与信判断が確率変動するときの倒産企業の信用リスク値分布のモデル化 - Skew-normal分布の応用 -

要旨あり金融リスクの統計解析原著論

Missense allele of a single nucleotide polymorphism rs2294008 attenuated antitumor effects of prostate stem cell antigen in gallbladder cancer cells

Background: Prostate stem cell antigen (PSCA), an organ-dependent tumor suppressor, is down regulated in gallbladder cancer (GBC). It is anticipated that the missense allele C of the single nucleotide polymorphism (SNP) rs2294008 (T/C) in the translation initiation codon of the gene affects the gene′s biological function and has some influence on GBC susceptibility. We examined the biological effect of the C allele on the function of the gene and the relation between the C allele and GBC susceptibility. Materials and Methods: Functional analysis of the SNP was conducted by introducing PSCA cDNA harboring the allele to a GBC cell line TGBC- 1TKB and performing colony formation assays in vitro and tumor formation assays in mice. The effect on transcriptional regulation was assessed by reporter assays. The association study was conducted on 44 Japanese GBC cases and 173 controls. Results: The PSCA cDNA harboring the C allele showed lower cell growth inhibition activity (20% reduction) than that with the T allele. Concordantly, when injected into subcutaneous tissues of mice, the GBC cell line stably expressing the cDNA with the C allele formed tumors of almost the same size as that of the control cells, but the cell line expressing the cDNA with the T allele showed slower growth. The upstream DNA fragment harboring the C allele had more transcriptional activity than that with the T allele. The C allele showed positive correlation to GBC but no statistical significant odds ratio (OR = 1.77, 95% confidence interval 0.85-3.70, P value = 0.127 in dominant model). Conclusions: The missense allele was shown to have a biological effect, attenuating antitumor activities of PSCA, and consequently it may be a potential risk for GBC development. An association study in a larger sample size may reveal a significant association between the allele and GBC

Cognitive behavioral therapy for depression among adults in Japanese clinical settings: a single-group study

<p>Abstract</p> <p>Background</p> <p>Empirical support for cognitive behavioral therapy (CBT) for treating Japanese patients with major depression is lacking, therefore, a feasibility study of CBT for depression in Japanese clinical settings is urgently required.</p> <p>Findings</p> <p>A culturally adapted, 16-week manualized individual CBT program for Japanese patients with major depressive disorder was developed. A total of 27 patients with major depression were enrolled in a single-group study with the purpose of testing the feasibility of the program. Twenty six patients (96%) completed the study. The mean total score on the Beck Depression Inventory-II (BDI-II) for all patients (Intention-to-treat sample) improved from 32.6 to 11.7, with a mean change of 20.8 (95% confidence interval: 17.0 to 24.8). Within-group effect size at the endpoint assessment was 2.64 (Cohen's d). Twenty-one patients (77.7%) showed treatment response and 17 patients (63.0%) achieved remission at the end of the program. Significant improvement was observed in measurement of subjective and objective depression severity (assessed by BDI-II, Quick Inventory of Depressive Symptomatology-Self Rated, and Hamilton Depression Rating Scale), dysfunctional attitude (assessed by Dysfunctional Attitude Scale), global functioning (assessed by Global Assessment of Functioning of DSM-IV) and subjective well-being (assessed by WHO Subjective Well-being Inventory) (all p values < 0.001).</p> <p>Conclusions</p> <p>Our manualized treatment comprised of a 16-week individual CBT program for major depression appears feasible and may achieve favorable treatment outcomes among Japanese patients with major depression. Further research involving a larger sample in a randomized, controlled trial design is warranted.</p> <p>Trial registration</p> <p>UMIN-CTR UMIN000002542.</p

Technological and behavioural complexity in expedient industries: The importance of use-wear analysis for understanding flake assemblages

Expedient lithic technology has been described as unchanging and without or very limited presence of formal tool types. However, this premise seems to limit the discussion on technological and behavioural complexity when studying amorphous flake industries. To address this issue, we employed multi-stage use-wear analysis to identify features that are not detectable through macroscopic approach. Our analysis of chert tools from Leang Sarru, North Sulawesi indicated the use of both unmodified flakes and retouched tools for plant processing, and we detected evidence for the manufacture of composite tools. Microscopic wear traces on unretouched flakes show that these were attached to shafts for possible use as hafted tools, but not necessarily as projectiles. Our results suggest that simple flake assemblages can be part of complex tool production and present an alternative view on the seemingly unchanging lithic technology from the Late Pleistocene to the Holocene. Furthermore, our current understanding of expedient lithic technology should be reassessed as features that are not observable with standard morphological and technological analyses may be detected through use-wear analysis. Overall, the applied methodology and results of this study are relevant to Pleistocene and Early Holocene archaeological sites and assemblages that exhibit the dilemma of inferring technological and behavioural complexity through the analysis of simple stone tools

Lumi-Map, a real-time luciferase bioluminescence screen of mutants combined with MutMap, reveals Arabidopsis genes involved in PAMP-triggered immunity

Plants recognize pathogen-associated molecular patterns (PAMPs) to activate PAMP-triggered immunity (PTI). However, our knowledge of PTI signaling remains limited. In this report, we introduce Lumi-Map, a high-throughput platform for identifying causative single-nucleotide polymorphisms (SNPs) for studying PTI signaling components. In Lumi-Map, a transgenic reporter plant line is produced that contains a firefly luciferase (LUC) gene driven by a defense gene promoter, which generates luminescence upon PAMP treatment. The line is mutagenized and the mutants with altered luminescence patterns are screened by a high-throughput real-time bioluminescence monitoring system. Selected mutants are subjected to MutMap analysis, a whole-genome sequencingbased method of rapid mutation identification, to identify the causative SNP responsible for the luminescence pattern change. We generated nine transgenic Arabidopsis reporter lines expressing the LUC gene fused to multiple promoter sequences of defense-related genes. These lines generate luminescence upon activation of FLAGELLIN-SENSING 2 (FLS2) by flg22, a PAMP derived from bacterial flagellin. We selected the WRKY29-promoter reporter line to identify mutants in the signaling pathway downstream of FLS2. After screening 24,000 ethylmethanesulfonate-induced mutants of the reporter line, we isolated 22 mutants with altered WRKY29 expression upon flg22 treatment (abbreviated as awf mutants). Although five flg22-insensitive awf mutants harbored mutations in FLS2 itself, Lumi-Map revealed three genes not previously associated with PTI. Lumi-Map has the potential to identify novel PAMPs and their receptors as well as signaling components downstream of the receptors