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Showing papers by "Osaka University published in 2015"


Journal ArticleDOI
TL;DR: For a reversed-phase LC-MS/MS analysis of nine algal strains, MS-DIAL using an enriched LipidBlast library identified 1,023 lipid compounds, highlighting the chemotaxonomic relationships between theAlgal strains.
Abstract: Data-independent acquisition (DIA) in liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) provides comprehensive untargeted acquisition of molecular data. We provide an open-source software pipeline, which we call MS-DIAL, for DIA-based identification and quantification of small molecules by mass spectral deconvolution. For a reversed-phase LC-MS/MS analysis of nine algal strains, MS-DIAL using an enriched LipidBlast library identified 1,023 lipid compounds, highlighting the chemotaxonomic relationships between the algal strains.

1,609 citations


Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, Ovsat Abdinov4  +5117 moreInstitutions (314)
TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.

1,567 citations


Journal ArticleDOI
TL;DR: This work has developed a method called β-structure selection (BeStSel) for the secondary structure estimation that takes into account the twist of β-structures, and can predict the protein fold down to the topology level following the CATH classification from a single CD spectrum.
Abstract: Circular dichroism (CD) spectroscopy is a widely used technique for the study of protein structure. Numerous algorithms have been developed for the estimation of the secondary structure composition from the CD spectra. These methods often fail to provide acceptable results on α/β-mixed or β-structure–rich proteins. The problem arises from the spectral diversity of β-structures, which has hitherto been considered as an intrinsic limitation of the technique. The predictions are less reliable for proteins of unusual β-structures such as membrane proteins, protein aggregates, and amyloid fibrils. Here, we show that the parallel/antiparallel orientation and the twisting of the β-sheets account for the observed spectral diversity. We have developed a method called β-structure selection (BeStSel) for the secondary structure estimation that takes into account the twist of β-structures. This method can reliably distinguish parallel and antiparallel β-sheets and accurately estimates the secondary structure for a broad range of proteins. Moreover, the secondary structure components applied by the method are characteristic to the protein fold, and thus the fold can be predicted to the level of topology in the CATH classification from a single CD spectrum. By constructing a web server, we offer a general tool for a quick and reliable structure analysis using conventional CD or synchrotron radiation CD (SRCD) spectroscopy for the protein science research community. The method is especially useful when X-ray or NMR techniques fail. Using BeStSel on data collected by SRCD spectroscopy, we investigated the structure of amyloid fibrils of various disease-related proteins and peptides.

1,137 citations


Journal ArticleDOI
TL;DR: Advances in the development of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based fluorescent probes for biological studies over the past decade are covered.
Abstract: Fluorescence imaging techniques have been widely used to visualize biological molecules and phenomena. In particular, several studies on the development of small-molecule fluorescent probes have been carried out, because their fluorescence properties can be easily tuned by synthetic chemical modification. For this reason, various fluorescent probes have been developed for targeting biological components, such as proteins, peptides, amino acids, and ions, to the interior and exterior of cells. In this review, we cover advances in the development of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based fluorescent probes for biological studies over the past decade.

999 citations


Journal ArticleDOI
30 Sep 2015
TL;DR: This position paper position that a new shift is necessary in computing, taking the control of computing applications, data, and services away from some central nodes to the other logical extreme of the Internet, and refers to this vision of human-centered edge-device based computing as Edge-centric Computing.
Abstract: In many aspects of human activity, there has been a continuous struggle between the forces of centralization and decentralization. Computing exhibits the same phenomenon; we have gone from mainframes to PCs and local networks in the past, and over the last decade we have seen a centralization and consolidation of services and applications in data centers and clouds. We position that a new shift is necessary. Technological advances such as powerful dedicated connection boxes deployed in most homes, high capacity mobile end-user devices and powerful wireless networks, along with growing user concerns about trust, privacy, and autonomy requires taking the control of computing applications, data, and services away from some central nodes (the "core") to the other logical extreme (the "edge") of the Internet. We also position that this development can help blurring the boundary between man and machine, and embrace social computing in which humans are part of the computation and decision making loop, resulting in a human-centered system design. We refer to this vision of human-centered edge-device based computing as Edge-centric Computing. We elaborate in this position paper on this vision and present the research challenges associated with its implementation.

