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Showing papers by "University of Tokyo published in 2016"


Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

5,187 citations


Journal ArticleDOI
Theo Vos1, Christine Allen1, Megha Arora1, Ryan M Barber1  +696 moreInstitutions (260)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) as discussed by the authors was used to estimate the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.

5,050 citations


Journal ArticleDOI
Haidong Wang1, Mohsen Naghavi1, Christine Allen1, Ryan M Barber1  +841 moreInstitutions (293)
TL;DR: The Global Burden of Disease 2015 Study provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015, finding several countries in sub-Saharan Africa had very large gains in life expectancy, rebounding from an era of exceedingly high loss of life due to HIV/AIDS.

4,804 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, M. R. Abernathy3  +970 moreInstitutions (114)
TL;DR: This second gravitational-wave observation provides improved constraints on stellar populations and on deviations from general relativity.
Abstract: We report the observation of a gravitational-wave signal produced by the coalescence of two stellar-mass black holes. The signal, GW151226, was observed by the twin detectors of the Laser Interferometer Gravitational-Wave Observatory (LIGO) on December 26, 2015 at 03:38:53 UTC. The signal was initially identified within 70 s by an online matched-filter search targeting binary coalescences. Subsequent off-line analyses recovered GW151226 with a network signal-to-noise ratio of 13 and a significance greater than 5 σ. The signal persisted in the LIGO frequency band for approximately 1 s, increasing in frequency and amplitude over about 55 cycles from 35 to 450 Hz, and reached a peak gravitational strain of 3.4+0.7−0.9×10−22. The inferred source-frame initial black hole masses are 14.2+8.3−3.7M⊙ and 7.5+2.3−2.3M⊙ and the final black hole mass is 20.8+6.1−1.7M⊙. We find that at least one of the component black holes has spin greater than 0.2. This source is located at a luminosity distance of 440+180−190 Mpc corresponding to a redshift 0.09+0.03−0.04. All uncertainties define a 90 % credible interval. This second gravitational-wave observation provides improved constraints on stellar populations and on deviations from general relativity.

3,448 citations


Journal ArticleDOI
TL;DR: This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘ how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?'
Abstract: This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?’

3,335 citations


Journal ArticleDOI
Bin Zhou1, Yuan Lu2, Kaveh Hajifathalian2, James Bentham1  +494 moreInstitutions (170)
TL;DR: In this article, the authors used a Bayesian hierarchical model to estimate trends in diabetes prevalence, defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs in 200 countries and territories in 21 regions, by sex and from 1980 to 2014.

2,782 citations


Journal ArticleDOI
TL;DR: New genomic data from over 1,000 uncultivated and little known organisms, together with published sequences, are used to infer a dramatically expanded version of the tree of life, with Bacteria, Archaea and Eukarya included.
Abstract: The tree of life is one of the most important organizing principles in biology1. Gene surveys suggest the existence of an enormous number of branches2, but even an approximation of the full scale of the tree has remained elusive. Recent depictions of the tree of life have focused either on the nature of deep evolutionary relationships3–5 or on the known, well-classified diversity of life with an emphasis on eukaryotes6. These approaches overlook the dramatic change in our understanding of life's diversity resulting from genomic sampling of previously unexamined environments. New methods to generate genome sequences illuminate the identity of organisms and their metabolic capacities, placing them in community and ecosystem contexts7,8. Here, we use new genomic data from over 1,000 uncultivated and little known organisms, together with published sequences, to infer a dramatically expanded version of the tree of life, with Bacteria, Archaea and Eukarya included. The depiction is both a global overview and a snapshot of the diversity within each major lineage. The results reveal the dominance of bacterial diversification and underline the importance of organisms lacking isolated representatives, with substantial evolution concentrated in a major radiation of such organisms. This tree highlights major lineages currently underrepresented in biogeochemical models and identifies radiations that are probably important for future evolutionary analyses. An update to the ‘tree of life’ has revealed a dominance of bacterial diversity in many ecosystems and extensive evolution in some branches of the tree. It also highlights how few organisms we have been able to cultivate for further investigation.

1,614 citations


Journal ArticleDOI
Nicholas J Kassebaum1, Megha Arora1, Ryan M Barber1, Zulfiqar A Bhutta2  +679 moreInstitutions (268)
TL;DR: In this paper, the authors used the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015.

1,533 citations


Journal ArticleDOI
26 Jul 2016-eLife
TL;DR: The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
Abstract: Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.

