treatment efficacy was associated with a higher number of mutations in the tumors, and a tumor-specific T cell response paralleled tumor regression in one patient, suggesting that the genomic landscape of lung cancers shapes response to anti–PD-1 therapy.
Abstract: Immune checkpoint inhibitors, which unleash a patient’s own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non–small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden in tumors was associated with improved objective response, durable clinical benefit, and progression-free survival. Efficacy also correlated with the molecular smoking signature, higher neoantigen burden, and DNA repair pathway mutations; each factor was also associated with mutation burden. In one responder, neoantigen-specific CD8+ T cell responses paralleled tumor regression, suggesting that anti–PD-1 therapy enhances neoantigen-specific T cell reactivity. Our results suggest that the genomic landscape of lung cancers shapes response to anti–PD-1 therapy.

6,215 citations


Journal ArticleDOI
28 Aug 2015-Science
TL;DR: A large-scale assessment suggests that experimental reproducibility in psychology leaves a lot to be desired, and correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
Abstract: Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.

5,532 citations


Journal ArticleDOI
12 Jun 2015-Science
TL;DR: An approach for depositing high-quality FAPbI3 films, involving FAP bI3 crystallization by the direct intramolecular exchange of dimethylsulfoxide (DMSO) molecules intercalated in PbI2 with formamidinium iodide is reported.
Abstract: The band gap of formamidinium lead iodide (FAPbI3) perovskites allows broader absorption of the solar spectrum relative to conventional methylammonium lead iodide (MAPbI3). Because the optoelectronic properties of perovskite films are closely related to film quality, deposition of dense and uniform films is crucial for fabricating high-performance perovskite solar cells (PSCs). We report an approach for depositing high-quality FAPbI3 films, involving FAPbI3 crystallization by the direct intramolecular exchange of dimethylsulfoxide (DMSO) molecules intercalated in PbI2 with formamidinium iodide. This process produces FAPbI3 films with (111)-preferred crystallographic orientation, large-grained dense microstructures, and flat surfaces without residual PbI2. Using films prepared by this technique, we fabricated FAPbI3-based PSCs with maximum power conversion efficiency greater than 20%.

5,458 citations


Journal ArticleDOI
17 Jul 2015-Science
TL;DR: The adoption of data-intensive machine-learning methods can be found throughout science, technology and commerce, leading to more evidence-based decision-making across many walks of life, including health care, manufacturing, education, financial modeling, policing, and marketing.
Abstract: Machine learning addresses the question of how to build computers that improve automatically through experience. It is one of today’s most rapidly growing technical fields, lying at the intersection of computer science and statistics, and at the core of artificial intelligence and data science. Recent progress in machine learning has been driven both by the development of new learning algorithms and theory and by the ongoing explosion in the availability of online data and low-cost computation. The adoption of data-intensive machine-learning methods can be found throughout science, technology and commerce, leading to more evidence-based decision-making across many walks of life, including health care, manufacturing, education, financial modeling, policing, and marketing.

