Fatigue Limit Reliability Analysis for Notched Material with Some Kinds of Dense Inhomogeneities Using Fracture Mechanics

This study proposes a quantitative method for predicting fatigue limit reliability of a notched metal containing inhomogeneities. Since the fatigue fracture origin of the notched metal cannot be determined in advance because of stress nonuniformity, randomly distributed particles, and scatter of a matrix, it is difficult to predict the fatigue limit. The present method utilizes a stress-strength model incorporating the “statistical hardness characteristics of a matrix under small indentation loads” and the “statistical hardness characteristics required for non-propagation of fatigue cracks from microstructural defects”. The notch root is subdivided into small elements to eliminate the stress nonuniformity. The fatigue limit reliability is predicted by unifying the survival rates of the elements obtained by the stress-strength model according to the weakest link model. The method is applied to notched specimens of aluminum cast alloy JIS AC4B-T6 containing eutectic Si, Fe compounds and porosity. The fatigue strength reliability at 107 cycles, which corresponds to the fatigue limit reliability, is predicted. The fatigue limits of notch root radius ρ = 2, 1, 0.3, and 0.1 mm are obtained by rotating-bending fatigue tests. It is shown that the fatigue limits predicted by the present method are in good agreement with the experimental ones

The role of vitamin E in T-cell differentiation and the decrease of cellular immunity with aging

Spontaneously hypertensive rats (SHR)as a model for aging were used in this experiment and fed a regular (50 IU/Kg diet) or high vitamin E(500IU/Kg diet) diet for 6weeks. At 12weeks old, they were killed and assayed. Although proliferation of thymic lymphocytes was significantly decreased in SHR fed the regular diet compared to Wistar Kyoto rats (WKY) fed the same diet, high vitamin E diet enhanced proliferation of thymic lymphocytes in SHR to almost the levels in WKY fed the regular diet. In addition, the expressions of both CD4 and CD8 antigens on CD4+CD8+ T cells, immature T cells existing in thymic cortex, were also decreased in SHR, and significantly improved by high vitamin E diet. These results suggest that high vitamin E diet enhances thymic lymphocyte proliferation through increased T-cell differentiation in thymus. Then, the effect of vitamin E on T-cell differentiation in thymus was investigated by using male Fisher rats. Rats were divided into three groups;vitamin E-free, regular and high vitamin E groups and fed a diet containing various levels of vitamin E(0, 50 and 500IU/Kg diet) for 7weeks. Although the percentages of CD4+CD8- and CD4-CD8+ T cells in thymocytes were significantly greater in the high vitamin E group, the percentage of CD4+CD8- T cells inversely decreased in the vitamin E-free group compared to the regular group. We have tried to investigate the mechanism of the increased T-cell differentiation in thymus of rats fed the high vitamin E diet through cytokine production, and thymic epithelial cell (TEC) and macrophage functions. We have found that vitamin E enhances T-cell differentiation through the increase of not macrophage but TEC function in thymus, which is associated with the increased binding capacity of TEC to immature T cells via increased expression of adhesion molecule, ICAM-1. These results suggest that vitamin E is a potent nutrient for promoting health in the aged via the improvement of cellular immunity decreased with aging

Successful lung-protective ventilatory management during the VV-ECMO in a severe COVID-19 pneumonia patient with extensive pneumomediastinum and subcutaneous emphysema: a case report

BACKGROUND: Ventilatory management of respiratory failure with pneumomediastinum/subcutaneous emphysema is not established. Herein, we report a case of severe COVID-19 pneumonia with extensive pneumomediastinum/subcutaneous emphysema, rescued by thorough lung-protective ventilatory management after applying the VV-ECMO. CASE PRESENTATION: A 68-year-old male with no medical history was admitted to a local hospital and diagnosed with COVID-19 pneumonia. His pulmonary parameters worsened during invasive ventilation due to the development of pneumomediastinum/subcutaneous emphysema, and then he was transferred to our hospital. On arrival, we immediately decided to apply VV-ECMO and switch to ultraprotective ventilation. After maintaining the initial ventilation with a neuromuscular blocking agent for 2 days, we gradually increased PEEP while limiting PIP to 25 cmH2O. The patient was weaned off VV-ECMO on day 10; he was transferred to the medical ward after extubation. CONCLUSIONS: Lung-protective ventilatory management should be performed thoroughly during VV-ECMO in severe COVID-19 pneumonia with pneumomediastinum/subcutaneous emphysema