1,348 citations


Journal ArticleDOI
TL;DR: In this paper, the photocatalyst sheet design enables efficient and scalable water splitting using particulate semiconductors, which is a potentially scalable and economically feasible technology for converting solar energy into hydrogen.
Abstract: Photocatalytic water splitting using semiconductors is attractive for converting solar energy into hydrogen. An efficient and scalable system based on particulate photocatalyst sheets is now shown to exhibit energy conversion efficiency exceeding 1%. Photocatalytic water splitting using particulate semiconductors is a potentially scalable and economically feasible technology for converting solar energy into hydrogen1,2,3. Z-scheme systems based on two-step photoexcitation of a hydrogen evolution photocatalyst (HEP) and an oxygen evolution photocatalyst (OEP) are suited to harvesting of sunlight because semiconductors with either water reduction or oxidation activity can be applied to the water splitting reaction4,5. However, it is challenging to achieve efficient transfer of electrons between HEP and OEP particles6,7. Here, we present photocatalyst sheets based on La- and Rh-codoped SrTiO3 (SrTiO3:La, Rh; ref. 8) and Mo-doped BiVO4 (BiVO4:Mo) powders embedded into a gold (Au) layer. Enhancement of the electron relay by annealing and suppression of undesirable reactions through surface modification allow pure water (pH 6.8) splitting with a solar-to-hydrogen energy conversion efficiency of 1.1% and an apparent quantum yield of over 30% at 419 nm. The photocatalyst sheet design enables efficient and scalable water splitting using particulate semiconductors.

1,190 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Matthew Abernathy3  +978 moreInstitutions (112)
TL;DR: The first observational run of the Advanced LIGO detectors, from September 12, 2015 to January 19, 2016, saw the first detections of gravitational waves from binary black hole mergers as discussed by the authors.
Abstract: The first observational run of the Advanced LIGO detectors, from September 12, 2015 to January 19, 2016, saw the first detections of gravitational waves from binary black hole mergers. In this paper we present full results from a search for binary black hole merger signals with total masses up to 100M⊙ and detailed implications from our observations of these systems. Our search, based on general-relativistic models of gravitational wave signals from binary black hole systems, unambiguously identified two signals, GW150914 and GW151226, with a significance of greater than 5σ over the observing period. It also identified a third possible signal, LVT151012, with substantially lower significance, which has a 87% probability of being of astrophysical origin. We provide detailed estimates of the parameters of the observed systems. Both GW150914 and GW151226 provide an unprecedented opportunity to study the two-body motion of a compact-object binary in the large velocity, highly nonlinear regime. We do not observe any deviations from general relativity, and place improved empirical bounds on several high-order post-Newtonian coefficients. From our observations we infer stellar-mass binary black hole merger rates lying in the range 9−240Gpc−3yr−1. These observations are beginning to inform astrophysical predictions of binary black hole formation rates, and indicate that future observing runs of the Advanced detector network will yield many more gravitational wave detections.

Proceedings ArticleDOI
07 Mar 2016
TL;DR: OpenFace is the first open source tool capable of facial landmark detection, head pose estimation, facial action unit recognition, and eye-gaze estimation and allows for easy integration with other applications and devices through a lightweight messaging system.
Abstract: Over the past few years, there has been an increased interest in automatic facial behavior analysis and understanding. We present OpenFace — an open source tool intended for computer vision and machine learning researchers, affective computing community and people interested in building interactive applications based on facial behavior analysis. OpenFace is the first open source tool capable of facial landmark detection, head pose estimation, facial action unit recognition, and eye-gaze estimation. The computer vision algorithms which represent the core of OpenFace demonstrate state-of-the-art results in all of the above mentioned tasks. Furthermore, our tool is capable of real-time performance and is able to run from a simple webcam without any specialist hardware. Finally, OpenFace allows for easy integration with other applications and devices through a lightweight messaging system.

