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Journal ArticleDOI
TL;DR: This tutorial provides a structured approach for planning and reporting simulation studies, which involves defining aims, data‐generating mechanisms, estimands, methods, and performance measures (“ADEMP”).
Abstract: Simulation studies are computer experiments that involve creating data by pseudo‐random sampling. A key strength of simulation studies is the ability to understand the behavior of statistical methods because some “truth” (usually some parameter/s of interest) is known from the process of generating the data. This allows us to consider properties of methods, such as bias. While widely used, simulation studies are often poorly designed, analyzed, and reported. This tutorial outlines the rationale for using simulation studies and offers guidance for design, execution, analysis, reporting, and presentation. In particular, this tutorial provides a structured approach for planning and reporting simulation studies, which involves defining aims, data‐generating mechanisms, estimands, methods, and performance measures (“ADEMP”); coherent terminology for simulation studies; guidance on coding simulation studies; a critical discussion of key performance measures and their estimation; guidance on structuring tabular and graphical presentation of results; and new graphical presentations. With a view to describing recent practice, we review 100 articles taken from Volume 34 of Statistics in Medicine, which included at least one simulation study and identify areas for improvement.

578 citations


Journal ArticleDOI
TL;DR: This review considers the commonly used term of ‘aerosol transmission’ in the context of some infectious agents that are well-recognized to be transmissible via the airborne route, and discusses other agents, like influenza virus, where the potential for airborne transmission is much more dependent on various host, viral and environmental factors, and where its potential for aerosol transmission may be underestimated.
Abstract: Although short-range large-droplet transmission is possible for most respiratory infectious agents, deciding on whether the same agent is also airborne has a potentially huge impact on the types (and costs) of infection control interventions that are required. The concept and definition of aerosols is also discussed, as is the concept of large droplet transmission, and airborne transmission which is meant by most authors to be synonymous with aerosol transmission, although some use the term to mean either large droplet or aerosol transmission. However, these terms are often used confusingly when discussing specific infection control interventions for individual pathogens that are accepted to be mostly transmitted by the airborne (aerosol) route (e.g. tuberculosis, measles and chickenpox). It is therefore important to clarify such terminology, where a particular intervention, like the type of personal protective equipment (PPE) to be used, is deemed adequate to intervene for this potential mode of transmission, i.e. at an N95 rather than surgical mask level requirement. With this in mind, this review considers the commonly used term of ‘aerosol transmission’ in the context of some infectious agents that are well-recognized to be transmissible via the airborne route. It also discusses other agents, like influenza virus, where the potential for airborne transmission is much more dependent on various host, viral and environmental factors, and where its potential for aerosol transmission may be underestimated.

578 citations


Journal ArticleDOI
TL;DR: In this article, the authors acknowledge financial support from the EU under grant number 312483 ESTEEM2 and A.C.D. acknowledge funding from ERC under Grant number 259619 PHOTO EM.
Abstract: G.D., S.C., and C.D. acknowledge funding from ERC under grant number 259619 PHOTO EM. C.D. acknowledges financial support from the EU under grant number 312483 ESTEEM2. F.M., L.C. and A.D.C. acknowledge funding from “Polo Solare Organico” Regione Lazio, the “DSSCX” MIURPRIN2010 and FP7 ITN “Destiny”. G.D and S.C. thank Dr. Francisco de la Pena and Dr. Pierre Burdet for assistance with PCA analysis.

578 citations


Journal ArticleDOI
TL;DR: In this article, the authors reviewed evidence for interventions to reduce the prevalence and incidence of violence against women and girls, and found that women-centred, advocacy, and home-visitation programs can reduce a woman's risk of further victimisation, with less conclusive evidence for the preventive effect of programmes for perpetrators.

578 citations


Journal ArticleDOI
TL;DR: It was found that shortening the parent Al-soc-MOF-1 linker resulted in a noticeable enhancement in the working volumetric capacity at specific temperatures and pressures with amply conserved gravimetric uptake/working capacity.
Abstract: The molecular building block approach was employed effectively to construct a series of novel isoreticular, highly porous and stable, aluminum-based metal–organic frameworks with soc topology. From this platform, three compounds were experimentally isolated and fully characterized: namely, the parent Al-soc-MOF-1 and its naphthalene and anthracene analogues. Al-soc-MOF-1 exhibits outstanding gravimetric methane uptake (total and working capacity). It is shown experimentally, for the first time, that the Al-soc-MOF platform can address the challenging Department of Energy dual target of 0.5 g/g (gravimetric) and 264 cm3 (STP)/cm3 (volumetric) methane storage. Furthermore, Al-soc-MOF exhibited the highest total gravimetric and volumetric uptake for carbon dioxide and the utmost total and deliverable uptake for oxygen at relatively high pressures among all microporous MOFs. In order to correlate the MOF pore structure and functionality to the gas storage properties, to better understand the structure–propert...