Expression of EGF and, Ras and Myc Oncogene Products in Normal, Graves\u27 Thyroid, Adenoma, and Carcinoma of the Thyroid

An immunohistochemical study of EGF, and products of ras and myc oncogenes was carried out in 47 cases of non-neoplastic and neoplastic lesions of the thyroid. Normal thyroid tissues showed no significant immunostaining reaction to antibodies for EGF, and products of ras and myc oncogenes. The incidence of EGF positivity was 27%, 46% and 76% in Graves\u27 disease, follicular adenoma, and carcinoma, repectively. The incidence of positivity of ras oncogene product was 27%, 38%, and 82% in Graves\u27 disease, follicular adenoma and carcinoma, respectively. The incidence of positivity of myc oncogene product was 18%, 46% and 71% in Graves\u27 disease, Follicular adenoma, and carcinoma, respectively. These results suggest that EGF, and ras and myc oncogenes or proto-oncogenes play a role in neoplastic lesions of the thyroid

Population pharmacokinetic modeling of GS‐441524, the active metabolite of remdesivir, in Japanese COVID‐19 patients with renal dysfunction

腎障害患者におけるレムデシビルの薬物動態モデルを構築 --新型コロナウイルス感染症治療薬の適正使用に向けて--. 京都大学プレスリリース. 2021-11-25.Remdesivir, a prodrug of the nucleoside analog GS-441524, plays a key role in the treatment of coronavirus disease 2019 (COVID-19). However, owing to limited information on clinical trials and inexperienced clinical use, there is a lack of pharmacokinetic (PK) data in patients with COVID-19 with special characteristics. In this study, we aimed to measure serum GS-441524 concentrations and develop a population PK (PopPK) model. Remdesivir was administered at a 200 mg loading dose on the first day followed by 100 mg from day 2, based on the package insert, in patients with an estimated glomerular filtration rate (eGFR) greater than or equal to 30 ml/min. In total, 190 concentrations from 37 Japanese patients were used in the analysis. The GS-441524 trough concentrations were significantly higher in the eGFR less than 60 ml/min group than in the eGFR greater than or equal to 60 ml/min group. Extracorporeal membrane oxygenation in four patients hardly affected the total body clearance (CL) and volume of distribution (Vd) of GS-441524. A one-compartment model described serum GS-441524 concentration data. The CL and Vd of GS-441524 were significantly affected by eGFR readjusted by individual body surface area and age, respectively. Simulations proposed a dose regimen of 200 mg on day 1 followed by 100 mg once every 2 days from day 2 in patients with an eGFR of 30 ml/min or less. In conclusion, we successfully established a PopPK model of GS-441524 using retrospectively obtained serum GS-441524 concentrations in Japanese patients with COVID-19, which would be helpful for optimal individualized therapy of remdesivir

