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Showing papers in "Proceedings of the National Academy of Sciences of the United States of America in 2014"


Journal ArticleDOI
TL;DR: The analysis supports theory claiming that calls to increase the number of students receiving STEM degrees could be answered, at least in part, by abandoning traditional lecturing in favor of active learning and supports active learning as the preferred, empirically validated teaching practice in regular classrooms.
Abstract: creased by 0.47 SDs under active learning (n = 158 studies), and that the odds ratio for failing was 1.95 under traditional lecturing (n = 67 studies). These results indicate that average examination scores improved by about 6% in active learning sections, and that students in classes with traditional lecturing were 1.5 times more likely to fail than were students in classes with active learning. Heterogeneity analyses indicated that both results hold across the STEM disciplines, that active learning increases scores on concept inventories more than on course examinations, and that active learning appears effective across all class sizes—although the greatest effects are in small (n ≤ 50) classes. Trim and fill analyses and fail-safe n calculations suggest that the results are not due to publication bias. The results also appear robust to variation in the methodological rigor of the included studies, based on the quality of controls over student quality and instructor identity. This is the largest and most comprehensive metaanalysis of undergraduate STEM education published to date. The results raise questions about the continued use of traditional lecturing as a control in research studies, and support active learning as the preferred, empirically validated teaching practice in regular classrooms.

5,474 citations


Journal ArticleDOI
TL;DR: The results indicate that emotions expressed by others on Facebook influence the authors' own emotions, constituting experimental evidence for massive-scale contagion via social networks, and suggest that the observation of others' positive experiences constitutes a positive experience for people.
Abstract: Emotional states can be transferred to others via emotional contagion, leading people to experience the same emotions without their awareness. Emotional contagion is well established in laboratory experiments, with people transferring positive and negative emotions to others. Data from a large real-world social network, collected over a 20-y period suggests that longer-lasting moods (e.g., depression, happiness) can be transferred through networks [Fowler JH, Christakis NA (2008) BMJ 337:a2338], although the results are controversial. In an experiment with people who use Facebook, we test whether emotional contagion occurs outside of in-person interaction between individuals by reducing the amount of emotional content in the News Feed. When positive expressions were reduced, people produced fewer positive posts and more negative posts; when negative expressions were reduced, the opposite pattern occurred. These results indicate that emotions expressed by others on Facebook influence our own emotions, constituting experimental evidence for massive-scale contagion via social networks. This work also suggests that, in contrast to prevailing assumptions, in-person interaction and nonverbal cues are not strictly necessary for emotional contagion, and that the observation of others' positive experiences constitutes a positive experience for people.

2,476 citations


Journal ArticleDOI
TL;DR: Using data from the Malaspina 2010 circumnavigation, regional surveys, and previously published reports, this work shows a worldwide distribution of plastic on the surface of the open ocean, mostly accumulating in the convergence zones of each of the five subtropical gyres with comparable density.
Abstract: There is a rising concern regarding the accumulation of floating plastic debris in the open ocean. However, the magnitude and the fate of this pollution are still open questions. Using data from the Malaspina 2010 circumnavigation, regional surveys, and previously published reports, we show a worldwide distribution of plastic on the surface of the open ocean, mostly accumulating in the convergence zones of each of the five subtropical gyres with comparable density. However, the global load of plastic on the open ocean surface was estimated to be on the order of tens of thousands of tons, far less than expected. Our observations of the size distribution of floating plastic debris point at important size-selective sinks removing millimeter-sized fragments of floating plastic on a large scale. This sink may involve a combination of fast nano-fragmentation of the microplastic into particles of microns or smaller, their transference to the ocean interior by food webs and ballasting processes, and processes yet to be discovered. Resolving the fate of the missing plastic debris is of fundamental importance to determine the nature and significance of the impacts of plastic pollution in the ocean.

2,078 citations


Journal ArticleDOI
TL;DR: This work uses computational techniques to identify a high-performing neural network model that matches human performance on challenging object categorization tasks and shows that performance optimization—applied in a biologically appropriate model class—can be used to build quantitative predictive models of neural processing.
Abstract: The ventral visual stream underlies key human visual object recognition abilities. However, neural encoding in the higher areas of the ventral stream remains poorly understood. Here, we describe a modeling approach that yields a quantitatively accurate model of inferior temporal (IT) cortex, the highest ventral cortical area. Using high-throughput computational techniques, we discovered that, within a class of biologically plausible hierarchical neural network models, there is a strong correlation between a model’s categorization performance and its ability to predict individual IT neural unit response data. To pursue this idea, we then identified a high-performing neural network that matches human performance on a range of recognition tasks. Critically, even though we did not constrain this model to match neural data, its top output layer turns out to be highly predictive of IT spiking responses to complex naturalistic images at both the single site and population levels. Moreover, the model’s intermediate layers are highly predictive of neural responses in the V4 cortex, a midlevel visual area that provides the dominant cortical input to IT. These results show that performance optimization—applied in a biologically appropriate model class—can be used to build quantitative predictive models of neural processing.

