The Second Fundamental Theorem of Welfare Economics and the Existence of Competitive Equilibrium over an Infinite Horizon with General Consumption Sets

The purpose of this paper is to prove the second fundamental theorem of welfare economics and the existence of competitive equilibrium in production economies over an infinite horizon with general consumption sets. In the literature of the studies for an economy of infinite dimmentional commodity space, the second fundamental theorem of welfare economics was proved only approximately with uniform properness that is an assumption on consumers' preferences. The existence of competitive equilibrium was also shown under the assumption. However, when we turn to the study of the long run path of the economy, especially of sustainable growth, the assumption that uniformly bounds the rate of substitution among goods is inconsistent with some important preferences of growth theory. We proved the both theorems without uniform properness. The irreducibility of an economy and aggregate adequacy assumption plays the key role. Our model follows Boyd-McKenzie(1993) and generalize their strong irreducibility asuumption on the economy to the usual irreducibility.

Direct Measurement of the Thermodynamic Parameters of Amyloid Formation by Isothermal Titration Calorimetry

This research was originally published in the Journal of Biological Chemistry. József Kardos, Kaori Yamamoto, Kazuhiro Hasegawa, Hironobu Naiki and Yuji Goto. Direct Measurement of the Thermodynamic Parameters of Amyloid Formation by Isothermal Titration Calorimetry. J. Biol. Chem. 2004; 279, 55308-55314. © the American Society for Biochemistry and Molecular Biolog

Clinical Characteristics of Fragile X Syndrome Patients in Japan

[Background] Fragile X syndrome (FXS) is a well-known X-linked disorder clinically characterized by intellectual disability and autistic features. However, diagnosed Japanese FXS cases have been fewer than expected, and clinical features of Japanese FXS patients remain unknown. [Methods] We evaluated the clinical features of Japanese FXS patients using the results of a questionnaire-based survey. [Results] We presented the characteristics of seven patients aged 6 to 20 years. Long face and large ears were observed in five of seven patients. Macrocephaly was observed in four of five patients. The meaningful word was first seen at a certain time point between 18 and 72 months (median = 60 months). Developmental quotient or intellectual quotient ranged between 20 and 48 (median = 29). Behavioral disorders were seen in all patients (autistic spectrum disorder in six patients, hyperactivity in five patients). Five patients were diagnosed by polymerase chain reaction analysis, and two patients were diagnosed by the cytogenetic study. All physicians ordered FXS genetic testing for suspicious cases because of clinical manifestations. [Conclusion] In the present study, a long face, large ears, macrocephaly, autistic spectrum disorder, and hyperactivity were observed in almost cases, and these characteristics might be common features in Japanese FXS patients. Our finding indicated the importance of clinical manifestations to diagnosis FXS. However, the sample size of the present study is small, and these features are also seen to patients with other disorders. We consider that genetic testing for FXS should be performed on a wider range of intellectually disabled cases

Overexpression of Nuclear Receptor 5A1 Induces and Maintains an Intermediate State of Conversion between Primed and Naive Pluripotency

Naive and primed human pluripotent stem cells (hPSCs) have provided useful insights into the regulation of pluripotency. However, the molecular mechanisms regulating naive conversion remain elusive. Here, we report intermediate naive conversion induced by overexpressing nuclear receptor 5A1 (NR5A1) in hPSCs. The cells displayed some naive features, such as clonogenicity, glycogen synthase kinase 3β, and mitogen-activated protein kinase (MAPK) independence, expression of naive-associated genes, and two activated X chromosomes, but lacked others, such as KLF17 expression, transforming growth factor β independence, and imprinted gene demethylation. Notably, NR5A1 negated MAPK activation by fibroblast growth factor 2, leading to cell-autonomous self-renewal independent of MAPK inhibition. These phenotypes may be associated with naive conversion, and were regulated by a DPPA2/4-dependent pathway that activates the selective expression of naive-associated genes. This study increases our understanding of the mechanisms regulating the conversion from primed to naive pluripotency

Neighborhood Social Cohesion and Dementia-Related Stigma Among Mothers of Adolescents in the Pre- and Current COVID-19 Period: An Observational Study Using Population-Based Cohort Data

BACKGROUND: Middle-aged adults may be the ideal target group for dementia-related stigma reduction interventions to encourage the utilization of services among those who may become family caregivers. Neighborhood social cohesion may diminish dementia-related stigma, particularly in terms of perceived public attitudes. The COVID-19 pandemic can further negatively impact perceived public stigma. OBJECTIVE: To investigate the association between neighborhood social cohesion and dementia-related stigma during the pre- and current COVID-19 period. METHODS: We employed a cross-sectional design using data from a large population-based cohort, the Tokyo Teen Cohort, in Japan. Overall, 2,469 mothers of 16-year-old adolescents self-completed a questionnaire comprising nine dementia-related stigma questions evaluating perceived public and personal attitudes. Neighborhood social cohesion was assessed using a five-item instrument. The participants were divided into two groups according to the time of assessment: prior to the pandemic’s onset (February 2019–March 2020) and during the pandemic (April 2020–July 2021). A multiple regression analysis of stigma was performed using neighborhood social cohesion as an independent variable, and caring experience, age, educational level, and working status as covariates. RESULTS: Personal and perceived public stigma were significantly lower in participants who perceived greater neighborhood social cohesion. However, level of personal and perceived public stigma did not differ between pre- and during the pandemic period. CONCLUSIONS: Neighborhood social cohesion may be a modifiable factor for dementia-related stigma. A localized intervention to enhance social cohesion in the neighborhood community would promote the utilization of services among those who may become family caregivers

