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Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer

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World Journal of Gastroenterology 2015年第4期21卷 1275-1283页

作者： shigenori kadowaki Miho Kakuta Shuhei Takahashi Akemi Takahashi Yoshiko Arai Yoji Nishimura Toshimasa Yatsuoka Akira Ooki Kensei Yamaguchi Keitaro Matsuo Kei Muro Kiwamu Akagi Division of Gastroenterology Saitama Cancer CenterSaitama 362-0806Japan Department of Clinical Oncology Aichi Cancer Center HospitalAichi 464-8681Japan Division of Molecular Diagnosis and Cancer Prevention Saitama Cancer Center Saitama 362-0806Japan Division of Gastroenterological Surgery Saitama Cancer CenterSaitama 362-0806Japan Department of Preventive Medicine Kyushu University Faculty of Medical Sciences Fukuoka 812-8582Japan

AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability(MSI) status in Japanese colorectal cancer(CRC) ***: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage Ⅰ-Ⅲ CRC and examined associations of these mutations with disease-free survival(DFS) and overall survival(OS) using uni- and multivariate Cox proportional hazards ***: KRAS and BRAF mutations were detected in 312(38%) of 812 and 40(5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males(P = 0.02), while the presence of BRAF mutations was significantly associated with the female gender(P = 0.006), proximal tumor location(P < 0.001), mucinous or poorly differentiated histology(P < 0.001), and MSI-high tumors(P < 0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS(HR = 1.35; 95%CI: 1.03-1.75) and OS(HR = 1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS(HR = 2.20; 95%CI: 1.19-4.06) and OS(HR = 2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and ***: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, inJapanese patients with curatively resected CRC.

关键词： Colorectal cancer KRAS BRAF Microsatellite instabi

State Predictive Model Following Control System for Linear Time Delays

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International Journal of Automation and computing 2009年第2期6卷 186-191页

作者： shigenori Okubo Faculty of Engineering Yamagata University

In this paper, we propose a new state predictive model following control system （MFCS）. The considered system has linear time delays. With the MFCS method, we obtain a simple input control law. The bounded property of the internal states for the control is given and the utility of this control design is guaranteed. Finally, an example is given to illustrate the effectiveness of the proposed method.

关键词： State predictive time delays model following control system (MFCS) disturbances.

Origin of the Earth:A proposal of new model called ABEL

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Geoscience Frontiers 2017年第2期8卷 253-274页

作者： shigenori Maruyama Toshikazu Ebisuzaki Earth-Life Science Institute Tokyo Institute of Technology Institute for Study of the Earth's Interior Okayama University RIKEN

The Earth was born as a dry planet without atmosphere and ocean components at 4.56 Ga,with subsequent secondary accretion of bio-elements,such as carbon（C）,hydrogen（H）,oxygen（O）,and nitrogen（N） which peaked at 4.37-4.20 *** two-step formation model of the Earth we refer to as the advent of bio-elements model（ABEL Model） and the event of the advent of bio-elements（water component） as ABEL *** is clear that the solid Earth originated from enstatite chondrite-like dry material based on the similarity in oxygen isotopic composition and among other *** the other hand,Earth＇s water derives primarily from carbonaceous chondrite material based on the hydrogen isotopic *** present our ABEL model to explain this enigma between solid Earth and water,as well as secondary accretion of oxidizing bio-elements,which became a precursor to initiate metabolism to emerge life on a highly reductive *** ABEL Bombardment had not occurred,life never would have emerged on the ***,ABEL Bombardment is one of the most important events for this planet to evolve into a habitable *** chronology of ABEL Bombardment is informed through previous researches of the late heavy bombardment and the late veneer *** Bombardment is considered to have occurred during 4.37-4.20 Ga,which is the concept to redefine the standard late heavy bombardment and the late veneer ***,ABEL Bombardment is the trigger of the transition from stagnant lid tectonics to plate tectonics on this planet because of the injection of volatiles into the initial dry Earth.

关键词： Origin of Earth and life Advent of bin-elements (ABEL)Origin of water on the Earth ABEL Bombardment Habitable Trinity planet Initiation of plate tectonics

Formation of anorthosite on the Moon through magma ocean fractional crystallization

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Geoscience Frontiers 2017年第2期8卷 299-308页

作者： Tatsuyuki Arai shigenori Maruyama Department of Earth and Planetary Sciences Tokyo Institute of Technology2-12-10okayamaMeguro-kuTokyo 152-8551Japan Earth-Life Science Institute Tokyo Institute of Technology2-12-1 OokayamaMeguro-kuTokyo 152-8551Japan

