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Showing papers by "Tohoku University 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
TL;DR: In this paper, the authors demonstrate the possibility to precipitate a coherent reinforcing phase in a fcc-FeCoNiCr HEA matrix using minor additions of Ti and Al, and demonstrate that extraordinary balanced tensile properties at room temperature were achieved, which was due to a well combination of various hardening mechanisms, particularly precipitation hardening.

1,486 citations


Journal ArticleDOI
TL;DR: It is demonstrated that Nrf2 interferes with lipopolysaccharide-induced transcriptional upregulation of proinflammatory cytokines, including IL-6 and IL-1β, and establishes a molecular basis for an NRF2-mediated anti-inflammation approach.
Abstract: Nrf2 (NF-E2-related factor-2) transcription factor regulates oxidative/xenobiotic stress response and also represses inflammation. However, the mechanisms how Nrf2 alleviates inflammation are still unclear. Here, we demonstrate that Nrf2 interferes with lipopolysaccharide-induced transcriptional upregulation of proinflammatory cytokines, including IL-6 and IL-1β. Chromatin immunoprecipitation (ChIP)-seq and ChIP-qPCR analyses revealed that Nrf2 binds to the proximity of these genes in macrophages and inhibits RNA Pol II recruitment. Further, we found that Nrf2-mediated inhibition is independent of the Nrf2-binding motif and reactive oxygen species level. Murine inflammatory models further demonstrated that Nrf2 interferes with IL6 induction and inflammatory phenotypes in vivo. Thus, contrary to the widely accepted view that Nrf2 suppresses inflammation through redox control, we demonstrate here that Nrf2 opposes transcriptional upregulation of proinflammatory cytokine genes. This study identifies Nrf2 as the upstream regulator of cytokine production and establishes a molecular basis for an Nrf2-mediated anti-inflammation approach.

1,069 citations


Journal ArticleDOI
TL;DR: An improved search for neutrinoless double-beta (0νββ) decay of ^{136}Xe in the KamLAND-Zen experiment is presented and a significant reduction of the xenon-loaded liquid scintillator contaminant identified in previous searches is achieved.
Abstract: We present an improved search for neutrinoless double-beta (0νββ) decay of ^{136}Xe in the KamLAND-Zen experiment. Owing to purification of the xenon-loaded liquid scintillator, we achieved a significant reduction of the ^{110m}Ag contaminant identified in previous searches. Combining the results from the first and second phase, we obtain a lower limit for the 0νββ decay half-life of T_{1/2}^{0ν}>1.07×10^{26} yr at 90% C.L., an almost sixfold improvement over previous limits. Using commonly adopted nuclear matrix element calculations, the corresponding upper limits on the effective Majorana neutrino mass are in the range 61-165 meV. For the most optimistic nuclear matrix elements, this limit reaches the bottom of the quasidegenerate neutrino mass region.

1,055 citations


Journal ArticleDOI
TL;DR: The AFM/FM system is shown to be a promising building block for SOT devices as well as providing an attractive pathway towards neuromorphic computing.
Abstract: Spin-orbit torque (SOT)-induced magnetization switching shows promise for realizing ultrafast and reliable spintronics devices. Bipolar switching of the perpendicular magnetization by the SOT is achieved under an in-plane magnetic field collinear with an applied current. Typical structures studied so far comprise a nonmagnet/ferromagnet (NM/FM) bilayer, where the spin Hall effect in the NM is responsible for the switching. Here we show that an antiferromagnet/ferromagnet (AFM/FM) bilayer system also exhibits a SOT large enough to switch the magnetization of the FM. In this material system, thanks to the exchange bias of the AFM, we observe the switching in the absence of an applied field by using an antiferromagnetic PtMn and ferromagnetic Co/Ni multilayer with a perpendicular easy axis. Furthermore, tailoring the stack achieves a memristor-like behaviour where a portion of the reversed magnetization can be controlled in an analogue manner. The AFM/FM system is thus a promising building block for SOT devices as well as providing an attractive pathway towards neuromorphic computing.

