3D鋳型模型を使用して解明した未破裂脳動脈瘤の内皮細胞機能不全

京都大学新制・課程博士博士(医学)甲第24789号医博第4981号新制||医||1066(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 江木 盛時, 教授 湊谷 謙司, 教授 花川 隆学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Natural Evolution Strategy for Mixed-Integer Black-Box Optimization

This paper proposes a natural evolution strategy (NES) for mixed-integer black-box optimization (MI-BBO) that appears in real-world problems such as hyperparameter optimization of machine learning and materials design. This problem is difficult to optimize because plateaus where the values do not change appear when the integer variables are relaxed to the continuous ones. CMA-ES w. Margin that addresses the plateaus reportedly showed good performance on MI-BBO benchmark problems. However, it has been observed that the search performance of CMA-ES w. Margin deteriorates when continuous variables contribute more to the objective function value than integer ones. In order to address the problem of CMA-ES w. Margin, we propose Distance-weighted eXponential Natural Evolution Strategy taking account of Implicit Constraint and Integer (DX-NES-ICI). We compare the search performance of DX-NES-ICI with that of CMA-ES w. Margin through numerical experiments. As a result, DX-NES-ICI was up to 3.7 times better than CMA-ES w. Margin in terms of a rate of finding the optimal solutions on benchmark problems where continuous variables contribute more to the objective function value than integer ones. DX-NES-ICI also outperformed CMA-ES w. Margin on problems where CMA-ES w. Margin originally showed good performance.Comment: Accepted for GECCO'2

Agent-Based Simulation on Women's Role in a Family Line on Civil Service Examination in Chinese History

In this paper, following our previous work on civil service examinations in imperial China, we investigate women's role in a Chinese historical family line using an agent-based simulation (ABS) model with a grid oriented genetic algorithm (GOGA) framework. We utilize a GOGA framework, because our ABS had such large parameter spaces with real values that it required much greater computational resources. First, we studied the genealogical records. Second, based on that study, we implemented an agent-based model with the family lines branched out into two clusters to compare different family norms. Third, using an "inverse simulation" technique, we optimized the agent-based model in order to fit the simulation profiles to real profile data with real-coded GA. From these intensive experiments, we have found that (1) The combined influence of the father, uncle, mother and the aunt has important significance in maintaining a successful family norm, and (2) a particular role of the aunt to pass it on as well.Agent-Based Simulation, Grid Oriented Genetic Algorithm, Inverse Simulation, Family Norm, Civil Service Examination

CMA-ES with Learning Rate Adaptation: Can CMA-ES with Default Population Size Solve Multimodal and Noisy Problems?

The covariance matrix adaptation evolution strategy (CMA-ES) is one of the most successful methods for solving black-box continuous optimization problems. One practically useful aspect of the CMA-ES is that it can be used without hyperparameter tuning. However, the hyperparameter settings still have a considerable impact, especially for difficult tasks such as solving multimodal or noisy problems. In this study, we investigate whether the CMA-ES with default population size can solve multimodal and noisy problems. To perform this investigation, we develop a novel learning rate adaptation mechanism for the CMA-ES, such that the learning rate is adapted so as to maintain a constant signal-to-noise ratio. We investigate the behavior of the CMA-ES with the proposed learning rate adaptation mechanism through numerical experiments, and compare the results with those obtained for the CMA-ES with a fixed learning rate. The results demonstrate that, when the proposed learning rate adaptation is used, the CMA-ES with default population size works well on multimodal and/or noisy problems, without the need for extremely expensive learning rate tuning.Comment: Nominated for the best paper of GECCO'23 ENUM Track. We have corrected the error of Eq.(7

An Extended ISM for Globally Multimodal Function Optimization by Genetic Algorithms

When attempting to optimize a function where exists several big-valley structures, conventional GAs often fail to find the global optimum. Innately Split Model (ISM) is a framework of GAs, which is designed to avoid this phenomenon called UV-Phenomenon. However, ISM doesn't care about previously-searched areas by the past populations. Thus, it is possible that populations of ISM waste evaluation cost for redundant searches reaching previously-found optima. In this paper, we introduce Extended ISM (EISM) that uses search information of past populations as trap to suppress overlapping searches. To show performance of EISM, we apply it to some test functions, and analyze the behavior