1,705 citations


Journal ArticleDOI
TL;DR: Uncertainties related to the representation of carbon dioxide, nitrogen, and high temperature effects demonstrated here show that further research is urgently needed to better understand effects of climate change on agricultural production and to devise targeted adaptation strategies.
Abstract: Here we present the results from an intercomparison of multiple global gridded crop models (GGCMs) within the framework of the Agricultural Model Intercomparison and Improvement Project and the Inter-Sectoral Impacts Model Intercomparison Project. Results indicate strong negative effects of climate change, especially at higher levels of warming and at low latitudes; models that include explicit nitrogen stress project more severe impacts. Across seven GGCMs, five global climate models, and four representative concentration pathways, model agreement on direction of yield changes is found in many major agricultural regions at both low and high latitudes; however, reducing uncertainty in sign of response in mid-latitude regions remains a challenge. Uncertainties related to the representation of carbon dioxide, nitrogen, and high temperature effects demonstrated here show that further research is urgently needed to better understand effects of climate change on agricultural production and to devise targeted adaptation strategies.

1,704 citations


Journal ArticleDOI
TL;DR: High-resolution multiorgan expression data is generated showing that nearly half of all genes in the mouse genome oscillate with circadian rhythm somewhere in the body, and the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes.
Abstract: To characterize the role of the circadian clock in mouse physiology and behavior, we used RNA-seq and DNA arrays to quantify the transcriptomes of 12 mouse organs over time. We found 43% of all protein coding genes showed circadian rhythms in transcription somewhere in the body, largely in an organ-specific manner. In most organs, we noticed the expression of many oscillating genes peaked during transcriptional “rush hours” preceding dawn and dusk. Looking at the genomic landscape of rhythmic genes, we saw that they clustered together, were longer, and had more spliceforms than nonoscillating genes. Systems-level analysis revealed intricate rhythmic orchestration of gene pathways throughout the body. We also found oscillations in the expression of more than 1,000 known and novel noncoding RNAs (ncRNAs). Supporting their potential role in mediating clock function, ncRNAs conserved between mouse and human showed rhythmic expression in similar proportions as protein coding genes. Importantly, we also found that the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes. Many of these drugs have short half-lives and may benefit from timed dosage. In sum, this study highlights critical, systemic, and surprising roles of the mammalian circadian clock and provides a blueprint for advancement in chronotherapy.

1,642 citations


Journal ArticleDOI
TL;DR: From ∼1,000 observations of sea level, allowing for isostatic and tectonic contributions, this work quantified the rise and fall in global ocean and ice volumes for the past 35,000 years and provides new constraints on the fluctuation of ice volume in this interval.
Abstract: The major cause of sea-level change during ice ages is the exchange of water between ice and ocean and the planet's dynamic response to the changing surface load. Inversion of ∼1,000 observations for the past 35,000 y from localities far from former ice margins has provided new constraints on the fluctuation of ice volume in this interval. Key results are: (i) a rapid final fall in global sea level of ∼40 m in <2,000 y at the onset of the glacial maximum ∼30,000 y before present (30 ka BP); (ii) a slow fall to -134 m from 29 to 21 ka BP with a maximum grounded ice volume of ∼52 × 10(6) km(3) greater than today; (iii) after an initial short duration rapid rise and a short interval of near-constant sea level, the main phase of deglaciation occurred from ∼16.5 ka BP to ∼8.2 ka BP at an average rate of rise of 12 m⋅ka(-1) punctuated by periods of greater, particularly at 14.5-14.0 ka BP at ≥40 mm⋅y(-1) (MWP-1A), and lesser, from 12.5 to 11.5 ka BP (Younger Dryas), rates; (iv) no evidence for a global MWP-1B event at ∼11.3 ka BP; and (v) a progressive decrease in the rate of rise from 8.2 ka to ∼2.5 ka BP, after which ocean volumes remained nearly constant until the renewed sea-level rise at 100-150 y ago, with no evidence of oscillations exceeding ∼15-20 cm in time intervals ≥200 y from 6 to 0.15 ka BP.

1,558 citations


Journal ArticleDOI
TL;DR: A new statistical model and computer program, replicate MATS (rMATS), designed for detection of differential alternative splicing from replicate RNA-Seq data, which uses a hierarchical model to simultaneously account for sampling uncertainty in individual replicates and variability among replicates.
Abstract: Ultra-deep RNA sequencing (RNA-Seq) has become a powerful approach for genome-wide analysis of pre-mRNA alternative splicing. We previously developed multivariate analysis of transcript splicing (MATS), a statistical method for detecting differential alternative splicing between two RNA-Seq samples. Here we describe a new statistical model and computer program, replicate MATS (rMATS), designed for detection of differential alternative splicing from replicate RNA-Seq data. rMATS uses a hierarchical model to simultaneously account for sampling uncertainty in individual replicates and variability among replicates. In addition to the analysis of unpaired replicates, rMATS also includes a model specifically designed for paired replicates between sample groups. The hypothesis-testing framework of rMATS is flexible and can assess the statistical significance over any user-defined magnitude of splicing change. The performance of rMATS is evaluated by the analysis of simulated and real RNA-Seq data. rMATS outperformed two existing methods for replicate RNA-Seq data in all simulation settings, and RT-PCR yielded a high validation rate (94%) in an RNA-Seq dataset of prostate cancer cell lines. Our data also provide guiding principles for designing RNA-Seq studies of alternative splicing. We demonstrate that it is essential to incorporate biological replicates in the study design. Of note, pooling RNAs or merging RNA-Seq data from multiple replicates is not an effective approach to account for variability, and the result is particularly sensitive to outliers. The rMATS source code is freely available at rnaseq-mats.sourceforge.net/. As the popularity of RNA-Seq continues to grow, we expect rMATS will be useful for studies of alternative splicing in diverse RNA-Seq projects.