Journal ArticleDOI
Kurt Lejaeghere1, Gustav Bihlmayer2, Torbjörn Björkman3, Torbjörn Björkman4, Peter Blaha5, Stefan Blügel2, Volker Blum6, Damien Caliste7, Ivano E. Castelli8, Stewart J. Clark9, Andrea Dal Corso10, Stefano de Gironcoli10, Thierry Deutsch7, J. K. Dewhurst11, Igor Di Marco12, Claudia Draxl13, Claudia Draxl14, Marcin Dulak15, Olle Eriksson12, José A. Flores-Livas11, Kevin F. Garrity16, Luigi Genovese7, Paolo Giannozzi17, Matteo Giantomassi18, Stefan Goedecker19, Xavier Gonze18, Oscar Grånäs20, Oscar Grånäs12, E. K. U. Gross11, Andris Gulans13, Andris Gulans14, Francois Gygi21, D. R. Hamann22, P. J. Hasnip23, Natalie Holzwarth24, Diana Iusan12, Dominik B. Jochym25, F. Jollet, Daniel M. Jones26, Georg Kresse27, Klaus Koepernik28, Klaus Koepernik29, Emine Kucukbenli10, Emine Kucukbenli8, Yaroslav Kvashnin12, Inka L. M. Locht30, Inka L. M. Locht12, Sven Lubeck14, Martijn Marsman27, Nicola Marzari8, Ulrike Nitzsche29, Lars Nordström12, Taisuke Ozaki31, Lorenzo Paulatto32, Chris J. Pickard33, Ward Poelmans1, Matt Probert23, Keith Refson34, Keith Refson25, Manuel Richter29, Manuel Richter28, Gian-Marco Rignanese18, Santanu Saha19, Matthias Scheffler35, Matthias Scheffler13, Martin Schlipf21, Karlheinz Schwarz5, Sangeeta Sharma11, Francesca Tavazza16, Patrik Thunström5, Alexandre Tkatchenko36, Alexandre Tkatchenko13, Marc Torrent, David Vanderbilt22, Michiel van Setten18, Veronique Van Speybroeck1, John M. Wills37, Jonathan R. Yates26, Guo-Xu Zhang38, Stefaan Cottenier1 
25 Mar 2016-Science
TL;DR: A procedure to assess the precision of DFT methods was devised and used to demonstrate reproducibility among many of the most widely used DFT codes, demonstrating that the precisionof DFT implementations can be determined, even in the absence of one absolute reference code.
Abstract: The widespread popularity of density functional theory has given rise to an extensive range of dedicated codes for predicting molecular and crystalline properties. However, each code implements the formalism in a different way, raising questions about the reproducibility of such predictions. We report the results of a community-wide effort that compared 15 solid-state codes, using 40 different potentials or basis set types, to assess the quality of the Perdew-Burke-Ernzerhof equations of state for 71 elemental crystals. We conclude that predictions from recent codes and pseudopotentials agree very well, with pairwise differences that are comparable to those between different high-precision experiments. Older methods, however, have less precise agreement. Our benchmark provides a framework for users and developers to document the precision of new applications and methodological improvements.

Journal ArticleDOI
15 Dec 2016-Nature
TL;DR: Plastic bioelectronics is a research field that takes advantage of the inherent properties of polymers and soft organic electronics for applications at the interface of biology and electronics, which are soft, stretchable and mechanically conformable.
Abstract: Plastic bioelectronics is a research field that takes advantage of the inherent properties of polymers and soft organic electronics for applications at the interface of biology and electronics. The resulting electronic materials and devices are soft, stretchable and mechanically conformable, which are important qualities for interacting with biological systems in both wearable and implantable devices. Work is currently aimed at improving these devices with a view to making the electronic-biological interface as seamless as possible.

Journal ArticleDOI
TL;DR: There are significant roots in general and in particular to the CIRP community – which point towards CPPS, and expectations towards research in and implementation of CPS and CPPS are outlined.
Abstract: One of the most significant advances in the development of computer science, information and communication technologies is represented by the cyber-physical systems (CPS). They are systems of collaborating computational entities which are in intensive connection with the surrounding physical world and its on-going processes, providing and using, at the same time, data-accessing and data-processing services available on the Internet. Cyber-physical production systems (CPPS), relying on the latest, and the foreseeable further developments of computer science, information and communication technologies on one hand, and of manufacturing science and technology, on the other, may lead to the 4th industrial revolution, frequently noted as Industrie 4.0. The paper underlines that there are significant roots in general – and in particular to the CIRP community – which point towards CPPS. Expectations towards research in and implementation of CPS and CPPS are outlined and some case studies are introduced. Related new R&D challenges are highlighted.

