Cornell University

Recent work has shown that convolutional networks can be substantially deeper, more accurate, and efficient to train if they contain shorter connections between layers close to the input and those close to the output. In this paper, we embrace this observation and introduce the Dense Convolutional Network (DenseNet), which connects each layer to every other layer in a feed-forward fashion. Whereas traditional convolutional networks with L layers have L connections-one between each layer and its subsequent layer-our network has L(L+1)/2 direct connections. For each layer, the feature-maps of all preceding layers are used as inputs, and its own feature-maps are used as inputs into all subsequent layers. DenseNets have several compelling advantages: they alleviate the vanishing-gradient problem, strengthen feature propagation, encourage feature reuse, and substantially reduce the number of parameters. We evaluate our proposed architecture on four highly competitive object recognition benchmark tasks (CIFAR-10, CIFAR-100, SVHN, and ImageNet). DenseNets obtain significant improvements over the state-of-the-art on most of them, whilst requiring less memory and computation to achieve high performance. Code and pre-trained models are available at https://github.com/liuzhuang13/DenseNet.

Feature pyramids are a basic component in recognition systems for detecting objects at different scales. But pyramid representations have been avoided in recent object detectors that are based on deep convolutional networks, partially because they are slow to compute and memory intensive. In this paper, we exploit the inherent multi-scale, pyramidal hierarchy of deep convolutional networks to construct feature pyramids with marginal extra cost. A top-down architecture with lateral connections is developed for building high-level semantic feature maps at all scales. This architecture, called a Feature Pyramid Network (FPN), shows significant improvement as a generic feature extractor in several applications. Using a basic Faster R-CNN system, our method achieves state-of-the-art single-model results on the COCO detection benchmark without bells and whistles, surpassing all existing single-model entries including those from the COCO 2016 challenge winners. In addition, our method can run at 5 FPS on a GPU and thus is a practical and accurate solution to multi-scale object detection. Code will be made publicly available.

There is a need to standardize the NDF procedure. Procedures have varied because of the use of different amylases in attempts to remove starch interference. The original Bacillus subtilis enzyme Type IIIA (XIA) no longer is available and has been replaced by a less effective enzyme. For fiber work, a new enzyme has received AOAC approval and is rapidly displacing other amylases in analytical work. This enzyme is available from Sigma (Number A3306; Sigma Chemical Co., St. Louis, MO). The original publications for NDF and ADF (43, 53) and the Agricultural Handbook 379 (14) are obsolete and of historical interest only. Up to date procedures should be followed. Triethylene glycol has replaced 2-ethoxyethanol because of reported toxicity. Considerable development in regard to fiber methods has occurred over the past 5 yr because of a redefinition of dietary fiber for man and monogastric animals that includes lignin and all polysaccharides resistant to mammalian digestive enzymes. In addition to NDF, new improved methods for total dietary fiber and nonstarch polysaccharides including pectin and beta-glucans now are available. The latter are also of interest in rumen fermentation. Unlike starch, their fermentations are like that of cellulose but faster and yield no lactic acid. Physical and biological properties of carbohydrate fractions are more important than their intrinsic composition.

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies. Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics. The 1000 Genomes Project has sought to comprehensively catalogue human genetic variation across populations, providing a valuable public genomic resource. The data obtained so far have found applications ranging from association studies and fine mapping studies to the filtering of likely neutral variants in rare-disease cohorts. The authors now report on the final phase of the project, phase 3, which covers previously uncharacterized areas of human genetic diversity in terms of the populations sampled and categories of characterized variation. The sample now includes more than 2,500 individuals from 26 global populations, with low coverage whole-genome and deep exome sequencing, as well as dense microarray genotyping. They find that while most common variants are shared across populations, rarer variants are often restricted to closely related populations. The authors also demonstrate the use of the phase 3 dataset as a reference panel for imputation to improve the resolution in genetic association studies.