844 citations


Journal ArticleDOI
TL;DR: Author(s): Varki, Ajit; Cummings, Richard D; Aebi, Markus; Packer, Nicole H; Seeberger, Peter H; Esko, Jeffrey D; Stanley, Pamela; Hart, Gerald; Darvill, Alan; Kinoshita, Taroh; Prestegard, James J; Schnaar, Ronald L; Freeze, Hudson H; Marth, Jamey D; Bertozzi, Carolyn R.
Abstract: Author(s): Varki, Ajit; Cummings, Richard D; Aebi, Markus; Packer, Nicole H; Seeberger, Peter H; Esko, Jeffrey D; Stanley, Pamela; Hart, Gerald; Darvill, Alan; Kinoshita, Taroh; Prestegard, James J; Schnaar, Ronald L; Freeze, Hudson H; Marth, Jamey D; Bertozzi, Carolyn R; Etzler, Marilynn E; Frank, Martin; Vliegenthart, Johannes Fg; Lutteke, Thomas; Perez, Serge; Bolton, Evan; Rudd, Pauline; Paulson, James; Kanehisa, Minoru; Toukach, Philip; Aoki-Kinoshita, Kiyoko F; Dell, Anne; Narimatsu, Hisashi; York, William; Taniguchi, Naoyuki; Kornfeld, Stuart

735 citations


Journal ArticleDOI
Derrek P. Hibar1, Jason L. Stein1, Jason L. Stein2, Miguel E. Rentería3  +341 moreInstitutions (93)
09 Apr 2015-Nature
TL;DR: In this paper, the authors conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts.
Abstract: The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

721 citations


Journal ArticleDOI
TL;DR: The efficiency of antibiotics is compromised by a growing number of antibiotic-resistant pathogens and the magnitude of the problem recently prompted a number of international and national bodies to take actions to protect the public.
Abstract: Antibiotics represent one of the most successful forms of therapy in medicine. But the efficiency of antibiotics is compromised by a growing number of antibiotic-resistant pathogens. Antibiotic resistance, which is implicated in elevated morbidity and mortality rates as well as in the increased treatment costs, is considered to be one of the major global public health threats (www.who.int/drugresistance/en/) and the magnitude of the problem recently prompted a number of international and national bodies to take actions to protect the public (http://

714 citations


Journal ArticleDOI
01 Apr 2015-Cornea
TL;DR: This project reached consensus of ophthalmology experts from around the world regarding keratoconus and ectatic diseases, focusing on their definition, concepts, clinical management, and surgical treatments, and provides an insight into the current worldwide treatment of these conditions.
Abstract: Background Despite extensive knowledge regarding the diagnosis and management of keratoconus and ectatic corneal diseases, many controversies still exist. For that reason, there is a need for current guidelines for the diagnosis and management of these conditions. Purpose This project aimed to reach consensus of ophthalmology experts from around the world regarding keratoconus and ectatic diseases, focusing on their definition, concepts, clinical management, and surgical treatments. Methods The Delphi method was followed with 3 questionnaire rounds and was complemented with a face-to-face meeting. Thirty-six panelists were involved and allocated to 1 of 3 panels: definition/diagnosis, nonsurgical management, or surgical treatment. The level of agreement considered for consensus was two thirds. Results Numerous agreements were generated in definitions, methods of diagnosing, and management of keratoconus and other ectatic diseases. Nonsurgical and surgical treatments for these conditions, including the use of corneal cross-linking and corneal transplantations, were presented in a stepwise approach. A flowchart describing a logical management sequence for keratoconus was created. Conclusions This project resulted in definitions, statements, and recommendations for the diagnosis and management of keratoconus and other ectatic diseases. It also provides an insight into the current worldwide treatment of these conditions.