Journal ArticleDOI
23 Sep 2016-Science
TL;DR: A global genetic interaction network highlights the functional organization of a cell and provides a resource for predicting gene and pathway function and how coherent sets of negative or positive genetic interactions connect protein complex and pathways to map a functional wiring diagram of the cell.
Abstract: INTRODUCTION Genetic interactions occur when mutations in two or more genes combine to generate an unexpected phenotype. An extreme negative or synthetic lethal genetic interaction occurs when two mutations, neither lethal individually, combine to cause cell death. Conversely, positive genetic interactions occur when two mutations produce a phenotype that is less severe than expected. Genetic interactions identify functional relationships between genes and can be harnessed for biological discovery and therapeutic target identification. They may also explain a considerable component of the undiscovered genetics associated with human diseases. Here, we describe construction and analysis of a comprehensive genetic interaction network for a eukaryotic cell. RATIONALE Genome sequencing projects are providing an unprecedented view of genetic variation. However, our ability to interpret genetic information to predict inherited phenotypes remains limited, in large part due to the extensive buffering of genomes, making most individual eukaryotic genes dispensable for life. To explore the extent to which genetic interactions reveal cellular function and contribute to complex phenotypes, and to discover the general principles of genetic networks, we used automated yeast genetics to construct a global genetic interaction network. RESULTS We tested most of the ~6000 genes in the yeast Saccharomyces cerevisiae for all possible pairwise genetic interactions, identifying nearly 1 million interactions, including ~550,000 negative and ~350,000 positive interactions, spanning ~90% of all yeast genes. Essential genes were network hubs, displaying five times as many interactions as nonessential genes. The set of genetic interactions or the genetic interaction profile for a gene provides a quantitative measure of function, and a global network based on genetic interaction profile similarity revealed a hierarchy of modules reflecting the functional architecture of a cell. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections associated with defects in cell cycle progression or cellular proteostasis. Importantly, the global network illustrates how coherent sets of negative or positive genetic interactions connect protein complex and pathways to map a functional wiring diagram of the cell. CONCLUSION A global genetic interaction network highlights the functional organization of a cell and provides a resource for predicting gene and pathway function. This network emphasizes the prevalence of genetic interactions and their potential to compound phenotypes associated with single mutations. Negative genetic interactions tend to connect functionally related genes and thus may be predicted using alternative functional information. Although less functionally informative, positive interactions may provide insights into general mechanisms of genetic suppression or resiliency. We anticipate that the ordered topology of the global genetic network, in which genetic interactions connect coherently within and between protein complexes and pathways, may be exploited to decipher genotype-to-phenotype relationships.

