Full-Reference and Non-Reference Image Quality Assessment Based on Optimization Technique

学位記号番号 : 博理工甲第1142号博士の専攻分野の名称 : 博士(工学) 学位授与年月日 : 令和元年9月20日textapplication/pdfthesi

The development of group accounting in the United Kingdom : setting the scene

departmental bulletin pape

Delivery Parameter Variations and Early Clinical Outcomes of Volumetric Modulated Arc Therapy for 31 Prostate Cancer Patients: An Intercomparison of Three Treatment Planning Systems

The Scientific World Journal. 2013, 2013 (1), 289809journal articl

Observation of the DsJ(2317) and DsJ(2457) in B Decays

journal articl

Formation of Peer group in Which Children Enjoy Expression and Share it : Through Course Planning to Foster Children Who Enjoy Their Life (Education Practice in the Course of a Junior High Department of Tottori University school for Children with Special Needs)

departmental bulletin pape

DIMENSION AND PRODUCTS OF TOPOLOGICAL GROUPS : dedicated to Professor Akihiro Okuyama on his 60th birthday

application/pdfIn this paper, we prove that, for each pair ＄n,＄ ＄d＄ of positive integers with ＄n￥leqq d＄ , there is a subgroup ＄G_{nd}＄ of ＄R^{n+1}＄ satisfying dim ＄G_{nd}=n＄ and ＄￥dim(G_{nd})^{￥omega}=d＄ . We also prove that there is a separable metrizable precompact topological group ＄H_{nd}＄ satisfying the same property.departmental bulletin pape

<i>Sox2</i> Expression Is Regulated by a Negative Feedback Loop in Embryonic Stem Cells That Involves AKT Signaling and FoxO1

<div><p>The self-renewal and pluripotency of embryonic stem cells (ESC) is regulated by a highly integrated network of essential transcription factors, which includes Sox2. Previous studies have shown that elevating Sox2 on its own in mouse ESC induces differentiation and inhibits the expression of endogenous Sox2 at the protein and mRNA level. These findings led us to hypothesize that increases in Sox2 activate a negative feedback loop that inhibits the transcription of the endogenous <i>Sox</i>2 gene. To test this hypothesis, we used i-OSKM-ESC, which elevate Sox2 in conjunction with Oct4, Klf4, and c-Myc when treated with doxycycline (Dox). Elevating the expression of these four transcription factors in i-OSKM-ESC does not induce differentiation, but it represses expression of endogenous Sox2. We determined that increases of Sox2 in i-OSKM-ESC lead to increases in activated AKT and inactivation of FoxO1 (an activator of <i>Sox2</i>), as well as decreases in binding of FoxO1 to the 5'flanking region of <i>Sox2</i>. Importantly, we determined that inhibition of AKT in Dox-treated i-OSKM-ESC leads to re-expression of endogenous <i>Sox2</i> at the mRNA and protein level and reactivation of FoxO1. These findings argue that AKT signaling is part of the negative feedback loop that helps carefully control the transcription of <i>Sox2</i> in ESC by modulating the binding of FoxO1 to the <i>Sox2</i> gene. Collectively, our findings provide new insights into the mechanisms that enable ESC to carefully regulate the levels of Sox2 and retain their stem cell properties.</p></div

Elevating SOX2 Levels Deleteriously Affects the Growth of Medulloblastoma and Glioblastoma Cells

<div><p>Medulloblastomas and glioblastomas are devastating tumors that respond poorly to treatment. These tumors have been shown to express SOX2 and overexpression of SOX2 has been correlated with poor prognosis. Although knockdown of SOX2 impairs the growth and tumorigenicity of brain tumor cells, it was unclear how elevating SOX2 levels would affect their fate. Interestingly, studies conducted with neural stem cells have shown that small increases or decreases in the level of this transcription factor significantly alter their fate. Here, we report that elevating SOX2 3-fold above endogenous levels in U87 and U118 glioblastoma, and DAOY medulloblastoma cells significantly impairs their ability to proliferate. We extended these findings and determined that elevating SOX2 in DAOY cells remodels their cell-cycle profile by increasing the proportion of cells in the G1-compartment, and induces the expression of genes associated with differentiation. Furthermore, we show that elevating SOX2 leads to a dramatic induction of CD133 expression in DAOY cells, yet inhibits the ability of both CD133⁺ and CD133⁻ cells to form neurospheres. Together, these findings argue that SOX2 levels must be carefully controlled in glioblastomas and medulloblastomas to maintain their fate. Equally important, our data suggests that increases in the expression of SOX2 during brain tumor progression are likely to be linked closely with changes in other critical genes that work in concert with SOX2 to enhance the tumorigenicity of brain tumors. Importantly, we demonstrate that this is also likely to be true for other cancers that express SOX2. Moreover, these studies demonstrate the advantage of using inducible promoters to study the effects of SOX2 elevation, as compared to gene expression systems that rely on constitutive expression.</p> </div

Co-immunoprecipitation of endogenous 293T cell HDAC2 by exogenous Flag-Sox2 constructs.

<p>The indicated constructs were transiently transfected into 293T cells, and nuclear proteins were prepared 1 day later. Flag-Sox2 proteins and associated proteins were co-immunoprecipitated from nuclear extracts using M2-beads. Immunoprecipitate eluates were used in western blot analyses, and were probed for either α-HDAC2 (top) or α-Flag (bottom). Protein for the control (mock) lane was from un-transfected 293T cells. This experiment was repeated, and similar results were observed.</p

Effects of two different AKT inhibitors on the expression of endogenous Sox2.

<p>i-OSKM-ESC were seeded at 1.5×10⁶ per 100 mm dish with or without 4 μg/ml Dox for 24 hours. (A) After the initial 24 hours, the cells were refed with fresh medium with or without 4 μg/ml Dox, and treated with 5 μM AKTiV or 5 μM AKT1/2i for an additional 24 hours where indicated. 48 hours after the cells were plated, nuclear and cytoplasmic protein extracts were prepared and equal amounts of nuclear and cytoplasmic protein were loaded into each well of an SDS-PAGE. Western blot analysis was performed by sequentially probing for pAKT(T308), pAKT (S473), Sox2 and HDAC1, which served as a protein loading control.</p