578 citations


Journal ArticleDOI
13 Aug 2019-Cells
TL;DR: A brief overview of MSC extraction methods and subsequent potential for differentiation is presented, and a comprehensive overview of their preclinical and clinical applications in regenerative medicine is presented.
Abstract: In recent decades, the biomedical applications of mesenchymal stem cells (MSCs) have attracted increasing attention. MSCs are easily extracted from the bone marrow, fat, and synovium, and differentiate into various cell lineages according to the requirements of specific biomedical applications. As MSCs do not express significant histocompatibility complexes and immune stimulating molecules, they are not detected by immune surveillance and do not lead to graft rejection after transplantation. These properties make them competent biomedical candidates, especially in tissue engineering. We present a brief overview of MSC extraction methods and subsequent potential for differentiation, and a comprehensive overview of their preclinical and clinical applications in regenerative medicine, and discuss future challenges.

578 citations


Journal ArticleDOI
14 Sep 2015-PLOS ONE
TL;DR: Analysis of the bacterial 16S ribosomal RNA (rRNA) gene by using a high-throughput culture-independent pyrosequencing method provided evidence of a moderate dysbiosis in the structure of gut microbiota in patients with MS, and phylogenetic tree analysis revealed that many of the clostridial species associated with MS might be distinct from those broadly associated with autoimmune conditions.
Abstract: The pathogenesis of multiple sclerosis (MS), an autoimmune disease affecting the brain and spinal cord, remains poorly understood. Patients with MS typically present with recurrent episodes of neurological dysfunctions such as blindness, paresis, and sensory disturbances. Studies on experimental autoimmune encephalomyelitis (EAE) animal models have led to a number of testable hypotheses including a hypothetical role of altered gut microbiota in the development of MS. To investigate whether gut microbiota in patients with MS is altered, we compared the gut microbiota of 20 Japanese patients with relapsing-remitting (RR) MS (MS20) with that of 40 healthy Japanese subjects (HC40) and an additional 18 healthy subjects (HC18). All the HC18 subjects repeatedly provided fecal samples over the course of months (158 samples in total). Analysis of the bacterial 16S ribosomal RNA (rRNA) gene by using a high-throughput culture-independent pyrosequencing method provided evidence of a moderate dysbiosis in the structure of gut microbiota in patients with MS. Furthermore, we found 21 species that showed significant differences in relative abundance between the MS20 and HC40 samples. On comparing MS samples to the 158 longitudinal HC18 samples, the differences were found to be reproducibly significant for most of the species. These taxa comprised primarily of clostridial species belonging to Clostridia clusters XIVa and IV and Bacteroidetes. The phylogenetic tree analysis revealed that none of the clostridial species that were significantly reduced in the gut microbiota of patients with MS overlapped with other spore-forming clostridial species capable of inducing colonic regulatory T cells (Treg), which prevent autoimmunity and allergies; this suggests that many of the clostridial species associated with MS might be distinct from those broadly associated with autoimmune conditions. Correcting the dysbiosis and altered gut microbiota might deserve consideration as a potential strategy for the prevention and treatment of MS.

578 citations


Journal ArticleDOI
06 Apr 2018-Science
TL;DR: It is observed that a single condensin complex is able to extrude tens of kilobase pairs of DNA at a force-dependent speed of up to 1500 base pairs per second, using the energy of adenosine triphosphate hydrolysis.
Abstract: It has been hypothesized that SMC protein complexes such as condensin and cohesin spatially organize chromosomes by extruding DNA into large loops. We directly visualized the formation and processive extension of DNA loops by yeast condensin in real time. Our findings constitute unambiguous evidence for loop extrusion. We observed that a single condensin complex is able to extrude tens of kilobase pairs of DNA at a force-dependent speed of up to 1500 base pairs per second, using the energy of adenosine triphosphate hydrolysis. Condensin-induced loop extrusion was strictly asymmetric, which demonstrates that condensin anchors onto DNA and reels it in from only one side. Active DNA loop extrusion by SMC complexes may provide the universal unifying principle for genome organization.