822 citations


Journal ArticleDOI
Yujiro Hayashi1
TL;DR: This review describes the importance and usefulness of pot-economy and one-pot reactions in current synthetic organic chemistry.
Abstract: The one-pot synthesis of a target molecule in the same reaction vessel is widely considered to be an efficient approach in synthetic organic chemistry. In this review, the characteristics and limitations of various one-pot syntheses of biologically active molecules are explained, primarily involving organocatalytic methods as key tactics. Besides catalysis, the pot-economy concepts presented herein are also applicable to organometallic and organic reaction methods in general.

686 citations


Journal ArticleDOI
24 Mar 2016
TL;DR: The past decade has seen remarkable progress in the understanding of functional bowel disorders such as IBS that will be summarized in this Primer.
Abstract: A 28-year-old woman presents with a 7-month history of recurrent, crampy pain in the left lower abdominal quadrant, bloating with abdominal distention, and frequent, loose stools. She reports having had similar but milder symptoms since childhood. She spends long times in the bathroom because she is worried about uncontrollable discomfort and fecal soiling if she does not completely empty her bowels before leaving the house. She feels anxious and fatigued and is frustrated that her previous physician did not seem to take her distress seriously. Physical examination is unremarkable except for tenderness over the left lower quadrant. How should her case be evaluated and treated?

635 citations


Journal ArticleDOI
TL;DR: In this paper, a new design of precoding and detection matrices for MIMO-NOMA is proposed and its performance is analyzed for the case with a fixed set of power allocation coefficients.
Abstract: This paper considers the application of multiple-input multiple-output (MIMO) techniques to nonorthogonal multiple access (NOMA) systems. A new design of precoding and detection matrices for MIMO-NOMA is proposed and its performance is analyzed for the case with a fixed set of power allocation coefficients. To further improve the performance gap between MIMO–NOMA and conventional orthogonal multiple access schemes, user pairing is applied to NOMA and its impact on the system performance is characterized. More sophisticated choices of power allocation coefficients are also proposed to meet various quality-of-service requirements. Finally, computer simulation results are provided to facilitate the performance evaluation of MIMO–NOMA and also demonstrate the accuracy of the developed analytical results.

629 citations


Journal ArticleDOI
14 Jan 2016-Nature
TL;DR: Traits generate trade-offs between performance with competition versus performance without competition, a fundamental ingredient in the classical hypothesis that the coexistence of plant species is enabled via differentiation in their successional strategies.
Abstract: Phenotypic traits and their associated trade-offs have been shown to have globally consistent effects on individual plant physiological functions, but how these effects scale up to influence competition, a key driver of community assembly in terrestrial vegetation, has remained unclear. Here we use growth data from more than 3 million trees in over 140,000 plots across the world to show how three key functional traits--wood density, specific leaf area and maximum height--consistently influence competitive interactions. Fast maximum growth of a species was correlated negatively with its wood density in all biomes, and positively with its specific leaf area in most biomes. Low wood density was also correlated with a low ability to tolerate competition and a low competitive effect on neighbours, while high specific leaf area was correlated with a low competitive effect. Thus, traits generate trade-offs between performance with competition versus performance without competition, a fundamental ingredient in the classical hypothesis that the coexistence of plant species is enabled via differentiation in their successional strategies. Competition within species was stronger than between species, but an increase in trait dissimilarity between species had little influence in weakening competition. No benefit of dissimilarity was detected for specific leaf area or wood density, and only a weak benefit for maximum height. Our trait-based approach to modelling competition makes generalization possible across the forest ecosystems of the world and their highly diverse species composition.

618 citations


Journal ArticleDOI
TL;DR: In this article, the authors showed that the precipitation of hard σ and μ intermetallic compounds tremendously strengthened the CoCrFeNiMo 0.3 HEA but without causing a serious embrittlement.

