HNF-1β過剰発現を呈する卵巣明細胞癌においてGSK-3βは新たなシグナル伝達経路を介在する

Deubiquitinase USP28 is a target gene of the transcription factor HNF1 homeobox β (HNF-1β), which promotes the survival of ovarian clear cell carcinoma (OCCC) cell lines. However, the pharmacological inhibition of HNF-1β can cause several adverse effects as it is abundantly expressed in numerous organ systems, including the kidney, liver, pancreas and digestive tract. Therefore, small interfering RNA (siRNA) screening was performed in the current study to identify other potential downstream targets of the HNF-1β-mediated pathway. The results revealed that glycogen synthase kinase-3β (GSK-3β) may be a potential downstream target affecting cell viability. To further clarify the effects of GSK-3β, two human OCCC cell lines, TOV-21G (HNF-1β overexpressing line) and ES2 (HNF-1β negative) were transfected with siRNA targeting GSK-3β or control vectors. Loss-of-function studies using RNAi-mediated gene silencing indicated that HNF-1β facilitated GSK-3β expression, resulting in the loss of phosphorylated nuclear factor-κB (p-NFκB) and the reduction of TOV-21G cell proliferation. The cell proliferation assay also revealed that GSK-3β inhibitors rescued the effects of HNF-1β silencing on cell viability in a dose-dependent manner. Furthermore, the GSK-3β inhibitor, AR-A014418, effectively inhibited tumor cell proliferation in a xenograft mouse model. In conclusion and to the best of our knowledge, the current study was the first to determine that GSK-3β is a target gene of HNF-1β. In addition, the results of the present study revealed the novel HNF-1β-GSK-3β-p-NFκB pathway, occurring in response to DNA damage. Targeting this pathway may therefore represent a putative, novel, anticancer strategy in patients with OCCC.博士（医学）・甲第785号・令和3年3月15日Copyright: © Kawaharaet al. This is an open access article distributed under theterms of CreativeCommons Attribution License(https://creativecommons.org/licenses/by-nc-nd/4.0/)

ドイツ介護保険法の改正

我が国では，高齢化の急速な進展とともに介護の需要もますます高まってきている．平成26年には，「地域におけ る医療及び介護の総合的な確保を推進するための関係法律の整備等に関する法律」により，「医療法」とともに「介護 保険法」が改正され，予防給付のうち，訪問介護・通所介護を地域支援事業に移行するという大きな改革が実施され ている．日本が介護保険制度の手本としたドイツにおいても，高齢化の進展にともなう介護の課題を解決するため， 2016年には，要介護度の基準を変更するという介護保険法の抜本的な改革が実施されている．本稿では，日本の今 後の介護保険制度を考える上で参考とすべく，現在のドイツの介護に関する課題とその解決策を検討して，介護保 険法がどのように改正されたかについて考察していく．　　　　　　　　　　In Japan, demand for nursing care is increasing more and more with the rapid progress of aging.　In 2008, the “Law on Improvement of Related Laws to Promote the Comprehensive Assurance of Medical Care and Nursing Care in the Region”, the“ Long-Term Care Insurance Law” was revised along with the“ Medical Law”, and among the preventive benefits, Major reforms are under way to shift visiting nursing care and home care to local community support projects.　Even in Germany, where Japan has modeled the nursing care insurance system, in order to solve the problem of nursing care accompanying progress of aging, reform of long-term care insurance law over nursing care of dementia is underway in 2015.　In this paper, in order to refer to Japan's future long-term care insurance system as a reference, we will examine the current issues concerning nursing care in Germany and its solutions and discuss how the nursing-care is treated

Methylation profiles of genes utilizing newly developed CpG island methylation microarray on colorectal cancer patients

Aberrant methylation of DNA has been shown to play an important role in a variety of human cancers, developmental disorders and aging. Hence, aberrant methylation patterns in genes can be a molecular marker for such conditions. Therefore, a reliable but uncomplicated method to detect DNA methylation is preferred, not merely for research purposes but for daily clinical practice. To achieve these aims, we have established a precise system to identify DNA methylation patterns based on an oligonucleotide microarray technology. Our microarray method has an advantage over conventional methods and is unique because it allows the precise measurement of the methylation patterns within a target region. Our simple signal detection system depends on using an avidin–biotinylated peroxidase complex and does not require an expensive laser scanner or hazardous radioisotope. In this study, we applied our technique to detect promoter methylation status of O(6)-methylguanine-DNA methyltransferase (MGMT) gene. Our easy-handling technology provided reproducible and precise measurement of methylated CpGs in MGMT promoter and, thus, our method may bring about a potential evolution in the handling of a variety of high-throughput DNA methylation analyses for clinical purposes

Method for determining the power-saved driving motion of manipulators by heuristic algorithms (In case of CP control)

