2017年06月29日

講演者氏名と概要

<Presentator's name and abstracts>

※ If you click the tab of date, you can see the presentator's name and abstracts of the date.

1st day (Thur., Nov., 5th)

Session 1-1: Modeling for biological systems (Chairperson: Masako Bando (Kyoto U. ))

Name: Tomoko Ohta
Affiliation: National Institute of Genetics
Title: "Population genetics: Its mathematical principles and some recent trends"
Abstracts Population genetics started by integrating Darwinian theory of natural selection and Mendelian genetics. The basic quantity is gene frequency in the population, and its change by natural selection and random genetic drift has been formulated. Before molecular biology started, the deterministic theory of gene frequency by natural selection was thought to be important for evolution. However since the proposal of the neutral theory of molecular evolution by Kimura (1968), stochastic change of gene frequency by random drift has been recognized to be significant for evolution. In the 21st century, large amount of genome sequence data have become available, and stochastic theory of population genetics is being applied to molecular data. In the neutral theory, new mutations are classified into three classes; deleterious, neutral and advantageous. On the other hand, the nearly neutral theory (Ohta 1973) assumes that the border line mutations between the selected and the neutral classes of mutations are important, and that the majority of such weakly selected mutations are slightly deleterious. Polymorphisms at the DNA level in human populations show abundance of rare alleles at functionally important sites that are in accord with the nearly neutral theory. The application of the nearly neutral theory toward clarification of the evolution of gene regulation is also expanding. It has been thought that, for morphological evolution, gene regulation is more important than gene, and recent progress at the molecular level on gene regulation and epigenetics needs to be integrated. A notable subject on this is the chromatin structure that controls gene expression pattern. Numerous molecular machineries are involved; DNA methylation, histone modification and others. The knowledge on the mechanisms that make genes responsive to environmental changes also needs special attention as they provide rapid adaptation to environmental changes. Here nuclear receptors that bind to hormones and vitamins are master regulators of transcription networks. These complex systems are robust and plastic, and many mutations at individual amino acid or nucleotide site have small effects and are nearly neutral.

 

Name: Yuki Sato
Affiliation: Kyoto University
Title: "Utilization of X-ray irradiation to elucidate the stem cell system in planarian"
Abstracts Recently, the concept of “stem cells” has become popular not only in academic fields but also among the general public because of the establishment of ES cells (embryonic stem cells) and iPS cells (induced pluripotent stem cells). These cells are pluripotent stem cells (PSCs), which are the cells that can produce all types of cells in the body, including germ-line cells, providing us the possibility of regenerative medicine. Toward the next step for regenerative medicine, we should know how these PSCs can be regulated in the adult body. We use the freshwater planarians Dugesia japonica as a model animal for studying the regulatory systems of PSCs in the adult body. While most adult animals do not possess PSCs, planarians possess PSCs, called neoblasts, distributed throughout their adult body. By using their neoblasts, planarians can perform asexual reproduction and regeneration even from a tiny body fragment within a week. To elucidate regulatory systems of PSCs, we observed behaviors of the neoblasts in detail by using X-ray irradiation, which is known to specifically eliminate neoblsts. For this, we irradiated half of the planarian body with X-ray (partial body irradiation), and observed migration of the neoblasts into the irradiated region from the non-irradiated region. In addition, low-dose X-ray irradiation resulted in survival of a fraction of the neoblasts, which enabled us to observe how the surviving neoblasts recovered their population by self-renewal. Here, we will introduce the utilization of X-ray irradiation in stem cell research, and our new findings about the regulatory systems of PSCs in the adult body.

 

Name: Yoichi Gondo
Affiliation: Riken
Title: "Detection of spontaneous mutations in mammalian genomes"
Abstracts Spontaneous mutations are the driving force of evolution. The Kimura’s neutral theory elucidated that the substitution rate in a large enough population is equal to the spontaneous mutation rate. The induced mutation rate is also one of the effective parameters to assess the environmental genetic risk factors. To estimate the induced mutation rate, it is also necessary to precisely estimate the background mutation rate (= spontaneous mutation rate). The advancement of new generation sequencers (NGS) have made it possible to detect and assess the spontaneous as well as induced mutations even in mammalian genome. For instance, the spontaneous mutation rate was reported to be about 1×10-8/bp/generation by human trio analyses. On the other hand, the mutation rate is known to be dependent on age, gender, genetic background and so forth. In order to depict the “golden standard” mutation rate and spectrum in mammals, we have been detecting and analyzing de novo spontaneous mutations in one of the standard inbred mouse strains, C57BL/6J, of which genomic DNA was subjected to the Mouse Genome Project. We carefully designed a novel mating scheme to accumulate spontaneous mutations without selective pressures. After the accumulation of spontaneous mutations in eight independent pedigrees, we conducted the whole-genome sequencing (WGS) and called single nucleotide variations (SNVs) in the eight offspring. We are validating and genotyping the called SNVs in all the mice of the 8 pedigrees to trace when, where and what kind of mutations arose. The newly developed mating scheme is directly applicable to any species that proliferate by sexual reproduction. The assessment for mutation rates and spectra with large-scale and high-resolution analyses should shed light on the experimental studies on mutagenesis, evolution, genotoxicity and others in various populations.

 

Name: Hana Dobrovoiny
Affiliation: Texas Christian University
Title: "Modeling of tumor growth and treatment with oncolytic viruses"
Abstracts One of the most promising areas in cancer treatment is the use of viruses to attack cancer cells. A number of oncolytic viruses have been identified to date that possess the ability to destroy or neutralize cancer cells while inflicting minimal damage upon healthy cells. Formulation of predictive models that correctly describe the evolution of infected tumor systems is critical to the successful application of oncolytic virus therapy. A number of different models have been proposed for analysis of a virus-infected tumor, but to date they have not investigated the effect of the infection on non-cancerous cells. We have extended the traditional framework to a 2-cell model that includes both cancerous and non-cancerous cells, allowing us to investigate the impact of viral infection on both populations. Analysis of the new framework reveals complex interaction between the populations and potential inability to simultaneously eliminate the virus and tumor populations while leaving non-cancerous cells unharmed.

