2,827 research outputs found

    Fabrication of a Silicon Nanowire on a Bulk Substrate by Use of a Plasma Etching and Total Ionizing Dose Effects on a Gate-All-Around Field-Effect Transistor

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    The gate all around transistor is investigated through experiment. The suspended silicon nanowire for the next generation is fabricated on bulk substrate by plasma etching method. The scallop pattern generated by Bosch process is utilized to form a floating silicon nanowire. By combining anisotropic and istropic silicon etch process, the shape of nanowire is accurately controlled. From the suspended nanowire, the gate all around transistor is demonstrated. As the silicon nanowire is fully surrounded by the gate, the device shows excellent electrostatic characteristics

    Production of Transgenic Cloned Miniature Pigs with Membrane-bound Human Fas Ligand (FasL) by Somatic Cell Nuclear Transfer

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    Cell-mediated xenograft rejection, including NK cells and CD8+ CTL, is a major obstacle in successful pig-to-human xenotransplantation. Human CD8+ CTL and NK cells display high cytotoxicity for pig cells, mediated at least in part by the Fas/FasL pathway. To prevent cell-mediated xenocytotoxicity, a membrane-bound form of human FasL (mFasL) was generated as an inhibitor for CTL and NK cell cytotoxicity that could not be cleaved by metalloproteinase to produce putative soluble FasL. We produced two healthy transgenic pigs harboring the mFasL gene via somatic cell nuclear transfer (SCNT). In a cytotoxicity assay using transgenic clonal cell lines and transgenic pig ear cells, the rate of CD8+ CTL-mediated cytotoxicity was significantly reduced in transgenic pig's ear cells compared with that in normal minipig fetal fibroblasts. Our data indicate that grafts of transgenic pigs expressing membrane-bound human FasL control the cellular immune response to xenografts, creating a window of opportunity to facilitate xenograft survival

    MOMENT RESISTANCE PERFORMANCE OF LARCH LAMINATED TIMBER BEAM-COLUMN JOINTS REINFORCED WITH CFRP

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    This study evaluates the moment resisting capacity of the drift pin larch beam-column joint with slotted-in steel plates of larch laminated timber. It is reinforced with carbon fiber reinforced plastic (CFRP) to suppress the brittle fracture of the beam-column joint and improve the joint capacity using larch laminated timber, a wood material manufactured by multi-layering of timber as a structural member of heavy timber.The average maximum moment capacity of the control specimen was 16.9 kN·m and the average maximum moments of the Type-A (volume ratio of joint reinforced with CFRP: 3.6%) and Type-B (volume ratio of joint reinforced with CFRP: 5.4%) were increased by 46% and 62%, respectively, compared to that of the control specimen. The capacity of the joint, such as the average yield capacity, ultimate moment capacity, and ductility ratio, of the control, Type-A, and Type-B specimens increased as the reinforcement ratio of the CFRP increased. For the failure mode of the control specimen, splitting failure occurred in both the column and beam members in the end distance direction. However, the splitting failure did not occur in the beam member due to the improvement of the joint and ductility of the specimens reinforced with the CFRP. The Type-A specimen had improved joint capacity and ductility compared to the control specimen; however, brittle failure occurred owing to the external force exceeding the joint capacity. However, in some of the Type-B specimens, the splitting failure did not occur in the column and beam members due to the CFRP reinforcement. Particularly, the Type-B3 specimen exhibited ductility

    The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma

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    <p>Abstract</p> <p>Background</p> <p><it>Klotho </it>was originally characterized as an anti-aging gene that predisposed Klotho-deficient mice to a premature aging-like syndrome. Recently, KLOTHO was reported to function as a secreted Wnt antagonist and as a tumor suppressor. Epigenetic gene silencing of secreted Wnt antagonists is considered a common event in a wide range of human malignancies. Abnormal activation of the canonical Wnt pathway due to epigenetic deregulation of Wnt antagonists is thought to play a crucial role in cervical tumorigenesis. In this study, we examined epigenetic silencing of <it>KLOTHO </it>in human cervical carcinoma.</p> <p>Results</p> <p>Loss of <it>KLOTHO </it>mRNA was observed in several cervical cancer cell lines and in invasive carcinoma samples, but not during the early, preinvasive phase of primary cervical tumorigenesis. <it>KLOTHO </it>mRNA was restored after treatment with either the DNA demethylating agent 2'-deoxy-5-azacytidine or histone deacetylase inhibitor trichostatin A. Methylation-specific PCR and bisulfite genomic sequencing analysis of the promoter region of <it>KLOTHO </it>revealed CpG hypermethylation in non-<it>KLOTHO</it>-expressing cervical cancer cell lines and in 41% (9/22) of invasive carcinoma cases. Histone deacetylation was also found to be the major epigenetic silencing mechanism for <it>KLOTHO </it>in the SiHa cell line. Ectopic expression of the secreted form of KLOTHO restored anti-Wnt signaling and anti-clonogenic activity in the CaSki cell line including decreased active β-catenin levels, suppression of T-cell factor/β-catenin target genes, such as <it>c-MYC </it>and <it>CCND1</it>, and inhibition of colony growth.</p> <p>Conclusions</p> <p>Epigenetic silencing of <it>KLOTHO </it>may occur during the late phase of cervical tumorigenesis, and consequent functional loss of KLOTHO as the secreted Wnt antagonist may contribute to aberrant activation of the canonical Wnt pathway in cervical carcinoma.</p

    Phosphorylation Status of RNA Polymerase II Carboxyl-terminal Domain in Porcine Oocytes and Early Embryos

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    Fertilization of the oocyte commences embryogenesis during which maternally inherited mRNAs are degraded and the embryonic genome is activated. Transcription of embryonic mRNA is initiated by embryonic genome activation (EGA). RNA polymerase II (RNA Pol II) is responsible for the synthesis of mRNAs and most small nuclear RNAs, and consists of 12 subunits, the largest of which characteristically harbors a unique C-terminal domain (CTD). Transcriptional activity of RNA Pol II is highly regulated, in particular, by phosphorylation of serine residues in the CTD. Here, we have shown the presence of RNA Pol II CTD phosphoisoforms in porcine oocytes and preimplantation embryos. The distribution pattern as well as phosphorylation dynamics in germinal vesicles and during embryogenesis differed in developmental stages with these isoforms, indicating a role of RNA Pol II CTD phosphorylation at the serine residue in transcriptional activation during both oocyte growth and embryonic genome activation. We additionally examined the effects of the RNA Pol II inhibitor, α-amanitin, on embryo development. Our results show that inhibition of polymerase, even at very early stages and for a short period of time, dramatically impaired blastocyst formation. These findings collectively suggest that the functionality of maternal RNA Pol II, and consequently, expression of early genes regulated by this enzyme are essential for proper embryo development
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