A number of recent studies have focused on the statistical properties of networked systems such as social networks and the Worldwide Web. Researchers have concentrated particularly on a few properties that seem to be common to many networks: the small-world property, power-law degree distributions, and network transitivity. In this article, we highlight another property that is found in many networks, the property of community structure, in which network nodes are joined together in tightly knit groups, between which there are only looser connections. We propose a method for detecting such communities, built around the idea of using centrality indices to find community boundaries. We test our method on computer-generated and real-world graphs whose community structure is already known and find that the method detects this known structure with high sensitivity and reliability. We also apply the method to two networks whose community structure is not well known--a collaboration network and a food web--and find that it detects significant and informative community divisions in both cases.

We present the first public version (v0.2) of the open-source and community-developed Python package, Astropy. This package provides core astronomy-related functionality to the community, including support for domain-specific file formats such as flexible image transport system (FITS) files, Virtual Observatory (VO) tables, and common ASCII table formats, unit and physical quantity conversions, physical constants specific to astronomy, celestial coordinate and time transformations, world coordinate system (WCS) support, generalized containers for representing gridded as well as tabular data, and a framework for cosmological transformations and conversions. Significant functionality is under activedevelopment, such as a model fitting framework, VO client and server tools, and aperture and point spread function (PSF) photometry tools. The core development team is actively making additions and enhancements to the current code base, and we encourage anyone interested to participate in the development of future Astropy versions.

We propose and study a set of algorithms for discovering community structure in networks-natural divisions of network nodes into densely connected subgroups. Our algorithms all share two definitive features: first, they involve iterative removal of edges from the network to split it into communities, the edges removed being identified using any one of a number of possible "betweenness" measures, and second, these measures are, crucially, recalculated after each removal. We also propose a measure for the strength of the community structure found by our algorithms, which gives us an objective metric for choosing the number of communities into which a network should be divided. We demonstrate that our algorithms are highly effective at discovering community structure in both computer-generated and real-world network data, and show how they can be used to shed light on the sometimes dauntingly complex structure of networked systems.

Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome. 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. The Human Microbiome Project (HMP), supported by the National Institutes of Health Common Fund, has the goal of characterizing the microbial communities that inhabit and interact with the human body in sickness and in health. In two Articles in this issue of Nature, the HMP Consortium presents the first population-scale details of the organismal and functional composition of the microbiota across five areas of the body. An associated News & Views discusses the initial results — which, along with those of a series of co-publications, already constitute the most extensive catalogue of organisms and genes related to the human microbiome yet published — and highlights some of the major questions that the project will tackle in the next few years.

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This review describes a new paradigm of electronics based on the spin degree of freedom of the electron. Either adding the spin degree of freedom to conventional charge-based electronic devices or using the spin alone has the potential advantages of nonvolatility, increased data processing speed, decreased electric power consumption, and increased integration densities compared with conventional semiconductor devices. To successfully incorporate spins into existing semiconductor technology, one has to resolve technical issues such as efficient injection, transport, control and manipulation, and detection of spin polarization as well as spin-polarized currents. Recent advances in new materials engineering hold the promise of realizing spintronic devices in the near future. We review the current state of the spin-based devices, efforts in new materials fabrication, issues in spin transport, and optical spin manipulation.

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues was last updated in 2008. Since then, there have been numerous advances in the identification of unique biomarkers associated with some myeloid neoplasms and acute leukemias, largely derived from gene expression analysis and next-generation sequencing that can significantly improve the diagnostic criteria as well as the prognostic relevance of entities currently included in the WHO classification and that also suggest new entities that should be added. Therefore, there is a clear need for a revision to the current classification. The revisions to the categories of myeloid neoplasms and acute leukemia will be published in a monograph in 2016 and reflect a consensus of opinion of hematopathologists, hematologists, oncologists, and geneticists. The 2016 edition represents a revision of the prior classification rather than an entirely new classification and attempts to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition. The major changes in the classification and their rationale are presented here.

A broader approach to research in hu- j man development is proposed that focuses on the pro- gressive accommodation, throughout the life span, between the growing human organism and the changing environments in which it actually lives and grows. The latter include not only the immediate settings containing the developing person but also the larger social contexts, both formal and informal, in which these settings are embedded. In terms of method, the approach emphasizes the use of rigorousj^d^igned exp_erjments, both naturalistic and contrived, beginning in the early stages of the research process. The chang- ing relation between person and environment is con- ceived in systems terms. These systems properties are set forth in a series of propositions, each illus- trated by concrete research examples.