683 citations


Journal ArticleDOI
TL;DR: A printable elastic conductor with a high initial conductivity and a record high conductivity when stretched to 215% strain is reported and the feasibility of inks is demonstrated by fabricating a stretchable organic transistor active matrix on a rubbery stretchability-gradient substrate with unimpaired functionality.
Abstract: The development of advanced flexible large-area electronics such as flexible displays and sensors will thrive on engineered functional ink formulations for printed electronics where the spontaneous arrangement of molecules aids the printing processes. Here we report a printable elastic conductor with a high initial conductivity of 738 S cm−1 and a record high conductivity of 182 S cm−1 when stretched to 215% strain. The elastic conductor ink is comprised of Ag flakes, a fluorine rubber and a fluorine surfactant. The fluorine surfactant constitutes a key component which directs the formation of surface-localized conductive networks in the printed elastic conductor, leading to a high conductivity and stretchability. We demonstrate the feasibility of our inks by fabricating a stretchable organic transistor active matrix on a rubbery stretchability-gradient substrate with unimpaired functionality when stretched to 110%, and a wearable electromyogram sensor printed onto a textile garment. Printable electronics is highly desirable for high throughput device manufacture. Here, Matsuhisa et al. report an electric ink, made of a self-assembled network of sliver flakes on the surface of a fluorine rubber matrix, which exhibits high conductivity and mechanical durability to achieve this goal.

655 citations


Journal ArticleDOI
TL;DR: In this article, a virtual synchronous generator (VSG) with alternating moment of inertia (OMO) was proposed to enhance the response of the virtual machine in tracking the steady-state frequency.
Abstract: The virtual synchronous generator (VSG) is a control scheme applied to the inverter of a distributed generating unit to support power system stability by imitating the behavior of a synchronous machine. The VSG design of our research incorporates the swing equation of a synchronous machine to express a virtual inertia property. Unlike a real synchronous machine, the parameters of the swing equation of the VSG can be controlled in real time to enhance the fast response of the virtual machine in tracking the steady-state frequency. Based on this concept, the VSG with alternating moment of inertia is elaborated in this paper. The damping effect of the alternating inertia scheme is investigated by transient energy analysis. In addition, the performance of the proposed inertia control in stability of nearby machines in power system is addressed. The idea is supported by simulation and experimental results, which indicates remarkable performance in the fast damping of oscillations.

Journal ArticleDOI
28 Aug 2015-Science
TL;DR: It is reported that microbiota-induced Tregs express the nuclear hormone receptor RORγt and differentiate along a pathway that also leads to TH17 cells, and acts as a key factor in balancing immune responses at mucosal surfaces.
Abstract: Changes to the symbiotic microbiota early in life, or the absence of it, can lead to exacerbated type 2 immunity and allergic inflammations. Although it is unclear how the microbiota regulates type 2 immunity, it is a strong inducer of proinflammatory T helper 17 (TH17) cells and regulatory T cells (Tregs) in the intestine. Here, we report that microbiota-induced Tregs express the nuclear hormone receptor RORγt and differentiate along a pathway that also leads to TH17 cells. In the absence of RORγt+ Tregs, TH2-driven defense against helminths is more efficient, whereas TH2-associated pathology is exacerbated. Thus, the microbiota regulates type 2 responses through the induction of type 3 RORγt+ Tregs and TH17 cells and acts as a key factor in balancing immune responses at mucosal surfaces.

Journal ArticleDOI
TL;DR: This Review discusses the underlying mechanisms that are required for rapid and effective recall antibody responses in memory B cells, focusing on the contributions of other types of cells, such as memory T follicular helper cells.
Abstract: The immune system can remember a previously experienced pathogen and can evoke an enhanced response to reinfection that depends on memory lymphocyte populations. Recent advances in tracking antigen-experienced memory B cells have revealed the existence of distinct classes of cells that have considerable functional differences. Some of these differences seem to be determined by the stimulation history during memory cell formation. To induce rapid recall antibody responses, the contributions of other types of cells, such as memory T follicular helper cells, have also now begun to be appreciated. In this Review, we discuss these and other recent advances in our understanding of memory B cells, focusing on the underlying mechanisms that are required for rapid and effective recall antibody responses.