597 citations


Journal ArticleDOI
TL;DR: A new structure with the third geometry, that is, with the easy axis collinear with the current (along the x axis), is presented and the switching operation driven by the spin-orbit torque due to Ta with a negative spin Hall angle is demonstrated.
Abstract: Spin-orbit torque, a torque brought about by in-plane current via the spin-orbit interactions in heavy-metal/ferromagnet nanostructures, provides a new pathway to switch the magnetization direction. Although there are many recent studies, they all build on one of two structures that have the easy axis of a nanomagnet lying orthogonal to the current, that is, along the z or y axes. Here, we present a new structure with the third geometry, that is, with the easy axis collinear with the current (along the x axis). We fabricate a three-terminal device with a Ta/CoFeB/MgO-based stack and demonstrate the switching operation driven by the spin-orbit torque due to Ta with a negative spin Hall angle. Comparisons with different geometries highlight the previously unknown mechanisms of spin-orbit torque switching. Our work offers a new avenue for exploring the physics of spin-orbit torque switching and its application to spintronics devices.

Journal ArticleDOI
TL;DR: In this article, the authors report nanoporous bimetallic (Co1−xFex)2P phosphides with controllable compositions and tuneable porosity, which are fabricated by the combination of metallurgical alloy design and electrochemical etching.
Abstract: Alloying is an important approach to improving catalytic activities and realizing new functions of heterogeneous catalysts, which has extensively been employed in fabricating noble metal based bimetallic catalysts. However, it is technically unviable in the synthesis of alloyed transition metal compounds, which are emerging as important catalysts for water splitting, in a controllable manner using conventional wet chemical methods. Here we report nanoporous bimetallic (Co1−xFex)2P phosphides with controllable compositions and tuneable porosity, which are fabricated by the combination of metallurgical alloy design and electrochemical etching. By tailoring the Co/Fe ratios and nanoporosity, the bimetallic phosphides exhibit versatile catalytic activities towards HER and OER in acidic and basic electrolytes. As both the cathode and the anode of an electrolyser, nanoporous (Co0.52Fe0.48)2P shows an outstanding performance in water electrolysis, comparable to the commercial electrolyser with paired Pt/C and IrO2 catalysts.

Journal ArticleDOI
TL;DR: This work identifies the Weyl points and demonstrates that they are connected by different sets of Fermi arcs for each of the two surface terminations and finds new surface 'track states' that form closed loops and are unique to type II Weyl semimetals.
Abstract: In a type I Dirac or Weyl semimetal, the low-energy states are squeezed to a single point in momentum space when the chemical potential μ is tuned precisely to the Dirac/Weyl point. Recently, a type II Weyl semimetal was predicted to exist, where the Weyl states connect hole and electron bands, separated by an indirect gap. This leads to unusual energy states, where hole and electron pockets touch at the Weyl point. Here we present the discovery of a type II topological Weyl semimetal state in pure MoTe2, where two sets of Weyl points (, ) exist at the touching points of electron and hole pockets and are located at different binding energies above EF. Using angle-resolved photoemission spectroscopy, modelling, density functional theory and calculations of Berry curvature, we identify the Weyl points and demonstrate that they are connected by different sets of Fermi arcs for each of the two surface terminations. We also find new surface 'track states' that form closed loops and are unique to type II Weyl semimetals. This material provides an exciting, new platform to study the properties of Weyl fermions.

Journal ArticleDOI
TL;DR: It is found that the composite nature of antiferromagnetic Skyrmions gives rise to different dynamical behavior due to both an applied current and temperature effects.
Abstract: Skyrmions are topologically protected entities in magnetic materials which have the potential to be used in spintronics for information storage and processing. However, Skyrmions in ferromagnets have some intrinsic difficulties which must be overcome to use them for spintronic applications, such as the inability to move straight along current. We show that Skyrmions can also be stabilized and manipulated in antiferromagnetic materials. An antiferromagnetic Skyrmion is a compound topological object with a similar but of opposite sign spin texture on each sublattice, which, e.g., results in a complete cancellation of the Magnus force. We find that the composite nature of antiferromagnetic Skyrmions gives rise to different dynamical behavior due to both an applied current and temperature effects.