Journal ArticleDOI
16 Sep 2016-Science
TL;DR: The toxicity associated with the nuclease-based CRISPR/Cas9 system was greatly reduced in the Target-AID complexes, and it was demonstrated that off-target effects were comparable to those of conventional CRISpr/Cas systems, with a reduced risk of indel formation.
Abstract: INTRODUCTION To combat invading pathogens, cells develop an adaptive immune response by changing their own genetic information. In vertebrates, the generation of genetic variation (somatic hypermutation) is an essential process for diversification and affinity maturation of antibodies that function to detect and sequester various foreign biomolecules. The activation-induced cytidine deaminase (AID) carries out hypermutation by modifying deoxycytidine bases in the variable region of the immunoglobulin locus that produces antibody. AID-generated deoxyuridine in DNA is mutagenic as it can be miss-recognized as deoxythymine, resulting in C to T mutations. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated) is a prokaryotic adaptive immune system that records and degrades invasive foreign DNA or RNA. The CRISPR/Cas system cleaves and incorporates foreign DNA/RNA segments into the genomic region called the CRISPR array. The CRISPR array is transcribed to produce crispr-RNA that serves as guide RNA (gRNA) for recognition of the complementary foreign DNA/RNA in a ribonucleoprotein complex with Cas proteins, which degrade the target. The CRISPR/Cas system has been repurposed as a powerful genome editing tool, because it can be programmed to cleave specific DNA sequence by providing custom gRNAs. RATIONALE Although the precise mechanism by which AID specifically mutates the immunoglobulin locus remains elusive, targeting of AID activity is facilitated by the formation of a single-stranded DNA region, such as a transcriptional RNA/DNA hybrid (R-loop). The CRISPR/Cas system can be engineered to be nuclease-inactive. The nuclease-inactive form is capable of unfolding the DNA double strand in a protospacer adjacent motif (PAM) sequence-dependent manner so that the gRNA binds to complementary target DNA strand and forms an R-loop. The nuclease-deficient CRISPR/Cas system may serve as a suitable DNA-targeting module for AID to catalyze site-specific mutagenesis. RESULTS To determine whether AID activity can be specifically targeted by the CRISPR/Cas system, we combined dCas9 (a nuclease-deficient mutant of Cas9) from Streptococcus pyogenes and an AID ortholog, PmCDA1 from sea lamprey, to form a synthetic complex (Target-AID) by either engineering a fusion between the two proteins or attaching a SH3 (Src 3 homology) domain to the C terminus of dCas9 and a SHL (SH3 interaction ligand) to the C terminus of PmCDA1. Both of these complexes performed highly efficient site-directed mutagenesis. The mutational spectrum was analyzed in yeast and demonstrated that point mutations were dominantly induced at cytosines within the range of three to five bases surrounding the –18 position upstream of the PAM sequence on the noncomplementary strand to gRNA. The toxicity associated with the nuclease-based CRISPR/Cas9 system was greatly reduced in the Target-AID complexes. Combination of PmCDA1 with the nickase Cas9(D10A) mutant, which retains cleavage activity for noncomplementary single-stranded DNA, was more efficient in yeast but also induced deletions as well as point mutations in mammalian cells. Addition of the uracil DNA glycosylase inhibitor protein, which blocks the initial step of the uracil base excision repair pathway, suppressed collateral deletions and further improved targeting efficiency. Potential off-target effects were assessed by whole-genome sequencing of yeast as well as deep sequencing of mammalian cells for regions that contain mismatched target sequences. These results showed that off-target effects were comparable to those of conventional CRISPR/Cas systems, with a reduced risk of indel formation. CONCLUSION By expanding the genome editing potential of the CRISPR/Cas9 system by deaminase-mediated hypermutation, Target-AID demonstrated a very narrow range of targeted nucleotide substitution without the use of template DNA. Nickase Cas9 and uracil DNA glycosylase inhibitor protein can be used to boost the targeting efficiency. The reduced cytotoxicity will be beneficial for use in cells that are sensitive to artificial nucleases. Use of other types of nucleotide-modifying enzymes and/or other CRISPR-related systems with different PAM requirements will expand our genome-editing repertoire and capacity.

Journal ArticleDOI
01 Jun 2016-Methods
TL;DR: The details of the core algorithms in MEG AHIT v0.1 are described, and the new modules to upgrade MEGAHIT to version v1.0 are shown, which gives better assembly quality, runs faster and uses less memory.

Journal ArticleDOI
TL;DR: In this article, the Pacific decadal oscillation (PDO) is not a single phenomenon, but is instead the result of a combination of different physical processes, including remote tropical forcing and local North Pacific atmosphere-ocean interactions, which operate on different time scales to drive similar PDO-like SST anomaly patterns.
Abstract: The Pacific decadal oscillation (PDO), the dominant year-round pattern of monthly North Pacific sea surface temperature (SST) variability, is an important target of ongoing research within the meteorological and climate dynamics communities and is central to the work of many geologists, ecologists, natural resource managers, and social scientists. Research over the last 15 years has led to an emerging consensus: the PDO is not a single phenomenon, but is instead the result of a combination of different physical processes, including both remote tropical forcing and local North Pacific atmosphere–ocean interactions, which operate on different time scales to drive similar PDO-like SST anomaly patterns. How these processes combine to generate the observed PDO evolution, including apparent regime shifts, is shown using simple autoregressive models of increasing spatial complexity. Simulations of recent climate in coupled GCMs are able to capture many aspects of the PDO, but do so based on a balance of ...

Journal ArticleDOI
Abstract: Increasingly, people are becoming less likely to have direct contact with nature (natural environments and their associated wildlife) in their everyday lives. Over 20 years ago, Robert M Pyle termed this ongoing alienation the “extinction of experience”, but the phenomenon has continued to receive surprisingly limited attention. Here, we present current understanding of the extinction of experience, with particular emphasis on its causes and consequences, and suggest future research directions. Our review illustrates that the loss of interaction with nature not only diminishes a wide range of benefits relating to health and well-being, but also discourages positive emotions, attitudes, and behavior with regard to the environment, implying a cycle of disaffection toward nature. Such serious implications highlight the importance of reconnecting people with nature, as well as focusing research and public policy on addressing and improving awareness of the extinction of experience.