Journal ArticleDOI
Emanuele Di Angelantonio1, Stephen Kaptoge1, David Wormser1, Peter Willeit1, Adam S. Butterworth1, Narinder Bansal1, Linda M. O’Keeffe1, Pei Gao1, Angela M. Wood1, Stephen Burgess1, Daniel F. Freitag1, Lisa Pennells1, Sanne A.E. Peters2, Carole L. Hart3, Lise Lund Håheim4, Richard F. Gillum5, Børge G. Nordestgaard6, Bruce M. Psaty7, Bu B. Yeap8, Matthew Knuiman8, Paul J. Nietert9, Jussi Kauhanen10, Jukka T. Salonen11, Lewis H. Kuller12, Leon A. Simons13, Yvonne T. van der Schouw2, Elizabeth Barrett-Connor14, Randi Selmer15, Carlos J. Crespo16, Beatriz L. Rodriguez17, W. M. Monique Verschuren, Veikko Salomaa18, Kurt Svärdsudd19, Pim van der Harst20, Cecilia Björkelund21, Lars Wilhelmsen21, Robert B. Wallace22, Hermann Brenner23, Philippe Amouyel24, Elizabeth L M Barr25, Hiroyasu Iso26, Altan Onat27, Maurizio Trevisan28, Ralph B. D'Agostino29, Cyrus Cooper30, Cyrus Cooper31, Maryam Kavousi32, Lennart Welin, Ronan Roussel33, Ronan Roussel34, Frank B. Hu35, Shinichi Sato, Karina W. Davidson36, Barbara V. Howard37, Maarten J.G. Leening32, Annika Rosengren21, Marcus Dörr38, Dorly J. H. Deeg39, Stefan Kiechl, Coen D.A. Stehouwer40, Aulikki Nissinen18, Simona Giampaoli41, Chiara Donfrancesco41, Daan Kromhout42, Jackie F. Price43, Annette Peters, Tom W. Meade44, Edoardo Casiglia45, Debbie A Lawlor46, John Gallacher47, Dorothea Nagel48, Oscar H. Franco32, Gerd Assmann, Gilles R. Dagenais, J. Wouter Jukema49, Johan Sundström19, Mark Woodward50, Eric J. Brunner51, Kay-Tee Khaw1, Nicholas J. Wareham52, Eric A. Whitsel53, Inger Njølstad54, Bo Hedblad55, Sylvia Wassertheil-Smoller56, Gunnar Engström55, Wayne D. Rosamond53, Elizabeth Selvin57, Naveed Sattar3, Simon G. Thompson1, John Danesh1 
University of Cambridge1, Utrecht University2, University of Glasgow3, University of Oslo4, Howard University5, Copenhagen University Hospital6, University of Washington7, University of Western Australia8, Medical University of South Carolina9, University of Eastern Finland10, Analytical Services11, University of Pittsburgh12, University of New South Wales13, University of California, San Diego14, Norwegian Institute of Public Health15, Portland State University16, University of Hawaii17, National Institutes of Health18, Uppsala University19, University Medical Center Groningen20, University of Gothenburg21, University of Iowa22, German Cancer Research Center23, Pasteur Institute24, Baker IDI Heart and Diabetes Institute25, Osaka University26, Istanbul University27, City College of New York28, Boston University29, University of Oxford30, University of Southampton31, Erasmus University Rotterdam32, Paris Diderot University33, French Institute of Health and Medical Research34, Harvard University35, Columbia University Medical Center36, MedStar Health37, Greifswald University Hospital38, VU University Amsterdam39, Maastricht University Medical Centre40, Istituto Superiore di Sanità41, Wageningen University and Research Centre42, University of Edinburgh43, University of London44, University of Padua45, University of Bristol46, Cardiff University47, Ludwig Maximilian University of Munich48, Leiden University Medical Center49, University of Sydney50, University College London51, Medical Research Council52, University of North Carolina at Chapel Hill53, University of Tromsø54, Lund University55, Albert Einstein College of Medicine56, Johns Hopkins University57
07 Jul 2015-JAMA
TL;DR: Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
Abstract: IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