Management of Natural History collections: criteria and parameters of evaluation

[ES] Las colecciones de historia natural son una herramienta básica para la investigación científica y el estudio de la distribución en el pasado de muchas especies, así como de la propia historia de la ciencia. Además del uso científico de estas colecciones, destacan otros como el histórico, el divulgativo-pedagógico y el estético. De ahí la importancia que tiene una gestión eficaz de las mismas, la cual implica diversos aspectos, que van desde la conservación y su mantenimiento, su inventario, ordenación y procesamiento informático hasta las múltiples tareas relacionadas con su uso en consultas, visitas, préstamos científicos y participación en actividades de carácter divulgativo. En este artículo se examinan los criterios para evaluar la gestión de las colecciones de historia natural y se definen una serie de parámetros, útiles para medir el estado de una colección y su evolución en el tiempo, tanto en su crecimiento como en su uso, principalmente. Se ejemplifica todo ello en el grupo de los poliquetos, del que el Museo Nacional de Ciencias Naturales de Madrid (MNCN) cuenta con una estimable colección, y se comparan los resultados, según varios parámetros seleccionados, con los de otras colecciones de poliquetos de diversas instituciones de todo el mundo.[EN] Natural History collections are a basic and essential tool for scientific research, the study of the distribution in the past of many species of animals and plants and the History of Science. As well as the scientific aspect of these collections, stand outs other uses as the historic one, the educational and the aesthetic. All these are reasons that show the importance of an effective management of the Natural History collections as well as the several tasks related to it, as consults, visits, scientific loans and educational activities. In this article various criteria and useful parameters are provided for evaluating the curatorial state of a Natural History collection and its evolution, both in growth and use mainly. Finally, an example based on the Polychaeta, an estimable group in the Invertebrates Collection of the Museo Nacional de Ciencias Naturales of Madrid (MNCN), is provided. The results of several selected parameters are compared with other Polychaeta collections from several institutions around the world.Peer reviewe

Endogenous secretory receptor for advanced glycation end-products inhibits amyloid-β 1-42 uptake into mouse brain

The cell-surface receptor for advanced glycation end-products (RAGE) has been implicated in the development of diabetic vascular complications and Alzheimer\u27s disease. RAGE has been considered to be involved in amyloid-β 1-42 (Aβ 1-42) uptake into brain. In the present study, we demonstrate that endogenous secretory RAGE (esRAGE), a decoy form of RAGE generated by alternative RNA processing, is able to inhibit Aβ 1-42 influx into mouse brain. Surface plasmon resonance and competitive binding assays revealed that human Aβ 1-42 interacted with human esRAGE within the immunoglobulin V type region. We next examined the uptake and distribution of 125I-labeled human Aβ 1-42 in various organs and body fluids of newly created mice overexpressing human esRAGE as well as RAGE-null and wild-type (WT) mice. The transition of the 125I-labeled Aβ 1-42 from circulation to brain parenchyma peaked at 30 min after the injection into WT mice, but this was significantly blunted in esRAGE-overexpressing and RAGE-null mice. Significant reduction in 125I-labeled Aβ 1-42-derived photo-stimulated luminescence were marked in ventricles, cerebral cortex, hippocampus, especially CA1 and CA3 regions, putamen, and thalamus. The results thus suggest the potential of esRAGE in protection against the development of Alzheimer\u27s disease. © 2012 - IOS Press and the authors. All rights reserved.Thesis of Sugihara Takahiro / 学位論文 医学甲第2227 杉原 崇

Intracrine activity involving NAD-dependent circadian steroidogenic activity governs age-associated meibomian gland dysfunction

新たなイントラクライン機構を用いた加齢性眼疾患治療へ --眼局所のホルモンの加齢変化とサーカディアンリズムが鍵--. 京都大学プレスリリース. 2022-02-14.Canonically, hormones are produced in the endocrine organs and delivered to target tissues. However, for steroids, the concept of tissue intracrinology, whereby hormones are produced in the tissues where they exert their effect without release into circulation, has been proposed, but its role in physiology/disease remains unclear. The meibomian glands in the eyelids produce oil to prevent tear evaporation, which reduces with aging. Here, we demonstrate that (re)activation of local intracrine activity through nicotinamide adenine dinucleotide (NAD+)-dependent circadian 3β-hydroxyl-steroid dehydrogenase (3β-HSD) activity ameliorates age-associated meibomian gland dysfunction and accompanying evaporative dry eye disease. Genetic ablation of 3β-HSD nullified local steroidogenesis and led to atrophy of the meibomian gland. Conversely, reactivation of 3β-HSD activity by boosting its coenzyme NAD+ availability improved glandular cell proliferation and alleviated the dry eye disease phenotype. Both women and men express 3β-HSD in the meibomian gland. Enhancing local steroidogenesis may help combat age-associated meibomian gland dysfunction