Detection of CpG Methylation in G-Quadruplex Forming Sequences Using G-Quadruplex Ligands

Genomic DNA methylation is involved in many diseases and is expected to be a specific biomarker for even the pre-symptomatic diagnosis of many diseases. Thus, a rapid and inexpensive detection method is required for disease diagnosis. We have previously reported that cytosine methylation in G-quadruplex (G4)-forming oligonucleotides develops different G4 topologies. In this study, we developed a method for detecting CpG methylation in G4-forming oligonucleotides based on the structural differences between methylated and unmethylated G4 DNAs. The differences in G4 topologies due to CpG methylation can be discriminated by G4 ligands. We performed a binding assay between methylated or unmethylated G4 DNAs and G4 ligands. The binding abilities of fluorescent G4 ligands to BCL-2, HRAS1, HRAS2, VEGF G4-forming sequences were examined by fluorescence-based microtiter plate assay. The differences in fluorescence intensities between methylated and unmethylated G4 DNAs were statistically significant. In addition to fluorescence detection, the binding of G4 ligand to DNA was detected by chemiluminescence. A significant difference was also detected in chemiluminescence intensity between methylated and unmethylated DNA. This is the first study on the detection of CpG methylation in G4 structures, focusing on structural changes using G4 ligands

Biological Dose Evaluation Of Radiotherapy By Equivalent Dose In 2Gy Fractions (EQD2) In Recurrent Glioblastoma.

The standard treatment for glioblastoma is surgery followed by radiation therapy (RT) and temozolomide (TMZ) chemotherapy. A total dose of 60 Gy given in 2 Gy fractions (fr) with concurrent and adjuvant TMZ has been recommended; however, local recurrences are frequent and the prognosis remains very poor. In this study, the equivalent dose in 2Gy fr (EQD2) at the recurrent site of glioblastoma was assessed to evaluate the biological effect of RT on glioblastoma considering that α/β ratios might vary from 1 to 10 Gy. Recurrences were found in gross tumor volume (GTV) areas in all 11 patients, and 8 of them also showed recurrence in clinical target volume (CTV). Differences in EQD2 according to α/β ratios were relatively small in high-dose areas around 60 Gy; however, low-dose areas often showed significant differences of EQD2 according to the α/β ratios. In patients that received 60 Gy in 2 Gy fr, EQD2 was less than the original physical dose and became smaller as the α/β ratio became smaller. The comparison of the dose distribution of EQD2 and dose volume histogram (DVH) of EQD2 between α/β ratios 1 and 10 suggested that little difference was found in relatively high-dose areas but a significant difference was found in low-dose areas. In contrast, if the fraction size was larger than 2 Gy, EQD2 was greater than the original physical dose and it became larger as the α/β ratio became smaller. In conclusion, this study showed that the standard RT 60 Gy in 2 Gy fr is insufficient for glioblastoma, and it suggested that biological effects might differ significantly according to each fraction size of radiation and α/β ratio of the linear quadratic (LQ) model

脳幹部転移性脳腫瘍に対する寡分割定位放射線治療の治療成績

Background: To assess the neuroimaging and clinical outcomes in patients with brainstem metastasis (BSM) treated with linac-based fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. Methods: Between May 2007 and January 2017, 24 patients (15 male and 9 female) with BSM (25 lesions: midbrain, 10; pons, 13; and medulla oblongata, 2) were consecutively treated with linac-based fSRT. BSM originated from the lung (n = 18, 75.0%), colon (n = 3, 12.5%), and breast (n = 3, 12.5%). The median patient age was 67.0 (range: 42-80) years. Recursive partition analysis classified 2 patients as class I, 17 as class II, and 5 as class III. Overall survival was calculated using the Kaplan-Meier method. Results: Tumor volume ranged from 0.01 to 7.49 cm3 (median: 0.233 cm3), and patients were treated with a dose of 24-40 Gy in 7-13 fractions. The median OS was 9 months after fSRT (95% confidence interval 4.104-13.896). Large tumor volume, presence of brainstem-related symptoms, poor pretreatment Karnofsky performance status, and recursive partition analysis class III were significantly associated with low overall survival. Tumor volume decreased in 18 metastatic lesions, remained stable in 6, and increased in 1. No patient exhibited permanent radiation injury. Grade 2 nausea and vomiting according to the Common Terminology Criteria for Adverse Events 4.0 occurred in 1 patient who received corticosteroids. Conclusions: Linac-based fSRT with a micro-multileaf collimator delivered in the doses of 24-40 Gy in 7-13 fractions is a safe and effective local therapy for patients with BSM.博士（医学）・乙第1450号・令和2年3月16日Copyright © 2019 Elsevier Inc. All rights reserved