| 1. |
- Kanai, M, et al.
(author)
-
- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
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| 5. |
- Namkoong, H, et al.
(author)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
-
Journal article (peer-reviewed)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 6. |
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| 7. |
- Wang, QBS, et al.
(author)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
-
Journal article (peer-reviewed)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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| 8. |
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| 9. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Research review (peer-reviewed)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. 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 vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased 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. 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. 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 autophagy assays, we hope to encourage technical innovation in the field.
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| 10. |
- Achberger, Christine, 1968, et al.
(author)
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State of the Climate in 2011
- 2012
-
In: Bulletin of the American Meteorological Society. - 0003-0007. ; 93:7
-
Journal article (peer-reviewed)abstract
- Large-scale climate patterns influenced temperature and weather patterns around the globe in 2011. In particular, a moderate-to-strong La Nina at the beginning of the year dissipated during boreal spring but reemerged during fall. The phenomenon contributed to historical droughts in East Africa, the southern United States, and northern Mexico, as well the wettest two-year period (2010-11) on record for Australia, particularly remarkable as this follows a decade-long dry period. Precipitation patterns in South America were also influenced by La Nina. Heavy rain in Rio de Janeiro in January triggered the country's worst floods and landslides in Brazil's history. The 2011 combined average temperature across global land and ocean surfaces was the coolest since 2008, but was also among the 15 warmest years on record and above the 1981-2010 average. The global sea surface temperature cooled by 0.1 degrees C from 2010 to 2011, associated with cooling influences of La Nina. Global integrals of upper ocean heat content for 2011 were higher than for all prior years, demonstrating the Earth's dominant role of the oceans in the Earth's energy budget. In the upper atmosphere, tropical stratospheric temperatures were anomalously warm, while polar temperatures were anomalously cold. This led to large springtime stratospheric ozone reductions in polar latitudes in both hemispheres. Ozone concentrations in the Arctic stratosphere during March were the lowest for that period since satellite records began in 1979. An extensive, deep, and persistent ozone hole over the Antarctic in September indicates that the recovery to pre-1980 conditions is proceeding very slowly. Atmospheric carbon dioxide concentrations increased by 2.10 ppm in 2011, and exceeded 390 ppm for the first time since instrumental records began. Other greenhouse gases also continued to rise in concentration and the combined effect now represents a 30% increase in radiative forcing over a 1990 baseline. Most ozone depleting substances continued to fall. The global net ocean carbon dioxide uptake for the 2010 transition period from El Nino to La Nina, the most recent period for which analyzed data are available, was estimated to be 1.30 Pg C yr(-1), almost 12% below the 29-year long-term average. Relative to the long-term trend, global sea level dropped noticeably in mid-2010 and reached a local minimum in 2011. The drop has been linked to the La Nina conditions that prevailed throughout much of 2010-11. Global sea level increased sharply during the second half of 2011. Global tropical cyclone activity during 2011 was well-below average, with a total of 74 storms compared with the 1981-2010 average of 89. Similar to 2010, the North Atlantic was the only basin that experienced above-normal activity. For the first year since the widespread introduction of the Dvorak intensity-estimation method in the 1980s, only three tropical cyclones reached Category 5 intensity level-all in the Northwest Pacific basin. The Arctic continued to warm at about twice the rate compared with lower latitudes. Below-normal summer snowfall, a decreasing trend in surface albedo, and above-average surface and upper air temperatures resulted in a continued pattern of extreme surface melting, and net snow and ice loss on the Greenland ice sheet. Warmer-than-normal temperatures over the Eurasian Arctic in spring resulted in a new record-low June snow cover extent and spring snow cover duration in this region. In the Canadian Arctic, the mass loss from glaciers and ice caps was the greatest since GRACE measurements began in 2002, continuing a negative trend that began in 1987. New record high temperatures occurred at 20 m below the land surface at all permafrost observatories on the North Slope of Alaska, where measurements began in the late 1970s. Arctic sea ice extent in September 2011 was the second-lowest on record, while the extent of old ice (four and five years) reached a new record minimum that was just 19% of normal. On the opposite pole, austral winter and spring temperatures were more than 3 degrees C above normal over much of the Antarctic continent. However, winter temperatures were below normal in the northern Antarctic Peninsula, which continued the downward trend there during the last 15 years. In summer, an all-time record high temperature of -12.3 degrees C was set at the South Pole station on 25 December, exceeding the previous record by more than a full degree. Antarctic sea ice extent anomalies increased steadily through much of the year, from briefly setting a record low in April, to well above average in December. The latter trend reflects the dispersive effects of low pressure on sea ice and the generally cool conditions around the Antarctic perimeter.