Session 1-2: Biological effects of radiation: Radiation epidemiology and medical statistics (Chairperson: TBA (TBA ))

Name: Mark Little
Affiliation: US National Cancer Institute, Radiation Epidemiology Branch
Title: "Low-dose and low-dose-rate epidemiology of cancer and non-cancer effects "
Abstracts The detrimental tissue-reaction (deterministic) and stochastic effects associated with moderate and high dose ionizing radiation (X-ray) exposure are well known. In contrast to tissue-reaction effects, for stochastic effects scientific committees such as ICRP (e.g. Report 103, 2007) and UNSCEAR (e.g. UNSCEAR 2006 report) generally assume (for regulatory purposes) that at sufficiently low doses there is a positive linear component to the dose response, i.e., that there is no threshold, or beneficial effect. There is accumulating direct evidence of excess risk of cancer and various other health endpoints in a large number of populations exposed at moderate and low doses, which will be reviewed. In particular, there is evidence of excess risk of most types of cancer associated with radiation exposures of the order of 10-20 mGy from diagnostic x-ray exposure in the Oxford Survey of Childhood Cancers and in various other groups exposed in utero, (Wakeford & Little Int J Radiat Biol 2003;79:293-309), although this data remains somewhat controversial. There is also evidence of excess risk of childhood leukemia associated with natural background radiation exposure, at doses of the order of 10-20 mGy, in a large UK population-based case-control study (Kendall et al Leukemia 2013;27:3-9). At slightly higher doses, increased risks of leukemia and brain cancer have been observed in pediatrically-exposed groups given multiple computerized tomography examinations, at doses of about 60 mGy to the respective tissues (red bone marrow, brain)(Pearce et al Lancet 2012;380:499-505). The excess risks in all of these studies are consistent with those in the Japanese atomic bomb survivor data. Evidence has recently emerged of an association between lower doses (< 0.5 Gy) and late circulatory disease. In particular, a recent systematic review and meta-analysis suggested an excess radiation-associated risk at occupational and environmental dose levels (< 0.5 Gy) (Little et al. Environ Health Perspect 2012;120:1503-11). However, the presence and magnitude of the excess circulatory disease risk at low doses is still relatively controversial, and much remains unknown as to the shape of the dose response.

 

Name: Shiro Tanaka
Affiliation: Kyoto University
Title: "Critiques on epidemiology: How were we being misled?"
Abstracts Epidemiology is academically defined as the science of disease in specified populations. Well-known findings from epidemiology include vitamin B1 and beriberi, smoking and lung cancer, and X-rays and childhood leukemia. Unfortunately, they are selected, successful examples. In its history, epidemiological studies seem almost constitutionally contradictory - positive and negative findings on radon exposure and lung cancer, pesticide residues and breast cancer, abortions and breast cancer, and electromagnetic fields and leukemia. How were we being misled? Statistical analysis in experimental physics is straightforward but not in epidemiology. In this talk, I will review methodological difficulties of epidemiology, clarifying the reasons why mathematical techniques like regression modeling often do not work.

 

Name: Kenichi Yoshikawa
Affiliation: Doshisha University
Title: "Extending Physics through the Exotic Events in Life: Simple Theory and Real-World Modeling"
Abstracts Living organisms on the earth maintain their lives by creating specific spatio-temporal structure in a self-emergent manner. In the present paper, we will try to interpret the dynamical aspects of life accompanied by the development of physical consideration. We will focus our attention onto the significant role of cross-talks among different levels of hierarchy on life; from molecule, through cell and organ, up to the level of ontogenesis. 1) On-off switching of large number of genes embedded in genomic DNA1 We will describe the intrinsic on/off property of a giant DNA molecule, which has been confirmed through the experimental observation on DNA molecules. We will also discuss the biological significance of the discrete nature of the conformational transition in relation to robust on/off switching of large number of genes on the process of cell-differentiation. 2) Field hypothesis on living cell2 We show unique physic-chemical properties observed in micro systems as the simple model of living cell, including i) Protein synthesis is markedly accelerated in small aqueous droplet covered by phospholipid, and ii) In a crowded microsphere, DNA undergoes a transition from tightly packed state onto an elongated state accompanied by its localization on the membrane surface. 3) Non-Turing scenario of body-organization during development3 Over the period of half-century, Turing model has been almost the sole hypothesis to explain the formation of stable spatial pattern in multicellular organisms. The Turing model is based on a framework with spatially continuous, together with the dominant diffusion of inhibitor with respect to activator. On the contrary, we propose a simple reaction-diffusion model under the framework with two characteristic features: i) dominant diffusion of activator, and ii) spatial discreteness on the ensemble of cells. [Refs.] (1) A. A. Zinchenko and KY, Curr. Op. Coll. Inter. Sci., 44, 325(2015). M. Tsuchiya, A. Giuliani, M. Hashimoto, J. Erenpreisa and KY, Plos One, 10, 0128565(2015). (2) T. Hamada and KY, Materials, 5, 2292 (2012): C.-Y. Shew and KY, J. Phys. Cond. Matt., 27, 064118(2015). (3) H. Nagahara, KY, et al., Phys Rev E, 80, 021906 (2009); Chem. Phys. Lett, 494, 88(2010).

Session 1-3: Poster session

See "Poster session" tab.

2nd day (Fri., Nov., 6th)

Session 2-1:Radiation dosimetry (Chairperson: TBA (TBA))

Name: Masaharu Tsubokura
Affiliation: University of Tokyo, Minamisoma Municipal General Hospital, Japan
Title: "The current situation of the radiation exposure screening program in Hama-dori and the future tasks"
Abstracts Since the Fukushima Dai-ichi nuclear power plant disaster, a regular internal radiation exposure-screening program has been in place in Fukushima. From these results, we know that the levels of chronic internal exposure among residents have been kept at a very low level. However, the level of awareness and the feeling of anxiety that the residents have experienced about the current situation vary by individuals. When the number of residents who are no longer interested in radiation, people who avoid consuming locally grown produce also exist, especially among the young generation. Within Minamisoma city, approximately 75 % of parents with small children have answered that they intentionally avoid eating locally grown produce. When the number of individuals who attend information seminars is decreasing, there is a strong opposition against using locally produced rice. Furthermore, many students are continuing to feel worried about their future especially about their health, pregnancy and delivery. There are various possible causes to the current trend such as the distrust relationship between farmers and consumers, issues associated with compensations and radiation-contamination levels, and the cultural differences. While education and risk communication could be one of the solutions to the current complexity in Fukushima, it is in the process of trial and error. The education on radiation and health is not merely about radiation protection, but it is also a part of the public education aiming for children to regain their self-esteem and to avoid isolation. Similarly, the interventions in place after the disaster including the internal radiation exposure-screening program are not just for measuring and reducing the levels of exposure. It is also important for maintaining the individual’s dignity, and for protecting the regional culture and history. In this session, I would like to discuss about the current local situation in the context of radiation issues and other public health problems that have arisen after the incident, and the direction in which we much move forward.

