2,043 research outputs found
Coseismic slip distribution of the 2005 off Miyagi earthquake (M7.2) estimated by inversion of teleseismic and regional seismograms
Long-term and interdisciplinary research on forest ecosystem functions: challenges at Takayama site since 1993
Development of a Multi-Step Leukemogenesis Model of MLL-Rearranged Leukemia Using Humanized Mice
Mixed-lineage-leukemia (MLL) fusion oncogenes are intimately involved in acute leukemia and secondary therapy-related acute leukemia. To understand MLL-rearranged leukemia, several murine models for this disease have been established. However, the mouse leukemia derived from mouse hematopoietic stem cells (HSCs) may not be fully comparable with human leukemia. Here we developed a humanized mouse model for human leukemia by transplanting human cord blood-derived HSCs transduced with an MLL-AF10 oncogene into a supra-immunodeficient mouse strain, NOD/Shi-scid, IL-2Rγ−/− (NOG) mice. Injection of the MLL-AF10-transduced HSCs into the liver of NOG mice enhanced multilineage hematopoiesis, but did not induce leukemia. Because active mutations in ras genes are often found in MLL-related leukemia, we next transduced the gene for a constitutively active form of K-ras along with the MLL-AF10 oncogene. Eight weeks after transplantation, all the recipient mice had developed acute monoblastic leukemia (the M5 phenotype in French-American-British classification). We thus successfully established a human MLL-rearranged leukemia that was derived in vivo from human HSCs. In addition, since the enforced expression of the mutant K-ras alone was insufficient to induce leukemia, the present model may also be a useful experimental platform for the multi-step leukemogenesis model of human leukemia
Nuclear dependence of the transverse-single-spin asymmetry for forward neutron production in polarized collisions at GeV
During 2015 the Relativistic Heavy Ion Collider (RHIC) provided collisions of
transversely polarized protons with Au and Al nuclei for the first time,
enabling the exploration of transverse-single-spin asymmetries with heavy
nuclei. Large single-spin asymmetries in very forward neutron production have
been previously observed in transversely polarized collisions at
RHIC, and the existing theoretical framework that was successful in describing
the single-spin asymmetry in collisions predicts only a moderate
atomic-mass-number () dependence. In contrast, the asymmetries observed at
RHIC in collisions showed a surprisingly strong dependence in
inclusive forward neutron production. The observed asymmetry in Al
collisions is much smaller, while the asymmetry in Au collisions is a
factor of three larger in absolute value and of opposite sign. The interplay of
different neutron production mechanisms is discussed as a possible explanation
of the observed dependence.Comment: 315 authors, 8 pages, 4 figures, 1 table. v2 is version accepted for
publication in Phys. Rev. Lett. Plain text data tables for the points plotted
in figures for this and previous PHENIX publications are (or will be)
publicly available at http://www.phenix.bnl.gov/papers.htm
Epigenetic Features of Human Mesenchymal Stem Cells Determine Their Permissiveness for Induction of Relevant Transcriptional Changes by SYT-SSX1
BACKGROUND: A characteristic SYT-SSX fusion gene resulting from the chromosomal translocation t(X;18)(p11;q11) is detectable in almost all synovial sarcomas, a malignant soft tissue tumor widely believed to originate from as yet unidentified pluripotent stem cells. The resulting fusion protein has no DNA binding motifs but possesses protein-protein interaction domains that are believed to mediate association with chromatin remodeling complexes. Despite recent advances in the identification of molecules that interact with SYT-SSX and with the corresponding wild type SYT and SSX proteins, the mechanisms whereby the SYT-SSX might contribute to neoplastic transformation remain unclear. Epigenetic deregulation has been suggested to be one possible mechanism. METHODOLOGY/PRINCIPAL FINDINGS: We addressed the effect of SYT/SSX expression on the transcriptome of four independent isolates of primary human bone marrow mesenchymal stem cells (hMSC). We observed transcriptional changes similar to the gene expression signature of synovial sarcoma, principally involving genes whose regulation is linked to epigenetic factors, including imprinted genes, genes with transcription start sites within a CpG island and chromatin related genes. Single population analysis revealed hMSC isolate-specific transcriptional changes involving genes that are important for biological functions of stem cells as well as genes that are considered to be molecular markers of synovial sarcoma including IGF2, EPHRINS, and BCL2. Methylation status analysis of sequences at the H19/IGF2 imprinted locus indicated that distinct epigenetic features characterize hMSC populations and condition the transcriptional effects of SYT-SSX expression. CONCLUSIONS/SIGNIFICANCE: Our observations suggest that epigenetic features may define the cellular microenvironment in which SYT-SSX displays its functional effects
Search for Neutral Higgs Bosons in Events with Multiple Bottom Quarks at the Tevatron
The combination of searches performed by the CDF and D0 collaborations at the
Fermilab Tevatron Collider for neutral Higgs bosons produced in association
with b quarks is reported. The data, corresponding to 2.6 fb-1 of integrated
luminosity at CDF and 5.2 fb-1 at D0, have been collected in final states
containing three or more b jets. Upper limits are set on the cross section
multiplied by the branching ratio varying between 44 pb and 0.7 pb in the Higgs
boson mass range 90 to 300 GeV, assuming production of a narrow scalar boson.
Significant enhancements to the production of Higgs bosons can be found in
theories beyond the standard model, for example in supersymmetry. The results
are interpreted as upper limits in the parameter space of the minimal
supersymmetric standard model in a benchmark scenario favoring this decay mode.Comment: 10 pages, 2 figure
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