Journal ArticleDOI
TL;DR: Current knowledge of the possible mechanisms associated with H2O2-induced abiotic oxidative stress tolerance in plants is reviewed, with special reference to antioxidant metabolism.
Abstract: Plants are constantly challenged by various abiotic stresses that negatively affect growth and productivity worldwide. During the course of their evolution, plants have developed sophisticated mechanisms to recognize external signals allowing them to respond appropriately to environmental conditions, although the degree of adjustability or tolerance to specific stresses differs from species to species. Overproduction of reactive oxygen species (ROS) (hydrogen peroxide, H2O2; superoxide, O2ˉ˙; hydroxyl radical, OH. and singlet oxygen, 1O2) is enhanced under abiotic and/or biotic stresses, which can cause oxidative damage to plant macromolecules and cell structures, leading to inhibition of plant growth and development, or to death. Among the various ROS, freely diffusible and relatively long-lived H2O2 acts as a central player in stress signal transduction pathways. These pathways can then activate multiple acclamatory responses that reinforce resistance to various abiotic and biotic stressors. To utilize H2O2 as a signaling molecule, non-toxic levels must be maintained in a delicate balancing act between H2O2 production and scavenging. Several recent studies have demonstrated that the H2O2-priming can enhance abiotic stress tolerance by modulating ROS detoxification and by regulating multiple stress-responsive pathways and gene expression. Despite the importance of the H2O2-priming, little is known about how this process improves the tolerance of plants to stress. Understanding the mechanisms of H2O2-priming-induced abiotic stress tolerance will be valuable for identifying biotechnological strategies to improve abiotic stress tolerance in crop plants. This review is an overview of our current knowledge of the possible mechanisms associated with H2O2-induced abiotic oxidative stress tolerance in plants, with special reference to antioxidant metabolism.

Journal ArticleDOI
TL;DR: Vaccination of mice and ferrets with H1–SS–np elicited broadly cross-reactive antibodies that completely protected mice and partially protected ferrets against lethal heterosubtypic H5N1 influenza virus challenge despite the absence of detectable H 5N1 neutralizing activity in vitro.
Abstract: Barney Graham and colleagues have developed a hemagglutinin stem–based nanoparticle as a vaccine that confers protection against different influenza strains in mice and ferrets.

Journal ArticleDOI
TL;DR: The ongoing advancements in microelectrode technology are introduced, with focus on achieving higher resolution and quality of recordings by means of monolithic integration with on-chip circuitry.
Abstract: Microelectrode arrays and microprobes have been widely utilized to measure neuronal activity, both in vitro and in vivo. The key advantage is the capability to record and stimulate neurons at multiple sites simultaneously. However, unlike the single-cell or single-channel resolution of intracellular recording, microelectrodes detect signals from all possible sources around the sensor. Here, we review the current understanding of microelectrode signals and the techniques for analyzing them. We introduce the ongoing advancements in microelectrode technology, with focus on achieving higher resolution and quality of recordings by means of monolithic integration with on-chip circuitry. We show how recent advanced microelectrode array measurement methods facilitate the understanding of single neurons as well as network function.

Journal ArticleDOI
TL;DR: Recent findings regarding the molecular mechanisms of apoptosis PtdSer exposure and the clearance of apoptotic cells are discussed.