1,546 citations


Journal ArticleDOI
TL;DR: This first report (to the authors' knowledge) on MXene composites of any kind, shows that adding polymer binders/spacers between atomically thin MXenes layers or reinforcing polymers with MXenes results in composite films that have excellent flexibility, good tensile and compressive strengths, and electrical conductivity that can be adjusted over a wide range.
Abstract: MXenes, a new family of 2D materials, combine hydrophilic surfaces with metallic conductivity Delamination of MXene produces single-layer nanosheets with thickness of about a nanometer and lateral size of the order of micrometers The high aspect ratio of delaminated MXene renders it promising nanofiller in multifunctional polymer nanocomposites Herein, Ti 3 C 2 T x MXene was mixed with either a charged polydiallyldimethylammonium chloride (PDDA) or an electrically neutral polyvinyl alcohol (PVA) to produce Ti 3 C 2 T x /polymer composites The as-fabricated composites are flexible and have electrical conductivities as high as 22 × 10 4 S/m in the case of the Ti 3 C 2 T x /PVA composite film and 24 × 10 5 S/m for pure Ti 3 C 2 T x films The tensile strength of the Ti 3 C 2 T x /PVA composites was significantly enhanced compared with pure Ti 3 C 2 T x or PVA films The intercalation and confinement of the polymer between the MXene flakes not only increased flexibility but also enhanced cationic intercalation, offering an impressive volumetric capacitance of ∼530 F/cm 3 for MXene/PVA-KOH composite film at 2 mV/s To our knowledge, this study is a first, but crucial, step in exploring the potential of using MXenes in polymer-based multifunctional nanocomposites for a host of applications, such as structural components, energy storage devices, wearable electronics, electrochemical actuators, and radiofrequency shielding, to name a few

1,545 citations


Journal ArticleDOI
TL;DR: It is found that reductions in the abundance and presence of soil organisms results in the decline of multiple ecosystem functions, including plant diversity and nutrient cycling and retention, suggesting that below-ground biodiversity is a key resource for maintaining the functioning of ecosystems.
Abstract: Biodiversity loss has become a global concern as evidence accumulates that it will negatively affect ecosystem services on which society depends. So far, most studies have focused on the ecological consequences of above-ground biodiversity loss; yet a large part of Earth’s biodiversity is literally hidden below ground. Whether reductions of biodiversity in soil communities below ground have consequences for the overall performance of an ecosystem remains unresolved. It is important to investigate this in view of recent observations that soil biodiversity is declining and that soil communities are changing upon land use intensification. We established soil communities differing in composition and diversity and tested their impact on eight ecosystem functions in model grassland communities. We show that soil biodiversity loss and simplification of soil community composition impair multiple ecosystem functions, including plant diversity, decomposition, nutrient retention, and nutrient cycling. The average response of all measured ecosystem functions (ecosystem multifunctionality) exhibited a strong positive linear relationship to indicators of soil biodiversity, suggesting that soil community composition is a key factor in regulating ecosystem functioning. Our results indicate that changes in soil communities and the loss of soil biodiversity threaten ecosystem multifunctionality and sustainability.

1,410 citations


Journal ArticleDOI
TL;DR: It is demonstrated that the short-chain fatty acid n-butyrate, which is secreted in high amounts by commensal bacteria, can modulate the function of intestinal macrophages, the most abundant immune cell type in the lamina propria, and elucidate a pathway in which the host may maintain tolerance to intestinal microbiota by rendering lamina Propria macrophage hyporesponsive to commensals through the down-regulation of proinflammatory effectors.
Abstract: Given the trillions of microbes that inhabit the mammalian intestines, the host immune system must constantly maintain a balance between tolerance to commensals and immunity against pathogens to avoid unnecessary immune responses against otherwise harmless bacteria. Misregulated responses can lead to inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. The mechanisms by which the immune system maintains this critical balance remain largely undefined. Here, we demonstrate that the short-chain fatty acid n-butyrate, which is secreted in high amounts by commensal bacteria, can modulate the function of intestinal macrophages, the most abundant immune cell type in the lamina propria. Treatment of macrophages with n-butyrate led to the down-regulation of lipopolysaccharide-induced proinflammatory mediators, including nitric oxide, IL-6, and IL-12, but did not affect levels of TNF-α or MCP-1. These effects were independent of toll-like receptor signaling and activation of G-protein-coupled receptors, two pathways that could be affected by short-chain fatty acids. In this study, we provide several lines of evidence that suggest that these effects are due to the inhibition of histone deacetylases by n-butyrate. These findings elucidate a pathway in which the host may maintain tolerance to intestinal microbiota by rendering lamina propria macrophages hyporesponsive to commensal bacteria through the down-regulation of proinflammatory effectors.