 

Name: Mamoru Fujiwara
Affiliation: Osaka University
Title: "What we learn from the large-scale soil sampling for radioactive nuclides emitted from the Fukushima Dai-ichi Nuclear Power Plant accident"
Abstracts After the accident of the Fukushima Dai-ichi Nuclear Power Plant (NPP) of Tokyo Electric Power Company (TEPCO) in March 2011, radioactive nuclides were spread out over the Fukushima area. We started to monitor the radioactive nuclei discharged by the accident at the Fukushima Dai-ichi NPP. We compiled measurement results of ambient dose rates at a height of 1m above the ground surface, and “soil deposition density map” for deposition densities by radioactive nuclides deposited on soil. The areas within 80 km from the Fukushima Daiichi NPP were divided into 2 km×2 km grids, whereas the areas between 80 km and 100 km and areas of Fukushima prefecture out of that scope were divided into 10 km×10 km grids. Ambient dose rates were measured at a height of 1m above the ground surface at one location each in these divided grids (nearly 2,200 locations in total), and soil samples were collected at five points in principle at each location. Measurement of ambient dose rates and soil sampling was performed with 440 persons in total from the 107 different organizations including researchers from Osaka University, Kyoto University, University of Tsukuba, the University of Tokyo, the Japan Atomic Energy Agency, and the Japan Chemical Analysis Center, and members of the local support team of the Federation of Electric Power Companies of Japan, etc. Nuclide analysis of soil samples was performed by 291 persons in total from 21 organizations. After making a brief report on the large-scale soil sampling for radioactive nuclides emitted from the TEPCO Fukushima Dai-ichi NPP accident, I would like to discuss the following subjects: 1.What happened in the Japanese academy community after the TEPCO Fukushima Dai-ichi NPP accident? 2.What was worried about the radioactive fallouts? 3.What were the difficulties in organizing an emergency term consisting of many independent research institutes? 4.What do we study from the NPP accident for future? 5.What should we prepare for urgent accidents?

 

Name: Nobuhiro Toyota
Affiliation: Osaka University
Title: "Development of gamma camera for the visualization of radioactive cesium to support Fukushima people recovering from nuclear disaster"
Abstracts It is important to visualize radioactivity that contaminated the land all over Fukushima district caused by the accident of nuclear power plant in March, 2011.The gamma camera was the device originally invented to obtain visual imaging in the field of nuclear medicine for radioisotope diagnosis in the history.In order to help clean up operation of radioactive Cesium, so called decontamination, several types of gamma camera has been so far developed with different combination of collimator and detector. Gamma camera with single pin hole type collimator was first introduced for the decontamination of radioactive Cesium in Fukushima 1) and another gamma camera, detecting Compton scattering of gamma ray, was then developed. 2) The third generation of the device, Cesium camera, was developed two years ago by the author with UK engineer using coded aperture mask technology. 3) The newest type of gamma camera, Cesium viewer, was developed last month by a Japanese manufacturer using 64 pin holes collimator, the specifications of which are as follows: Weight: 8 kg Capturing time: one minutes Detector: 64 units of Cesium iodide crystals with multi pixel photon counter Angle of scope: 60 degree Resolution angle; 3 degree Cesium viewer is expected to replace the conventional areal monitoring system with NaI scintillation survey meter for finding hot spots in the back ground radiation emitted by Cesium 137 on the ground. It will also help the risk communication with Fukushima people in existing radiation exposure situation to understand the location of hot spots and how the decontamination work has been finished before their coming back home. It is also planned to draw the radioactive Cesium mapping from the sky getting the device ride on the radio controlled helicopter, drone. Other applications of the device will be extended to searching radioactive source by fire fighters, police men and self-defending army and others against terror attack. References 1) Hitachi Ltd, Hitachi Hyoron, 94, p678 (2012) 2) Hamamatsu Photonics, http://www.jst.go.jp/pr/announce/2-130910 3) Toyota Radiation Research Institute, JP 2014-193175 approved on February 5, 2015

Session 2-2:Modeling for biological systems (Chairperson: Ohtsura Niwa (RERF))

Name: Osamu Yamamoto
Affiliation: Hiroshima University (retired)
Title: "Revision of Radiation Biology -Importance of Dose-Rate-"
Abstracts 1. Stochastic Effect  The dose-effect relationship for stochastic effect of tumorigenesis should be sigmoidal with a threshold, and the dose rate-effect relationship comes to be linear with no threshold. On the other hand, the dose-effect relationship for stochastic effect of life shortening is linear, and the dose rate-effect relationship is parabolic. 2. A-Bomb Radiation Effect The incidence of solid tumor, leukemia, and chromosome aberration with A-bomb radiation exposure is caused by the radiation dose rate effect. The dose effect might appear at the dose more than 2 Gy. 3. Biological Half-Life Biological half-time should be reconsidered. Release of RI from body is not necessarily exponential. For example, HTO decreases linearly by time, and Sc-137 is reached a plateau always. 4. Radiation Weighting Factor (or RBE) and Equivalent Dose. Radiation weighting factor (or RBE) is not constant. It is variable depending on the dose rate. Therefore, equivalent dose is also variable depending on the dose rate. 5. Effective Dose Effective dose = Equivalent dose x Tissue Weighting Factor. In this formula, "Equivalent dose" is "Equivalent dose / A-bomb radiation exposure time", that is, dose rate. Thereore, Effective dose is not "dose".

 

Name: Ohtsura Niwa
Affiliation: Radiation Effects Research Foundation
Title: "Science and the implication of the LNT model"
Abstracts The current radiation protection system and almost any protection system against detrimental agents are to protect people from the health risk of such agents. Therefore, the risk estimation is one of the key elements for those protection systems, especially when the dose of the agent in question becomes too low to obtain the magnitude of the risk. In the development of the ICRP system of radiation protection, the LNT model and several other risk models came to serve for the risk assessment of radiation at low doses and low dose rates (ICRP 2007). Yet, mechanistic bases of these models are largely lacking even now, and they rely mainly on the epidemiological observations of atomic bomb survivors. In this talk, efforts are made to understand mechanistic natures of the LNT and other risk models by applying the hit model for the physical action of radiation and the classic multistage carcinogenesis model of Armitage/ Doll. Whenever such understanding is found to be incomplete, tissue and whole body biology are applied to supplement the knowledge. Following issues will be discussed in my talk. Firstly, the target of radiation carcinogenesis is assumed to be the tissue stem cells since their long residence in a body is well fit for the requirement for accumulation of multiple mutations to gain malignancy. Nevertheless, progenitors are also known to be the target for hematopoietic and epithelial cancers. Then radiation is assumed to give only a few mutations, often one and sometime two. Radiation is assumed to act as an absolute carcinogen by giving mutation directly through its DNA double strand breaks. Under this scenario, leukemia is induced by radiation with relatively short latencies and linear and or quadratic dose responses. Thus, radiation induction of leukemia can be described by the absolute risk model. In contrast, solid cancer requires multiple mutations to which radiation is assumed to contribute one or two. In this scenario, the dose response of radiation carcinogenesis should be linear and the latency is relatively long to accumulate enough number of mutations. In addition, the relative risk model should be the one to choose to assess the magnitude of the risk. Biology would explain any deviation from the above described dose responses, latencies and risk models of radiation carcinogenesis.

