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Institution

University of Tokyo

EducationTokyo, Japan
About: University of Tokyo is a education organization based out in Tokyo, Japan. It is known for research contribution in the topics: Population & Gene. The organization has 134564 authors who have published 337567 publications receiving 10178620 citations. The organization is also known as: Todai & Universitas Tociensis.


Papers
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Journal ArticleDOI
16 Oct 2008-Nature
TL;DR: It is demonstrated that downregulation of ALK through RNA interference suppresses proliferation of neuroblastoma cells harbouring mutated ALK, and that ALK-specific kinase inhibitors might improve its clinical outcome.
Abstract: Neuroblastoma in advanced stages is one of the most intractable paediatric cancers, even with recent therapeutic advances Neuroblastoma harbours a variety of genetic changes, including a high frequency of MYCN amplification, loss of heterozygosity at 1p36 and 11q, and gain of genetic material from 17q, all of which have been implicated in the pathogenesis of neuroblastoma However, the scarcity of reliable molecular targets has hampered the development of effective therapeutic agents targeting neuroblastoma Here we show that the anaplastic lymphoma kinase (ALK), originally identified as a fusion kinase in a subtype of non-Hodgkin's lymphoma (NPM-ALK) and more recently in adenocarcinoma of lung (EML4-ALK), is also a frequent target of genetic alteration in advanced neuroblastoma According to our genome-wide scans of genetic lesions in 215 primary neuroblastoma samples using high-density single-nucleotide polymorphism genotyping microarrays, the ALK locus, centromeric to the MYCN locus, was identified as a recurrent target of copy number gain and gene amplification Furthermore, DNA sequencing of ALK revealed eight novel missense mutations in 13 out of 215 (61%) fresh tumours and 8 out of 24 (33%) neuroblastoma-derived cell lines All but one mutation in the primary samples (12 out of 13) were found in stages 3-4 of the disease and were harboured in the kinase domain The mutated kinases were autophosphorylated and displayed increased kinase activity compared with the wild-type kinase They were able to transform NIH3T3 fibroblasts as shown by their colony formation ability in soft agar and their capacity to form tumours in nude mice Furthermore, we demonstrate that downregulation of ALK through RNA interference suppresses proliferation of neuroblastoma cells harbouring mutated ALK We anticipate that our findings will provide new insights into the pathogenesis of advanced neuroblastoma and that ALK-specific kinase inhibitors might improve its clinical outcome

853 citations

Journal ArticleDOI
Zhenqiang Su, Paweł P. Łabaj1, Sheng Li2, Jean Thierry-Mieg3  +161 moreInstitutions (54)
TL;DR: The complete SEQC data sets, comprising >100 billion reads, provide unique resources for evaluating RNA-seq analyses for clinical and regulatory settings, and measurement performance depends on the platform and data analysis pipeline, and variation is large for transcript-level profiling.
Abstract: We present primary results from the Sequencing Quality Control (SEQC) project, coordinated by the US Food and Drug Administration. Examining Illumina HiSeq, Life Technologies SOLiD and Roche 454 platforms at multiple laboratory sites using reference RNA samples with built-in controls, we assess RNA sequencing (RNA-seq) performance for junction discovery and differential expression profiling and compare it to microarray and quantitative PCR (qPCR) data using complementary metrics. At all sequencing depths, we discover unannotated exon-exon junctions, with >80% validated by qPCR. We find that measurements of relative expression are accurate and reproducible across sites and platforms if specific filters are used. In contrast, RNA-seq and microarrays do not provide accurate absolute measurements, and gene-specific biases are observed for all examined platforms, including qPCR. Measurement performance depends on the platform and data analysis pipeline, and variation is large for transcript-level profiling. The complete SEQC data sets, comprising >100 billion reads (10Tb), provide unique resources for evaluating RNA-seq analyses for clinical and regulatory settings.