Lunar anorthosite is a major rock of the lunar highlands,which formed as a result of plagioclasefloatation in the lunar magma ocean（LMO）.Constraints on the sufficient conditions that resulted in the formation of a thick pure anorthosite（mode of plagioclase 〉95 vol.%） is a key to reveal the early magmatic evolution of the terrestrial *** form the pure lunar anorthosite,plagioclase should have separated from the magma ocean with low crystal *** networks of plagioclase and mafic minerals develop when the crystal fraction in the magma（φ） is higher than ca.40-60 vol.%,which inhibit the formation of pure *** contrast,when φ is small,the magma ocean is highly turbulent,and plagioclase is likely to become entrained in the turbulent magma rather than separated from the *** determine the necessary conditions in which anorthosite forms from the LMO,this study adopted the energy criterion formulated by *** composition of melt,temperature,and pressure when plagioclase crystallizes are constrained by using MELTS/pMELTS to calculate the density and viscosity of the *** plagioclase starts to crystallize,the Mg~# of melt becomes 0.59 at 1291 *** density of the melt is smaller than that of plagioclase for P 〉 2.1 kbar（ca.50 km deep）,and the critical diameter of plagioclase to separate from the melt becomes larger than the typical crystal diameter of plagioclase（1.8-3 cm）.This suggests that plagioclase is likely entrained in the LMO just after the plagioclase starts to *** the Mg~# of melt becomes 0.54 at 1263 C,the density of melt becomes larger than that of plagioclase even for 0 *** the Mg~# of melt decreases down to 0.46 at 1218 C,the critical diameter of plagioclase to separate from the melt becomes 1.5-2.5 cm,which is nearly equal to the typical plagioclase of the lunar *** suggests that plagioclase could separate from the *** of the differences between the Earth and the Moon is the presenc

关键词： Moon Anorthosite Magma ocean MELTS Fractional crystallization

Origins of building blocks of life: A review

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Geoscience Frontiers 2018年第4期9卷 1117-1153页

作者： Norio Kitadai shigenori Maruyama Earth-Life Science Institute Tokyo Institute of Technology

How and where did life on Earth originate？ To date, various environments have been proposed as plausible sites for the origin of life. However, discussions have focused on a limited stage of chemical evolution, or emergence of a specific chemical function of proto-biological systems. It remains unclear what geochemical situations could drive all the stages of chemical evolution, ranging from condensation of simple inorganic compounds to the emergence of self-sustaining systems that were evolvable into modern biological ones. In this review, we summarize reported experimental and theoretical findings for prebiotic chemistry relevant to this topic, including availability of biologically essential elements（N and P） on the Hadean Earth, abiotic synthesis of life＇s building blocks（amino acids, peptides, ribose, nucleobases, fatty acids, nucleotides, and oligonucleotides）, their polymerizations to bio-macromolecules（peptides and oligonucleotides）, and emergence of biological functions of replication and compartmentalization. It is indicated from the overviews that completion of the chemical evolution requires at least eight reaction conditions of（1） reductive gas phase,（2） alkaline pH,（3） freezing temperature,（4）fresh water,（5） dry/dry-wet cycle,（6） coupling with high energy reactions,（7） heating-cooling cycle in water, and（8） extraterrestrial input of life＇s building blocks and reactive nutrients. The necessity of these mutually exclusive conditions clearly indicates that life＇s origin did not occur at a single setting; rather, it required highly diverse and dynamic environments that were connected with each other to allow intratransportation of reaction products and reactants through fluid circulation. Future experimental research that mimics the conditions of the proposed model are expected to provide further constraints on the processes and mechanisms for the origin of life.

关键词： Astrobiology Biochemistry Chemical evolution Extraterrestrial life Hadean Earth Hydrothermal systems

United theory of biological evolution:Disaster-forced evolution through Supernova,radioactive ash fall-outs,genome instability,and mass extinctions

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Geoscience Frontiers 2015年第1期6卷 103-119页

作者： Toshikazu Ebisuzaki shigenori Maruyama RIKEN 2-1Hirosawa Earth-Life Science Institute Tokyo Institute of Technology

We present the disaster-forced biological evolution model as a general framework that includes Darwinian ＂phylogenic gradualism＂, Eldredge-Gould＇s ＂punctuated equilibrium＂, mass extinctions, and allopatric, parapatric, and sympatric speciation. It describes how reproductive isolation of organisms is established through global disasters due to supernova encounters and local disasters due to radioactive volcanic ash fall-outs by continental alkaline volcanism. Our new evolution model uniquely highlights three major factors of disaster-forced speciation： enhanced mutation rate by higher natural radiation level, smaller population size, and shrunken habitat size （i.e., isolation among the individual pop- ulations）. We developed a mathematical model describing speciation of a half-isolated group from a parental group, taking into account the population size （Ne）, immigration rate （m）, and mutation rate （μ）. The model gives a quantitative estimate of the speciation, which is consistent with the observations of speciation speed. For example, the speciation takes at least 105 generations, if mutation rate is less than 10 3 per generation per individual. This result is consistent with the previous studies, in which μ is assumed to be 10 3-10-5. On the other hand, the speciation is much faster （less than l0S generations） for the case that μ is as large as 0.1 in parapatric conditions （m 〈 μ）. Even a sympatric （m ~ 1 ） speciatiou can occur within 103 generations, if mutation rate is very high （μ- 1 mutation per individual per generation）, and if Ne 〈 20-30. Such a high mutation rate is possible during global disasters due to supernova encounters and local disasters due to radioactive ash fall-outs. They raise natural radiation level by a factor of 100-1000. Such rapid speciation events can also contribute to macro-evolution during mass extinction events, such as observed during the Cambrian explosion of biodiversity. A similar rapid speciation （though in a much smaller scale）