Session 2-3:JMELODI workshop (Chairperson: TBA (TBA)) 

Name: Takahiro Wada
Affiliation: Kansai University
Title: "The necessity of JMELODI"
Abstracts After the disaster at Fukushima Daiichi Nuclear Power Plant, the scientist community could not announce clearly how serious the effects of the radiation would be either in the short term or in the long term. This is because of the lack of the basic consensus in the community on the biological effects of low dose and low dose-rate radiation. We believe that thorough discussions among scientists from various disciplines with different cultural backgrounds are necessary to achieve the consensus. In October, a new committee has been established in JSPS for the multidisciplinary research on biological effects of radiation. We expect that this committee is a step towards the establishment of a national project on low dose and low dose-rate radiation.

 

Name: Toshihiro Higuchi
Affiliation: Kyoto University
Title: "Origins of the Linear Non-Threshold (LNT) Relationship As a Model for Radiation Protection, 1948-1958"
Abstracts The assumption of the linear and non-threshold (LNT) relationship between doses and effects is central to radiation protection. Experts have long debated whether LNT is scientifically valid. In this paper, I will take a different approach, exploring the origins of LNT as a practical model used in radiation protection. Drawing on historical documents of NCRP, ICRP, BEAR (US: now BEIR), and MRC (UK), I will show that the LNT model emerged not all at once, but over the span of a decade and only in pieces. Central to this development was a concurrent shift in the scientific and non-scientific contexts in the early atomic age. Scientifically, there emerged a new set of data indicating the existence of risks even below the "tolerance dose." None of them, however, was decisive by itself to prove LNT as a scientific fact. Instead, radiation protection experts interpreted various data in light of practical needs and demographic assumptions, making one small change at a time which in practice assumed or favored LNT. When LNT model was firmly inscribed into radiation protection, it was a culmination of this incremental change rather than a sudden departure from the threshold hypothesis. The talk will be divided into three parts. First, I will discuss the impact of practical needs, explaining how U.S. experts, troubled with dose control at nuclear installations and test sites, took the lead in the integration of daily limits over a longer duration, first for a working week (6 days) and then for 10 or 13 weeks. Second, I will discuss the impact of demographic assumptions, explaining how British experts led the reappraisal of LNT from the point of view of public health concerning the whole or substantial part of the population. Finally, I will explain how ICRP came to discuss LNT and adopt the concept of limiting the accumulated dose in its 1958 basic recommendations.

 

Name: TBA
Affiliation: TBA
Title: "TBA"
Abstracts TBA

3rt day (Sat., Nov., 7th)

Session 3-1: Biological effects of radiation (Chairperson: TBA (TBA))

Name: Yoshihisa Matsumoto
Affiliation: Tokyo Institute of Technology
Title: " Mechanisms of the Repair of DNA Double-strand Breaks"
Abstracts Ionizing radiation is thought to exert its various biological effects through damages on DNA. It is estimated that 1 Gy of low LET radiation produces approximately 500 base damages, 1,000 single-strand breaks and 40 double-strand breaks (DSBs) on DNA. DSB is considered the most critical among various types of DNA damages. DSBs are repaired through homologous recombination (HR) and non-homologous end joining (NHEJ). HR is a reaction to reconstitute the sequence around DSB by referring to homologous chromosome or sister chromatid as the template and, therefore, is considered highly accurate. On the other hand, NHEJ is a reaction to join two DNA ends and, therefore, may sometimes incur nucleotide deletions or insertions at the junction or joining with incorrect partner, leading to chromosomal aberrations like deletions, inversions or translocations. NHEJ can be further classified into canonical (or classical) NHEJ (C-NHEJ) and alternative (or atypical) NHEJ (A-NHEJ). C-NHEJ is thought more ordered and more accurate than A-NHEJ and is involved in V(D)J recombination in immune systems. There processes are in competition with each other but there are also mechanisms to choose the most appropriate one depending on circumstances: species, life cycle phase, cell cycle phase, complexity of DNA damage and chromatin structure. I review the molecular mechanisms and interrelationships of these DSB repair processes and also discuss important points of consideration in incorporating DSB repair for the physical modeling of radiation biological effects.

 

Name: Yuichi Tsunoyama
Affiliation: Kyoto University
Title: "The history of radiation induced mutagenesis in plants and WAM model. "
Abstracts In plants, ionizing radiation has been irradiated to various crops for the purpose of breeding. The results of the oldest historical experiments, has been reported by L. J. Stadler in 1928. He found that the germinating seeds of maize were artificially mutagenized by irradiation of X-ray and gamma ray. In recent years, radiation breeding is one of the useful breeding techniques. Among historical and enormous quantity of data of radiation breeding experiments, there exist results of experiments focused on the dose rate. Some of the experimental results of radiation-induced mutations in plant species were very good agreement with a mathematical model “Whack-A-Mole (WAM) model”, which we newly propose.

 

Name: Heiko Enderling
Affiliation: H. Lee Moffitt Cancer Center and Research Inst.
Title: "Moffitt Cancer Center"
Abstracts Tumors are complex dynamic systems with interactions on multiple spatial and temporal scales. Progress in integrated mathematical oncology, a powerful approach that iteratively utilizes experimental and clinical data to build calibrated quantitative models, may help advance our understanding of how tumors grow and, most importantly, how they respond to therapy. We discuss models for two different therapeutic approaches. First, we discuss non-invasive prediction of radiation response to personalize radiotherapy fractionation for head and neck cancer. We introduce the proliferation saturation index (PSI), which is defined as a ratio of tumor volume to tumor carrying capacity as influenced by the host. PSI is estimated from routine pre-radiotherapy computed tomography scans and a deterministic tumor growth model. Response to standard of care and alternative fractionation protocols is calculated as a function of pretreatment PSI, to assess which patients may benefit from different fractionation protocols. Second, we discuss the synergy of radiation and immunotherapy to purposefully induce abscopal effects on a per patient basis. We present a mathematical framework of systemic T cell trafficking after local immune activation at a single metastatic lesion. The model can account for patient-specific anatomic distribution of metastatic sites, the physiologic blood flow fractions to tumor-bearing organs, tumor burden in each tissue, and homing cues of immune cells. Through integration of a dynamical model of tumor-immune interactions, we simulate metastases development subject to dynamic T cell trafficking patterns. We show that metastatic sites participate differently in systemic immune surveillance and therefore the success in triggering the abscopal effect depends, at least in part, on which metastatic site is selected for localized therapy.