Journal ArticleDOI
TL;DR: The Ni(0)/PCy3 system was identified by Dankwardt et al. as discussed by the authors, who showed that the unique ability of a low-valent nickel species to activate otherwise unreactive C(aryl)−O bonds of aryl ethers renders it difficult to use them in catalytic reactions among the phenol derivatives.
Abstract: ConspectusArene synthesis has been revolutionized by the invention of catalytic cross-coupling reactions, wherein aryl halides can be coupled with organometallic and organic nucleophiles. Although the replacement of aryl halides with phenol derivatives would lead to more economical and ecological methods, success has been primarily limited to activated phenol derivatives such as triflates. Aryl ethers arguably represent one of the most ideal substrates in terms of availability, cost, safety, and atom efficiency. However, the robust nature of the C(aryl)–O bonds of aryl ethers renders it extremely difficult to use them in catalytic reactions among the phenol derivatives.In 1979, Wenkert reported a seminal work on the nickel-catalyzed cross-coupling of aryl ethers with Grignard reagents. However, it was not until 2004 that the unique ability of a low-valent nickel species to activate otherwise unreactive C(aryl)–O bonds was appreciated with Dankwardt’s identification of the Ni(0)/PCy3 system, which signific...

Journal ArticleDOI
TL;DR: Immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria based on guidance for the determination of tumour progression outlined by the immune-related response criteria and the RANO working group are described.
Abstract: Immunotherapy is a promising area of therapy in patients with neuro-oncological malignancies. However, early-phase studies show unique challenges associated with the assessment of radiological changes in response to immunotherapy reflecting delayed responses or therapy-induced inflammation. Clinical benefit, including long-term survival and tumour regression, can still occur after initial disease progression or after the appearance of new lesions. Refinement of the response assessment criteria for patients with neuro-oncological malignancies undergoing immunotherapy is therefore warranted. Herein, a multinational and multidisciplinary panel of neuro-oncology immunotherapy experts describe immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria based on guidance for the determination of tumour progression outlined by the immune-related response criteria and the RANO working group. Among patients who demonstrate imaging findings meeting RANO criteria for progressive disease within 6 months of initiating immunotherapy, including the development of new lesions, confirmation of radiographic progression on follow-up imaging is recommended provided that the patient is not significantly worse clinically. The proposed criteria also include guidelines for the use of corticosteroids. We review the role of advanced imaging techniques and the role of measurement of clinical benefit endpoints including neurological and immunological functions. The iRANO guidelines put forth in this Review will evolve successively to improve their usefulness as further experience from immunotherapy trials in neuro-oncology accumulate.

Journal ArticleDOI
TL;DR: It is found that recombinant laminin-511 E8 fragments are useful matrices for maintaining hESCs and hiPSCs when used in combination with a completely xeno-free (Xf) medium, StemFit™, and results indicate thatHiPSCs can be generated and maintained under this novel Ff and Xf culture system.
Abstract: In order to apply human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) to regenerative medicine, the cells should be produced under restricted conditions conforming to GMP guidelines. Since the conventional culture system has some issues that need to be addressed to achieve this goal, we developed a novel culture system. We found that recombinant laminin-511 E8 fragments are useful matrices for maintaining hESCs and hiPSCs when used in combination with a completely xeno-free (Xf) medium, StemFit™. Using this system, hESCs and hiPSCs can be easily and stably passaged by dissociating the cells into single cells for long periods, without any karyotype abnormalities. Human iPSCs could be generated under feeder-free (Ff) and Xf culture systems from human primary fibroblasts and blood cells, and they possessed differentiation abilities. These results indicate that hiPSCs can be generated and maintained under this novel Ff and Xf culture system.

Journal ArticleDOI
TL;DR: The Japan Cancer Surveillance Research Group aimed to estimate the cancer incidence in Japan in 2009 based on data collected from 32 of 37 population-based cancer registries, as part of the Monitoring of Cancer Incidence in Japan project.
Abstract: The Japan Cancer Surveillance Research Group aimed to estimate the cancer incidence in Japan in 2009 based on data collected from 32 of 37 population-based cancer registries, as part of the Monitoring of Cancer Incidence in Japan (MCIJ) project. The incidence of only primary invasive cancer in Japan for 2009 was estimated to be 775 601. Stomach cancer and breast cancer were the leading types of cancer in males and females, respectively.