578 citations


Journal ArticleDOI
TL;DR: A thermochromic solar cell for smart photovoltaic window applications utilizing the structural phase transitions in inorganic halide perovskite caesium lead iodide/bromide is demonstrated.
Abstract: Smart photovoltaic windows represent a promising green technology featuring tunable transparency and electrical power generation under external stimuli to control the light transmission and manage the solar energy. Here, we demonstrate a thermochromic solar cell for smart photovoltaic window applications utilizing the structural phase transitions in inorganic halide perovskite caesium lead iodide/bromide. The solar cells undergo thermally-driven, moisture-mediated reversible transitions between a transparent non-perovskite phase (81.7% visible transparency) with low power output and a deeply coloured perovskite phase (35.4% visible transparency) with high power output. The inorganic perovskites exhibit tunable colours and transparencies, a peak device efficiency above 7%, and a phase transition temperature as low as 105 °C. We demonstrate excellent device stability over repeated phase transition cycles without colour fade or performance degradation. The photovoltaic windows showing both photoactivity and thermochromic features represent key stepping-stones for integration with buildings, automobiles, information displays, and potentially many other technologies.

578 citations


Journal ArticleDOI
TL;DR: The potential for the Mediterranean diet to act as a key player in cardiovascular disease prevention, and attempt to identify certain aspects of the diet that are particularly beneficial for cardioprotection are highlighted.

578 citations


Journal ArticleDOI
TL;DR: A brief, inexpensive screening test for sarcopenia would be helpful for clinicians and their patients by developing a simple five‐item questionnaire (SARC‐F) based on cardinal features or consequences of sarc Openia.
Abstract: Background A brief, inexpensive screening test for sarcopenia would be helpful for clinicians and their patients. To screen for persons with sarcopenia, we developed a simple five-item questionnaire (SARC-F) based on cardinal features or consequences of sarcopenia. Methods We investigated the utility of SARC-F in the African American Health (AAH) study, Baltimore Longitudinal Study of Aging (BLSA), and National Health and Nutrition Examination Survey (NHANES). Internal consistency reliability for SARC-F was determined using Cronbach's alpha. We evaluated SARC-F factorial validity using principal components analysis and criterion validity by examining its association with exam-based indicators of sarcopenia. Construct validity was examined using cross-sectional and longitudinal differences among those with high (≥4) vs. low (<4) SARC-F scores for mortality and health outcomes. Results SARC-F exhibited good internal consistency reliability and factorial, criterion, and construct validity. AAH participants with SARC-F scores ≥ 4 had more Instrumental Activity of Daily Living (IADL) deficits, slower chair stand times, lower grip strength, lower short physical performance battery scores, and a higher likelihood of recent hospitalization and of having a gait speed of <0.8 m/s. SARC-F scores ≥ 4 in AAH also were associated with 6 year IADL deficits, slower chair stand times, lower short physical performance battery scores, having a gait speed of <0.8 m/s, being hospitalized recently, and mortality. SARC-F scores ≥ 4 in the BLSA cohort were associated with having more IADL deficits and lower grip strength (both hands) in cross-sectional comparisons and with IADL deficits, lower grip strength (both hands), and mortality at follow-up. NHANES participants with SARC-F scores ≥ 4 had slower 20 ft walk times, had lower peak force knee extensor strength, and were more likely to have been hospitalized recently in cross-sectional analyses. Conclusions The SARC-F proved internally consistent and valid for detecting persons at risk for adverse outcomes from sarcopenia in AAH, BLSA, and NHANES.