Session 3-2: Medical physics (Chairperson: TBA (TBA))

Name: Takashi Sasaki
Affiliation: High Energy Accelerator Research Organization, KEK
Title: "Quantitative Approach in Radiotherapy"
Abstracts Modern medical treatments are considered to be performed based on clear evidence with quantitative evaluations of various phenomena. Survival rates for the both of cancer and normal cells for given dose distributions should be such one in treatment planning of radiotherapy. However, medical doctors still have to make a decision empirically because there is no tool available for quantitative evaluation of influences of radiation in cell levels for the given patients. The development of Gean4 begins in 1994 by the international collaboration among KEK, CERN and others. Geant4 that is a software toolkit for simulating interactions between particles and matter is widely used for various medical applications. Based on Geant4, Geant4-DNA is designed and implemented to calculate the effects of radiation in cell levels covering not only physical but chemical processes also. Following those efforts, a CUDA prototype of a Geant4 subset and Geant4-DNA has been developed to answer the strong demands in computing power for the calculation due to the nature of complexity in Geant4-DNA. The current version of the prototype that runs on an NVIDIA K20 GPU reveals more than 200 times speed up against one CPU core. We continue further research and development toward providing a tool for a quantitative evaluation of effects of radiation in cell levels for individual persons.

 

Name: Hidetaka Arimura
Affiliation: Kyushu University
Title: "Niche researches between computational image analysis and radiotherapy physics"
Abstracts The biological effect of radiation was recognized as a beneficial potential for treatment of malignant tumor after W.C. Rontgen had discovered x-ray in 1895, which may be considered the birth of radiation therapy. What are mainly required in radiation therapy from medical physics point of view are: high conformity of dose distributions to tumor volumes, decrease of normal tissue doses, and accurate tumor localization. For achieving these major requirements of radiation therapy, “harmonious relationships” between computational image analysis and radiotherapy physics have been built. The laboratory of the author has focused on a niche research field bridging between computational image analysis and radiotherapy physics to increase the accuracy of radiation therapy. The niche research field includes, for instance, the reduction of the intra- and inter-observer variations in contours of gross tumor volume (gross palpable or visible/demonstrable extent and location of malignant growth) in radiation treatment planning, and the quantitative evaluation of the robustness of beam directions in particle therapy using power spectral analysis of water-equivalent path length images in particle beam’s eye views. The talk of the author will introduce several niche studies on how computational image analysis can give beneficial impacts on radiation therapy.

Session 3-3: Nuclear physics for medicine (Chairperson: TBA (TBA))

Name: Mitsuhiro Fukuda
Affiliation: Osaka University
Title: "Activities of the consortium for medicine, mathematics, and physics at Osaka University"
Abstracts TBA

 

Name: Akihiro Haga
Affiliation: Univ. of Tokyo
Title: "Discussion: Perspective of medical physics"
Abstracts TBA

 

Name: Hiroshi Toki
Affiliation: Osaka University
Title: "Concluding remark"
Abstracts TBA

Poster session

Name: ALMasri Hussein Yousef
Affiliation: Al-Quds University
Title: "Estimation of patient dose from brain CT examinations"
Abstracts The amount of radiation dose received during brain CT, is calculated by two scanner and compared to Virtualdose software calculation. Two comparisons were made in this study: 1.Dose variation between two different CT scanners. 2.Dose variation between two CT scanners and Virtualdose software. The importance of the study stems from the following: 1.This study is the first of its type in assessing radiation dose variation between different CT scanners manufactures installed in Palestine. 2.Assessing radiation dose originating from different types of CT scanners. 3.Comparing radiation dose originating from installed CT scanners with Virtualdose calculation software.

 

Name: Sugai Hiroyuki
Affiliation: Gunma University
Title: "Photon Production Unconsidered in Simulation"
Abstracts When a target is irradiated with a particle beam, a variety of secondary particles are generated. Both the primary beam and secondary particles affect absorbed dose for the target. Among the secondary particles, a production cross section of photons is so large that a continuum energy spectrum is formed by generated photons. Until now, a number of production mechanisms of photons are proposed. In a region of particle therapy, Secondary electron Bremsstrahlung (SEB), Atomic Bremsstrahlung (AB), Quasi-Free Electron Bremsstrahlung (QFEB), Radiative Electron Capture (REC) and gamma-rays are main ones. Since not all mechanisms are understood, nobody knows how each component affects the absorbed dose distribution. In typical simulation codes Geant4 and PHITS, some of the above mechanisms are not taken into account. Therefore, simulation by means of Geant4 and PHITS might underestimate absorbed dose and/or radiation damage for biological targets.

 

Name: Nakane Kazuaki
Affiliation: Osaka University
Title: "A homology-based image analyzing method for detecting the cancer region from the digital slide "
Abstracts Computer assisted pathological diagnosis is now an issue of importance in the current situations of shortage of diagnostic pathologists. Various methods have been proposed, but cancer tissue is difficult to recognize because of its complex morphology. We have no effective system yet. One of the common characteristic of cancer is an“Uncontrolled cell-division”, namely“the lack of contact inhibition of cell growth”. Recently, we focus on this characteristic, our group proposed a simple mathematical model for the identification of tumor areas within normal tissue utilizing the changes in the Betti numbers in tumorigenesis. Although we have many false positive and the potential of miss the undifferentiated type of cancer, this system is very effective to detect the ROI (a part of tissue that contains important information for diagnosis). In this talk, we will introduce this system and its numerical results. And we will introduce applications other than cancer images.