Journal ArticleDOI
TL;DR: The direct-drive, laser-based approach to inertial confinement fusion (ICF) is reviewed from its inception following the demonstration of the first laser to its implementation on the present generation of high-power lasers as mentioned in this paper.
Abstract: The direct-drive, laser-based approach to inertial confinement fusion (ICF) is reviewed from its inception following the demonstration of the first laser to its implementation on the present generation of high-power lasers. The review focuses on the evolution of scientific understanding gained from target-physics experiments in many areas, identifying problems that were demonstrated and the solutions implemented. The review starts with the basic understanding of laser–plasma interactions that was obtained before the declassification of laser-induced compression in the early 1970s and continues with the compression experiments using infrared lasers in the late 1970s that produced thermonuclear neutrons. The problem of suprathermal electrons and the target preheat that they caused, associated with the infrared laser wavelength, led to lasers being built after 1980 to operate at shorter wavelengths, especially 0.35 μm—the third harmonic of the Nd:glass laser—and 0.248 μm (the KrF gas laser). The main physics areas relevant to direct drive are reviewed. The primary absorption mechanism at short wavelengths is classical inverse bremsstrahlung. Nonuniformities imprinted on the target by laser irradiation have been addressed by the development of a number of beam-smoothing techniques and imprint-mitigation strategies. The effects of hydrodynamic instabilities are mitigated by a combination of imprint reduction and target designs that minimize the instability growth rates. Several coronal plasma physics processes are reviewed. The two-plasmon–decay instability, stimulated Brillouin scattering (together with cross-beam energy transfer), and (possibly) stimulated Raman scattering are identified as potential concerns, placing constraints on the laser intensities used in target designs, while other processes (self-focusing and filamentation, the parametric decay instability, and magnetic fields), once considered important, are now of lesser concern for mainline direct-drive target concepts. Filamentation is largely suppressed by beam smoothing. Thermal transport modeling, important to the interpretation of experiments and to target design, has been found to be nonlocal in nature. Advances in shock timing and equation-of-state measurements relevant to direct-drive ICF are reported. Room-temperature implosions have provided an increased understanding of the importance of stability and uniformity. The evolution of cryogenic implosion capabilities, leading to an extensive series carried out on the 60-beam OMEGA laser [Boehly et al., Opt. Commun. 133, 495 (1997)], is reviewed together with major advances in cryogenic target formation. A polar-drive concept has been developed that will enable direct-drive–ignition experiments to be performed on the National Ignition Facility [Haynam et al., Appl. Opt. 46(16), 3276 (2007)]. The advantages offered by the alternative approaches of fast ignition and shock ignition and the issues associated with these concepts are described. The lessons learned from target-physics and implosion experiments are taken into account in ignition and high-gain target designs for laser wavelengths of 1/3 μm and 1/4 μm. Substantial advances in direct-drive inertial fusion reactor concepts are reviewed. Overall, the progress in scientific understanding over the past five decades has been enormous, to the point that inertial fusion energy using direct drive shows significant promise as a future environmentally attractive energy source.

Journal ArticleDOI
TL;DR: In this article, the authors discuss recent progress in the explorations of topological materials beyond topological insulators; specifically, they focus on topological crystalline insulators and bulk topological superconductors.
Abstract: In this review, we discuss recent progress in the explorations of topological materials beyond topological insulators; specifically, we focus on topological crystalline insulators and bulk topological superconductors. The basic concepts, model Hamiltonians, and novel electronic properties of these new topological materials are explained. The key role of symmetries that underlie their topological properties is elucidated. Key issues in their materials realizations are also discussed.