Journal ArticleDOI
TL;DR: In this paper, the electric field-induced superconductivity in molybdenum disulphide (MoS2) was investigated by means of magneto-transport measurements, uncovering evidence of spin-momentum locking.
Abstract: The electric-field-induced superconducting properties of MoS2 are investigated by means of magneto-transport measurements, uncovering evidence of spin–momentum locking. Symmetry-breaking has been known to play a key role in non-centrosymmetric superconductors with strong spin–orbit interactions (SOIs; refs 1,2,3,4,5,6). The studies, however, have been so far mainly focused on a particular type of SOI, known as the Rashba SOI (ref. 7), whereby the electron spin is locked to its momentum at a right-angle, thereby leading to an in-plane helical spin texture. Here we discuss electric-field-induced superconductivity in molybdenum disulphide (MoS2), which exhibits a fundamentally different type of intrinsic SOI, manifested by an out-of-plane Zeeman-type spin polarization of energy valleys8,9,10. We find an upper critical field of approximately 52 T at 1.5 K, which indicates an enhancement of the Pauli limit by a factor of four as compared to that in centrosymmetric conventional superconductors. Using realistic tight-binding calculations, we reveal that this unusual behaviour is due to an inter-valley pairing that is symmetrically protected by Zeeman-type spin–valley locking against external magnetic fields. Our study sheds light on the interplay of inversion asymmetry with SOIs in confined geometries, and its role in superconductivity.

Journal ArticleDOI
TL;DR: In this article, a combined theoretical and experimental approach was proposed to improve the sluggish HER kinetics of MoS2 electrocatalysts through engineering the water dissociation sites by doping Ni atoms into MoS 2 nanosheets.
Abstract: Earth-abundant MoS2 is widely reported as a promising HER electrocatalyst in acidic solutions, but it exhibits extremely poor HER activities in alkaline media due to the slow water dissociation process. Here we present a combined theoretical and experimental approach to improve the sluggish HER kinetics of MoS2 electrocatalysts through engineering the water dissociation sites by doping Ni atoms into MoS2 nanosheets. The Ni sites thus introduced can effectively reduce the kinetic energy barrier of the initial water-dissociation step and facilitate the desorption of the −OH that are formed. As a result, the developed Ni-doped MoS2 nanosheets (Ni-MoS2) show an extremely low HER overpotential of ∼98 mV at 10 mA cm−2 in 1 M KOH aqueous solution, which is superior to those (>220 mV at 10 mA cm−2) of reported MoS2 electrocatalysts.

Journal ArticleDOI
TL;DR: It is shown that HER-active a-MoSx, prepared either as nanoparticles or as films, is a molecular-based coordination polymer consisting of discrete [Mo3S13](2-) building blocks that provides a basis for revisiting the mechanism of a- MoSx catalytic activity, as well as explaining some of its special properties such as reductive activation and corrosion.
Abstract: Molybdenum sulfides are very attractive noble-metal-free electrocatalysts for the hydrogen evolution reaction (HER) from water. The atomic structure and identity of the catalytically active sites have been well established for crystalline molybdenum disulfide (c-MoS2) but not for amorphous molybdenum sulfide (a-MoSx), which exhibits significantly higher HER activity compared to its crystalline counterpart. Here we show that HER-active a-MoSx, prepared either as nanoparticles or as films, is a molecular-based coordination polymer consisting of discrete [Mo3S13]2- building blocks. Of the three terminal disulfide (S22-) ligands within these clusters, two are shared to form the polymer chain. The third one remains free and generates molybdenum hydride moieties as the active site under H2 evolution conditions. Such a molecular structure therefore provides a basis for revisiting the mechanism of a-MoSx catalytic activity, as well as explaining some of its special properties such as reductive activation and corrosion. Our findings open up new avenues for the rational optimization of this HER electrocatalyst as an alternative to platinum.