Journal ArticleDOI
TL;DR: The abundance of PBHs required to explain the suggested lower bound on the event rate roughly coincides with the existing upper limit set by the nondetection of the cosmic microwave background spectral distortion, which implies that the proposed PBH scenario may be tested in the not-too-distant future.
Abstract: A theoretical analysis examines the possibility that the gravitational wave signal (GW150914) detected by LIGO was due to the coalescence of primordial black holes created by the extremely dense matter present in the early Universe.

Journal ArticleDOI
TL;DR: TGF-β is introduced as the best-studied factor among the TGF- β family proteins, with its diversity of roles in the control of cell proliferation and differentiation, wound healing and immune system, and its key roles in pathology, for example, skeletal diseases, fibrosis, and cancer.
Abstract: The transforming growth factor-β (TGF-β) is the prototype of the TGF-β family of growth and differentiation factors, which is encoded by 33 genes in mammals and comprises homo- and heterodimers. This review introduces the reader to the TGF-β family with its complexity of names and biological activities. It also introduces TGF-β as the best-studied factor among the TGF-β family proteins, with its diversity of roles in the control of cell proliferation and differentiation, wound healing and immune system, and its key roles in pathology, for example, skeletal diseases, fibrosis, and cancer.

Journal ArticleDOI
TL;DR: The final results of the search for the lepton flavour violating decay were presented in this paper, based on the full dataset collected by the MEG experiment at the Paul Scherrer Institut in the period 2009-2013.
Abstract: The final results of the search for the lepton flavour violating decay $$\mathrm {\mu }^+ \rightarrow \mathrm {e}^+ \mathrm {\gamma }$$ based on the full dataset collected by the MEG experiment at the Paul Scherrer Institut in the period 2009–2013 and totalling $$7.5\times 10^{14}$$ stopped muons on target are presented. No significant excess of events is observed in the dataset with respect to the expected background and a new upper limit on the branching ratio of this decay of $$ \mathcal{B} (\mu ^+ \rightarrow \mathrm{e}^+ \gamma ) < 4.2 \times 10^{-13}$$ (90 % confidence level) is established, which represents the most stringent limit on the existence of this decay to date.

Journal ArticleDOI
04 Nov 2016-Science
TL;DR: The results are consistent with the proposition that smoking increases cancer risk by increasing the somatic mutation load, although direct evidence for this mechanism is lacking in some smoking-related cancer types.
Abstract: Tobacco smoking increases the risk of at least 17 classes of human cancer. We analyzed somatic mutations and DNA methylation in 5243 cancers of types for which tobacco smoking confers an elevated risk. Smoking is associated with increased mutation burdens of multiple distinct mutational signatures, which contribute to different extents in different cancers. One of these signatures, mainly found in cancers derived from tissues directly exposed to tobacco smoke, is attributable to misreplication of DNA damage caused by tobacco carcinogens. Others likely reflect indirect activation of DNA editing by APOBEC cytidine deaminases and of an endogenous clocklike mutational process. Smoking is associated with limited differences in methylation. The results are consistent with the proposition that smoking increases cancer risk by increasing the somatic mutation load, although direct evidence for this mechanism is lacking in some smoking-related cancer types.