 

Name: KATO TOSHIKO
Affiliation: None
Title: "Epidemiology of the atomic bomb survivors and Chernobyl to Fukushima accidents"
Abstracts The Radiation Effects Research Foundation (RERF) is a scientific organization dedicated to studying health effects of atomic bomb radiation. The research results have been utilized by international and other organizations as a source of basic information for establishing radiation protection standards. Nuclear regulation authority claims "The difficulty to prove the increase of cancer risk below 100 mSv is internationally admitted" and supports the policy of returning people to less than 20 mSv/y zone. Epidemiology of the atomic bomb survivors is examined. 1. It is said in "Matters elucidated thus far by RERF studies" that the risk increases in proportion to radiation dose above around 100 to 200 mSv, but association remains unclear below that level. This contradicts the result of the original paper: The dose-response appears to be linear, without any apparent threshold below which effects may not occur. 2. Excess risks indicate that higher risks are associated with younger age at exposure. Cancer risk for exposure at 10 is higher by more than 5 times larger than that at 50. 3. In the life span study (LSS), the excess risk of survivors who were within 2.5km of either hypocenter at the time of bombing (ATB) ("significant" radiation exposure) is derived by comparing with the risk for survivors who were 2.5-10km ATB ("non significant" radiation exposure). Is radiation exposure of the atomic bomb survivors 2.5-10km from hypocenter truly non significant? RERF considers that involvement of residual radiation is within the range of error in terms of initial radiation dose estimates. However, Peace declaration of Hiroshima city demands expansion of the "black rain areas" to 20km or more. If residual radiation and internal exposure is of considerable amount, excess cancer risk due to radiation exposure may have been estimated too low. 4. Childhood thyroid Cancer in Fukushima seems to increase at faster speed than that in Chernobyl.

 

Name: KUMAZAWA Shigeru
Affiliation: Formerly JAERI/ JNES/ NSC
Title: "A BASIC MODEL OF RISK CONTROL IN HEALTH PHYSICS"
Abstracts 1. OBJECTIVE This paper is to raise a question “What is risk control in the life phenomenon?” which is somewhat analogous to modelling the distribution of doses not only increased on the law of proportionate effect due to exposure situation but also reduced adequately by feedback mechanism not to approach dose limits. 2. BACKGROUD The distribution of doses to ionizing radiation is often deviated from the log-normal (LN) model at the higher dose due to radiation protection. In 1980 the hybrid log-normal (HLN) model (unification of log-normal and normal) was developed at JAERI with the feedback reduction of doses increased on the law of proportionate effect. The HLN model is defined for variate X that the function hyb(ρX) = ρX + ln ρX is normally distributed, where ρ > 0. The stochastic process of exposure situation produces the increment dose ΔXi = εi Xi / (1 + ρXi) or Δhyb(ρXi) = εi at each stage where εi is a random coefficient of exposure stimulus and ρ is an overall feedback factor of dose reduction. The HLN model was reviewed as a better fit to actual data by the UNSCEAR 1982 report (paras.20, 32, Appendix H) and it was used as an excellent fit to almost all observed doses including a parameter that reflects the effect of active control efforts to limit worker exposure in the report EPA 520/1-84-005 (1984). 3. RISK CONTROL IN THE LIFE PHENOMENON The characteristics of the dose distribution reveals the simple formalization of risk control how to mediate between risk increasing with a beneficial activity and risk restraining not approaching intolerable level, excluding negligible risk. In the life phenomenon the cellular repair or defense system works effectively only in a moderately significant damage situation, that is, not negligible risk or intolerable risk (i.e., a saturation of cellular defense system) but controllable risk situation. It is important to identify the invariant form of controlling a controllable risk applicable not only for radiation protection but also for cellular defense system as seeking health physics or seeking a law of risk control minimizing the consumption of relevant available energy in physics. Health Physics should be to find the principle of adequate risk control against uncertain adverse stimuli with getting the nutritious energy, matter and information from the environment for life. The hybrid function hyb(ρX) is equal to ln ρX for ρX less than about 0.1, and equal to ρX for ρX more than about 5. Thus the hybrid function consists of three scale regions, logarithmic, hybrid and linear scales, which may be corresponding to express three regions (negligible, controllable and intolerable risks), respectively. Radiation exposure is potential to randomly cause adverse stimuli on man or cell/organ/tissue but there are some countermeasures to mitigate large effects of controllable risk in biological defense systems as well as in radiation protection. The simplest macroscopic form of risk control is ΔX = ε X / (1 + ρX) or Δhyb(ρX) = ε. In conclusion this presentation suggests that the hybrid function developed in health physics affords the formulation of the dose-response relationship as a risk control in the life phenomenon shown by some examples and it provides the useful concept of hybrid scale and hybrid-hybrid section paper.

 

Name: Hirano Yoshiyuki
Affiliation: Gunma University
Title: "Estimation of survival curve using microdosimetric kinetic model and Geant4-DNA in targeted radionuclide therapy "
Abstracts Microdosimetric kinetic model is used for an estimation of survival curves of cell lines in particle therapy, which is based on specific energy (energy deposition in microscopic region). In NIRS Japan, targeted radionuclide therapy using alpha or Auger isotopes is investigated aimed at clinical treatment. The isotopes are transported to cell nucleus by an anti-body. Then, we calculated specific energies using a Monte Carlo simulation Geant4-DNA and estimated survival curves for At-211 (alpha) and In-111 (Auger), respectively. In addition, we compared survivals in the cases of isotope remains at cell membrane and is transported to nucleus. We confirmed At-211 at nucleus was more efficient for cell killing than other cases. The present study will be helpful for designing radiopharamceuticals and treatment planning.

 

Name: Hamaoka Yutaka
Affiliation: Kieo University
Title: "A Possible Warning from Fukushima: An Update"
Abstracts INTRODUCTION: After the Fukushima?Daiichi nuclear power plant disaster, thyroid screening was performed in subjects who were aged ?18 years. This study examined the relationship between the number of participants with thyroid nodules and radiation dose, using publicly available municipality level data (N=59). METHODS: Poisson regression was applied to that data. The numbers of participants with smaller nodule (<5mm), with larger nodule (>5.1mm), and sum of them are explained by UNSCEAR estimated thyroid dose, average age at exposure, and average age at screening. RESULTS: Although the UNSCEAR thyroid dose was insignificant for prevalence of thyroid cancer (including suspicious cases), it was positive and significant for smaller nodules (b=18.76, t-value=3.79, p<0.01), larger nodule (b=11.45, t-value=2.16, p=0.03), and sum of them (b=18.26, t-value=5.27, p<0.01). CONCLUSIONS: Although this was an ecological study at the municipality level, our results are consistent with previous studies that confirm significant relationships with radiation exposure and prevalence of nodule (Nagataki et al. 1994; Imaizumi et al. 2015; Schneider et al. 1993). According to follow up studies of a-bomb (Imaizumi et al 2005) and Chernobyl (Hayashida et al. 2012), nodule group has larger risk of thyroid cancer. Our results might indicate an early warning for future incidence of thyroid cancer. Health follow-up for children in Fukushima is necessary.