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| 11. |
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- 2019
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Journal article (peer-reviewed)
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| 12. |
- Adcox, K, et al.
(author)
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PHENIX detector overview
- 2003
-
In: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 469-479
-
Journal article (peer-reviewed)abstract
- The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 13. |
- Carninci, P, et al.
(author)
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The transcriptional landscape of the mammalian genome
- 2005
-
In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5740, s. 1559-1563
-
Journal article (peer-reviewed)abstract
- This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5′ and 3′ boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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| 14. |
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| 15. |
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| 16. |
- Sakatani, N., et al.
(author)
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Anomalously porous boulders on (162173) Ryugu as primordial materials from its parent body
- 2021
-
In: Nature Astronomy. - : Springer Nature. - 2397-3366. ; 5:8, s. 766-774
-
Journal article (peer-reviewed)abstract
- Planetesimals—the initial stage of the planetary formation process—are considered to be initially very porous aggregates of dusts1,2, and subsequent thermal and compaction processes reduce their porosity3. The Hayabusa2 spacecraft found that boulders on the surface of asteroid (162173) Ryugu have an average porosity of 30–50% (refs. 4,5,6), higher than meteorites but lower than cometary nuclei7, which are considered to be remnants of the original planetesimals8. Here, using high-resolution thermal and optical imaging of Ryugu’s surface, we discovered, on the floor of fresh small craters (<20 m in diameter), boulders with reflectance (~0.015) lower than the Ryugu average6 and porosity >70%, which is as high as in cometary bodies. The artificial crater formed by Hayabusa2’s impact experiment9 is similar to these craters in size but does not have such high-porosity boulders. Thus, we argue that the observed high porosity is intrinsic and not created by subsequent impact comminution and/or cracking. We propose that these boulders are the least processed material on Ryugu and represent remnants of porous planetesimals that did not undergo a high degree of heating and compaction3. Our multi-instrumental analysis suggests that fragments of the highly porous boulders are mixed within the surface regolith globally, implying that they might be captured within collected samples by touch-down operations10,11.
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| 17. |
- Sugita, S., et al.
(author)
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The geomorphology, color, and thermal properties of Ryugu: Implications for parent-body processes
- 2019
-
In: Science. - : AAAS. - 0036-8075 .- 1095-9203. ; 364:6437
-
Journal article (peer-reviewed)abstract
- Asteroids fall to Earth in the form of meteorites, but these provide little information about their origins. The Japanese mission Hayabusa2 is designed to collect samples directly from the surface of an asteroid and return them to Earth for laboratory analysis. Three papers in this issue describe the Hayabusa2 team's study of the near-Earth carbonaceous asteroid 162173 Ryugu, at which the spacecraft arrived in June 2018 (see the Perspective by Wurm). Watanabeet al.measured the asteroid's mass, shape, and density, showing that it is a “rubble pile” of loose rocks, formed into a spinning-top shape during a prior period of rapid spin. They also identified suitable landing sites for sample collection. Kitazatoet al.used near-infrared spectroscopy to find ubiquitous hydrated minerals on the surface and compared Ryugu with known types of carbonaceous meteorite. Sugitaet al.describe Ryugu's geological features and surface colors and combined results from all three papers to constrain the asteroid's formation process. Ryugu probably formed by reaccumulation of rubble ejected by impact from a larger asteroid. These results provide necessary context to understand the samples collected by Hayabusa2, which are expected to arrive on Earth in December 2020.Science, this issue p.268, p.272, p.eaaw0422; see also p.230
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Elekes, Z., et al.
(author)
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Shape coexistence in 66Se
- 2023
-
In: Physics Letters B. - : Elsevier. - 0370-2693 .- 1873-2445. ; 844
-
Journal article (peer-reviewed)abstract
- The nuclear structure of 66Se, nucleus beyond the N=Z line on the proton-rich side of the valley of stability, was investigated by the neutron knock-out reaction 67Se(12C,X)66Se using a 12C target. The analysis of the singles spectrum of the γ-rays emitted during the de-excitation of the populated low-lying excited states revealed two previously detected (927(4) keV, 1460(32) keV) and three new (744(6) keV, 1210(17) keV, 1661(23) keV) transitions. The 744-keV, the 1210-keV, and the 1460-keV transitions were found to be in coincidence with the one at 927 keV. The spectrum coincident with the 927-keV transition showed a further possible transition at 299(35) keV, which was obscured by significant atomic background in the singles spectrum. This transition might correspond to a peak previously reported at 273(5) keV that could not be assigned to 66Se unambiguously. Based on a comparison of the experimental data to theoretical calculations, four new excited states are proposed which suggest that 66Se exhibits shape coexistence.