Journal ArticleDOI
22 Dec 2016-Nature
TL;DR: In this paper, the authors used graph theory to predict the self-assembly of even larger tetravalent Goldberg polyhedra, which should be more stable, enabling another member of this polyhedron family to be assembled from 144 components: 48 palladium ions and 96 bent ligands.
Abstract: Rational control of the self-assembly of large structures is one of the key challenges in chemistry, and is believed to become increasingly difficult and ultimately impossible as the number of components involved increases. So far, it has not been possible to design a self-assembled discrete molecule made up of more than 100 components. Such molecules-for example, spherical virus capsids-are prevalent in nature, which suggests that the difficulty in designing these very large self-assembled molecules is due to a lack of understanding of the underlying design principles. For example, the targeted assembly of a series of large spherical structures containing up to 30 palladium ions coordinated by up to 60 bent organic ligands was achieved by considering their topologies. Here we report the self-assembly of a spherical structure that also contains 30 palladium ions and 60 bent ligands, but belongs to a shape family that has not previously been observed experimentally. The new structure consists of a combination of 8 triangles and 24 squares, and has the symmetry of a tetravalent Goldberg polyhedron. Platonic and Archimedean solids have previously been prepared through self-assembly, as have trivalent Goldberg polyhedra, which occur naturally in the form of virus capsids and fullerenes. But tetravalent Goldberg polyhedra have not previously been reported at the molecular level, although their topologies have been predicted using graph theory. We use graph theory to predict the self-assembly of even larger tetravalent Goldberg polyhedra, which should be more stable, enabling another member of this polyhedron family to be assembled from 144 components: 48 palladium ions and 96 bent ligands.

Journal ArticleDOI
TL;DR: This work makes use of an interface-driven spin-orbit coupling mechanism-the Rashba effect-in the oxide two-dimensional electron system (2DES) LaAlO3/SrTiO3 to achieve spin-to-charge conversion with unprecedented efficiency.
Abstract: The spin–orbit interaction couples the electrons’ motion to their spin. As a result, a charge current running through a material with strong spin–orbit coupling generates a transverse spin current (spin Hall effect, SHE) and vice versa (inverse spin Hall effect, ISHE). The emergence of SHE and ISHE as charge-to-spin interconversion mechanisms offers a variety of novel spintronic functionalities and devices, some of which do not require any ferromagnetic material. However, the interconversion efficiency of SHE and ISHE (spin Hall angle) is a bulk property that rarely exceeds ten percent, and does not take advantage of interfacial and low-dimensional effects otherwise ubiquitous in spintronic hetero- and mesostructures. Here, we make use of an interface-driven spin–orbit coupling mechanism—the Rashba effect—in the oxide two-dimensional electron system (2DES) LaAlO3/SrTiO3 to achieve spin-to-charge conversion with unprecedented efficiency. Through spin pumping, we inject a spin current from a NiFe film into the oxide 2DES and detect the resulting charge current, which can be strongly modulated by a gate voltage. We discuss the amplitude of the effect and its gate dependence on the basis of the electronic structure of the 2DES and highlight the importance of a long scattering time to achieve efficient spin-to-charge interconversion. The Rashba effect at the LaAlO3/SrTiO3 interface is shown to enable large and gate-tunable spin-to-charge conversion through the inverse Rashba–Edelstein effect.The spin current is injected, through spin pumping, from a NiFe film.

