脳動脈瘤開頭手術は, 1960年代のmicrosurgery導入後1990年代にほぼ成熟した. 血管内治療は1991年のGDC発表以降普及し, 破裂脳動脈瘤に関し2002年にはクリッピングを凌ぐ成績が発表された. 最近もバルーン補助コイル塞栓, flow diverterなど発展しつつある. 未破裂動脈瘤では破裂率研究が大きく進歩した. 基礎研究では動脈瘤形成が血管壁の炎症から始まること, 発生・増大に流体力学的機序が関与していることが明確になり, 脳動脈瘤感受性遺伝子領域も報告された. 未破裂瘤でのより個別化された破裂リスク推定, 瘤形成・増大機序に基づいた予防・治療の開発に脳動脈瘤克服の可能性を期待したい.

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Fukushima daiichi nuclear power station are contaminated with high levels of radioactivity. Robot performing decontamination activity is necessary because human can not go in the building. When performing the decontamination activities, it is necessary to prevent diffusion of contaminants and get over the step in the building. To solve this problem, We made a robot named "SHAR" which is able to do decontamination activities. This robot was using 8 mecanum wheels that was cut in half. As a result, it is possible to the steps of 100 [mm] in the forward and backward direction, and 50 [mm] in the sideways direction.

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In affected nuclear power plants, robots are necessary because it is dangerous for humans to approach the disaster site to collect information. To effectively perform this work, these robots must climb stairs and

obstacles. Current stair climbing methods include the use of trilobed wheels and crawlers. However, if there is a narrow landing between the stairs, these robots may collide with the wall while turning. Therefore, our purpose is to develop robots that can continuously climb stairs with narrow landings. To achieve this, we examined a method in which the robot moves laterally without turning, and climbs the stairs backwards. In this research, we propose a mechanism that implements Mecanum wheels at each end of trilobed wheels. Before designing this mechanism, we developed a prototype trilobed wheel robot for stair climbing and an eight-wheel Mecanum robot for omni-directional movement, and confirmed that both mechanisms functioned as expected. Finally, we designed and built the proposed mechanism for our final robot. Our experiments confirmed that the robot can move omni-directionally without turning, as well as climb the first and second steps of the stairs. Although it was unable to climb three steps, we believe that adjusting the robot’s center of gravity can solve this problem. During stair descension, the robot slipped without using the trilobed wheels. This can be solved by applying an anti-slip measure to the Mecanum wheels. Thus, we can conclude that our proposed mechanism shows the prospect that our robot can effectively climb stairs with a narrow landing.

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Studies have shown that reduced oxygen tension (hypoxia) in solid tumours adversely affects the outcome of radiotherapy. Despite being an independent prognostic marker of poor treatment outcome, hypoxia represents a physiological difference that can be utilised for selective cancer treatment. Since severe hypoxia (pO₂<0.3%; 2.5 mmHg) does not occur in normal tissue, it may be exploited for therapeutic gain. Accurate targeting of oxygen-deprived cells within a tumour mass may be achieved using hypoxia-targeted gene therapy. For gene therapy three separate issues need to be considered: 1) delivery of a gene to the tumour, 2) regulation of gene expression and 3) therapeutic efficacy. Each of these aspects is outlined here, with a view to gene therapy of the hypoxic tumour environment. It is proposed that by combining hypoxia-selective gene delivery with hypoxia-specific gene expression and oxygen-sensitive prodrug activation, radioresistant hypoxic tumour tissues may be effectively targeted.

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A new approach to the fabrication of multilayer mirrors on an atomic scale at soft x-ray wavelengths

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Recently, global issues concerning energy and environment have been the subjects for discussions. Moreover, several related programs are undertaken for the promotion of using worldwide biomass resources in response to the issue. In this paper the concept to a global tetralemma consisting of four issues such as population, food, energy and environment is discussed from the viewpoint of agricultural engineering based on the proposal of using "Rice" which can certainly contribute a lot as one of the key resources to cover at least three of the issues of food, energy and environment simultaneously. The possibility of using Rice for bio-ethanol production is also discussed from the viewpoint of improving the situations of two issues of energy and environment in global tetralemma

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Local recurrence and distant metastasis frequently occur after radiation therapy for cancer and can be fatal. Evidence obtained from radiochemical and radiobiological studies has revealed these problems to be caused, at least in part, by a tumor-specific microenvironment, hypoxia. Moreover, a transcription factor, hypoxia-inducible factor 1 (HIF-1), was identified as pivotal to hypoxia-mediated radioresistance. To the problems, radiation oncologists have recently obtained powerful tools, such as "simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT), which enables a booster dose of radiation to be delivered to small target fractions in a malignant tumor", "hypoxia-selective cytotoxins/drugs", and "HIF-1 inhibitors" etc. In order to fully exploit these innovative and interdisciplinary strategies in cancer therapy, it is critical to unveil the characteristics, intratumoral localization, and dynamics of hypoxia/HIF-1-active tumor cells during tumor growth and after radiation therapy. We have performed optical imaging experiments using tumor-bearing mice and revealed that the locations of HIF-1-active tumor cells changes dramatically as tumors grow. Moreover, HIF-1 activity changes markedly after radiation therapy. This review overviews 1) fundamental problems surrounding tumor hypoxia in current radiation therapy, 2) the function of HIF-1 in tumor radioresistance, 3) the dynamics of hypoxic tumor cells during tumor growth and after radiation therapy, and 4) how we should the difficulties with radiation therapy using innovative interdisciplinary technologies.