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| 23. |
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| 24. |
- Applegate, K. E., et al.
(author)
-
Individual response of humans to ionising radiation : governing factors and importance for radiological protection
- 2020
-
In: Radiation and Environmental Biophysics. - : Springer Science and Business Media LLC. - 0301-634X .- 1432-2099. ; 59:2, s. 185-209
-
Research review (peer-reviewed)abstract
- Tissue reactions and stochastic effects after exposure to ionising radiation are variable between individuals but the factors and mechanisms governing individual responses are not well understood. Individual responses can be measured at different levels of biological organization and using different endpoints following varying doses of radiation, including: cancers, non-cancer diseases and mortality in the whole organism; normal tissue reactions after exposures; and, cellular endpoints such as chromosomal damage and molecular alterations. There is no doubt that many factors influence the responses of people to radiation to different degrees. In addition to the obvious general factors of radiation quality, dose, dose rate and the tissue (sub)volume irradiated, recognized and potential determining factors include age, sex, life style (e.g., smoking, diet, possibly body mass index), environmental factors, genetics and epigenetics, stochastic distribution of cellular events, and systemic comorbidities such as diabetes or viral infections. Genetic factors are commonly thought to be a substantial contributor to individual response to radiation. Apart from a small number of rare monogenic diseases such as ataxia telangiectasia, the inheritance of an abnormally responsive phenotype among a population of healthy individuals does not follow a classical Mendelian inheritance pattern. Rather it is considered to be a multi-factorial, complex trait.
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| 25. |
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
- Nakaso, K, et al.
(author)
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Evaluation of the change in the morphology of gold nanoparticles during sintering
- 2002
-
In: Journal of Aerosol Science. - 0021-8502. ; 33:7, s. 1061-1074
-
Journal article (peer-reviewed)abstract
- Morphological changes of agglomerates consisting of nanometer primary gold particles were studied experimentally and theoretically. Gold aerosol nanoparticles were produced using the evaporation/condensation method, and the change in agglomerate size by reheating was examined experimentally using a tandem DMA setup. Numerical calculations, based on two extreme mechanisms to reshape agglomerates, i.e., subsequent coalescence of primary particles and subsequent rearrangement of primary particles, were carried out. By comparison with the experimental results, the sintering time and the rate constant of restructuring were obtained. Using these values, the change in particle size for different generation conditions could be calculated. The change in morphology of agglomerates can be explained from the comparison of the experimental results with the theoretical calculations: agglomerates with smaller primary particles will compact mainly by the subsequent coalescence of primary particles, while agglomerates with larger primary particles will compact mainly by a rearrangement of primary particles.
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| 32. |
- Ollila, Hanna M., et al.
(author)
-
Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy
- 2023
-
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
-
Journal article (peer-reviewed)abstract
- Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix (R). Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix (R).
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| 33. |
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| 34. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Jin, Kui-Juan, et al.
(author)
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Terahertz frequency radiation from Bloch oscillations in GaAs/Al0.3Ga0.7As superlattices
- 2003
-
In: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 68:15: 153315
-
Journal article (peer-reviewed)abstract
- We have performed a joint theoretical and experimental study to investigate the terahertz radiation from Bloch oscillations in a GaAs/Al0.3Ga0.7As superlattice under the condition that there is no Zener tunneling. The total radiation intensity has been calculated with a semiclassical approach in the low field regime where the Wannier-Stark ladder (WSL) cannot be resolved, and with an exact numerical solution in the high field regime where the WSL is well formed. With an adjustment of the intensity units, without fitting material parameters, the calculated results agree almost perfectly with the measured data given in arbitrary units. Consequently, our work gives convincing evidence that the measured THz radiation is due to the Bloch oscillations.
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| 39. |
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| 40. |
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| 41. |
- Sekine, N, et al.