Journal ArticleDOI
TL;DR: In this paper, the authors discuss recent progress in the explorations of topological materials beyond topological insulators; specifically, they focus on topological crystalline insulators and bulk topological superconductors.
Abstract: In this review, we discuss recent progress in the explorations of topological materials beyond topological insulators; specifically, we focus on topological crystalline insulators and bulk topological superconductors. The basic concepts, model Hamiltonians, and novel electronic properties of these new topological materials are explained. The key role of the symmetries that underlie their topological properties is elucidated. Key issues in their materials realizations are also discussed.

Journal ArticleDOI
TL;DR: The operational diagnostic criteria for benign paroxysmal positional vertigo (BPPV) were formulated by the Committee for Classification of Vestibular Disorders of the Barany Society as discussed by the authors.
Abstract: This article presents operational diagnostic criteria for benign paroxysmal positional vertigo (BPPV), formulated by the Committee for Classification of Vestibular Disorders of the Barany Society. The classification reflects current knowledge of clinical aspects and pathomechanisms of BPPV and includes both established and emerging syndromes of BPPV. It is anticipated that growing understanding of the disease will lead to further development of this classification.

Journal ArticleDOI
06 Feb 2015-Science
TL;DR: The realization of chain-growth polymerization is reported by designing metastable monomers with a shape-promoted intramolecular hydrogen-bonding network that enables optical resolution of a racemic monomer.
Abstract: Over the past decade, major progress in supramolecular polymerization has had a substantial effect on the design of functional soft materials. However, despite recent advances, most studies are still based on a preconceived notion that supramolecular polymerization follows a step-growth mechanism, which precludes control over chain length, sequence, and stereochemical structure. Here we report the realization of chain-growth polymerization by designing metastable monomers with a shape-promoted intramolecular hydrogen-bonding network. The monomers are conformationally restricted from spontaneous polymerization at ambient temperatures but begin to polymerize with characteristics typical of a living mechanism upon mixing with tailored initiators. The chain growth occurs stereoselectively and therefore enables optical resolution of a racemic monomer.

Journal ArticleDOI
TL;DR: Advances in the knowledge of the roles of autophagy and its components in immunity, including innate immunity, inflammatory responses and adaptive immunity are introduced.
Abstract: Autophagy is an intracellular bulk degradation system that is highly conserved in eukaryotes. The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes. In addition, studies have revealed other roles for the autophagic machinery beyond autophagy. In this Review, we introduce advances in the knowledge of the roles of autophagy and its components in immunity, including innate immunity, inflammatory responses and adaptive immunity.

Journal ArticleDOI
TL;DR: This work employed two different kinds of host-guest inclusion complexes of β-cyclodextrin with adamantane and ferrocene to bind polymers together to form a supramolecular hydrogel (βCD-Ad-Fc gel), which showed self-healing ability when damaged and responded to redox stimuli by expansion or contraction.
Abstract: Supramolecular materials cross-linked between polymer chains by noncovalent bonds have the potential to provide dynamic functions that are not produced by covalently cross-linked polymeric materials. We focused on the formation of supramolecular polymeric materials through host-guest interactions: a powerful method for the creation of nonconventional materials. We employed two different kinds of host-guest inclusion complexes of β-cyclodextrin (βCD) with adamantane (Ad) and ferrocene (Fc) to bind polymers together to form a supramolecular hydrogel (βCD-Ad-Fc gel). The βCD-Ad-Fc gel showed self-healing ability when damaged and responded to redox stimuli by expansion or contraction. Moreover, the βCD-Ad-Fc gel showed a redox-responsive shape-morphing effect. We thus succeeded in deriving three functions from the introduction of two kinds of functional units into a supramolecular material.

Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, S. Abdel Khalek4  +2815 moreInstitutions (169)
TL;DR: In this article, a search for new phenomena in final states with an energetic jet and large missing transverse momentum was performed using 20.3 fb(-1) of root s = 8 TeV data collected in 2012.
Abstract: Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb(-1) of root s = 8 TeV data collected in 2012 ...