Journal ArticleDOI
TL;DR: It is shown that climate change is likely to exacerbate regional and global water scarcity considerably and GHM uncertainty is particularly dominant in many regions affected by declining water resources, suggesting a high potential for improved water resource projections through hydrological model development.
Abstract: Water scarcity severely impairs food security and economic prosperity in many countries today. Expected future population changes will, in many countries as well as globally, increase the pressure on available water resources. On the supply side, renewable water resources will be affected by projected changes in precipitation patterns, temperature, and other climate variables. Here we use a large ensemble of global hydrological models (GHMs) forced by five global climate models and the latest greenhouse-gas concentration scenarios (Representative Concentration Pathways) to synthesize the current knowledge about climate change impacts on water resources. We show that climate change is likely to exacerbate regional and global water scarcity considerably. In particular, the ensemble average projects that a global warming of 2 °C above present (approximately 2.7 °C above preindustrial) will confront an additional approximate 15% of the global population with a severe decrease in water resources and will increase the number of people living under absolute water scarcity (<500 m3 per capita per year) by another 40% (according to some models, more than 100%) compared with the effect of population growth alone. For some indicators of moderate impacts, the steepest increase is seen between the present day and 2 °C, whereas indicators of very severe impacts increase unabated beyond 2 °C. At the same time, the study highlights large uncertainties associated with these estimates, with both global climate models and GHMs contributing to the spread. GHM uncertainty is particularly dominant in many regions affected by declining water resources, suggesting a high potential for improved water resource projections through hydrological model development.

Journal ArticleDOI
TL;DR: A periodic cycle of PM episodes in Beijing is demonstrated that is governed by meteorological conditions and characterized by two distinct aerosol formation processes of nucleation and growth, but with a small contribution from primary emissions and regional transport of particles.
Abstract: As the world’s second largest economy, China has experienced severe haze pollution, with fine particulate matter (PM) recently reaching unprecedentedly high levels across many cities, and an understanding of the PM formation mechanism is critical in the development of efficient mediation policies to minimize its regional to global impacts. We demonstrate a periodic cycle of PM episodes in Beijing that is governed by meteorological conditions and characterized by two distinct aerosol formation processes of nucleation and growth, but with a small contribution from primary emissions and regional transport of particles. Nucleation consistently precedes a polluted period, producing a high number concentration of nano-sized particles under clean conditions. Accumulation of the particle mass concentration exceeding several hundred micrograms per cubic meter is accompanied by a continuous size growth from the nucleation-mode particles over multiple days to yield numerous larger particles, distinctive from the aerosol formation typically observed in other regions worldwide. The particle compositions in Beijing, on the other hand, exhibit a similarity to those commonly measured in many global areas, consistent with the chemical constituents dominated by secondary aerosol formation. Our results highlight that regulatory controls of gaseous emissions for volatile organic compounds and nitrogen oxides from local transportation and sulfur dioxide from regional industrial sources represent the key steps to reduce the urban PM level in China.

Journal ArticleDOI
TL;DR: Strong and robust support is found for a sister-group relationship between land plants and one group of streptophyte green algae, the Zygnematophyceae, and suggests that phylogenetic hypotheses used to understand the evolution of fundamental plant traits should be reevaluated.
Abstract: Reconstructing the origin and evolution of land plants and their algal relatives is a fundamental problem in plant phylogenetics, and is essential for understanding how critical adaptations arose, including the embryo, vascular tissue, seeds, and flowers. Despite advances in molecular systematics, some hypotheses of relationships remain weakly resolved. Inferring deep phylogenies with bouts of rapid diversification can be problematic; however, genome-scale data should significantly increase the number of informative characters for analyses. Recent phylogenomic reconstructions focused on the major divergences of plants have resulted in promising but inconsistent results. One limitation is sparse taxon sampling, likely resulting from the difficulty and cost of data generation. To address this limitation, transcriptome data for 92 streptophyte taxa were generated and analyzed along with 11 published plant genome sequences. Phylogenetic reconstructions were conducted using up to 852 nuclear genes and 1,701,170 aligned sites. Sixty-nine analyses were performed to test the robustness of phylogenetic inferences to permutations of the data matrix or to phylogenetic method, including supermatrix, supertree, and coalescent-based approaches, maximum-likelihood and Bayesian methods, partitioned and unpartitioned analyses, and amino acid versus DNA alignments. Among other results, we find robust support for a sister-group relationship between land plants and one group of streptophyte green algae, the Zygnematophyceae. Strong and robust support for a clade comprising liverworts and mosses is inconsistent with a widely accepted view of early land plant evolution, and suggests that phylogenetic hypotheses used to understand the evolution of fundamental plant traits should be reevaluated.