4,545 citations


Journal ArticleDOI
Kristin G. Ardlie, David S. DeLuca, Ayellet V. Segrè, Timothy J. Sullivan, Taylor Young, Ellen Gelfand, Casandra A. Trowbridge, Julian Maller, Taru Tukiainen, Monkol Lek, Lucas D. Ward, Pouya Kheradpour, Benjamin Iriarte, Yan Meng, Cameron D. Palmer, Tõnu Esko, Wendy Winckler, Joel N. Hirschhorn, Manolis Kellis, Daniel G. MacArthur, Gad Getz, Andrey A. Shabalin, Gen Li, Yi-Hui Zhou, Andrew B. Nobel, Ivan Rusyn, Fred A. Wright, Tuuli Lappalainen, Pedro G. Ferreira, Halit Ongen, Manuel A. Rivas, Alexis Battle, Sara Mostafavi, Jean Monlong, Michael Sammeth, Marta Melé, Ferran Reverter, Jakob M. Goldmann, Daphne Koller, Roderic Guigó, Mark I. McCarthy, Emmanouil T. Dermitzakis, Eric R. Gamazon, Hae Kyung Im, Anuar Konkashbaev, Dan L. Nicolae, Nancy J. Cox, Timothée Flutre, Xiaoquan Wen, Matthew Stephens, Jonathan K. Pritchard, Zhidong Tu, Bin Zhang, Tao Huang, Quan Long, Luan Lin, Jialiang Yang, Jun Zhu, Jun Liu, Amanda Brown, Bernadette Mestichelli, Denee Tidwell, Edmund Lo, Mike Salvatore, Saboor Shad, Jeffrey A. Thomas, John T. Lonsdale, Michael T. Moser, Bryan Gillard, Ellen Karasik, Kimberly Ramsey, Christopher Choi, Barbara A. Foster, John Syron, Johnell Fleming, Harold Magazine, Rick Hasz, Gary Walters, Jason Bridge, Mark Miklos, Susan L. Sullivan, Laura Barker, Heather M. Traino, Maghboeba Mosavel, Laura A. Siminoff, Dana R. Valley, Daniel C. Rohrer, Scott D. Jewell, Philip A. Branton, Leslie H. Sobin, Mary Barcus, Liqun Qi, Jeffrey McLean, Pushpa Hariharan, Ki Sung Um, Shenpei Wu, David Tabor, Charles Shive, Anna M. Smith, Stephen A. Buia, Anita H. Undale, Karna Robinson, Nancy Roche, Kimberly M. Valentino, Angela Britton, Robin Burges, Debra Bradbury, Kenneth W. Hambright, John Seleski, Greg E. Korzeniewski, Kenyon Erickson, Yvonne Marcus, Jorge Tejada, Mehran Taherian, Chunrong Lu, Margaret J. Basile, Deborah C. Mash, Simona Volpi, Jeffery P. Struewing, Gary F. Temple, Joy T. Boyer, Deborah Colantuoni, Roger Little, Susan E. Koester, Latarsha J. Carithers, Helen M. Moore, Ping Guan, Carolyn C. Compton, Sherilyn Sawyer, Joanne P. Demchok, Jimmie B. Vaught, Chana A. Rabiner, Nicole C. Lockhart 
08 May 2015-Science
TL;DR: The landscape of gene expression across tissues is described, thousands of tissue-specific and shared regulatory expression quantitative trait loci (eQTL) variants are cataloged, complex network relationships are described, and signals from genome-wide association studies explained by eQTLs are identified.
Abstract: Understanding the functional consequences of genetic variation, and how it affects complex human disease and quantitative traits, remains a critical challenge for biomedicine. We present an analysi...

4,418 citations


Journal ArticleDOI
27 Feb 2015-Science
TL;DR: It is found that the diffusion lengths in CH3NH3PbI3 single crystals grown by a solution-growth method can exceed 175 micrometers under 1 sun (100 mW cm−2) illumination and exceed 3 millimeters under weak light for both electrons and holes.
Abstract: Long, balanced electron and hole diffusion lengths greater than 100 nanometers in the polycrystalline organolead trihalide compound CH3NH3PbI3 are critical for highly efficient perovskite solar cells. We found that the diffusion lengths in CH3NH3PbI3 single crystals grown by a solution-growth method can exceed 175 micrometers under 1 sun (100 mW cm(-2)) illumination and exceed 3 millimeters under weak light for both electrons and holes. The internal quantum efficiencies approach 100% in 3-millimeter-thick single-crystal perovskite solar cells under weak light. These long diffusion lengths result from greater carrier mobility, longer lifetime, and much smaller trap densities in the single crystals than in polycrystalline thin films. The long carrier diffusion lengths enabled the use of CH3NH3PbI3 in radiation sensing and energy harvesting through the gammavoltaic effect, with an efficiency of 3.9% measured with an intense cesium-137 source.