Journal ArticleDOI
Adam M. Session1, Adam M. Session2, Yoshinobu Uno3, Taejoon Kwon4, Taejoon Kwon5, Jarrod Chapman1, Atsushi Toyoda6, Shuji Takahashi7, Akimasa Fukui8, Akira Hikosaka7, Atsushi Suzuki7, Mariko Kondo9, Simon J. van Heeringen10, Ian K. Quigley11, Sven Heinz11, Hajime Ogino12, Haruki Ochi13, Uffe Hellsten1, Jessica B. Lyons2, Oleg Simakov14, Nicholas H. Putnam, Jonathan C. Stites, Yoko Kuroki, Toshiaki Tanaka15, Tatsuo Michiue9, Minoru Watanabe16, Ozren Bogdanovic17, Ryan Lister17, Georgios Georgiou10, Sarita S. Paranjpe10, Ila van Kruijsbergen10, Shengquiang Shu1, Joseph W. Carlson1, Tsutomu Kinoshita18, Yuko Ohta19, Shuuji Mawaribuchi20, Jerry Jenkins1, Jane Grimwood1, Jeremy Schmutz1, Therese Mitros2, Sahar V. Mozaffari21, Yutaka Suzuki9, Yoshikazu Haramoto22, Takamasa S. Yamamoto23, Chiyo Takagi23, Rebecca Heald2, Kelly E. Miller2, Christian D. Haudenschild24, Jacob O. Kitzman25, Takuya Nakayama26, Yumi Izutsu27, Jacques Robert28, Joshua D. Fortriede29, Kevin A. Burns, Vaneet Lotay30, Kamran Karimi30, Yuuri Yasuoka14, Darwin S. Dichmann2, Martin F. Flajnik19, Douglas W. Houston31, Jay Shendure25, Louis DuPasquier32, Peter D. Vize30, Aaron M. Zorn29, Michihiko Ito20, Edward M. Marcotte5, John B. Wallingford5, Yuzuru Ito22, Makoto Asashima22, Naoto Ueno23, Naoto Ueno33, Yoichi Matsuda3, Gert Jan C. Veenstra10, Asao Fujiyama6, Asao Fujiyama34, Asao Fujiyama33, Richard M. Harland2, Masanori Taira9, Daniel S. Rokhsar1, Daniel S. Rokhsar14, Daniel S. Rokhsar2 
20 Oct 2016-Nature
TL;DR: The Xenopus laevis genome is sequenced and it is estimated that the two diploid progenitor species diverged around 34 million years ago and combined to form an allotetraploid around 17–18 Ma, where more than 56% of all genes were retained in two homoeologous copies.
Abstract: To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of 'fossil' transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma. More than 56% of all genes were retained in two homoeologous copies. Protein function, gene expression, and the amount of conserved flanking sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.

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TL;DR: This work demonstrates ultraflexible and conformable three-color, highly efficient polymer light-emitting diodes (PLEDs) and organic photodetectors (OPDs) to realize optoelectronic skins (oe-skins) that introduce multiple electronic functionalities such as sensing and displays on the surface of human skin.
Abstract: Thin-film electronics intimately laminated onto the skin imperceptibly equip the human body with electronic components for health-monitoring and information technologies. When electronic devices are worn, the mechanical flexibility and/or stretchability of thin-film devices helps to minimize the stress and discomfort associated with wear because of their conformability and softness. For industrial applications, it is important to fabricate wearable devices using processing methods that maximize throughput and minimize cost. We demonstrate ultraflexible and conformable three-color, highly efficient polymer light-emitting diodes (PLEDs) and organic photodetectors (OPDs) to realize optoelectronic skins (oe-skins) that introduce multiple electronic functionalities such as sensing and displays on the surface of human skin. The total thickness of the devices, including the substrate and encapsulation layer, is only 3 μm, which is one order of magnitude thinner than the epidermal layer of human skin. By integrating green and red PLEDs with OPDs, we fabricate an ultraflexible reflective pulse oximeter. The device unobtrusively measures the oxygen concentration of blood when laminated on a finger. On-skin seven-segment digital displays and color indicators can visualize data directly on the body.

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TL;DR: Exposure to interpersonal violence had the strongest associations with subsequent traumatic events, and limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence.
Abstract: BACKGROUND: Considerable research has documented that exposure to traumatic events has negative effects on physical and mental health. Much less research has examined the predictors of traumatic event exposure. Increased understanding of risk factors for exposure to traumatic events could be of considerable value in targeting preventive interventions and anticipating service needs. METHOD: General population surveys in 24 countries with a combined sample of 68 894 adult respondents across six continents assessed exposure to 29 traumatic event types. Differences in prevalence were examined with cross-tabulations. Exploratory factor analysis was conducted to determine whether traumatic event types clustered into interpretable factors. Survival analysis was carried out to examine associations of sociodemographic characteristics and prior traumatic events with subsequent exposure. RESULTS: Over 70% of respondents reported a traumatic event; 30.5% were exposed to four or more. Five types - witnessing death or serious injury, the unexpected death of a loved one, being mugged, being in a life-threatening automobile accident, and experiencing a life-threatening illness or injury - accounted for over half of all exposures. Exposure varied by country, sociodemographics and history of prior traumatic events. Being married was the most consistent protective factor. Exposure to interpersonal violence had the strongest associations with subsequent traumatic events. CONCLUSIONS: Given the near ubiquity of exposure, limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence. Identifying mechanisms that account for the associations of prior interpersonal violence with subsequent trauma is critical to develop interventions to prevent revictimization. Language: en