 

Name: Hamaoka Yutaka
Affiliation: Keio University
Title: "Individual Level Data Model is More Effective to Detect Radiation Effect: Re-Analysis of US Nuclear Worker Data"
Abstracts INTRODUCTION: Although individual level data are recorded, most of the radiation-epidemiological studies apply the Mantel-Haenszel score test or the Poisson regression model to tabulated data by age, sex, dose, and other covariates. This aggregation can lead to a loss of information, inefficient estimation, and weaker statistical power when detecting the risk of a low dose. METHODS: US DOE three nuclear sites (Hanford, Oak Ridge and Rocky Flats : Gilbert et al. 1993) data was re-analyzed. Hazard model was applied to the data with explanatory variables: age, sex, race, calendar year of first employment, age at first employment, site dummy, length of employment, latency dummy, and cumulative dose. Natural experiment approach was applied to analyze exposure history: workers were classified based on exposure history. RESULTS: Radiation cumulative dose was positive and significant for solid cancer (beta=0.097, z=3.11 ,p<0.01). Nuclear workers' exposure history was classified into six exposure patterns. Adding interaction term between cumulative dose and exposure pattern improved model fit (AIC=42674 vs. 42668). Workers exposed late 1950s has more risk of solid cancer mortality (beta=0.050, z=2.76 ,p<0.01). CONCLUSIONS: For the same data, Gilbert et al. (1993) applied the Mantel-Hansel score test and Poisson regression to tabulated data. They failed to detect effect of radiation exposure. To analyze low does effects, models that utilize individual data are more effective.

 

Name: Omata Kazumi
Affiliation: National Center for Global Health and Medicine
Title: "Dynamics of Cardiac Hypertrophy and Heart Failure "
Abstracts In a living organism, the amount of molecules varies moment by moment, and at the same time, the homeostasis is maintained. When one focuses on a group of closely related molecules, the variation in their amount can be represented by a trajectory in a phase space composed by this group of molecules, and the homeostasis implies that the phase space includes a stationary point. If a living organism or a part of it does not function in a correct manner, the stationary point must be located at an incorrect position. We can refer to this state as disease. The present study has investigated heart failure induced by cardiac hypertrophy. I described it in a set of rate equations or “equations of motion” concerning cardiac hypertrophy and proteins such as Hif-1, VEGF, and p53, and analyzed what effects the input parameters have on the variation in the trajectory and stationary point in the phase space. I interpret that the improvement of cardiac hypertrophy corresponds to giving the stationary point back toward the correct position, and suggest a few possibilities mathematically for the treatment of cardiac hypertrophy: control of the reaction constants, amount of molecules, and reaction mechanism.

 

Name: OZAKI AKIHIKO
Affiliation: Minami Soma Municipal General Hospital
Title: "Delayed hospital visits in breast cancer patients in Fukushima, Japan: a retrospective comparative analysis before and after the Great East Japan Earthquake and the subsequent nuclear accident "
Abstracts Introduction In patients with symptomatic cancer, delay in first presentation may lead to advanced stage at diagnosis, potentially contributing to poor survival. However, little information is available about the possible influence of mass disasters on delayed hospital visits. Minamisoma City, located within a 30 kilometers radius from the nuclear power plant, experienced the Great East Japan Earthquake and the subsequent nuclear accident. These disasters may have impacted the behavioral patterns of cancer patients. Objectives To assess the change of the proportion of the delayed hospital visits in breast cancer patients before and after the disasters. Methods The study population comprised of 120 symptomatic breast cancer patients, diagnosed from January 2008 through March 2015 in the two main cancer centers in Minamisoma City. All the patients were citizens of Minamisoma City when the diagnosis was made. Demographic and clinical information was extracted from medical records. Results The proportion of patients with ?1 year delay significantly increased after the disaster. Among the 9 patients with ?1 year delay, 8 presented with cancer in stage 3 or 4. Living without a child was associated with increased ratio of ?1 year delay with the odds ratio of 8.64 (95% CI: 1.01-74.09, p value = 0.049). Discussion Mass disasters may impact behavioral patterns of cancer patients, possibly due to psychosocial stress and worsened access to health care. Health care providers should keep in mind that socially isolated patients may be particularly vulnerable after disasters..

 

Name: Chhatkuli Ritu Bhusal
Affiliation: Department of Bioengineering, The University of Tokyo
Title: "Markerless tumor tracking for moving tumors using pre4DCBCT for image guided radiation therapy "
Abstracts 4DCBCT is being popular in clinical sites lately, its acquisition in real time is not possible. The purpose of this study is to evaluate the viability of markerless tumor tracking system for the moving tumor based on phase recognition using prior obtained 4DCBCT and template matching.

 

Name: Kihara Hiroshi
Affiliation: Himeji Hinomoto College
Title: "Expansion of Whack-A-Mole Model to a time-lag phase of radiation effect"
Abstracts Manabe et al. proposed Whack-A-Mole Model to explain the radiation effect on animals. I expand this theory in order to explain time-lag effect of the radiation based on the allosteric model.

 

Name: Magome Taiki
Affiliation: The University of Tokyo Hospital
Title: "Survival time prediction after radiotherapy for high-grade glioma patients based on machine learning technique "
Abstracts Recent advancement in radiotherapy techniques offers many patient-specific decisions for radiotherapy planning. Therefore, accurate prediction of treatment outcomes would be useful for treatment planners as a computer-aided decision-making tool. The aim of this study is to predict survival time after radiotherapy for high-grade glioma patients. The survival time after radiotherapy was predicted based on a multiple linear regression analysis and artificial neural network (ANN) by using 204 candidate features. Our preliminary result showed the ANN prediction model had higher accuracy than the linear regression model. The proposed method has a potential to predict the outcome after radiotherapy with each patient-specific situation.

 

Name: Nakano Masahiro
Affiliation: The University of Tokyo Hospital
Title: "Time-ordered cone-beam CT image reconstruction for pelvic region"
Abstracts Four-dimensional (4D) cone-beam CT (CBCT) technique has improved the accuracy of radiotherapy and it has been known as image-guided radiotherapy (IGRT). However the current technique supposes periodic respiratory motion, and there are few approaches to visualize organs with non-periodic time-ordered motion such as gastrointestinal peristaltic motion. In this study, we propose 4D CBCT image reconstruction of pelvic region using 4D half-scan reconstruction technique. Image mosaicing process is also proposed in this study to extend projection data acquired by asymmetrically located flat-panel detector (FPD).

 

Name: Kon Daisuke
Affiliation: The University of Tokyo
Title: "Measurement and Calculation of Doses Outside the Treatment Volume from Gamma Knife Radiosurgery"
Abstracts The purpose of this study is to investigate factors contributing to organ dose outside the patient’s head in treatment with Leksell Gamma Knife. An anthropomorphic phantom and radio-photoluminescence glass dosimeters were used to measure doses outside of the target volume. Moreover, we have carried out simulations of radiation transport in the measurement situation. The EGS5 Monte Carlo code was used to create the program for the simulation. The results of simulations show significant changes of photon characteristics depending on position in the treatment unit. We found that accuracy of the non-target dose evaluation still can be improved.