Journal ArticleDOI
12 Jan 2016-JAMA
TL;DR: Kidney failure risk equations developed in a Canadian population showed high discrimination and adequate calibration when validated in 31 multinational cohorts, but the original risk equations overestimated risk in some non-North American cohorts.
Abstract: Importance Identifying patients at risk of chronic kidney disease (CKD) progression may facilitate more optimal nephrology care. Kidney failure risk equations, including such factors as age, sex, estimated glomerular filtration rate, and calcium and phosphate concentrations, were previously developed and validated in 2 Canadian cohorts. Validation in other regions and in CKD populations not under the care of a nephrologist is needed. Objective To evaluate the accuracy of the risk equations across different geographic regions and patient populations through individual participant data meta-analysis. Data Sources Thirty-one cohorts, including 721 357 participants with CKD stages 3 to 5 in more than 30 countries spanning 4 continents, were studied. These cohorts collected data from 1982 through 2014. Study Selection Cohorts participating in the CKD Prognosis Consortium with data on end-stage renal disease. Data Extraction and Synthesis Data were obtained and statistical analyses were performed between July 2012 and June 2015. Using the risk factors from the original risk equations, cohort-specific hazard ratios were estimated and combined using random-effects meta-analysis to form new pooled kidney failure risk equations. Original and pooled kidney failure risk equation performance was compared, and the need for regional calibration factors was assessed. Main Outcomes and Measures Kidney failure (treatment by dialysis or kidney transplant). Results During a median follow-up of 4 years of 721 357 participants with CKD, 23 829 cases kidney failure were observed. The original risk equations achieved excellent discrimination (ability to differentiate those who developed kidney failure from those who did not) across all cohorts (overallCstatistic, 0.90; 95% CI, 0.89-0.92 at 2 years;Cstatistic at 5 years, 0.88; 95% CI, 0.86-0.90); discrimination in subgroups by age, race, and diabetes status was similar. There was no improvement with the pooled equations. Calibration (the difference between observed and predicted risk) was adequate in North American cohorts, but the original risk equations overestimated risk in some non-North American cohorts. Addition of a calibration factor that lowered the baseline risk by 32.9% at 2 years and 16.5% at 5 years improved the calibration in 12 of 15 and 10 of 13 non-North American cohorts at 2 and 5 years, respectively (P = .04 andP = .02). Conclusions and Relevance Kidney failure risk equations developed in a Canadian population showed high discrimination and adequate calibration when validated in 31 multinational cohorts. However, in some regions the addition of a calibration factor may be necessary.

Journal ArticleDOI
Cristian Pattaro, Alexander Teumer1, Mathias Gorski2, Audrey Y. Chu3  +732 moreInstitutions (157)
TL;DR: A meta-analysis of genome-wide association studies for estimated glomerular filtration rate suggests that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
Abstract: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Journal ArticleDOI
TL;DR: The enzymatic polymerizations allowed the first in vitro synthesis of natural polysaccharides having complicated structures like cellulose, amylose, xylan, chitin, hyaluronan, and chondroitin, and producing minimal byproducts.
Abstract: The present article comprehensively reviews the macromolecular synthesis using enzymes as catalysts. Among the six main classes of enzymes, the three classes, oxidoreductases, transferases, and hydrolases, have been employed as catalysts for the in vitro macromolecular synthesis and modification reactions. Appropriate design of reaction including monomer and enzyme catalyst produces macromolecules with precisely controlled structure, similarly as in vivo enzymatic reactions. The reaction controls the product structure with respect to substrate selectivity, chemo-selectivity, regio-selectivity, stereoselectivity, and choro-selectivity. Oxidoreductases catalyze various oxidation polymerizations of aromatic compounds as well as vinyl polymerizations. Transferases are effective catalysts for producing polysaccharide having a variety of structure and polyesters. Hydrolases catalyzing the bond-cleaving of macromolecules in vivo, catalyze the reverse reaction for bond forming in vitro to give various polysacchar...

Journal ArticleDOI
TL;DR: The Global Ocean Observing System (GOOS) as discussed by the authors uses a global array of profiling floats to sample the upper 2,000 m of the ocean globally and uniformly in space and time.
Abstract: More than 90% of the heat energy accumulation in the climate system between 1971 and the present has been in the ocean. Thus, the ocean plays a crucial role in determining the climate of the planet. Observing the oceans is problematic even under the most favourable of conditions. Historically, shipboard ocean sampling has left vast expanses, particularly in the Southern Ocean, unobserved for long periods of time. Within the past 15 years, with the advent of the global Argo array of profiling floats, it has become possible to sample the upper 2,000 m of the ocean globally and uniformly in space and time. The primary goal of Argo is to create a systematic global network of profiling floats that can be integrated with other elements of the Global Ocean Observing System. The network provides freely available temperature and salinity data from the upper 2,000 m of the ocean with global coverage. The data are available within 24 hours of collection for use in a broad range of applications that focus on examining climate-relevant variability on seasonal to decadal timescales, multidecadal climate change, improved initialization of coupled ocean–atmosphere climate models and constraining ocean analysis and forecasting systems.