4,393 citations


Journal ArticleDOI
30 Jan 2015-Science
TL;DR: An antisolvent vapor-assisted crystallization approach is reported that enables us to create sizable crack-free MAPbX3 single crystals with volumes exceeding 100 cubic millimeters, which enabled a detailed characterization of their optical and charge transport characteristics.
Abstract: The fundamental properties and ultimate performance limits of organolead trihalide MAPbX3 (MA = CH3NH3(+); X = Br(-) or I(-)) perovskites remain obscured by extensive disorder in polycrystalline MAPbX3 films. We report an antisolvent vapor-assisted crystallization approach that enables us to create sizable crack-free MAPbX3 single crystals with volumes exceeding 100 cubic millimeters. These large single crystals enabled a detailed characterization of their optical and charge transport characteristics. We observed exceptionally low trap-state densities on the order of 10(9) to 10(10) per cubic centimeter in MAPbX3 single crystals (comparable to the best photovoltaic-quality silicon) and charge carrier diffusion lengths exceeding 10 micrometers. These results were validated with density functional theory calculations.

3,939 citations


Journal ArticleDOI
03 Apr 2015-Science
TL;DR: Observations indicate that neoantigen load may form a biomarker in cancer immunotherapy and provide an incentive for the development of novel therapeutic approaches that selectively enhance T cell reactivity against this class of antigens.
Abstract: The clinical relevance of T cells in the control of a diverse set of human cancers is now beyond doubt. However, the nature of the antigens that allow the immune system to distinguish cancer cells from noncancer cells has long remained obscure. Recent technological innovations have made it possible to dissect the immune response to patient-specific neoantigens that arise as a consequence of tumor-specific mutations, and emerging data suggest that recognition of such neoantigens is a major factor in the activity of clinical immunotherapies. These observations indicate that neoantigen load may form a biomarker in cancer immunotherapy and provide an incentive for the development of novel therapeutic approaches that selectively enhance T cell reactivity against this class of antigens.

Journal ArticleDOI
27 Feb 2015-Science
TL;DR: The design and fabrication of a metal-free carbon nanodot–carbon nitride (C3N4) nanocomposite is reported and its impressive performance for photocatalytic solar water splitting is demonstrated.
Abstract: The use of solar energy to produce molecular hydrogen and oxygen (H2 and O2) from overall water splitting is a promising means of renewable energy storage. In the past 40 years, various inorganic and organic systems have been developed as photocatalysts for water splitting driven by visible light. These photocatalysts, however, still suffer from low quantum efficiency and/or poor stability. We report the design and fabrication of a metal-free carbon nanodot-carbon nitride (C3N4) nanocomposite and demonstrate its impressive performance for photocatalytic solar water splitting. We measured quantum efficiencies of 16% for wavelength λ = 420 ± 20 nanometers, 6.29% for λ = 580 ± 15 nanometers, and 4.42% for λ = 600 ± 10 nanometers, and determined an overall solar energy conversion efficiency of 2.0%. The catalyst comprises low-cost, Earth-abundant, environmentally friendly materials and shows excellent stability.

Journal ArticleDOI
03 Apr 2015-Science
TL;DR: The way forward for this class of novel agents lies in the ability to understand human immune responses in the tumor microenvironment, which will provide valuable information regarding the dynamic nature of the immune response and regulation of additional pathways that will need to be targeted through combination therapies to provide survival benefit for greater numbers of patients.
Abstract: Immune checkpoint therapy, which targets regulatory pathways in T cells to enhance antitumor immune responses, has led to important clinical advances and provided a new weapon against cancer. This therapy has elicited durable clinical responses and, in a fraction of patients, long-term remissions where patients exhibit no clinical signs of cancer for many years. The way forward for this class of novel agents lies in our ability to understand human immune responses in the tumor microenvironment. This will provide valuable information regarding the dynamic nature of the immune response and regulation of additional pathways that will need to be targeted through combination therapies to provide survival benefit for greater numbers of patients.