Journal ArticleDOI
TL;DR: Two new series of hybrid two-dimensional (2D) perovskites that adopt the Dion-Jacobson (DJ) structure type are presented, which are the first complete homologous series reported in halide perovkite chemistry.
Abstract: The three-dimensional hybrid organic–inorganic perovskites have shown huge potential for use in solar cells and other optoelectronic devices. Although these materials are under intense investigation, derivative materials with lower dimensionality are emerging, offering higher tunability of physical properties and new capabilities. Here, we present two new series of hybrid two-dimensional (2D) perovskites that adopt the Dion–Jacobson (DJ) structure type, which are the first complete homologous series reported in halide perovskite chemistry. Lead iodide DJ perovskites adopt a general formula A′An–1PbnI3n+1 (A′ = 3-(aminomethyl)piperidinium (3AMP) or 4-(aminomethyl)piperidinium (4AMP), A = methylammonium (MA)). These materials have layered structures where the stacking of inorganic layers is unique as they lay exactly on top of another. With a slightly different position of the functional group in the templating cation 3AMP and 4AMP, the as-formed DJ perovskites show different optical properties, with the 3A...

Journal ArticleDOI
TL;DR: This article proposes a fast algorithm to compute quartet-based support for each branch of a given species tree with regard to a given set of gene trees and evaluates the precision and recall of the local PP on a wide set of simulated and biological datasets.
Abstract: Species tree reconstruction is complicated by effects of incomplete lineage sorting, commonly modeled by the multi-species coalescent model (MSC). While there has been substantial progress in developing methods that estimate a species tree given a collection of gene trees, less attention has been paid to fast and accurate methods of quantifying support. In this article, we propose a fast algorithm to compute quartet-based support for each branch of a given species tree with regard to a given set of gene trees. We then show how the quartet support can be used in the context of the MSC to compute (1) the local posterior probability (PP) that the branch is in the species tree and (2) the length of the branch in coalescent units. We evaluate the precision and recall of the local PP on a wide set of simulated and biological datasets, and show that it has very high precision and improved recall compared with multi-locus bootstrapping. The estimated branch lengths are highly accurate when gene tree estimation error is low, but are underestimated when gene tree estimation error increases. Computation of both the branch length and local PP is implemented as new features in ASTRAL.

Journal ArticleDOI
TL;DR: It is demonstrated that dissipation still plays a dominant role in structuring large fluctuations arbitrarily far from equilibrium, and a linear-response-like bound on the large deviation function for currents in Markov jump processes is proved.
Abstract: Near equilibrium, small current fluctuations are described by a Gaussian distribution with a linear-response variance regulated by the dissipation. Here, we demonstrate that dissipation still plays a dominant role in structuring large fluctuations arbitrarily far from equilibrium. In particular, we prove a linear-response-like bound on the large deviation function for currents in Markov jump processes. We find that nonequilibrium current fluctuations are always more likely than what is expected from a linear-response analysis. As a small-fluctuations corollary, we derive a recently conjectured uncertainty bound on the variance of current fluctuations.

Journal ArticleDOI
TL;DR: The AG method is generalized to solve nonconvex and possibly stochastic optimization problems and it is demonstrated that by properly specifying the stepsize policy, the AG method exhibits the best known rate of convergence for solving general non Convex smooth optimization problems by using first-order information, similarly to the gradient descent method.
Abstract: In this paper, we generalize the well-known Nesterov's accelerated gradient (AG) method, originally designed for convex smooth optimization, to solve nonconvex and possibly stochastic optimization problems. We demonstrate that by properly specifying the stepsize policy, the AG method exhibits the best known rate of convergence for solving general nonconvex smooth optimization problems by using first-order information, similarly to the gradient descent method. We then consider an important class of composite optimization problems and show that the AG method can solve them uniformly, i.e., by using the same aggressive stepsize policy as in the convex case, even if the problem turns out to be nonconvex. We demonstrate that the AG method exhibits an optimal rate of convergence if the composite problem is convex, and improves the best known rate of convergence if the problem is nonconvex. Based on the AG method, we also present new nonconvex stochastic approximation methods and show that they can improve a few existing rates of convergence for nonconvex stochastic optimization. To the best of our knowledge, this is the first time that the convergence of the AG method has been established for solving nonconvex nonlinear programming in the literature.

Journal ArticleDOI
TL;DR: Examples of CT definitions, interventions, assessments, and models across a variety of disciplines are shown, with a call for more extensive research in this area.