(author)
-
Bloch gain in AlGaAs/GaAs semiconductor superlattices
- 2004
-
In: Proceedings of the Eleventh International Conference on Modulated Semiconductor Structures (Physica E: Low-dimensional Systems and Nanostructures). - : Elsevier BV. - 1386-9477. ; 21:2-4, s. 858-862
-
Conference paper (peer-reviewed)abstract
- We have investigated terahertz (THz) emission due to dynamical electron transport in wide miniband GaAs/Al0.3Ga0.7As superlattices. By noting that the time-domain THz emission spectroscopy contains the information on the step response of the electron system to the bias electric field, the obtained THz spectra were compared with the high-frequency conductivities predicted for miniband transport. Excellent agreement between theory and experiment strongly supports that the THz gain due to Bloch oscillating electrons persists at least up to 1.7 THz. It was also found that Zener tunneling into the second miniband sets the high-frequency limit of the THz gain for the samples studied here. (C) 2003 Elsevier B.V. All rights reserved.
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| 42. |
- Shimada, A., et al.
(author)
-
Neural signal transmission measurements with a conductive polymer microelectrode array
- 2009
-
In: IEEJ Transactions on Electronics, Information and Systems. - : Institute of Electrical Engineers of Japan (IEE Japan). - 0385-4221 .- 1348-8155. ; 129:2, s. 267-271+10
-
Journal article (peer-reviewed)abstract
- The neural activity of dissociated cultures of mouse cerebral cortical neurons was measured with a conductive polymer microelectrode array. Each electrode was electrochemically polymerized from (3,4-ethylenedioxythiophene)- poly(styrenesulfonate) and ethylenedioxythiophene on indium tin oxide electrodes. The spike activity of the cortical neurons was measured with the conducting polymer MEA and spike train cross-correlograms were calculated to predict the type of synaptic connection. Both excitatory and inhibitory synaptic connections were identified after 6-8 days in vitro. These results show that it is possible to determine the interaction between excitatory and inhibitory neurons in relation to information processing with this new polymer electrode.
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| 43. |
- Shimada, K, et al.
(author)
-
Frequent genetic alterations in immune checkpoint-related genes in intravascular large B-cell lymphoma
- 2021
-
In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 137:11, s. 1491-1502
-
Journal article (peer-reviewed)abstract
- Intravascular large B-cell lymphoma (IVLBCL) is a unique type of extranodal lymphoma characterized by selective growth of tumor cells in small vessels without lymphadenopathy. Greater understanding of the molecular pathogenesis of IVLBCL is hampered by the paucity of lymphoma cells in biopsy specimens, creating a limitation in obtaining sufficient tumor materials. To uncover the genetic landscape of IVLBCL, we performed whole-exome sequencing (WES) of 21 patients with IVLBCL using plasma-derived cell-free DNA (cfDNA) (n = 18), patient-derived xenograft tumors (n = 4), and tumor DNA from bone marrow (BM) mononuclear cells (n = 2). The concentration of cfDNA in IVLBCL was significantly higher than that in diffuse large B-cell lymphoma (DLBCL) (P < .0001) and healthy donors (P = .0053), allowing us to perform WES; most mutations detected in BM tumor DNA were successfully captured in cfDNA and xenograft. IVLBCL showed a high frequency of genetic lesions characteristic of activated B-cell–type DLBCL, with the former showing conspicuously higher frequencies (compared with nodal DLBCL) of mutations in MYD88 (57%), CD79B (67%), SETD1B (57%), and HLA-B (57%). We also found that 8 IVLBCL (38%) harbored rearrangements of programmed cell death 1 ligand 1 and 2 (PD-L1/PD-L2) involving the 3′ untranslated region; such rearrangements are implicated in immune evasion via PD-L1/PD-L2 overexpression. Our data demonstrate the utility of cfDNA and imply important roles for immune evasion in IVLBCL pathogenesis and PD-1/PD-L1/PD-L2 blockade in therapeutics for IVLBCL.
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| 44. |
- Shimada, Yuichi J., et al.