Journal ArticleDOI
30 Jan 2015-Science
TL;DR: A solution-based hot-casting technique is demonstrated to grow continuous, pinhole-free thin films of organometallic perovskites with millimeter-scale crystalline grains that are applicable to several other material systems plagued by polydispersity, defects, and grain boundary recombination in solution-processed thin films.
Abstract: State-of-the-art photovoltaics use high-purity, large-area, wafer-scale single-crystalline semiconductors grown by sophisticated, high-temperature crystal growth processes. We demonstrate a solution-based hot-casting technique to grow continuous, pinhole-free thin films of organometallic perovskites with millimeter-scale crystalline grains. We fabricated planar solar cells with efficiencies approaching 18%, with little cell-to-cell variability. The devices show hysteresis-free photovoltaic response, which had been a fundamental bottleneck for the stable operation of perovskite devices. Characterization and modeling attribute the improved performance to reduced bulk defects and improved charge carrier mobility in large-grain devices. We anticipate that this technique will lead the field toward synthesis of wafer-scale crystalline perovskites, necessary for the fabrication of high-efficiency solar cells, and will be applicable to several other material systems plagued by polydispersity, defects, and grain boundary recombination in solution-processed thin films.

Journal ArticleDOI
02 Jan 2015-Science
TL;DR: Graphene and related two-dimensional crystals and hybrid systems showcase several key properties that can address emerging energy needs, in particular for the ever growing market of portable and wearable energy conversion and storage devices.
Abstract: Graphene and related two-dimensional crystals and hybrid systems showcase several key properties that can address emerging energy needs, in particular for the ever growing market of portable and wearable energy conversion and storage devices. Graphene's flexibility, large surface area, and chemical stability, combined with its excellent electrical and thermal conductivity, make it promising as a catalyst in fuel and dye-sensitized solar cells. Chemically functionalized graphene can also improve storage and diffusion of ionic species and electric charge in batteries and supercapacitors. Two-dimensional crystals provide optoelectronic and photocatalytic properties complementing those of graphene, enabling the realization of ultrathin-film photovoltaic devices or systems for hydrogen production. Here, we review the use of graphene and related materials for energy conversion and storage, outlining the roadmap for future applications.

Journal ArticleDOI
06 Mar 2015-Science
TL;DR: Large-scale single-cell RNA sequencing is used to classify cells in the mouse somatosensory cortex and hippocampal CA1 region and found 47 molecularly distinct subclasses, comprising all known major cell types in the cortex.
Abstract: The mammalian cerebral cortex supports cognitive functions such as sensorimotor integration, memory, and social behaviors. Normal brain function relies on a diverse set of differentiated cell types, including neurons, glia, and vasculature. Here, we have used large-scale single-cell RNA sequencing (RNA-seq) to classify cells in the mouse somatosensory cortex and hippocampal CA1 region. We found 47 molecularly distinct subclasses, comprising all known major cell types in the cortex. We identified numerous marker genes, which allowed alignment with known cell types, morphology, and location. We found a layer I interneuron expressing Pax6 and a distinct postmitotic oligodendrocyte subclass marked by Itpr2. Across the diversity of cortical cell types, transcription factors formed a complex, layered regulatory code, suggesting a mechanism for the maintenance of adult cell type identity.

Journal ArticleDOI
27 Nov 2015-Science
TL;DR: Comparison of melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, suggests that manipulating the microbiota may modulate cancer immunotherapy.
Abstract: T cell infiltration of solid tumors is associated with favorable patient outcomes, yet the mechanisms underlying variable immune responses between individuals are not well understood. One possible modulator could be the intestinal microbiota. We compared melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, which were eliminated upon cohousing or after fecal transfer. Sequencing of the 16S ribosomal RNA identified Bifidobacterium as associated with the antitumor effects. Oral administration of Bifidobacterium alone improved tumor control to the same degree as programmed cell death protein 1 ligand 1 (PD-L1)–specific antibody therapy (checkpoint blockade), and combination treatment nearly abolished tumor outgrowth. Augmented dendritic cell function leading to enhanced CD8+ T cell priming and accumulation in the tumor microenvironment mediated the effect. Our data suggest that manipulating the microbiota may modulate cancer immunotherapy.