Journal ArticleDOI
01 Aug 2020
TL;DR: This Viewpoint provides a framework for the application of digital technologies in pandemic management and response, highlighting ways in which successful countries have adopted these technologies for pandemic planning, surveillance, testing, contact tracing, quarantine, and health care.
Abstract: Summary With high transmissibility and no effective vaccine or therapy, COVID-19 is now a global pandemic Government-coordinated efforts across the globe have focused on containment and mitigation, with varying degrees of success Countries that have maintained low COVID-19 per-capita mortality rates appear to share strategies that include early surveillance, testing, contact tracing, and strict quarantine The scale of coordination and data management required for effective implementation of these strategies has—in most successful countries—relied on adopting digital technology and integrating it into policy and health care This Viewpoint provides a framework for the application of digital technologies in pandemic management and response, highlighting ways in which successful countries have adopted these technologies for pandemic planning, surveillance, testing, contact tracing, quarantine, and health care

Proceedings ArticleDOI
01 Oct 2017
TL;DR: In this article, a structured segment network (SSN) is proposed to model the temporal structure of each action instance via a structured temporal pyramid, and a decomposed discriminative model comprising two classifiers, respectively for classifying actions and determining completeness.
Abstract: Detecting actions in untrimmed videos is an important yet challenging task. In this paper, we present the structured segment network (SSN), a novel framework which models the temporal structure of each action instance via a structured temporal pyramid. On top of the pyramid, we further introduce a decomposed discriminative model comprising two classifiers, respectively for classifying actions and determining completeness. This allows the framework to effectively distinguish positive proposals from background or incomplete ones, thus leading to both accurate recognition and localization. These components are integrated into a unified network that can be efficiently trained in an end-to-end fashion. Additionally, a simple yet effective temporal action proposal scheme, dubbed temporal actionness grouping (TAG) is devised to generate high quality action proposals. On two challenging benchmarks, THUMOS14 and ActivityNet, our method remarkably outperforms previous state-of-the-art methods, demonstrating superior accuracy and strong adaptivity in handling actions with various temporal structures.

Journal ArticleDOI
15 Jan 2016-Science
TL;DR: Dwarf open reading frame (DWORF) is the only endogenous peptide known to activate the SERCA pump by physical interaction and provides a means for enhancing muscle contractility.
Abstract: Muscle contraction depends on release of Ca2+ from the sarcoplasmic reticulum (SR) and reuptake by the Ca2+adenosine triphosphatase SERCA. We discovered a putative muscle-specific long noncoding RNA that encodes a peptide of 34 amino acids and that we named dwarf open reading frame (DWORF). DWORF localizes to the SR membrane, where it enhances SERCA activity by displacing the SERCA inhibitors, phospholamban, sarcolipin, and myoregulin. In mice, overexpression of DWORF in cardiomyocytes increases peak Ca2+ transient amplitude and SR Ca2+ load while reducing the time constant of cytosolic Ca2+ decay during each cycle of contraction-relaxation. Conversely, slow skeletal muscle lacking DWORF exhibits delayed Ca2+ clearance and relaxation and reduced SERCA activity. DWORF is the only endogenous peptide known to activate the SERCA pump by physical interaction and provides a means for enhancing muscle contractility.

Journal ArticleDOI
TL;DR: This Cancer Immunology at the Crossroads article focuses on cancer vaccines and immune checkpoint blockade as a forum for reviewing preclinical and clinical data demonstrating the interplay between immunotherapy and chemotherapy.
Abstract: Although cancer chemotherapy has historically been considered immune suppressive, it is now accepted that certain chemotherapies can augment tumor immunity. The recent success of immune checkpoint inhibitors has renewed interest in immunotherapies, and in combining them with chemotherapy to achieve additive or synergistic clinical activity. Two major ways that chemotherapy promotes tumor immunity are by inducing immunogenic cell death as part of its intended therapeutic effect and by disrupting strategies that tumors use to evade immune recognition. This second strategy, in particular, is dependent on the drug, its dose, and the schedule of chemotherapy administration in relation to antigen exposure or release. In this Cancer Immunology at the Crossroads article, we focus on cancer vaccines and immune checkpoint blockade as a forum for reviewing preclinical and clinical data demonstrating the interplay between immunotherapy and chemotherapy.