关键词： Speciation Supernova encounter Continental alkaline volcanism Cichlid Great African ape Cambrian explosion

Nuclear geyser model of the origin of life:Driving force to promote the synthesis of building blocks of life

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Geoscience Frontiers 2017年第2期8卷 275-298页

作者： Toshikazu Ebisuzaki shigenori Maruyama RIKEN Earth-Life Science Institute Tokyo Institute of Technology

We propose the nuclear geyser model to elucidate an optimal site to bear the first *** model overcomes the difficulties that previously proposed models have *** geyser is a geyser driven by a natural nuclear reactor,which was likely common in the Hadean Earth,because of a much higher abundance of 235U as nuclear *** nuclear geyser supplies the following：（1）high-density ionizing radiation to promote chemical chain reactions that even tar can be used for intermediate material to restart chemical reactions,（2）a system to maintain the circulation of material and energy,which includes cyclic environmental conditions（warm/cool,dry/wet,etc.）to enable to produce complex organic compounds,（3）a lower temperature than 100℃ as not to break down macromolecular organic compounds,（4）a locally reductive environment depending on rock types exposed along the geyser wall,and（5）a container to confine and accumulate volatile *** five factors are the necessary conditions that the birth place of life must *** the nuclear geyser can meet all five,in contrast to the previously proposed birth sites,such as tidal flat,submarine hydrothermal vent,and outer *** nuclear reactor and associated geyser,which maintain the circulations of material and energy with its surrounding environment,are regarded as the nuclear geyser system that enables numerous kinds of chemical reactions to synthesize complex organic compounds,and where the most primitive metabolism could be generated.

关键词： Origin of life Chemical evolution Natural nuclear reactor Aqueous electron Radiation chemistry

Reactions between olivine and CO2-rich seawater at 300℃:Implications for H2 generation and CO2 sequestration on the early Earth

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Geoscience Frontiers 2017年第2期8卷 387-396页

作者： Hisahiro Ueda Yusuke Sawaki shigenori Maruyama Department of Earth and Planetary Sciences Tokyo Institute of Technology2-12-1 OokayamaMeguro-kuTokyo 152-8551Japan Earth-Life Science Institute Tokyo Institute of Technology2-12-1 OokayamaMeguro-kuTokyo 152-8551Japan

To understand the influence of fluid CO2 on ultramafic rock-hosted seafloor hydrothermal systems on the early Earth,we monitored the reaction between San Carlos olivine and a CO2-rich NaCl fluid at 300 C and 500 *** the experiments,the total carbonic acid concentration（∑XO2） in the fluid decreased from approximately 65 to 9 mmol/*** minerals,magnesite,and subordinate amount of dolomite were formed via the water-rock *** H2 concentration in the fluid reached approximately 39 mmol/kg within 2736 h,which is relatively lower than the concentration generated by the reaction between olivine and a CO2-free NaCl solution at the same *** seen in previous hydrothermal experiments using komatiite,ferrous iron incorporation into Mg-bearing carbonate minerals likely limited iron oxidation in the fluids and the resulting H2 generation during the olivine *** carbonate mineralogy over the temperature range of natural hydrothermal fields,H2 generation is likely suppressed at temperatures below approximately 300℃ due to the formation of the Mg-bearing ***,H_2 concentration in fluid at 300℃ could be still high due to the temperature dependency of magnetite stability in ultramafic ***,the Mg-bearing carbonates may play a key role in the ocean-atmosphere system on the early *** studies suggest that the subduction of carbonated ultramafic rocks may transport surface CO2 species into the deep *** process may have reduced the huge initial amount of CO2 on the surface of the early *** approximate calculations demonstrate that the subduction of the Mg-bearing carbonates formed in komatiite likely played a crucial role as one of the CO2 carriers from the surface to the deep mantle,even in hot subduction zones.

关键词： Olivine CO2-rich condition Early Earth Hydrothermal alteration Serpentinization Experiment

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Habitable Trinity

Geoscience Frontiers 2015年第1期6卷 95-101页

作者： James M.Dohm shigenori Maruyama Earth-Life Science Institute Tokyo Institute of Technology

Habitable Trinity is a newly proposed concept of a habitable environment. This concept indicates that the coexistence of an atmosphere （consisting largely of C and N）, an ocean （H and 0）, and a landmass （supplier of nutrients） accompanying continuous material circulation between these three components driven by the Sun is one of the minimum requirements for life to emerge and evolve. The life body consists of C, O, H, N and other various nutrients, and therefore, the presence of water, only, is not a sufficient condition. Habitable Trinity environment must he maintained to supply necessary components for life body. Our Habitable Trinity concept can also be applied to other planets and moons such as Mars, Europa, Titan, and even exoplanets as a useful index in the quest for life-containing planetary bodies.

关键词： Habitable Trinity Ocean Atmosphere Landmass Sun