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TL;DR: The possibility to change the molecular assembled structures of organic and organometallic materials through mechanical stimulation is emerging as a general and powerful concept for the design of functional materials, enabling the development of molecular materials with mechanoresponsive luminescence characteristics.
Abstract: The possibility to change the molecular assembled structures of organic and organometallic materials through mechanical stimulation is emerging as a general and powerful concept for the design of functional materials. In particular, the photophysical properties such as photoluminescence color, quantum yield, and emission lifetime of organic and organometallic fluorophores can significantly depend on the molecular packing, enabling the development of molecular materials with mechanoresponsive luminescence characteristics. Indeed, an increasing number of studies have shown in recent years that mechanical force can be utilized to change the molecular arrangement, and thereby the optical response, of luminescent molecular assemblies of π-conjugated organic or organometallic molecules. Here, the development of such mechanoresponsive luminescent (MRL) molecular assemblies consisting of organic or organometallic molecules is reviewed and emerging trends in this research field are summarized. After a brief introduction of mechanoresponsive luminescence observed in molecular assemblies, the concept of "luminescent molecular domino" is introduced, before molecular materials that show turn-on/off of photoluminescence in response to mechanical stimulation are reviewed. Mechanically stimulated multicolor changes and water-soluble MRL materials are also highlighted and approaches that combine the concept of MRL molecular assemblies with other materials types are presented in the last part of this progress report.

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TL;DR: This work shows real-time (response time of ∼20 ms), large-area, normal pressure monitoring under different, complex bending conditions, and test the suitability of the sensor for soft robotics and medical applications.
Abstract: Measuring small normal pressures is essential to accurately evaluate external stimuli in curvilinear and dynamic surfaces such as natural tissues. Usually, sensitive and spatially accurate pressure sensors are achieved through conformal contact with the surface; however, this also makes them sensitive to mechanical deformation (bending). Indeed, when a soft object is pressed by another soft object, the normal pressure cannot be measured independently from the mechanical stress. Here, we show a pressure sensor that measures only the normal pressure, even under extreme bending conditions. To reduce the bending sensitivity, we use composite nanofibres of carbon nanotubes and graphene. Our simulations show that these fibres change their relative alignment to accommodate bending deformation, thus reducing the strain in individual fibres. Pressure sensitivity is maintained down to a bending radius of 80 μm. To test the suitability of our sensor for soft robotics and medical applications, we fabricated an integrated sensor matrix that is only 2 μm thick. We show real-time (response time of ∼20 ms), large-area, normal pressure monitoring under different, complex bending conditions. A composite fibrous material made of carbon nanotubes and graphene responds to small pressure but not to bending deformation.

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Kyle S. Dawson1, Jean-Paul Kneib2, Will J. Percival3, Shadab Alam4  +155 moreInstitutions (51)
TL;DR: The Extended Baryon Oscillation Spectroscopic Survey (eBOSS) as mentioned in this paper uses four different tracers of the underlying matter density field to expand the volume covered by BOSS and map the large-scale structures over the relatively unconstrained redshift range 0.6 0.87.
Abstract: In a six-year program started in 2014 July, the Extended Baryon Oscillation Spectroscopic Survey (eBOSS) will conduct novel cosmological observations using the BOSS spectrograph at Apache Point Observatory. These observations will be conducted simultaneously with the Time Domain Spectroscopic Survey (TDSS) designed for variability studies and the Spectroscopic Identification of eROSITA Sources (SPIDERS) program designed for studies of X-ray sources. In particular, eBOSS will measure with percent-level precision the distance-redshift relation with baryon acoustic oscillations (BAO) in the clustering of matter. eBOSS will use four different tracers of the underlying matter density field to vastly expand the volume covered by BOSS and map the large-scale-structures over the relatively unconstrained redshift range 0.6 0.6 sample of BOSS galaxies. With ~195,000 new emission line galaxy redshifts, we expect BAO measurements of d_A(z) to an accuracy of 3.1% and H(z) to 4.7% at an effective redshift of z = 0.87. A sample of more than 500,000 spectroscopically confirmed quasars will provide the first BAO distance measurements over the redshift range 0.9 2.1; these new data will enhance the precision of dA(z) and H(z) at z > 2.1 by a factor of 1.44 relative to BOSS. Furthermore, eBOSS will provide improved tests of General Relativity on cosmological scales through redshift-space distortion measurements, improved tests for non-Gaussianity in the primordial density field, and new constraints on the summed mass of all neutrino species. Here, we provide an overview of the cosmological goals, spectroscopic target sample, demonstration of spectral quality from early data, and projected cosmological constraints from eBOSS.