Journal ArticleDOI
TL;DR: Artificial semiconductor heterostructures built from single-layer WSe2 and MoS2 observe a large Stokes-like shift of ∼100 meV between the photoluminescence peak and the lowest absorption peak that is consistent with a type II band alignment having spatially direct absorption but spatially indirect emission.
Abstract: Semiconductor heterostructures are the fundamental platform for many important device applications such as lasers, light-emitting diodes, solar cells, and high-electron-mobility transistors. Analogous to traditional heterostructures, layered transition metal dichalcogenide heterostructures can be designed and built by assembling individual single layers into functional multilayer structures, but in principle with atomically sharp interfaces, no interdiffusion of atoms, digitally controlled layered components, and no lattice parameter constraints. Nonetheless, the optoelectronic behavior of this new type of van der Waals (vdW) semiconductor heterostructure is unknown at the single-layer limit. Specifically, it is experimentally unknown whether the optical transitions will be spatially direct or indirect in such hetero-bilayers. Here, we investigate artificial semiconductor heterostructures built from single-layer WSe2 and MoS2. We observe a large Stokes-like shift of ∼100 meV between the photoluminescence peak and the lowest absorption peak that is consistent with a type II band alignment having spatially direct absorption but spatially indirect emission. Notably, the photoluminescence intensity of this spatially indirect transition is strong, suggesting strong interlayer coupling of charge carriers. This coupling at the hetero-interface can be readily tuned by inserting dielectric layers into the vdW gap, consisting of hexagonal BN. Consequently, the generic nature of this interlayer coupling provides a new degree of freedom in band engineering and is expected to yield a new family of semiconductor heterostructures having tunable optoelectronic properties with customized composite layers.

Journal ArticleDOI
TL;DR: Overall, the results suggest that male brains are structured to facilitate connectivity between perception and coordinated action, whereas female brains are designed to facilitate communication between analytical and intuitive processing modes.
Abstract: Sex differences in human behavior show adaptive complementarity: Males have better motor and spatial abilities, whereas females have superior memory and social cognition skills. Studies also show sex differences in human brains but do not explain this complementarity. In this work, we modeled the structural connectome using diffusion tensor imaging in a sample of 949 youths (aged 8–22 y, 428 males and 521 females) and discovered unique sex differences in brain connectivity during the course of development. Connection-wise statistical analysis, as well as analysis of regional and global network measures, presented a comprehensive description of network characteristics. In all supratentorial regions, males had greater within-hemispheric connectivity, as well as enhanced modularity and transitivity, whereas between-hemispheric connectivity and cross-module participation predominated in females. However, this effect was reversed in the cerebellar connections. Analysis of these changes developmentally demonstrated differences in trajectory between males and females mainly in adolescence and in adulthood. Overall, the results suggest that male brains are structured to facilitate connectivity between perception and coordinated action, whereas female brains are designed to facilitate communication between analytical and intuitive processing modes.

Journal ArticleDOI
TL;DR: The results indicate that direct human impacts on the water cycle in some regions, e.g., parts of Asia and in the western United States, are of the same order of magnitude, or even exceed impacts to be expected for moderate levels of global warming (+2 K).
Abstract: Humans directly change the dynamics of the water cycle through dams constructed for water storage, and through water withdrawals for industrial, agricultural, or domestic purposes. Climate change is expected to additionally affect water supply and demand. Here, analyses of climate change and direct human impacts on the terrestrial water cycle are presented and compared using a multimodel approach. Seven global hydrological models have been forced with multiple climate projections, and with and without taking into account impacts of human interventions such as dams and water withdrawals on the hydrological cycle. Model results are analyzed for different levels of global warming, allowing for analyses in line with temperature targets for climate change mitigation. The results indicate that direct human impacts on the water cycle in some regions, e.g., parts of Asia and in the western United States, are of the same order of magnitude, or even exceed impacts to be expected for moderate levels of global warming (+2 K). Despite some spread in model projections, irrigation water consumption is generally projected to increase with higher global mean temperatures. Irrigation water scarcity is particularly large in parts of southern and eastern Asia, and is expected to become even larger in the future.

Journal ArticleDOI
TL;DR: A toolbox for high-efficiency genome engineering of Drosophila melanogaster consisting of transgenic Cas9 lines and versatile guide RNA (gRNA) expression plasmids is reported, which will facilitate the rapid evaluation of mutant phenotypes of specific genes and the precise modification of the genome with single-nucleotide precision.
Abstract: The type II clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system has emerged recently as a powerful method to manipulate the genomes of various organisms. Here, we report a toolbox for high-efficiency genome engineering of Drosophila melanogaster consisting of transgenic Cas9 lines and versatile guide RNA (gRNA) expression plasmids. Systematic evaluation reveals Cas9 lines with ubiquitous or germ-line–restricted patterns of activity. We also demonstrate differential activity of the same gRNA expressed from different U6 snRNA promoters, with the previously untested U6:3 promoter giving the most potent effect. An appropriate combination of Cas9 and gRNA allows targeting of essential and nonessential genes with transmission rates ranging from 25–100%. We also demonstrate that our optimized CRISPR/Cas tools can be used for offset nicking-based mutagenesis. Furthermore, in combination with oligonucleotide or long double-stranded donor templates, our reagents allow precise genome editing by homology-directed repair with rates that make selection markers unnecessary. Last, we demonstrate a novel application of CRISPR/Cas-mediated technology in revealing loss-of-function phenotypes in somatic cells following efficient biallelic targeting by Cas9 expressed in a ubiquitous or tissue-restricted manner. Our CRISPR/Cas tools will facilitate the rapid evaluation of mutant phenotypes of specific genes and the precise modification of the genome with single-nucleotide precision. Our results also pave the way for high-throughput genetic screening with CRISPR/Cas.