Journal ArticleDOI
09 Jul 2015-Nature
TL;DR: High coverage methylomes are reported that catalogue cytosine methylation in all contexts for the major human organ systems, integrated with matched transcriptomes and genomic sequence.
Abstract: Understanding the diversity of human tissues is fundamental to disease and requires linking genetic information, which is identical in most of an individual's cells, with epigenetic mechanisms that could have tissue-specific roles. Surveys of DNA methylation in human tissues have established a complex landscape including both tissue-specific and invariant methylation patterns. Here we report high coverage methylomes that catalogue cytosine methylation in all contexts for the major human organ systems, integrated with matched transcriptomes and genomic sequence. By combining these diverse data types with each individuals' phased genome, we identified widespread tissue-specific differential CG methylation (mCG), partially methylated domains, allele-specific methylation and transcription, and the unexpected presence of non-CG methylation (mCH) in almost all human tissues. mCH correlated with tissue-specific functions, and using this mark, we made novel predictions of genes that escape X-chromosome inactivation in specific tissues. Overall, DNA methylation in several genomic contexts varies substantially among human tissues.

Journal ArticleDOI
TL;DR: In this article, an IRS-aided multiuser system with one RIS deployed to assist in the downlink communications from a multi-antenna access point (AP) to multiple singleantenna users is considered, and an optimization problem to minimize the total transmit power at the AP by jointly designing the AP transmit beamforming and the RIS reflect beamforming, subject to the users' individual signal-to-interference-plus-noise ratio (SINR) constraints.
Abstract: Intelligent reflecting surface (IRS) that enables the control of wireless propagation environment has recently emerged as a promising cost-effective technology for boosting the spectral and energy efficiency of future wireless communication systems. Prior works on IRS are mainly based on the ideal phase shift model assuming full signal reflection by each of its elements regardless of the phase shift, which, however, is practically difficult to realize. In contrast, we propose in this paper a practical phase shift model that captures the phase-dependent amplitude variation in the element-wise reflection design. Based on the proposed model and considering an IRS-aided multiuser system with one IRS deployed to assist in the downlink communications from a multi-antenna access point (AP) to multiple single-antenna users, we formulate an optimization problem to minimize the total transmit power at the AP by jointly designing the AP transmit beamforming and the IRS reflect beamforming, subject to the users’ individual signal-to-interference-plus-noise ratio (SINR) constraints. Iterative algorithms are proposed to find suboptimal solutions to this problem efficiently by utilizing the alternating optimization (AO) as well as penalty-based optimization techniques. Moreover, to draw essential insight, we analyze the asymptotic performance loss of the IRS-aided system that employs practical phase shifters but assumes the ideal phase shift model for beamforming optimization, as the number of IRS elements goes to infinity. Simulation results unveil substantial performance gains achieved by the proposed beamforming optimization based on the practical phase shift model as compared to the conventional ideal model.

Journal ArticleDOI
TL;DR: This paper revises and discusses these antimicrobial activities of dietary polyphenols and their relevance for human health, shedding light on the importance of polyphenol structure recognition by specific enzymes produced by intestinal microbial taxa.
Abstract: Polyphenolic compounds are plant nutraceuticals showing a huge structural diversity, including chlorogenic acids, hydrolyzable tannins, and flavonoids (flavonols, flavanones, flavan-3-ols, anthocyanidins, isoflavones, and flavones). Most of them occur as glycosylated derivatives in plants and foods. In order to become bioactive at human body, these polyphenols must undergo diverse intestinal transformations, due to the action of digestive enzymes, but also by the action of microbiota metabolism. After elimination of sugar tailoring (generating the corresponding aglycons) and diverse hydroxyl moieties, as well as further backbone reorganizations, the final absorbed compounds enter the portal vein circulation towards liver (where other enzymatic transformations take place) and from there to other organs, including behind the digestive tract or via blood towards urine excretion. During this transit along diverse tissues and organs, they are able to carry out strong antiviral, antibacterial, and antiparasitic activities. This paper revises and discusses these antimicrobial activities of dietary polyphenols and their relevance for human health, shedding light on the importance of polyphenols structure recognition by specific enzymes produced by intestinal microbial taxa.