This study proposes a method for suppressing the torques of the manipulators, with considering the effect of inertial forces in order to achieve the power-saved drive. The present study generates the trajectories, which here reveal time profiles of positions, velocities and accelerations of the entire path of the output point of manipulators. The trajectories of manipulators are introduced by determining both the initial position and motion curves for the entire path. This study expresses the motion curve as a polynomial and determines its coefficients. The initial pose and unknown coefficients are decided by a heuristic algorithm to achieve power-saved drive. As such problems have non-linearity and multi-peak solutions, it is difficult to find out the optimum one. Thus, this study uses a heuristic algorithm "SHA" to determine the appropriate motions of manipulators, because the heuristic algorithm is, as well known, an effective solution for such complicated problem. This study determines the optimal motions of the PUMA560 comprising spatial 3 degrees-of-freedom by the proposed method, and verifies its availability

Three topics of monopole dynamics in abelian projected QCD

Three topics about monopole dynamics after abelian projection are reported. The first is the new and detailed analyses of $SU(2)$ monopole action obtained after the block-spin transformation on the dual lattice. The $b=na(\beta)$ dependence for all couplings are well fitted with a universal curve. The distance dependence of the couplings is well reproduced by a massive propagator with the mass $m=0.8$ in unit of $b$. The second is the $SU(3)$ monopole action recently obtained. The third is new interesting gauges showing abelian and monopole dominances as in the maximally abelian gauge.Comment: Talk presented at LATTICE96(topology), 4 Pages, 7 eps figure

A Study on High School and Undergraduate Students’ Learning Motivation : A Case of Joint Management of the Educational Relationship between K Agricultural High School and A University for the “K Agricultural High School & A University Program"

This paper introduces the joint management of an educational relationship between K Agricultural High School and A University, and reports the program's effects to increase students' motivation for learning at both schools. In the program, first, the high school students presented the results of their project based learning, and the university students and university instructor gave comments. Next, the high school students received a lecture from the university instructor and a research report from the university student. Finally, the high school students, university students, and instructors attended a social gathering. An analysis of responses to the study questionnaire suggests that students’ motivation for learning increased at both schools, except the university students who have high motivation originally

Non-Gaussian Error Contribution to Likelihood Analysis of the Matter Power Spectrum

We study the sample variance of the matter power spectrum for the standard Lambda Cold Dark Matter universe. We use a total of 5000 cosmological N-body simulations to study in detail the distribution of best-fit cosmological parameters and the baryon acoustic peak positions. The obtained distribution is compared with the results from the Fisher matrix analysis with and without including non-Gaussian errors. For the Fisher matrix analysis, we compute the derivatives of the matter power spectrum with respect to cosmological parameters using directly full nonlinear simulations. We show that the non-Gaussian errors increase the unmarginalized errors by up to a factor 5 for k_{max}=0.4h/Mpc if there is only one free parameter provided other parameters are well determined by external information. On the other hand, for multi-parameter fitting, the impact of the non-Gaussian errors is significantly mitigated due to severe parameter degeneracies in the power spectrum. The distribution of the acoustic peak positions is well described by a Gaussian distribution, with its width being consistent with the statistical interval predicted from the Fisher matrix. We also examine systematic bias in the best-fit parameter due to the non-Gaussian errors. The bias is found to be smaller than the 1 sigma statistical error for both the cosmological parameters and the acoustic scale positions.Comment: 12 pages, 10 figures, accepted for publication in ApJ, minor change

Simulations of Wide-Field Weak Lensing Surveys I: Basic Statistics and Non-Gaussian Effects

We study the lensing convergence power spectrum and its covariance for a standard LCDM cosmology. We run 400 cosmological N-body simulations and use the outputs to perform a total of 1000 independent ray-tracing simulations. We compare the simulation results with analytic model predictions. The semi-analytic model based on Smith et al.(2003) fitting formula underestimates the convergence power by ~30% at arc-minute angular scales. For the convergence power spectrum covariance, the halo model reproduces the simulation results remarkably well over a wide range of angular scales and source redshifts. The dominant contribution at small angular scales comes from the sample variance due to the number fluctuations of halos in a finite survey volume. The signal-to-noise ratio for the convergence power spectrum is degraded by the non-Gaussian covariances by up to a factor 5 for a weak lensing survey to z_s ~1. The probability distribution of the convergence power spectrum estimators, among the realizations, is well approximated by a chi-square distribution with broadened variance given by the non-Gaussian covariance, but has a larger positive tail. The skewness and kurtosis have non-negligible values especially for a shallow survey. We argue that a prior knowledge on the full distribution may be needed to obtain an unbiased estimate on the ensemble averaged band power at each angular scale from a finite volume survey.Comment: 11 pages, 11 figures. Accepted for publication in the Astrophysical Journal. Corrected typo in the equation of survey window function below Equation (18). The results unchange