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Oral antiplatelet agents targeting the platelet P2Y12 receptor are an integral component of treating patients with acute coronary syndrome and those undergoing percutaneous coronary intervention. Clopidogrel has been the most commonly used agent in this respect worldwide. However, there are certain shortcomings of clopdiogrel, the most important of which is the wide response variability of platelet inhibition. The response to clopidogrel is affected by various clinical variables, genetic variations involved in its activation, and drug-drug interactions. Therefore, clinicians are faced with challenges in situations where high inhibition of platelets is necessary and in cases where the response to clopidogrel may be suboptimal. There are various ways of overcoming the response variability and this review will focus on the practical methods available. Namely, the data and evidence regarding increasing the dose of clopidogrel, adding cilostazol to standard dual antiplatelet therapy, and switching to more recently developed agents will be covered. (Circ J 2012; 76: 287-292)

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Australia is a continent of extremes with respect to water resources; relative abundance in the tropical north where few people live and relative scarcity in the more populated, temperate south. In addition, both south and north are affected by wet/dry seasonal climatic conditions and the south, in particular, by increasing climate variability marked generally by declining rainfall. In the south, previous poor governance systems have led to the over allocation of surface and groundwater supplies and there is increasing competition for water from irrigators, urban/domestic, industrial and mining users. As a consequence, there has been a major deleterious impact on the health of many rivers and their associated environments. Therefore, Australia is confronted with a major question; can water productivity and water governance be improved to ensure environmentally sustainable and productive river systems? This paper examines how this may be achieved. It concludes that economic reforms coupled with scientific and management innovation may alleviate many of the water scarcity issues.

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When a molybdenite was dissolved and treated by the conventional chemical procedure, it was difficult to achieve the isotopic equilibrium between the ¹⁸⁷Os radiogenically accumulated in the molybdenite and“common”Os added as a kind of internal standard, even after chemically complete decomposition. It is evident that this isotopic disequilibrium effect results in deterioration of Re-Os age for the molybdenite. A newly developed analytical technique employing a microwave digestion was found out to promote the isotopic equilibration of Os from two sources and to provide us with the ages concordant with those obtained by other geochronometers.

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We reported the major findings of our research based on our own academic achievement tests towards elementary school and junior high school pupils in 2002. We then pointed out the fact that the differences of achievement between social groups have been expanded. Nowadays, that issue is seen to be one of the most serious educational problems in contemporary Japan. Although the differences of various educational outcomes such as academic achievements or educational aspirations between social groups are always emphasized, it is surprising that they seldom discuss about the ways in which those differences could be made smaller. I myself have been exploring the issue in these several years. In this paper, I will describe the progress and the future directions of our academic exploration on this particular educational issue.

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　The Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine (founding director; CEO Hideoki Ogawa), was founded in 2002, supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. Since 2013, we have been focusing on intractable itch supported by Strategic Research Foundation Grant-aided Project for Private Universities from MEXT. We have been conducting research on elucidating the pathogenesis of intractable itch and developing preventive and therapeutic methods, and the results of our research have been highly evaluated both in Japan and overseas. After the end of the above support project, Asia’s first itch research center, Juntendo Itch Research Center (JIRC), was established at our institute to promote research in this field and to return the results of our research to society. In addition, our institute has held four academic symposiums about “Aiming to

intractable itch” since 2014 in order to develop itch research in Japan. The 5 ^th Symposium, which was the first since JIRC was established, was held on December 7, 2019. In this “What’s New from Juntendo University, Tokyo”, we report selected aspects of the 5 ^th Symposium and advances in the field of itch research.

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At present, atherosclerosis is one of the most important field in clinical and research medicine. Because it is closely related to cardiovascular (CV) and endocrine disorders such as coronary artery disease, cardiometabolic disorders, much research on how to manage atherosclerosis has been performed. The low-density lipoprotein cholesterol (LDL-C) concentration has been established as an independent risk factor for developing atherosclerosis, and considerable effort has been committed to educating both physicians and the general public on the importance of lowering LDL-C with statins. Although statins have already significantly improved CV outcomes, patients with LDL-C target levels achieved by intense statin therapy still have significant remaining CV risk. Statins already play a central role in managing hyperlipidemia; however, residual risk with statins is an important field of managing remaining CV risk. Recent studies have suggested residual cholesterol and inflammation risks in causing CV events. In the current review, we will discuss residual risk and suggest strategies to

it in the statins era.