Journal ArticleDOI
TL;DR: A series of questions are explored to highlight some insights that comparative genomics has produced and how it could revolutionize medicine in terms of speed and accuracy of finding pathogens and knowing how to treat them.
Abstract: Since the first two complete bacterial genome sequences were published in 1995, the science of bacteria has dramatically changed. Using third-generation DNA sequencing, it is possible to completely sequence a bacterial genome in a few hours and identify some types of methylation sites along the genome as well. Sequencing of bacterial genome sequences is now a standard procedure, and the information from tens of thousands of bacterial genomes has had a major impact on our views of the bacterial world. In this review, we explore a series of questions to highlight some insights that comparative genomics has produced. To date, there are genome sequences available from 50 different bacterial phyla and 11 different archaeal phyla. However, the distribution is quite skewed towards a few phyla that contain model organisms. But the breadth is continuing to improve, with projects dedicated to filling in less characterized taxonomic groups. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system provides bacteria with immunity against viruses, which outnumber bacteria by tenfold. How fast can we go? Second-generation sequencing has produced a large number of draft genomes (close to 90 % of bacterial genomes in GenBank are currently not complete); third-generation sequencing can potentially produce a finished genome in a few hours, and at the same time provide methlylation sites along the entire chromosome. The diversity of bacterial communities is extensive as is evident from the genome sequences available from 50 different bacterial phyla and 11 different archaeal phyla. Genome sequencing can help in classifying an organism, and in the case where multiple genomes of the same species are available, it is possible to calculate the pan- and core genomes; comparison of more than 2000 Escherichia coli genomes finds an E. coli core genome of about 3100 gene families and a total of about 89,000 different gene families. Why do we care about bacterial genome sequencing? There are many practical applications, such as genome-scale metabolic modeling, biosurveillance, bioforensics, and infectious disease epidemiology. In the near future, high-throughput sequencing of patient metagenomic samples could revolutionize medicine in terms of speed and accuracy of finding pathogens and knowing how to treat them.

Journal ArticleDOI
TL;DR: A sulfur host that overcomes both obstacles at once for the success of lithium–sulfur batteries by using the polar shells to prevent their outward diffusion and avoids the need for chemically bonding all lithium-polysulfides on the surfaces of polar particles.
Abstract: Lithium-sulfur batteries show advantages for next-generation electrical energy storage due to their high energy density and cost effectiveness. Enhancing the conductivity of the sulfur cathode and moderating the dissolution of lithium polysulfides are two key factors for the success of lithium-sulfur batteries. Here we report a sulfur host that overcomes both obstacles at once. With inherent metallic conductivity and strong adsorption capability for lithium-polysulfides, titanium monoxide@carbon hollow nanospheres can not only generate sufficient electrical contact to the insulating sulfur for high capacity, but also effectively confine lithium-polysulfides for prolonged cycle life. Additionally, the designed composite cathode further maximizes the lithium-polysulfide restriction capability by using the polar shells to prevent their outward diffusion, which avoids the need for chemically bonding all lithium-polysulfides on the surfaces of polar particles.

Journal ArticleDOI
TL;DR: A fake news data repository FakeNewsNet is presented, which contains two comprehensive data sets with diverse features in news content, social context, and spatiotemporal information, and is discussed for potential applications on fake news study on social media.
Abstract: Social media has become a popular means for people to consume and share the news. At the same time, however, it has also enabled the wide dissemination of fake news, that is, news with intentionally false information, causing significant negative effects on society. To mitigate this problem, the research of fake news detection has recently received a lot of attention. Despite several existing computational solutions on the detection of fake news, the lack of comprehensive and community-driven fake news data sets has become one of major roadblocks. Not only existing data sets are scarce, they do not contain a myriad of features often required in the study such as news content, social context, and spatiotemporal information. Therefore, in this article, to facilitate fake news-related research, we present a fake news data repository FakeNewsNet, which contains two comprehensive data sets with diverse features in news content, social context, and spatiotemporal information. We present a comprehensive description of the FakeNewsNet, demonstrate an exploratory analysis of two data sets from different perspectives, and discuss the benefits of the FakeNewsNet for potential applications on fake news study on social media.