 

Name: Masaharu Tsubokura
Affiliation: University of Tokyo, Minamisoma Municipal General Hospital, Japan
Title: "The current situation of the radiation exposure screening program in Hama-dori and the future tasks"
Abstracts Since the Fukushima Dai-ichi nuclear power plant disaster, a regular internal radiation exposure-screening program has been in place in Fukushima. From these results, we know that the levels of chronic internal exposure among residents have been kept at a very low level. However, the level of awareness and the feeling of anxiety that the residents have experienced about the current situation vary by individuals. When the number of residents who are no longer interested in radiation, people who avoid consuming locally grown produce also exist, especially among the young generation. Within Minamisoma city, approximately 75 % of parents with small children have answered that they intentionally avoid eating locally grown produce. When the number of individuals who attend information seminars is decreasing, there is a strong opposition against using locally produced rice. Furthermore, many students are continuing to feel worried about their future especially about their health, pregnancy and delivery. There are various possible causes to the current trend such as the distrust relationship between farmers and consumers, issues associated with compensations and radiation-contamination levels, and the cultural differences. While education and risk communication could be one of the solutions to the current complexity in Fukushima, it is in the process of trial and error. The education on radiation and health is not merely about radiation protection, but it is also a part of the public education aiming for children to regain their self-esteem and to avoid isolation. Similarly, the interventions in place after the disaster including the internal radiation exposure-screening program are not just for measuring and reducing the levels of exposure. It is also important for maintaining the individual’s dignity, and for protecting the regional culture and history. In this session, I would like to discuss about the current local situation in the context of radiation issues and other public health problems that have arisen after the incident, and the direction in which we much move forward.

 

Name: Manabe Yuichiro
Affiliation: Osaka University
Title: "Whack-A-Mole Model: Towards a Unified Description of Biological Effects Caused by Radiation Exposure"
Abstracts We present a novel model to for estimating biological effects caused by artificial radiation exposure, i.e., the Whack-A-Mole (WAM) model. It is important to take into account the recovery effects during the time course of cellular reactions. The inclusion of dose-rate dependence is essential in the risk estimation of low-dose radiation, while nearly all the existing theoretical models rely on the total dose dependence only. By analyzing experimental data of the relationship between the radiation dose and the induced mutation frequency of five organisms, namely, mouse, Drosophila, chrysanthemum, maize, Tradescantia, we found that all the data can be reproduced by the WAM model. Most remarkably, a scaling function, which is derived from the WAM model, consistently accounts for the observed mutation frequencies of the five organisms. This is the first rationale to account for the dose rate dependence as well as to provide a unified understanding of a general feature of organisms.

 

Name: Wada Takahiro
Affiliation: Kansai University
Title: "Study of biological effects of long-term exposure to low dose-rate radiation with Whack-A-Mole model"
Abstracts By adopting Whack-A-Mole (WAM) model, which we have recently proposed to estimate the biological effects of artificial radiations. We show how the explicit dose rate dependence built in WAM plays a key role to estimate biological effects cause by radiation exposure. The result may replace the so-called DDREF, the concept of which has long been adopted to is proposed is compared with conventionally used Linear-Quadratic model. Basic properties of WAM model are discussed emphasizing on the dose-rate dependence. By adopting the parameters that are determined to fit the mega mouse experiments, biological effects of long-term exposure to extremely low dose-rate radiation are discussed. In WAM model, the effects of the long-term exposure show a saturation property, which makes a clear distinction from the LNT hypothesis which predicts a linear increase of the effects with time.

 

Name: Bando Masako
Affiliation: Kyoto University, Osaka University
Title: "Challenge to use the concept of Effective Dose Rate in place of Doubling Dose"
Abstracts This report presents the comparison of spontaneous mutation frequencies with those induced by artificial radiation exposure of living objects such as human, mice, and Drosophila and plants, chrysanthemum, maize, Tradescantia. Spontaneous mutation is a fact of life so far as living objects are alive. It was Muller who first introduced the concept of “doubling dose”, which provided us with a tool to make across-species comparisons, and is currently used by radiation protection organizations to estimate biological Effects of Ionizing Radiation. This although the mutation frequency itself varies from species to species. This is because the order of doubling doses are almost of the same order among different experimental conditions, different species. However we should note that it is varies with the dose rate even under the condition of the same total dose. This indicates the importance of dose rate rather than total dose. We have performed a kinetic reaction model accounting explicit dose rate dependence, which we name “WAM model”. The key features is that WAM model reproduces the dose rate dependence quite well. Our challenge is, based on the WAM model, to introduce the so called “effective dose rate”, the dose rate with which will induce the same total amount of spontaneous frequency. In WAM the mutation frequency is defined as d/dt(F(t))=A-BF(t), with A=a_0 + a_1*d, B=b_0+b_1*d where d is the dose rate whose importance have been emphasized above. The term A, B represent the increase and decrease contribution to F, respectively. The solution of this differential equation is easily obtained for the case where radiation exposure starts at t=0 with constant dose rate d; F(t)=A/B*(1-exp(-B*t))*(F(t)-F(0))*F(0); , with F(0) being the control value coming from spontaneous mutation. With 4 parameters, a_0, a_1, b_0, b_1which are to be determined from the data, we can predict the time development of F for any given dose rate. The condition for stationary state is F=B/A. The model reproduces the experimental data of 5 species quite well; all of which fall on the universal scaling function with the scaled time. The parameter a_1 is so called sensitivity, whereas the spontaneous mutation comes from a_0 term, It can be expressed as a_0 =a_1 *d_{eff} by introducing the notation of effective dose rate , d_{eff}. From the parameters obtained from the mouse data we find d_{eff}=1.10 [mGy/h], which is significantly larger than that coming from average natural background radiation, 0.2 microGy/h. Note that the value d_{eff}=1.10 [mGy/h] is to be compared with those estimated from DSB counting for human, d_{eff}=1.38 [mGy/h] (Sugawara) or 8.4mGy/h owing to the double-strand DNA breaks caused by endogenous reactive oxygen species (Tubiana et al.) which are almost of the same order. We shall investigate and report the details of effective dose rate and compare those of other species and see how the “effective dose rate” works as an improvement of “doubling dose”.

 

Name: Uno Kazuko
Affiliation: Louis Pasteur Center for Medical Research
Title: "TBA"
Abstracts TBA

 

Name: Yuki Shimada
Affiliation: Minamisoma municipal Hospital
Title: "Temporary housing residents' health 4 years after Fukushima Daiichi nuclear disaster"
Abstracts TBA