Journal ArticleDOI
27 Mar 2015-Science
TL;DR: The stresses bees are experiencing from climate change, infectious diseases, and insecticides are reviewed, with concern that the authors may be nearing a “pollination crisis” in which crop yields begin to fall.
Abstract: Bees are subject to numerous pressures in the modern world. The abundance and diversity of flowers has declined, bees are chronically exposed to cocktails of agrochemicals, and they are simultaneously exposed to novel parasites accidentally spread by humans. Climate change is likely to exacerbate these problems in the future. Stressors do not act in isolation; for example pesticide exposure can impair both detoxification mechanisms and immune responses, rendering bees more susceptible to parasites. It seems certain that chronic exposure to multiple, interacting stressors is driving honey bee colony losses and declines of wild pollinators, but such interactions are not addressed by current regulatory procedures and studying these interactions experimentally poses a major challenge. In the meantime, taking steps to reduce stress on bees would seem prudent; incorporating flower-rich habitat into farmland, reducing pesticide use through adopting more sustainable farming methods, and enforcing effective quarantine measures on bee movements are all practical measures that should be adopted. Effective monitoring of wild pollinator populations is urgently needed to inform management strategies into the future.

Journal ArticleDOI
11 Dec 2015-Science
TL;DR: A computational model is described that learns in a similar fashion and does so better than current deep learning algorithms and can generate new letters of the alphabet that look “right” as judged by Turing-like tests of the model's output in comparison to what real humans produce.
Abstract: People learning new concepts can often generalize successfully from just a single example, yet machine learning algorithms typically require tens or hundreds of examples to perform with similar accuracy. People can also use learned concepts in richer ways than conventional algorithms-for action, imagination, and explanation. We present a computational model that captures these human learning abilities for a large class of simple visual concepts: handwritten characters from the world's alphabets. The model represents concepts as simple programs that best explain observed examples under a Bayesian criterion. On a challenging one-shot classification task, the model achieves human-level performance while outperforming recent deep learning approaches. We also present several "visual Turing tests" probing the model's creative generalization abilities, which in many cases are indistinguishable from human behavior.

Journal ArticleDOI
27 Nov 2015-Science
TL;DR: A key role is revealed for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade, which is found to depend on distinct Bacteroides species in mice and patients.
Abstract: Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis–specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.

Journal ArticleDOI
04 Dec 2015-Science
TL;DR: Efficient organic-inorganic perovskite light-emitting diodes were made with nanograin crystals that lack metallic lead, which helped to confine excitons and avoid their quenching.
Abstract: Organic-inorganic hybrid perovskites are emerging low-cost emitters with very high color purity, but their low luminescent efficiency is a critical drawback. We boosted the current efficiency (CE) of perovskite light-emitting diodes with a simple bilayer structure to 42.9 candela per ampere, similar to the CE of phosphorescent organic light-emitting diodes, with two modifications: We prevented the formation of metallic lead (Pb) atoms that cause strong exciton quenching through a small increase in methylammonium bromide (MABr) molar proportion, and we spatially confined the exciton in uniform MAPbBr3 nanograins (average diameter = 99.7 nanometers) formed by a nanocrystal pinning process and concomitant reduction of exciton diffusion length to 67 nanometers. These changes caused substantial increases in steady-state photoluminescence intensity and efficiency of MAPbBr3 nanograin layers.

Journal ArticleDOI
07 Aug 2015-Science
TL;DR: In this article, the experimental discovery of a Weyl semimetal, tantalum arsenide (TaAs), was reported, which is a new state of matter that hosts Weyl fermions as emergent quasiparticles and admits a topological classification that protects Fermi arcs on the boundary of a bulk sample.
Abstract: A Weyl semimetal is a new state of matter that hosts Weyl fermions as emergent quasiparticles and admits a topological classification that protects Fermi arc surface states on the boundary of a bulk sample. This unusual electronic structure has deep analogies with particle physics and leads to unique topological properties. We report the experimental discovery of a Weyl semimetal, tantalum arsenide (TaAs). Using photoemission spectroscopy, we directly observe Fermi arcs on the surface, as well as the Weyl fermion cones and Weyl nodes in the bulk of TaAs single crystals. We find that Fermi arcs terminate on the Weyl fermion nodes, consistent with their topological character. Our work opens the field for the experimental study of Weyl fermions in physics and materials science.

