178 research outputs found

    Planar CuO_2 hole density estimation in multilayered high-T_c cuprates

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    We report that planar CuO_2 hole densities in high-T_c cuprates are consistently determined by the Cu-NMR Knight shift. In single- and bi-layered cuprates, it is demonstrated that the spin part of the Knight shift K_s(300 K) at room temperature monotonically increases with the hole density pp from underdoped to overdoped regions, suggesting that the relationship of K_s(300 K) vs. p is a reliable measure to determine p. The validity of this K_s(300 K)-p relationship is confirmed by the investigation of the p-dependencies of hyperfine magnetic fields and of spin susceptibility for single- and bi-layered cuprates with tetragonal symmetry. Moreover, the analyses are compared with the NMR data on three-layered Ba_2Ca_2Cu_3O_6(F,O)_2, HgBa_2Ca_2Cu_3O_{8+delta}, and five-layered HgBa_2Ca_4Cu_5O_{12+delta}, which suggests the general applicability of the K_s(300 K)-p relationship to multilayered compounds with more than three CuO_2 planes. We remark that the measurement of K_s(300 K) enables us to separately estimate p for each CuO_2 plane in multilayered compounds, where doped hole carriers are inequivalent between outer CuO_2 planes and inner CuO_2 planes.Comment: 7 pages, 5 figures, 2 Tables, to be published in Physical Review

    Signet Ring Cell Gastric Cancer Occurring after Radiation Therapy for Helicobacter pylori-Uninfected Mucosa-Associated Lymphoid Tissue Lymphoma

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    Helicobacter pylori infection is the major cause for mucosa-associated lymphoid tissue (MALT) lymphoma and gastric cancers. On the other hand, gastric cancers are known to arise from gastric mucosal atrophy. We here report a case of signet ring cell gastric cancer that developed after radiation therapy for MALT lymphoma in H. pylori-uninfected patient whose stomach did not show gastric mucosal atrophy. A 58-year-old female was referred to our hospital for treatment of gastric MALT lymphoma. This patient was not infected with H. pylori, and upper gastrointestinal endoscopy revealed that she did not have gastric mucosal atrophy but had submucosal tumor-like MALT lymphoma lesion in the anterior wall of the upper gastric body. Since conventional eradication therapy was ineffective, her whole stomach was irradiated as a second-line therapy. The MALT lymphoma lesion turned into complete remission state after the therapy. The patient was followed every 6 months by upper gastrointestinal endoscopy for 4 years as complete remission until a newly developed decolorized depressed lesion was detected in the greater curvature of the proximal antrum, a completely different location from the MALT lymphoma lesion. A biopsy specimen from the lesion contained signet ring cell carcinoma, and she was successfully treated by endoscopic submucosal dissection. No signs of recurrence have been detected so far. The radiation therapy for MALT lymphoma might be associated with the occurrence of this signet ring cell gastric cancer, and since MALT lymphoma is indolent in nature, this case suggests that careful consideration is required when choosing the second-line therapy for MALT lymphoma patients

    Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis: evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results

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    <p>Abstract</p> <p>Background</p> <p>In stereotactic body radiotherapy (SBRT) for lung tumors, reducing tumor movement is necessary. In this study, we evaluated changes in tumor movement and percutaneous oxygen saturation (SpO<sub>2</sub>) levels, and preliminary clinical results of SBRT using the BodyFIX immobilization system.</p> <p>Methods</p> <p>Between 2004 and 2006, 53 consecutive patients were treated for 55 lesions; 42 were stage I non-small cell lung cancer (NSCLC), 10 were metastatic lung cancers, and 3 were local recurrences of NSCLC. Tumor movement was measured with fluoroscopy under breath holding, free breathing on a couch, and free breathing in the BodyFIX system. SpO<sub>2 </sub>levels were measured with a finger pulseoximeter under each condition. The delivered dose was 44, 48 or 52 Gy, depending on tumor diameter, in 4 fractions over 10 or 11 days.</p> <p>Results</p> <p>By using the BodyFIX system, respiratory tumor movements were significantly reduced compared with the free-breathing condition in both craniocaudal and lateral directions, although the amplitude of reduction in the craniocaudal direction was 3 mm or more in only 27% of the patients. The average SpO<sub>2 </sub>did not decrease by using the system. At 3 years, the local control rate was 80% for all lesions. Overall survival was 76%, cause-specific survival was 92%, and local progression-free survival was 76% at 3 years in primary NSCLC patients. Grade 2 radiation pneumonitis developed in 7 patients.</p> <p>Conclusion</p> <p>Respiratory tumor movement was modestly suppressed by the BodyFIX system, while the SpO<sub>2 </sub>level did not decrease. It was considered a simple and effective method for SBRT of lung tumors. Preliminary results were encouraging.</p

    BMP4 induction of trophoblast from mouse embryonic stem cells in defined culture conditions on laminin