Journal ArticleDOI
TL;DR: The objectives and framework of the first, fast-tracked phase of the Inter-Sectoral Impact Model Intercomparison Project, based on global impact models, are outlined and an overview of the participating models, input data, and scenario set-up is provided.
Abstract: The Inter-Sectoral Impact Model Intercomparison Project offers a framework to compare climate impact projections in different sectors and at different scales. Consistent climate and socio-economic input data provide the basis for a cross-sectoral integration of impact projections. The project is designed to enable quantitative synthesis of climate change impacts at different levels of global warming. This report briefly outlines the objectives and framework of the first, fast-tracked phase of Inter-Sectoral Impact Model Intercomparison Project, based on global impact models, and provides an overview of the participating models, input data, and scenario set-up.

Journal ArticleDOI
TL;DR: Coastal flood damage and adaptation costs under 21st century sea-level rise are assessed on a global scale taking into account a wide range of uncertainties in continental topography data, population data, protection strategies, socioeconomic development and sea- level rise.
Abstract: Coastal flood damage and adaptation costs under 21st century sea-level rise are assessed on a global scale taking into account a wide range of uncertainties in continental topography data, population data, protection strategies, socioeconomic development and sea-level rise. Uncertainty in global mean and regional sea level was derived from four different climate models from the Coupled Model Intercomparison Project Phase 5, each combined with three land-ice scenarios based on the published range of contributions from ice sheets and glaciers. Without adaptation, 0.2-4.6% of global population is expected to be flooded annually in 2100 under 25-123 cm of global mean sea-level rise, with expected annual losses of 0.3-9.3% of global gross domestic product. Damages of this magnitude are very unlikely to be tolerated by society and adaptation will be widespread. The global costs of protecting the coast with dikes are significant with annual investment and maintenance costs of US$ 12-71 billion in 2100, but much smaller than the global cost of avoided damages even without accounting for indirect costs of damage to regional production supply. Flood damages by the end of this century are much more sensitive to the applied protection strategy than to variations in climate and socioeconomic scenarios as well as in physical data sources (topography and climate model). Our results emphasize the central role of long-term coastal adaptation strategies. These should also take into account that protecting large parts of the developed coast increases the risk of catastrophic consequences in the case of defense failure.

Journal ArticleDOI
TL;DR: It is found that most terrestrial ectotherms are insufficiently tolerant of high temperatures to survive the warmest potential body temperatures in exposed habitats and must therefore thermoregulate by using shade, burrows, or evaporative cooling and show why heat-tolerance limits are relatively invariant in comparison with cold limits.
Abstract: Physiological thermal-tolerance limits of terrestrial ectotherms often exceed local air temperatures, implying a high degree of thermal safety (an excess of warm or cold thermal tolerance). However, air temperatures can be very different from the equilibrium body temperature of an individual ectotherm. Here, we compile thermal-tolerance limits of ectotherms across a wide range of latitudes and elevations and compare these thermal limits both to air and to operative body temperatures (theoretically equilibrated body temperatures) of small ectothermic animals during the warmest and coldest times of the year. We show that extreme operative body temperatures in exposed habitats match or exceed the physiological thermal limits of most ectotherms. Therefore, contrary to previous findings using air temperatures, most ectotherms do not have a physiological thermal-safety margin. They must therefore rely on behavior to avoid overheating during the warmest times, especially in the lowland tropics. Likewise, species living at temperate latitudes and in alpine habitats must retreat to avoid lethal cold exposure. Behavioral plasticity of habitat use and the energetic consequences of thermal retreats are therefore critical aspects of species’ vulnerability to climate warming and extreme events.

Journal ArticleDOI
TL;DR: It is shown here that most exosomes derived from standard preparations do not harbor many copies of miRNA molecules, and are, therefore, individually unlikely to be functional as vehicles for miRNA-based communication.
Abstract: Exosomes have been proposed as vehicles for microRNA (miRNA) -based intercellular communication and a source of miRNA biomarkers in bodily fluids. Although exosome preparations contain miRNAs, a quantitative analysis of their abundance and stoichiometry is lacking. In the course of studying cancer-associated extracellular miRNAs in patient blood samples, we found that exosome fractions contained a small minority of the miRNA content of plasma. This low yield prompted us to perform a more quantitative assessment of the relationship between miRNAs and exosomes using a stoichiometric approach. We quantified both the number of exosomes and the number of miRNA molecules in replicate samples that were isolated from five diverse sources (i.e., plasma, seminal fluid, dendritic cells, mast cells, and ovarian cancer cells). Regardless of the source, on average, there was far less than one molecule of a given miRNA per exosome, even for the most abundant miRNAs in exosome preparations (mean ± SD across six exosome sources: 0.00825 ± 0.02 miRNA molecules/exosome). Thus, if miRNAs were distributed homogenously across the exosome population, on average, over 100 exosomes would need to be examined to observe one copy of a given abundant miRNA. This stoichiometry of miRNAs and exosomes suggests that most individual exosomes in standard preparations do not carry biologically significant numbers of miRNAs and are, therefore, individually unlikely to be functional as vehicles for miRNA-based communication. We propose revised models to reconcile the exosome-mediated, miRNA-based intercellular communication hypothesis with the observed stoichiometry of miRNAs associated with exosomes.