Journal ArticleDOI
TL;DR: In this paper, a review of the literature that investigated differences in physical activity and sedentary behaviour before vs during the COVID-19 lockdown was presented, with the majority of studies reporting decreases in physical activities and increases in sedentary behaviours during their respective lockdowns across several populations.
Abstract: Objective In March 2020, several countries banned unnecessary outdoor activities during COVID-19, commonly called ‘lockdowns. These lockdowns have the potential to impact associated levels of physical activity and sedentary behaviour. Given the numerous health outcomes associated with physical activity and sedentary behaviour, the aim of this review was to summarise literature that investigated differences in physical activity and sedentary behaviour before vs during the COVID-19 lockdown. Design, data sources and eligibility criteria Electronic databases were searched from November 2019 to October 2020 using terms and synonyms relating to physical activity, sedentary behaviour and COVID-19. The coprimary outcomes were changes in physical activity and/or sedentary behaviour captured via device-based measures or self-report tools. Risk of bias was measured using the Newcastle-Ottawa Scale. Results Sixty six articles met the inclusion criteria and were included in the review (total n=86 981). Changes in physical activity were reported in 64 studies, with the majority of studies reporting decreases in physical activity and increases in sedentary behaviours during their respective lockdowns across several populations, including children and patients with a variety of medical conditions. Conclusion Given the numerous physical and mental benefits of increased physical activity and decreased sedentary behaviour, public health strategies should include the creation and implementation of interventions that promote safe physical activity and reduce sedentary behaviour should other lockdowns occur.

Proceedings ArticleDOI
18 Jun 2018
TL;DR: In this paper, the role of motifs in scene graph representation is investigated and the Stacked Motif Networks (SFN) architecture is proposed to capture higher order motifs.
Abstract: We investigate the problem of producing structured graph representations of visual scenes. Our work analyzes the role of motifs: regularly appearing substructures in scene graphs. We present new quantitative insights on such repeated structures in the Visual Genome dataset. Our analysis shows that object labels are highly predictive of relation labels but not vice-versa. We also find that there are recurring patterns even in larger subgraphs: more than 50% of graphs contain motifs involving at least two relations. Our analysis motivates a new baseline: given object detections, predict the most frequent relation between object pairs with the given labels, as seen in the training set. This baseline improves on the previous state-of-the-art by an average of 3.6% relative improvement across evaluation settings. We then introduce Stacked Motif Networks, a new architecture designed to capture higher order motifs in scene graphs that further improves over our strong baseline by an average 7.1% relative gain. Our code is available at github.com/rowanz/neural-motifs.

Journal ArticleDOI
Bruce Wang1, Ludan Zhao1, Matt Fish1, Catriona Y. Logan1, Roel Nusse1 
13 Aug 2015-Nature
TL;DR: A cell population in the liver that subserves homeostatic hepatocyte renewal is identified, its anatomical niche is characterized, and molecular signals that regulate its activity are identified.
Abstract: The source of new hepatocytes in the uninjured liver has remained an open question. By lineage tracing using the Wnt-responsive gene Axin2 in mice, we identify a population of proliferating and self-renewing cells adjacent to the central vein in the liver lobule. These pericentral cells express the early liver progenitor marker Tbx3, are diploid, and thereby differ from mature hepatocytes, which are mostly polyploid. The descendants of pericentral cells differentiate into Tbx3-negative, polyploid hepatocytes, and can replace all hepatocytes along the liver lobule during homeostatic renewal. Adjacent central vein endothelial cells provide Wnt signals that maintain the pericentral cells, thereby constituting the niche. Thus, we identify a cell population in the liver that subserves homeostatic hepatocyte renewal, characterize its anatomical niche, and identify molecular signals that regulate its activity.

Proceedings ArticleDOI
07 Dec 2015
TL;DR: This paper presents a focused study to narrow the semantic gap with an architecture based on Deep Neural Network (DNN), which leverages the representational power of high-level semantics encoded in DNNs pretrained for object recognition.
Abstract: Saliency in Context (SALICON) is an ongoing effort that aims at understanding and predicting visual attention. Conventional saliency models typically rely on low-level image statistics to predict human fixations. While these models perform significantly better than chance, there is still a large gap between model prediction and human behavior. This gap is largely due to the limited capability of models in predicting eye fixations with strong semantic content, the so-called semantic gap. This paper presents a focused study to narrow the semantic gap with an architecture based on Deep Neural Network (DNN). It leverages the representational power of high-level semantics encoded in DNNs pretrained for object recognition. Two key components are fine-tuning the DNNs fully convolutionally with an objective function based on the saliency evaluation metrics, and integrating information at different image scales. We compare our method with 14 saliency models on 6 public eye tracking benchmark datasets. Results demonstrate that our DNNs can automatically learn features particularly for saliency prediction that surpass by a big margin the state-of-the-art. In addition, our model ranks top to date under all seven metrics on the MIT300 challenge set.