853 citations

Journal ArticleDOI
TL;DR: The Palaeoclimate Modelling Intercomparison Project (POMIP) as discussed by the authors evaluated model performance against the geologic record of environmental responses to climate changes and provided a unique opportunity to test model performance outside this limited climate range.
Abstract: There is large uncertainty about the magnitude of warming and how rainfall patterns will change in response to any given scenario of future changes in atmospheric composition and land use. The models used for future climate projections were developed and calibrated using climate observations from the past 40 years. The geologic record of environmental responses to climate changes provides a unique opportunity to test model performance outside this limited climate range. Evaluation of model simulations against palaeodata shows that models reproduce the direction and large-scale patterns of past changes in climate, but tend to underestimate the magnitude of regional changes. As part of the effort to reduce model-related uncertainty and produce more reliable estimates of twenty-first century climate, the Palaeoclimate Modelling Intercomparison Project is systematically applying palaeoevaluation techniques to simulations of the past run with the models used to make future projections. This evaluation will provide assessments of model performance, including whether a model is sufficiently sensitive to changes in atmospheric composition, as well as providing estimates of the strength of biosphere and other feedbacks that could amplify the model response to these changes and modify the characteristics of climate variability.

852 citations

Journal ArticleDOI
01 Jan 1986-Nature
TL;DR: Southern hybridization analysis of DNA from normal leukocytes and CHU-2 cells suggests that the human genome contains only one gene for G-CSF and that some rearrangement has occurred within one of the alleles of the G- CSF gene in CHU -2 cells.
Abstract: Granulocyte colony-stimulating factor (G-CSF) is a member of the CSF family of hormone-like glycoproteins that regulate haematopoietic cell proliferation and differentiation1,2, and G-CSF almost exclusively stimulates the colony formation of granulocytes from committed precursor cells in semi-solid agar culture2. Recently, Nomura et al.3 have established a human squamous carcinoma cell line (designated CHU-2) from a human oral cavity tumour which produces large quantities of CSF constitutively, and the CSF produced by CHU-2 cells has been purified to homogeneity from the conditioned medium. We have now determined the partial amino-acid sequence of the purified G-CSF protein, and by using oligonucleotides as probes, have isolated several clones containing G-CSF complementary DNA from the cDNA library prepared with messenger RNA from CHU-2 cells. The complete nucleotide sequences of two of these cDNAs were determined and the expression of the cDNA in monkey COS cells gave rise to a protein showing authentic G-CSF activity. Furthermore, Southern hybridization analysis of DNA from normal leukocytes and CHU-2 cells suggests that the human genome contains only one gene for G-CSF and that some rearrangement has occurred within one of the alleles of the G-CSF gene in CHU-2 cells.

851 citations

Journal ArticleDOI
TL;DR: The present approach using a 2DEG provides a new route to realize practical thermoelectric materials without the use of toxic heavy elements and enhances the Seebeck coefficient without reducing the electrical conductivity.
Abstract: Enhancement of the Seebeck coefficient (S ) without reducing the electrical conductivity (sigma) is essential to realize practical thermoelectric materials exhibiting a dimensionless figure of merit (ZT=S2 x sigma x T x kappa-1) exceeding 2, where T is the absolute temperature and kappa is the thermal conductivity. Here, we demonstrate that a high-density two-dimensional electron gas (2DEG) confined within a unit cell layer thickness in SrTiO(3) yields unusually large |S|, approximately five times larger than that of SrTiO(3) bulks, while maintaining a high sigma2DEG. In the best case, we observe |S|=850 microV K-1 and sigma2DEG=1.4 x 10(3) S cm-1. In addition, by using the kappa of bulk single-crystal SrTiO(3) at room temperature, we estimate ZT approximately 2.4 for the 2DEG, corresponding to ZT approximately 0.24 for a complete device having the 2DEG as the active region. The present approach using a 2DEG provides a new route to realize practical thermoelectric materials without the use of toxic heavy elements.

850 citations


Authors

Showing all 135252 results

NameH-indexPapersCitations
Ronald C. Kessler2741332328983
Donald P. Schneider2421622263641
George M. Whitesides2401739269833
Jing Wang1844046202769
Tadamitsu Kishimoto1811067130860
Yusuke Nakamura1792076160313
Dennis J. Selkoe177607145825
David L. Kaplan1771944146082
D. M. Strom1763167194314
Masayuki Yamamoto1711576123028
Krzysztof Matyjaszewski1691431128585
Yang Yang1642704144071
Qiang Zhang1611137100950
Kenji Kangawa1531117110059
Takashi Taniguchi1522141110658
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20241
2023354
20221,250
202112,942
202013,511
201912,656