The IntCal09 and Marine09 radiocarbon calibration curves have been revised utilizing newly available and updated data sets from 14 C measurements on tree rings, plant macrofossils, speleothems, corals, and foraminifera. The calibration curves were derived from the data using the random walk model (RWM) used to generate IntCal09 and Marine09, which has been revised to account for additional uncertainties and error structures. The new curves were ratified at the 21st International Radiocarbon conference in July 2012 and are available as Supplemental Material at www.radiocarbon.org. The database can be accessed at http://intcal.qub.ac.uk/intcal13/.

Molecular excitation by the simultaneous absorption of two photons provides intrinsic three-dimensional resolution in laser scanning fluorescence microscopy. The excitation of fluorophores having single-photon absorption in the ultraviolet with a stream of strongly focused subpicosecond pulses of red laser light has made possible fluorescence images of living cells and other microscopic objects. The fluorescence emission increased quadratically with the excitation intensity so that fluorescence and photo-bleaching were confined to the vicinity of the focal plane as expected for cooperative two-photon excitation. This technique also provides unprecedented capabilities for three-dimensional, spatially resolved photochemistry, particularly photolytic release of caged effector molecules.

The network structure of a hyperlinked environment can be a rich source of information about the content of the environment, provided we have effective means for understanding it. We develop a set of algorithmic tools for extracting information from the link structures of such environments, and report on experiments that demonstrate their effectiveness in a variety of context on the World Wide Web. The central issue we address within our framework is the distillation of broad search topics, through the discovery of “authorative” information sources on such topics. We propose and test an algorithmic formulation of the notion of authority, based on the relationship between a set of relevant authoritative pages and the set of “hub pages” that join them together in the link structure. Our formulation has connections to the eigenvectors of certain matrices associated with the link graph; these connections in turn motivate additional heuristrics for link-based analysis.

We present an update to our Galaxy-based web server for processing and visualizing deeply sequenced data. Its core tool set, deepTools, allows users to perform complete bioinformatic workflows ranging from quality controls and normalizations of aligned reads to integrative analyses, including clustering and visualization approaches. Since we first described our deepTools Galaxy server in 2014, we have implemented new solutions for many requests from the community and our users. Here, we introduce significant enhancements and new tools to further improve data visualization and interpretation. deepTools continue to be open to all users and freely available as a web service at deeptools.ie-freiburg.mpg.de The new deepTools2 suite can be easily deployed within any Galaxy framework via the toolshed repository, and we also provide source code for command line usage under Linux and Mac OS X. A public and documented API for access to deepTools functionality is also available.

By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations. This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual. This report by the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations. Integrative analyses reveal profiles of rare and common variants in different populations. The frequencies of rare variants vary across biological pathways, and hundreds of rare, non-coding variants at conserved sites — such as changes disrupting transcription-factor motifs — can be established for each individual.

Abstract Summary: Association analyses that exploit the natural diversity of a genome to map at very high resolutions are becoming increasingly important. In most studies, however, researchers must contend with the confounding effects of both population and family structure. TASSEL (Trait Analysis by aSSociation, Evolution and Linkage) implements general linear model and mixed linear model approaches for controlling population and family structure. For result interpretation, the program allows for linkage disequilibrium statistics to be calculated and visualized graphically. Database browsing and data importation is facilitated by integrated middleware. Other features include analyzing insertions/deletions, calculating diversity statistics, integration of phenotypic and genotypic data, imputing missing data and calculating principal components. Availability: The TASSEL executable, user manual, example data sets and tutorial document are freely available at http://www.maizegenetics.net/tassel. The source code for TASSEL can be found at http://sourceforge.net/projects/tassel. Contact: pjb39@cornell.edu

It is rigorously proved that at any nonzero temperature, a one- or two-dimensional isotropic spin-$S$ Heisenberg model with finite-range exchange interaction can be neither ferromagnetic nor antiferromagnetic. The method of proof is capable of excluding a variety of types of ordering in one and two dimensions.