Journal ArticleDOI
20 Nov 2015-Science
TL;DR: A highly concentrated aqueous electrolyte whose window was expanded to ~3.0 volts with the formation of an electrode-electrolyte interphase, which could potentially be replaced with a safer aQueous alternative to lithium-ion batteries.
Abstract: Lithium-ion batteries raise safety, environmental, and cost concerns, which mostly arise from their nonaqueous electrolytes. The use of aqueous alternatives is limited by their narrow electrochemical stability window (1.23 volts), which sets an intrinsic limit on the practical voltage and energy output. We report a highly concentrated aqueous electrolyte whose window was expanded to ~3.0 volts with the formation of an electrode-electrolyte interphase. A full lithium-ion battery of 2.3 volts using such an aqueous electrolyte was demonstrated to cycle up to 1000 times, with nearly 100% coulombic efficiency at both low (0.15 C) and high (4.5 C) discharge and charge rates.

Journal ArticleDOI
09 Oct 2015-Science
TL;DR: Investigating the roles of tumor-specific neoantigens and alterations in the tumor microenvironment in the response to ipilimumab found no recurrent neoantigen peptide sequences predicted responder patient populations, suggesting detailed integrated molecular characterization of large patient cohorts may be needed to identify robust determinants of response and resistance to immune checkpoint inhibitors.
Abstract: Monoclonal antibodies directed against cytotoxic T lymphocyte–associated antigen-4 (CTLA-4), such as ipilimumab, yield considerable clinical benefit for patients with metastatic melanoma by inhibiting immune checkpoint activity, but clinical predictors of response to these therapies remain incompletely characterized. To investigate the roles of tumor-specific neoantigens and alterations in the tumor microenvironment in the response to ipilimumab, we analyzed whole exomes from pretreatment melanoma tumor biopsies and matching germline tissue samples from 110 patients. For 40 of these patients, we also obtained and analyzed transcriptome data from the pretreatment tumor samples. Overall mutational load, neoantigen load, and expression of cytolytic markers in the immune microenvironment were significantly associated with clinical benefit. However, no recurrent neoantigen peptide sequences predicted responder patient populations. Thus, detailed integrated molecular characterization of large patient cohorts may be needed to identify robust determinants of response and resistance to immune checkpoint inhibitors.

Journal ArticleDOI
05 Jun 2015-Science
TL;DR: Examination of the news that millions of Facebook users' peers shared, what information these users were presented with, and what they ultimately consumed found that friends shared substantially less cross-cutting news from sources aligned with an opposing ideology.
Abstract: Exposure to news, opinion and civic information increasingly occurs through social media. How do these online networks influence exposure to perspectives that cut across ideological lines? Using de-identified data, we examined how 10.1 million U.S. Facebook users interact with socially shared news. We directly measured ideological homophily in friend networks, and examine the extent to which heterogeneous friends could potentially expose individuals to cross-cutting content. We then quantified the extent to which individuals encounter comparatively more or less diverse content while interacting via Facebook’s algorithmically ranked News Feed, and further studied users’ choices to click through to ideologically discordant content. Compared to algorithmic ranking, individuals’ choices about what to consume had a stronger effect limiting exposure to cross-cutting content.

Journal ArticleDOI
20 Nov 2015-Science
TL;DR: Heavy doped inorganic charge extraction layers in planar PSCs were used to achieve very rapid carrier extraction, even with 10- to 20-nanometer-thick layers, avoiding pinholes and eliminating local structural defects over large areas.
Abstract: The recent dramatic rise in power conversion efficiencies (PCEs) of perovskite solar cells (PSCs) has triggered intense research worldwide. However, high PCE values have often been reached with poor stability at an illuminated area of typically less than 0.1 square centimeter. We used heavily doped inorganic charge extraction layers in planar PSCs to achieve very rapid carrier extraction, even with 10- to 20-nanometer-thick layers, avoiding pinholes and eliminating local structural defects over large areas. The robust inorganic nature of the layers allowed for the fabrication of PSCs with an aperture area >1 square centimeter that have a PCE >15%, as certified by an accredited photovoltaic calibration laboratory. Hysteresis in the current-voltage characteristics was eliminated; the PSCs were stable, with >90% of the initial PCE remaining after 1000 hours of light soaking.