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    Because mouse embryonic stem cells (mESCs) do not contribute to the formation of extraembryonic placenta when they are injected into blastocysts, it is believed that mESCs do not differentiate into trophoblast whereas human embryonic stem cells (hESCs) can express trophoblast markers when exposed to bone morphogenetic protein 4 (BMP4) in vitro. To test whether mESCs have the potential to differentiate into trophoblast, we assessed the effect of BMP4 on mESCs in a defined monolayer culture condition. The expression of trophoblast-specific transcription factors such as Cdx2, Dlx3, Esx1, Gata3, Hand1, Mash2, and Plx1 was specifically upregulated in the BMP4-treated differentiated cells, and these cells expressed trophoblast markers. These results suggest that BMP4 treatment in defined culture conditions enabled mESCs to differentiate into trophoblast. This differentiation was inhibited by serum or leukemia inhibitory factor, which are generally used for mESC culture. In addition, we studied the mechanism underlying BMP4-directed mESC differentiation into trophoblast. Our results showed that BMP4 activates the Smad pathway in mESCs inducing Cdx2 expression, which plays a crucial role in trophoblast differentiation, through the binding of Smad protein to the Cdx2 genomic enhancer sequence. Our findings imply that there is a common molecular mechanism underlying hESC and mESC differentiation into trophoblast

    Anti-Aβ Drug Screening Platform Using Human iPS Cell-Derived Neurons for the Treatment of Alzheimer's Disease

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    Background:Alzheimer's disease (AD) is a neurodegenerative disorder that causes progressive memory and cognitive decline during middle to late adult life. The AD brain is characterized by deposition of amyloid β peptide (Aβ), which is produced from amyloid precursor protein by β- and γ-secretase (presenilin complex)-mediated sequential cleavage. Induced pluripotent stem (iPS) cells potentially provide an opportunity to generate a human cell-based model of AD that would be crucial for drug discovery as well as for investigating mechanisms of the disease. Methodology/Principal Findings:We differentiated human iPS (hiPS) cells into neuronal cells expressing the forebrain marker, Foxg1, and the neocortical markers, Cux1, Satb2, Ctip2, and Tbr1. The iPS cell-derived neuronal cells also expressed amyloid precursor protein, β-secretase, and γ-secretase components, and were capable of secreting Aβ into the conditioned media. Aβ production was inhibited by β-secretase inhibitor, γ-secretase inhibitor (GSI), and an NSAID; however, there were different susceptibilities to all three drugs between early and late differentiation stages. At the early differentiation stage, GSI treatment caused a fast increase at lower dose (Aβ surge) and drastic decline of Aβ production. Conclusions/Significance:These results indicate that the hiPS cell-derived neuronal cells express functional β- and γ-secretases involved in Aβ production; however, anti-Aβ drug screening using these hiPS cell-derived neuronal cells requires sufficient neuronal differentiation

    LOW-Γ JETS from COMPACT STELLAR MERGERS: CANDIDATE ELECTROMAGNETIC COUNTERPARTS to GRAVITATIONAL WAVE SOURCES

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    The American Astronomical Society. All rights reserved.Short gamma-ray bursts (GRBs) are believed to be produced by relativistic jets from mergers of neutron stars (NSs) or NSs and black-holes (BHs). If the Lorentz-factors Γ of jets from compact stellar mergers follow a similar power-law distribution to those observed for other high-energy astrophysical phenomena (e.g., blazars, active galactic nuclei), the population of jets should be dominated by low-Γ outflows. These jets will not produce prompt gamma-rays, but jet energy will be released as X-ray/optical/radio transients when they collide with the ambient medium. Using Monte Carlo simulations, we study the properties of such transients. Approximately 78% of merger jets Mpc result in failed GRBs if the jet Γ follows a power-law distribution of index -1.75. X-ray/optical transients from failed GRBs will have broad distributions of their characteristics: light-curves peak tp ∼ 0.1-10 days after a merger; flux peaks for X-ray 10-6 mJy ≲ Fx ≲ 10-2 mJy; and optical flux peaks at 14 ≲ mg ≲ 22. X-ray transients are detectable by Swift XRT, and ∼85% of optical transients will be detectable by telescopes with limiting magnitude mg ≳ 21, for well localized sources on the sky. X-ray/optical transients are followed by radio transients with peak times narrowly clustered around tp ∼ 10 days, and peak flux of ∼10-100 mJy at 10 GHz and ∼0.1 mJy at 150 MHz. By considering the all-sky rate of short GRBs within the LIGO/Virgo range, the rate of on-axis orphan afterglows from failed GRBs should be 2.6(26) per year for NS-NS(NS-BH) mergers, respectively. Since merger jets from gravitational-wave (GW) trigger events tend to be directed to us, a significant fraction of GW events could be associated with the on-axis orphan afterglow

    Virus-Infection or 5′ppp-RNA Activates Antiviral Signal through Redistribution of IPS-1 Mediated by MFN1

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    In virus-infected cells, RIG-I-like receptor (RLR) recognizes cytoplasmic viral RNA and triggers innate immune responses including production of type I and III interferon (IFN) and the subsequent expression of IFN-inducible genes. Interferon-β promoter stimulator 1 (IPS-1, also known as MAVS, VISA and Cardif) is a downstream molecule of RLR and is expressed on the outer membrane of mitochondria. While it is known that the location of IPS-1 is essential to its function, its underlying mechanism is unknown. Our aim in this study was to delineate the function of mitochondria so as to identify more precisely its role in innate immunity. In doing so we discovered that viral infection as well as transfection with 5′ppp-RNA resulted in the redistribution of IPS-1 to form speckle-like aggregates in cells. We further found that Mitofusin 1 (MFN1), a key regulator of mitochondrial fusion and a protein associated with IPS-1 on the outer membrane of mitochondria, positively regulates RLR-mediated innate antiviral responses. Conversely, specific knockdown of MFN1 abrogates both the virus-induced redistribution of IPS-1 and IFN production. Our study suggests that mitochondria participate in the segregation of IPS-1 through their fusion processes
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