Journal ArticleDOI
TL;DR: It is shown that missense variants in PRNP previously reported to be pathogenic are at least 30 times more common in the population than expected on the basis of genetic prion disease prevalence, a finding that supports the safety of therapeutic suppression of prion protein expression.
Abstract: More than 100,000 genetic variants are reported to cause Mendelian disease in humans, but the penetrance-the probability that a carrier of the purported disease-causing genotype will indeed develop the disease-is generally unknown. We assess the impact of variants in the prion protein gene (PRNP) on the risk of prion disease by analyzing 16,025 prion disease cases, 60,706 population control exomes, and 531,575 individuals genotyped by 23andMe Inc. We show that missense variants in PRNP previously reported to be pathogenic are at least 30 times more common in the population than expected on the basis of genetic prion disease prevalence. Although some of this excess can be attributed to benign variants falsely assigned as pathogenic, other variants have genuine effects on disease susceptibility but confer lifetime risks ranging from <0.1 to ~100%. We also show that truncating variants in PRNP have position-dependent effects, with true loss-of-function alleles found in healthy older individuals, a finding that supports the safety of therapeutic suppression of prion protein expression.


Journal ArticleDOI
TL;DR: The Japanese Association for Thoracic Surgery has conducted annual surveys of thoracic surgery throughout Japan since 1986 to determine the statistics regarding the number of procedures according to operative category.
Abstract: The Japanese Association for Thoracic Surgery has conducted annual surveys of thoracic surgery throughout Japan since 1986 to determine the statistics regarding the number of procedures according to operative category. Here, we have summarized the results from our annual survey of thoracic surgery performed during 2014.

Journal ArticleDOI
TL;DR: A new mechanistic definition of chronic pancreatitis is proposed that recognizes the complex nature of CP, separates risk factors from disease activity markers and disease endpoints, and allows for a rational approach to early diagnosis, classification and prognosis.

Journal ArticleDOI
TL;DR: It is shown that once understood, the anisotropic optical absorption appears to be a reliable and simple way to identify the crystalline orientation of BP, which cannot be determined from Raman spectroscopy without the explicit consideration of excitation wavelength and flake thickness, as commonly used previously.
Abstract: Orthorhombic black phosphorus (BP) and other layered materials, such as gallium telluride (GaTe) and tin selenide (SnSe), stand out among two-dimensional (2D) materials owing to their anisotropic in-plane structure. This anisotropy adds a new dimension to the properties of 2D materials and stimulates the development of angle-resolved photonics and electronics. However, understanding the effect of anisotropy has remained unsatisfactory to date, as shown by a number of inconsistencies in the recent literature. We use angle-resolved absorption and Raman spectroscopies to investigate the role of anisotropy on the electron–photon and electron–phonon interactions in BP. We highlight, both experimentally and theoretically, a nontrivial dependence between anisotropy and flake thickness and photon and phonon energies. We show that once understood, the anisotropic optical absorption appears to be a reliable and simple way to identify the crystalline orientation of BP, which cannot be determined from Raman spectrosc...

Journal ArticleDOI
TL;DR: In this paper, the spin-momentum locking of Dirac surface states offers intriguing possibilities for converting between charge and spin currents, and experiments show that fine tuning of the Fermi level is critical for maximizing the efficiency of such conversions.
Abstract: The spin–momentum locking of Dirac surface states offers intriguing possibilities for converting between charge and spin currents. Experiments show that fine tuning of the Fermi level is critical for maximizing the efficiency of such conversions.

Journal ArticleDOI
TL;DR: In this paper, Li et al. provided a fundamental understanding on the origin of the effective anchoring of LiPSs by N-doped carbon materials, which suppresses the shuttling of LiPss and produces significant improvement in the cycling performance of Li-S batteries.