(author)
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Impact of glycoprotein IIb/IIIa inhibitors on the efficacy and safety of ticagrelor compared with clopidogrel in patients with acute coronary syndromes : Analysis from the Platelet Inhibition and Patient Outcomes (PLATO) Trial
- 2016
-
In: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 177, s. 1-8
-
Journal article (peer-reviewed)abstract
- Background Ticagrelor reduced cardiovascular events compared with clopidogrel in PLATO without increasing overall major bleeding. We evaluated whether the use of glycoprotein IIb/IIIa inhibitor (GPI) impacts the relative efficacy and safety of ticagrelor compared with clopidogrel. Methods PLATO randomized 18,624 subjects with acute coronary syndrome to ticagrelor versus clopidogrel. The primary efficacy end point was cardiovascular death/myocardial infarction/stroke, and the primary safety end point was major bleeding. The use of GPI was at the physician's discretion and open-label. We evaluated outcomes at 30 days stratified by GPI use in the subgroup of 9,983 patients who underwent percutaneous coronary intervention (PCI) within 72 hours. Results A total of 4,020 (40%) received a GPI. Those receiving a GPI were more likely to be younger, be male, and undergo multivessel PCI. There was no interaction between treatment and GPI use for the primary efficacy and safety end points. Patients treated without GPI had a lower rate of definite stent thrombosis and higher rate of minor/major bleeding with ticagrelor compared with clopidogrel (P<.05), whereas there was no such difference with GPI (P interaction <.05). Conclusions In patients with acute coronary syndrome undergoing early PCI, the efficacy and safety of ticagrelor as compared with clopidogrel were not modified by GPI use according to the primary efficacy and safety end point of the trial, although there were indications of greater benefit on definite stent thrombosis and more major or minor bleeding with ticagrelor in patients without (vs with) GPI treatment.
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| 45. |
- Shimada, Y, et al.
(author)
-
Terahertz conductivity and possible Bloch gain in semiconductor superlattices
- 2003
-
In: Physical Review Letters. - 1079-7114. ; 90:4: 046806
-
Journal article (peer-reviewed)abstract
- We have investigated terahertz emission due to dynamical electron transport in wide-miniband GaAs/Al0.3Ga0.7As superlattices. By noting that the time-domain THz emission spectroscopy inherently measures the step-response of the electron system to the bias electric field, the obtained THz spectra were compared with the high-frequency conductivities predicted for miniband transport. Excellent agreement between theory and experiment strongly supports that the THz gain due to Bloch oscillating electrons persists at least up to 1.7 THz. It was also found that Zener tunneling into the second miniband sets the high-frequency limit to the THz gain for the samples studied here.
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| 46. |
- Vojvodic, A, et al.
(author)
-
Zener tunneling between Wannier-Stark levels in GaAs/AlGaAs superlattices
- 2005
-
In: Solid State Communications. - : Elsevier BV. - 1879-2766 .- 0038-1098. ; 136:11-12, s. 580-584
-
Journal article (peer-reviewed)abstract
- We have performed a detailed calculation of the inter-Wannier-Stark-ladder Zener tunneling probability P(F) in a wide-miniband GaAs/Al0.3Ga0.7As superlattice under a strong electric field F, the terahertz emission spectrum I(F) of which was measured experimentally. By comparing P(F) and I(F), we confirm that the oscillating behavior of I(F) is due to the Zener tunneling between Wannier-Stark levels.
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| 47. |
- Yamamoto, T., et al.
(author)
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An emerging phenotype of Xq22 microdeletions in females with severe intellectual disability, hypotonia and behavioral abnormalities
- 2014
-
In: Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1434-5161 .- 1435-232X. ; 59:6, s. 300-306
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Journal article (peer-reviewed)abstract
- The majority of Xq22 duplications seen in patients with Pelizaeus-Merzbacher disease (PMD) include proteolipid protein 1 (PLP1), the gene responsible for PMD, and neighboring genes. Some cases result from larger duplications up to 7 Mb in size. In comparison, the deletions including PLP1 seen in PMD patients are small. In this study, we present the genetic and clinical information for five female patients with deletions involving the Xq22 region, and review the correlation between the genotype and phenotype. Three of the five patients show similar large deletions (>3 Mb) ranging from Xq22.1 to Xq22.3 and all manifest severe intellectual disability, hypotonia and behavioral abnormalities. The most striking similarity among them are the behavioral problems, including poor eye contact and sleep disturbance. We propose that this represents an emerging distinctive microdeletion syndrome encompassing PLP1 in female patients. The possible candidate region responsible for such distinctive features has been narrowed down to the neighboring region for PLP1, including the interleukin 1 receptor accessory protein-like 2 (IL1RAPL2) gene and the clustered brain expressed X-linked (BEX) genes. The gene(s) responsible for severe neurological features in the patients in this study would be located in the regions proximate to PLP1; thus, males with the deletions involving the gene(s) would be lethal, and finally, the sizes of the deletions in PMD patients would be smaller than those of the duplications.
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