Journal ArticleDOI
TL;DR: It is reported that the gradient structure in engineering materials such as metals renders a unique extra strain hardening, which leads to high ductility, which is a hitherto unknown strategy to develop strong and ductile materials by architecting heterogeneous nanostructures.
Abstract: Gradient structures have evolved over millions of years through natural selection and optimization in many biological systems such as bones and plant stems, where the structures change gradually from the surface to interior. The advantage of gradient structures is their maximization of physical and mechanical performance while minimizing material cost. Here we report that the gradient structure in engineering materials such as metals renders a unique extra strain hardening, which leads to high ductility. The grain-size gradient under uniaxial tension induces a macroscopic strain gradient and converts the applied uniaxial stress to multiaxial stresses due to the evolution of incompatible deformation along the gradient depth. Thereby the accumulation and interaction of dislocations are promoted, resulting in an extra strain hardening and an obvious strain hardening rate up-turn. Such extraordinary strain hardening, which is inherent to gradient structures and does not exist in homogeneous materials, provides a hitherto unknown strategy to develop strong and ductile materials by architecting heterogeneous nanostructures.

Journal ArticleDOI
TL;DR: This work compares ensembles of water supply and demand projections driven by ensemble output from five global climate models and suggests surplus water supply could in principle support a net increase in irrigation, although substantial investments in irrigation infrastructure would be required.
Abstract: We compare ensembles of water supply and demand projections from 10 global hydrological models and six global gridded crop models. These are produced as part of the Inter-Sectoral Impacts Model Intercomparison Project, with coordination from the Agricultural Model Intercomparison and Improvement Project, and driven by outputs of general circulation models run under representative concentration pathway 8.5 as part of the Fifth Coupled Model Intercomparison Project. Models project that direct climate impacts to maize, soybean, wheat, and rice involve losses of 400-1,400 Pcal (8-24% of present-day total) when CO2 fertilization effects are accounted for or 1,400-2,600 Pcal (24-43%) otherwise. Freshwater limitations in some irrigated regions (western United States; China; and West, South, and Central Asia) could necessitate the reversion of 20-60 Mha of cropland from irrigated to rainfed management by end-of-century, and a further loss of 600-2,900 Pcal of food production. In other regions (northern/eastern United States, parts of South America, much of Europe, and South East Asia) surplus water supply could in principle support a net increase in irrigation, although substantial investments in irrigation infrastructure would be required.

Journal ArticleDOI
TL;DR: A first quantitative comparison of N2O emissions for all available studies that have used multiple N rates shows that a nonlinear emission factor better represents global emission patterns with lower uncertainty, offering more power for balancing the global N2 O budget and for designing effective mitigation strategies.
Abstract: Nitrous oxide (N2O) is a potent greenhouse gas (GHG) that also depletes stratospheric ozone. Nitrogen (N) fertilizer rate is the best single predictor of N2O emissions from agricultural soils, which are responsible for ∼ 50% of the total global anthropogenic flux, but it is a relatively imprecise estimator. Accumulating evidence suggests that the emission response to increasing N input is exponential rather than linear, as assumed by Intergovernmental Panel on Climate Change methodologies. We performed a metaanalysis to test the generalizability of this pattern. From 78 published studies (233 site-years) with at least three N-input levels, we calculated N2O emission factors (EFs) for each nonzero input level as a percentage of N input converted to N2O emissions. We found that the N2O response to N inputs grew significantly faster than linear for synthetic fertilizers and for most crop types. N-fixing crops had a higher rate of change in EF (ΔEF) than others. A higher ΔEF was also evident in soils with carbon >1.5% and soils with pH <7, and where fertilizer was applied only once annually. Our results suggest a general trend of exponentially increasing N2O emissions as N inputs increase to exceed crop needs. Use of this knowledge in GHG inventories should improve assessments of fertilizer-derived N2O emissions, help address disparities in the global N2O budget, and refine the accuracy of N2O mitigation protocols. In low-input systems typical of sub-Saharan Africa, for example, modest N additions will have little impact on estimated N2O emissions, whereas equivalent additions (or reductions) in excessively fertilized systems will have a disproportionately major impact.

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TL;DR: New space-based observations of chlorophyll fluorescence enable an accurate, global, and time-resolved measurement of crop photosynthesis, which is not possible from any other remote vegetation measurement, and indicates that SIF data can help improve global models for more accurate projections of agricultural productivity and climate impact on crop yields.
Abstract: Photosynthesis is the process by which plants harvest sunlight to produce sugars from carbon dioxide and water. It is the primary source of energy for all life on Earth; hence it is important to understand how this process responds to climate change and human impact. However, model-based estimates of gross primary production (GPP, output from photosynthesis) are highly uncertain, in particular over heavily managed agricultural areas. Recent advances in spectroscopy enable the space-based monitoring of sun-induced chlorophyll fluorescence (SIF) from terrestrial plants. Here we demonstrate that spaceborne SIF retrievals provide a direct measure of the GPP of cropland and grassland ecosystems. Such a strong link with crop photosynthesis is not evident for traditional remotely sensed vegetation indices, nor for more complex carbon cycle models. We use SIF observations to provide a global perspective on agricultural productivity. Our SIF-based crop GPP estimates are 50–75% higher than results from state-of-the-art carbon cycle models over, for example, the US Corn Belt and the Indo-Gangetic Plain, implying that current models severely underestimate the role of management. Our results indicate that SIF data can help us improve our global models for more accurate projections of agricultural productivity and climate impact on crop yields. Extension of our approach to other ecosystems, along with increased observational capabilities for SIF in the near future, holds the prospect of reducing uncertainties in the modeling of the current and future carbon cycle.