Journal ArticleDOI
22 May 2015-Science
TL;DR: This work identifies ocean microbial core functionality and reveals that >73% of its abundance is shared with the human gut microbiome despite the physicochemical differences between these two ecosystems.
Abstract: Microbes are dominant drivers of biogeochemical processes, yet drawing a global picture of functional diversity, microbial community structure, and their ecological determinants remains a grand challenge. We analyzed 7.2 terabases of metagenomic data from 243 Tara Oceans samples from 68 locations in epipelagic and mesopelagic waters across the globe to generate an ocean microbial reference gene catalog with >40 million nonredundant, mostly novel sequences from viruses, prokaryotes, and picoeukaryotes. Using 139 prokaryote-enriched samples, containing >35,000 species, we show vertical stratification with epipelagic community composition mostly driven by temperature rather than other environmental factors or geography. We identify ocean microbial core functionality and reveal that >73% of its abundance is shared with the human gut microbiome despite the physicochemical differences between these two ecosystems.

Journal ArticleDOI
03 Apr 2015-Science
TL;DR: The ability to genetically engineer lymphocytes to express conventional T cell receptors or chimeric antigen receptors has further extended the successful application of ACT for cancer treatment.
Abstract: Adoptive cell therapy (ACT) is a highly personalized cancer therapy that involves administration to the cancer-bearing host of immune cells with direct anticancer activity. ACT using naturally occurring tumor-reactive lymphocytes has mediated durable, complete regressions in patients with melanoma, probably by targeting somatic mutations exclusive to each cancer. These results have expanded the reach of ACT to the treatment of common epithelial cancers. In addition, the ability to genetically engineer lymphocytes to express conventional T cell receptors or chimeric antigen receptors has further extended the successful application of ACT for cancer treatment.

Journal ArticleDOI
18 Dec 2015-Science
TL;DR: At Atomic-scale characterization, supported by theoretical calculations, revealed structures reminiscent of fused boron clusters with multiple scales of anisotropic, out-of-plane buckling that are consistent with predictions of a highly an isotropic, 2D metal.
Abstract: At the atomic-cluster scale, pure boron is markedly similar to carbon, forming simple planar molecules and cage-like fullerenes. Theoretical studies predict that two-dimensional (2D) boron sheets will adopt an atomic configuration similar to that of boron atomic clusters. We synthesized atomically thin, crystalline 2D boron sheets (i.e., borophene) on silver surfaces under ultrahigh-vacuum conditions. Atomic-scale characterization, supported by theoretical calculations, revealed structures reminiscent of fused boron clusters with multiple scales of anisotropic, out-of-plane buckling. Unlike bulk boron allotropes, borophene shows metallic characteristics that are consistent with predictions of a highly anisotropic, 2D metal.

Journal ArticleDOI
11 Sep 2015-Science
TL;DR: Modular optimization of covalent organic frameworks (COFs) is reported, in which the building units are cobalt porphyrin catalysts linked by organic struts through imine bonds, to prepare a catalytic material for aqueous electrochemical reduction of CO2 to CO.
Abstract: Conversion of carbon dioxide (CO2) to carbon monoxide (CO) and other value-added carbon products is an important challenge for clean energy research. Here we report modular optimization of covalent organic frameworks (COFs), in which the building units are cobalt porphyrin catalysts linked by organic struts through imine bonds, to prepare a catalytic material for aqueous electrochemical reduction of CO2 to CO. The catalysts exhibit high Faradaic efficiency (90%) and turnover numbers (up to 290,000, with initial turnover frequency of 9400 hour(-1)) at pH 7 with an overpotential of -0.55 volts, equivalent to a 26-fold improvement in activity compared with the molecular cobalt complex, with no degradation over 24 hours. X-ray absorption data reveal the influence of the COF environment on the electronic structure of the catalytic cobalt centers.