Protein Transduction Method for Cerebrovascular Disorders

Many studies have shown that a motif of 11 consecutive arginines (11R) is one of the most effective protein transduction domains (PTD) for introducing proteins into the cell membrane. By conjugating this &#34;11R&#34;, all sorts of proteins can effectively and harmlessly be transferred into any kind of cell. We therefore examined the transduction efficiency of 11R in cerebral arteries and obtained results showing that 11R fused enhanced green fluorescent protein (11R-EGFP) immediately and effectively penetrated all layers of the rat basilar artery (BA), especially the tunica media. This method provides a revolutionary approach to cerebral arteries and ours is the first study to demonstrate the successful transductionof a PTD fused protein into the cerebral arteries. In this review, we present an outline of our studies and other key studies related to cerebral vasospasm and 11R, problems to be overcome, and predictions regarding future use of the 11R protein transduction method for cerebral vasospasm (CV).</p

ダンセイ キョウショクイン オ タイショウ トシタ フィットネス プログラム ジッシ ゼンゴ ノ ケツエキセイジョウ ノ ヘンカ

ln this study, we investigated blood profiles of male faculty members before and after the execution of fitness program which was earned out in the year 2004. 1. When we compared the average value of all 24 items of examinees, the value of RBC and hematocrit were significantly increased (p<0.05). These changes are all normal reference value. 2. The Value of TG showed higher than normal reference value. There was no significant difference. However after execution it showed higher value than before execution. 3. HDL-c showed higher value in after execution. However there was no significant difference. The exercise in this program might give a good influence to examinees. 4. We divided examinees in two groups : by the training frequency. High training frequency group showed high value of TG in both before and after the execution of the program, but the value was low in after execution than before execution. Low training frequency group showed within normal reference value of TG before execution but higher in after execution. This result indicated that amount of exercise gave influence on blood profiles. 5. We assumed that there were differences among individuals in the result of blood profiles of examinees. Not only the training frequency (amount of exercise), but also there were many inspection items which were influenced by mealswhich

Culture Conditions for Maintain Propagation, Long-term Survival and Germline Transmission of Chicken Primordial Germ Cell-Like Cells

Transplantation of primordial germ cells (PGCs), which are the progenitor cells of gametes, is a powerful tool for generation of transgenic chickens. However, the frequencies of transgene integration into the genome of purified PGCs still remain low. An in vitro culture system enabling chicken PGCs to propagate efficiently would be useful for efficient transgenesis of PGCs. In the present study, we optimized the culture conditions for chicken PGCs to enhance the proliferation and evaluated the germline transmission of cultured PGCs that proliferated for long periods of time. PGC-like cells (PGC-LCs), that have remarkably similar morphological characteristics to intact PGCs, could be derived by cultivation of blood containing PGCs obtained from 2.5-day-old chicken embryos according to the protocol of van de Lavoir et al. (2006). We determined which feeder cells and which growth factors were required to improve proliferation of PGC-LCs. Male PGC-LCs survival and proliferation were enhanced during culture in the basic medium containing either basic fibroblast growth factor (bFGF) alone or both bFGF and stem cell factor (SCF) on a feeder of buffalo rat liver (BRL) cells. Male PGC-LCs could be propagated in defined culture condition for extended periods. These cells expressed the germline-specific protein Vasa and undifferentiated cell marker stage-specific embryonic antigen-1 (SSEA-1) and pluripotency genes Nanog and PouV. Furthermore, Male PGC-LCs cultured for 225 d could migrate toward and colonize within recipient gonads and transmit to the next generation following transplantation. We succeeded in produce 3 offspring originating from long-term cultured PGC-LCs from a germline chimeric rooster (6%). The present study represents valuable steps toward defining a culture condition enabling PGC-LCs to propagate efficiently for long periods in vitro with maintenance of their commitment to the germline.ArticleJOURNAL OF POULTRY SCIENCE. 51(1):87-95 (2014)journal articl

Predominant accumulation of a 3-hydroxy-γ-decalactone in the male rectal gland complex of the Japanese orange fly, Bactrocera tsuneonis

The Japanese orange fly, Bactrocera tsuneonis, infests various citrus crops. While male pheromone components accumulated in the rectal glands are well characterized for Bactrocera, but information regarding the chemical factors involved in the life cycles of B. tsuneonis remains scarce. Herein, several volatile chemicals including a γ-decalactone, (3R, 4R)-3-hydroxy-4-decanolide [(3R, 4R)-HD], were identified as major components, along with acetamide and spiroketals as minor components in the rectal gland complexes of male B. tsuneonis flies. The lactone (3R, 4R)-HD was also identified in female rectal gland complexes. The amount of this compound in mature males was significantly higher than those observed in females and immature males. The lactone (3R, 4R)-HD was detected in flies fed with sucrose only, indicating that this lactone is not derived from dietary sources during adulthood, but biosynthesized in vivo. The predominant accumulation of (3R, 4R)-HD in mature males also suggests a possible role in reproductive behavior