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TL;DR: It is concluded that high- and low-frequency oscillations provide markers of feedforward and feedback processing, respectively.
Abstract: Cognitive functions rely on the coordinated activity of neurons in many brain regions, but the interactions between cortical areas are not yet well understood. Here we investigated whether low-frequency (α) and high-frequency (γ) oscillations characterize different directions of information flow in monkey visual cortex. We recorded from all layers of the primary visual cortex (V1) and found that γ-waves are initiated in input layer 4 and propagate to the deep and superficial layers of cortex, whereas α-waves propagate in the opposite direction. Simultaneous recordings from V1 and downstream area V4 confirmed that γ- and α-waves propagate in the feedforward and feedback direction, respectively. Microstimulation in V1 elicited γ-oscillations in V4, whereas microstimulation in V4 elicited α-oscillations in V1, thus providing causal evidence for the opposite propagation of these rhythms. Furthermore, blocking NMDA receptors, thought to be involved in feedback processing, suppressed α while boosting γ. These results provide new insights into the relation between brain rhythms and cognition.

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TL;DR: Significance This study provides evidence of change in the relative importance of different crop plants in national food supplies worldwide over the past 50 years, which heightens interdependence among countries in their food supplies, plant genetic resources, and nutritional priorities, and gives further urgency to nutrition development priorities aimed at bolstering food security.
Abstract: The narrowing of diversity in crop species contributing to the world’s food supplies has been considered a potential threat to food security. However, changes in this diversity have not been quantified globally. We assess trends over the past 50 y in the richness, abundance, and composition of crop species in national food supplies worldwide. Over this period, national per capita food supplies expanded in total quantities of food calories, protein, fat, and weight, with increased proportions of those quantities sourcing from energy-dense foods. At the same time the number of measured crop commodities contributing to national food supplies increased, the relative contribution of these commodities within these supplies became more even, and the dominance of the most significant commodities decreased. As a consequence, national food supplies worldwide became more similar in composition, correlated particularly with an increased supply of a number of globally important cereal and oil crops, and a decline of other cereal, oil, and starchy root species. The increase in homogeneity worldwide portends the establishment of a global standard food supply, which is relatively species-rich in regard to measured crops at the national level, but species-poor globally. These changes in food supplies heighten interdependence among countries in regard to availability and access to these food sources and the genetic resources supporting their production, and give further urgency to nutrition development priorities aimed at bolstering food security.

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TL;DR: Depletion of the cohesin complex or CTCF is depleted and the consequences of loss of these factors on higher-order chromatin organization, as well as the transcriptome, are examined, suggesting that CTCFs contribute differentially to Chromatin organization and gene regulation.
Abstract: Recent studies of genome-wide chromatin interactions have revealed that the human genome is partitioned into many self-associating topological domains. The boundary sequences between domains are enriched for binding sites of CTCC-binding factor (CTCF) and the cohesin complex, implicating these two factors in the establishment or maintenance of topological domains. To determine the role of cohesin and CTCF in higher-order chromatin architecture in human cells, we depleted the cohesin complex or CTCF and examined the consequences of loss of these factors on higher-order chromatin organization, as well as the transcriptome. We observed a general loss of local chromatin interactions upon disruption of cohesin, but the topological domains remain intact. However, we found that depletion of CTCF not only reduced intradomain interactions but also increased interdomain interactions. Furthermore, distinct groups of genes become misregulated upon depletion of cohesin and CTCF. Taken together, these observations suggest that CTCF and cohesin contribute differentially to chromatin organization and gene regulation.

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TL;DR: Observations ofBeta Pictoris clearly detect the planet, Beta Pictoris b, in a single 60-s exposure with minimal postprocessing, and fitting the Keplerian orbit of Beta Pic b using the new position together with previous astrometry gives a factor of 3 improvement in most parameters over previous solutions.
Abstract: The Gemini Planet Imager is a dedicated facility for directly imaging and spectroscopically characterizing extrasolar planets. It combines a very high-order adaptive optics system, a diffraction-suppressing coronagraph, and an integral field spectrograph with low spectral resolution but high spatial resolution. Every aspect of the Gemini Planet Imager has been tuned for maximum sensitivity to faint planets near bright stars. During first-light observations, we achieved an estimated H band Strehl ratio of 0.89 and a 5-σ contrast of 10(6) at 0.75 arcseconds and 10(5) at 0.35 arcseconds. Observations of Beta Pictoris clearly detect the planet, Beta Pictoris b, in a single 60-s exposure with minimal postprocessing. Beta Pictoris b is observed at a separation of 434 ± 6 milliarcseconds (mas) and position angle 211.8 ± 0.5°. Fitting the Keplerian orbit of Beta Pic b using the new position together with previous astrometry gives a factor of 3 improvement in most parameters over previous solutions. The planet orbits at a semimajor axis of [Formula: see text] near the 3:2 resonance with the previously known 6-AU asteroidal belt and is aligned with the inner warped disk. The observations give a 4% probability of a transit of the planet in late 2017.