ニーチェにおける「生理学」-彼の文化的「戦略」として-

早稲田大学博士(文学)早大学位記番号:新8231thesi

A combination of a DNA-chimera siRNA against PLK-1 and zoledronic acid suppresses the growth of malignant mesothelioma cells in vitro.

Although novel agents effective against malignant mesothelioma (MM) have been developed, the prognosis of patients with MM is still poor. We generated a DNA-chimeric siRNA against polo-like kinase-1 (PLK-1), which was more stable in human serum than the non-chimeric siRNA. The chimeric PLK-1 siRNA inhibited MM cell proliferation through the induction of apoptosis. Next, we investigated the effects of zoledronic acid (ZOL) on MM cells, and found that ZOL also induced apoptosis in MM cells. Furthermore, ZOL augmented the inhibitory effects of the PLK-1 siRNA. In conclusion, combining a PLK-1 siRNA with ZOL treatment is an attractive strategy against MM

Analysis of the Complete Open Reading Frame of Genotype 2b Hepatitis C Virus in Association with the Response to Peginterferon and Ribavirin Therapy

BACKGROUND AND AIMS: Patients infected with genotype 2b hepatitis C virus (HCV) generally can achieve favorable responses to pegylated-interferon plus ribavirin therapy (PEG-IFN/RBV). However, a proportion of patients show poorer responses and the correlation between viral sequence variation and treatment outcome remains unclear. METHODS: The pretreatment complete open reading frame (ORF) sequences of genotype 2b HCV determined by direct sequencing were investigated for correlation with the final outcome in a total of 60 patients. RESULTS: In this study group, 87.5% (14/16) of non-sustained virological response (non-SVR) patients (n = 16) were relapsers. Compared to sustained virological response (SVR) patients (n = 44), non-SVR patients were older and could not achieve prompt viral clearance after the therapy induction. Comparing each viral protein between the two groups, viral sequences were more diverse in SVR patients and that diversity was found primarily in the E1, p7, and NS5A proteins. In searching for specific viral regions associated with the final outcome, several regions in E2, p7, NS2, NS5A, and NS5B were extracted. Among these regions, part of the interferon sensitivity determining region (ISDR) was included. In these regions, amino acid substitutions were associated with the final outcome in an incremental manner, depending upon the number of substitutions. CONCLUSIONS: Viral sequences are more diverse in SVR patients than non-SVR patients receiving PEG-IFN/RBV therapy for genotype-2b HCV infection. Through systematic comparison of viral sequences, several specific regions, including part of the ISDR, were extracted as having significant correlation with the final outcome

Constraint from recent ATLAS results on non-universal sfermion mass models and naturalness

We investigate the impact of recent direct supersymmetry (SUSY) searches on a non-universal sfermion mass scenario focusing on naturalness. One of the advantages of this scenario is that the non-universality between third generation and first two generation sfermion masses can relax the tension between naturalness and constraints from flavour and CP violating observables. In the parameter region, where various phenomenological constraints are satisfied, the constraints to this scenario from ATLAS 165pb-1 "0-lepton" search and 35pb-1 "b-jet" search are much weaker than those to the constrained minimal SUSY standard model, because of differences in the main SUSY production processes and the main decay chains. Naturalness can be easily achieved in this scenario in accord with the current direct SUSY searches. An additional dedicated analysis may be needed to discover/exclude this scenario.Comment: 15 pages, 7 figures, 2 table

CP asymmetries of B to phi K_S and B to eta' K_S in SUSY GUT Model with Non-universal Sfermion Masses

We analyze CP asymmetries of B \to \phi K_S and B \to \eta' K_S in a supersymmetric grand unified theory in which only the third generation sfermions contained in 10(Q, U^c, E^c) of SU(5) can have a different mass from the others. One of the advantages of this nonuniversal mass model is that the first two generation sfermion masses can be large whereas both (left and right handed) stops are light so as to stabilize the weak scale. Therefore, we studied a minimal supersymmetric standard model parameter region in which a fine tuning in Higgs sector is relaxed owing to light masses of stops, gluino and higgsinos. In such a parameter region, the chargino contribution is as important as the gluino one. We show that the CP asymmetries of B \to \phi K_S and B \to \eta' K_S can deviate from their standard model predicted values by O(0.1) because of constructive interference between gluino and chargino contributions.Comment: 22 pages, 5 figure

Speech corpora in NINJAL, Japan demonstration of corpus concordance systems : Chunagon and Kotonoha

National Institute for Japanese Language and LinguisticsNational Institute for Japanese Language and LinguisticsNational Institute for Japanese Language and LinguisticsNational Institute for Japanese Language and LinguisticsNational Institute for Japanese Language and LinguisticsNational Institute for Japanese Language and LinguisticsNational Institute for Japanese Language and LinguisticsNational Institute for Japanese Language and LinguisticsNational Institute for Japanese Language and LinguisticsNational Institute for Japanese Language and LinguisticsNational Institute for Japanese Language and LinguisticsThe National Institute for Japanese Language and Linguistics, Japan (NINJAL, Japan) provides a demonstration site in the LPSS 2019 conference. This manuscript presents an overview of the demonstration of three corpora: Corpus of Spontaneous Japanese, Corpus of Everyday Japanese Conversation, and Corpus of Japanese Dialects.NINJAL also demonstrates two concordance systems. The first is "Chunagon (中納言)" which is a morpheme based concordance system that was made publicly available in 2011. The second is the currently developing system "Kotonoha" released in 2018 that enables query of multiple corpora in terms of register type and period

Endotoxemia by Porphyromonas gingivalis Injection Aggravates Non-alcoholic Fatty Liver Disease, Disrupts Glucose/Lipid Metabolism, and Alters Gut Microbiota in Mice

Many risk factors related to the development of non-alcoholic fatty liver disease (NAFLD) have been proposed, including the most well-known of diabetes and obesity as well as periodontitis. As periodontal pathogenic bacteria produce endotoxins, periodontal treatment can result in endotoxemia. The aim of this study was to investigate the effects of intravenous, sonicated Porphyromonas gingivalis (Pg) injection on glucose/lipid metabolism, liver steatosis, and gut microbiota in mice. Endotoxemia was induced in C57BL/6J mice (8 weeks old) by intravenous injection of sonicated Pg; Pg was deactivated but its endotoxin remained. The mice were fed a high-fat diet and administered sonicated Pg (HFPg) or saline (HFco) injections for 12 weeks. Liver steatosis, glucose metabolism, and gene expression in the liver were evaluated. 16S rRNA gene sequencing with metagenome prediction was performed on the gut microbiota. Compared to HFco mice, HFPg mice exhibited impaired glucose tolerance and insulin resistance along with increased liver steatosis. Liver microarray analysis demonstrated that 1278 genes were differentially expressed between HFco and HFPg mice. Gene set enrichment analysis showed that fatty acid metabolism, hypoxia, and TNFα signaling via NFκB gene sets were enriched in HFPg mice. Although sonicated Pg did not directly reach the gut, it changed the gut microbiota and decreased bacterial diversity in HFPg mice. Metagenome prediction in the gut microbiota showed enriched citrate cycle and carbon fixation pathways in prokaryotes. Overall, intravenous injection of sonicated Pg caused impaired glucose tolerance, insulin resistance, and liver steatosis in mice fed high-fat diets. Thus, blood infusion of Pg contributes to NAFLD and alters the gut microbiota

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)