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Particle engineering broadly refers to the controlled production of drug particles optimized for size, morphology, and structure. It encompasses both destructive (top-down) and constructive (bottom-up) particle formation processes, of which the most used for commercial dry powder inhaler products are milling and spray drying. In both cases, undesirable physicochemical changes may occur because of thermal and mechanical stresses and through interactions with solvents, and can be further potentiated through storage and interaction with atmospheric water. The occurrence and extent of these phenomena are dependent upon the process parameters and the starting material, which necessitates a thorough understanding of these factors to create a stable product with the necessary characteristics for lung deposition. This review covers commonly arising issues in particle engineering and mechanisms of prevention. Topics to be discussed relating to physical changes include (1) the unintended generation of crystalline disorder and amorphous regions in particles; (2) polymorphic transformations; (3) unintended crystallization when amorphization is desired; and (3) triboelectric charging. Topics to be discussed relating to chemical changes include (1) thermal and mechanically activated chemical reactions; and (2) crystalline disorder and chemical reactivity.

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The number of patients with chronic kidney disease (CKD) is on the rise worldwide, and there is urgent need for the development of effective plans against the increasing incidence of CKD. Podocytes, glomerular epithelial cells, are an integral part of the primary filtration unit of the kidney and form a slit membrane as a barrier to prevent proteinuria. The role of podocytes in the pathogenesis and progression of CKD is now recognized. Podocyte function depends on a specialized morphology with the arranged foot processes, which is directly related to their function. Epigenetic changes responsible for the regulation of gene expression related to podocyte morphology have been shown to be important in the pathogenesis of CKD. Although epigenetic mechanisms include DNA methylation, histone modifications, and RNA-based regulation, we have focused on DNA methylation changes because they are more stable than other epigenetic modifications. This review summarizes recent literature about the role of altered DNA methylation in the kidney, especially in glomerular podocytes, focusing on transcription factors and DNA damage responses that are closely associated with the formation of DNA methylation changes.

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  In developing countries, many people are unable to access basic healthcare services, resulting in many avoidable deaths and/or disabilities. The United Nations adopted the Millennium Development Goals in order to resolve this problem, and Japan has been contributing greatly to the achievement of these goals. In this context, in 2013 the Government of Japan proposed its Strategy on Global Health Diplomacy, and since then has been promoting Universal Health Coverage. Since the beginning of the 21st century, the particular importance of addressing neglected tropical diseases (NTDs) has been stressed by the international community. Nevertheless, of the 1 billion people world-wide who are currently living with NTDs, about three-fourths of these are living in poverty, and of these, nearly 65% are unable to acquire or access drugs for the prevention and treatment of these diseases. Under these circumstances, Japan decided to support the Global Health Innovative Technology (GHIT) Fund in order to support the research and development of drugs for people in developing countries, as well as the manufacture, supply and administration of these drugs. Over the last two years, the GHIT Fund has been supporting the research and development of five new candidate drugs for three NTDs (Chagas disease, leishmaniasis and malaria). Japan also hopes to stimulate domestic pharmaceutical industries in developing countries, as well as to increase international cooperation through various activities such the utilization of our capacity to research and develop new drugs.

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Genome scale synteny analysis, the analysis of relative gene-order conservation between species, can provide key insights into evolutionary chromosomal dynamics, rearrangement rates between species, and speciation analysis. With the rapid availability of multiple genomes, there is a need for efficient solutions to aid in comparative syntenic analysis. Current methods rely on homology assessment and multiple alignment based solutions to determine homologs of genetic markers between species and to infer syntenic relationships. One of the primary challenges facing multigenome syntenic analysis is the uncertainty posed by genome assembly data with un-sequenced gaps and possible assembly errors. Currently, manual intervention is necessary to tune and correct the results of homology assessment and synteny inference. This paper presents a novel automated approach to some of these limitations. It uses a graph based algorithm to infer sub-graphs denoting synteny chains with the objective of choosing the best locations for homologous elements, in the presence of paralogs, in order to maximize synteny. These synteny chains are expanded by merging sub-graphs based on various user defined thresholds for micro-syntenic scrambling. This approach comprehends and accommodates for contig and scaffold gaps in the assembly to determine homologous genetic elements that might either fall in unsequenced assembly gaps or lie on the edges of sequenced segments or on small fragments. Furthermore, it provides an automated solution for breakpoint analysis and a comparative study of chromosomal rearrangements between species. This approach was applied to a comparative study involving Drosophila. melanogaster and Drosophila.pseudoobscura genomes, as an example, and has been useful in analyzing inter-species syntenic relationships.

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The immune system has adopted somatic DNA alterations to the limitations of the genomic information. Activation induced cytidine deaminase (AID) is an essential enzyme to regulate class switch recombination (CSR), somatic hypermutation (SHM) and gene conversion (GC) of the immunoglobulin gene. AID is known to be required for DNA cleavage of S regions in CSR and V regions in SHM. However, its molecular mechanism is a focus of extensive debate. RNA editing hypothesis postulates that AID edits yet unknown mRNA, to generate specific endonucleases for CSR and SHM. By contrast, DNA deamination hypothesis assumes that AID deaminates cytosine in DNA, followed by DNA cleavage by base excision repair enzymes. We summarize the basic knowledge for molecular mechanisms for CSR and SHM and then discuss the importance of AID not only in the immune regulation but also in the genome instability.


(Contributed by Tasuku HONJO, M.J.A.)

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