Institute for Integrated Radiation and Nuclear Science, Kyoto University

The phonon density of states was measured by observing the nuclear resonant fluorescence of ${}^{57}$Fe versus the energy of incident x rays from a synchrotron radiation beam. An energy resolution of 6 meV was achieved by use of high-resolution crystal optics for the incident beam. Extremely low background levels were obtained via time discrimination of the nuclear fluorescent radiation.

The cytotoxic effects of alkylating agents are strongly attenuated by cellular DNA repair processes, necessitating a clear understanding of the repair mechanisms. Simple methylating agents form adducts at N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). O(6)-methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by O(6)-methylguanine-DNA methyltransferase, and O(6)MeG:T mispairs are recognized by the mismatch repair system (MMR). MMR cannot repair the O(6)MeG/T mispairs, which eventually lead to double-strand breaks. Bifunctional alkylating agents form interstrand cross-links (ICLs) which are more complex and highly cytotoxic. ICLs are repaired by complex of NER factors (e.g., endnuclease xeroderma pigmentosum complementation group F-excision repair cross-complementing rodent repair deficiency complementation group 1), Fanconi anemia repair, and homologous recombination. A detailed understanding of how cells cope with DNA damage caused by alkylating agents is therefore potentially useful in clinical medicine.

Iron-containing and manganese-containing superoxide dismutases were found in Plectonema boryanum. The Mn-enzyme occupies about 10% of total activity. The Fe-enzyme was purified to near homogeneity. It contains 2 atoms of iron per mol. Its molecular weight is 41,700 and it is composed of two subunits of identical molecular weight without disulfide linkage. Amino acid composition is presented. Electron paramagnetic resonance spectrum revealed that iron occurs in a high spin ferric form and in some anisotropic environment. The absorption spectrum and the absence of acid-labile enzymes are insensitive to cyanide. Although the Fe-enzyme is sensitive to hydrogen peroxide, the Mn-enzyme is not.

The mean droplet size and size distribution are important for detailed mechanistic modeling of annular two-phase flow. A large number of experimental data indicate that the standard Weber number criterion based on the relative velocity between droplets and gas flow predicts far too large droplet sizes. Therefore, it was postulated that the majority of the droplets were generated at the time of entrainment and the size distribution was the direct reflection of the droplet entrainment mechanism based on roll-wave shearing off. A detailed model of the droplet size in annular flow was then developed based on the above assumption. The correlations for the volume mean diameter as well as the size distribution were obtained in collaboration with a large number of experimental data. A comparison with experimental data indicated that indeed the postulated mechanism has been the dominant factor in determining the drop size. Furthermore, a large number of data can be successfully correlated by the present model. These correlations can supply accurate information on droplet size in annular flow which has not been available previously.

The complete sets of elastic constants of 4H and 6H silicon carbide single crystals were determined by Brillouin scattering. The elastic constants of 6H SiC are C11=501±4, C33=553±4, C44=163±4, C12=111±5, and C13=52±9 GPa; the corresponding ones of 4H SiC are the same within experimental uncertainties. The compressibility, 4.5×10−3 GPa, is about 3–5 times smaller than those reported for polycrystalline SiC materials.

Nanostructured graphite was prepared by mechanical milling under hydrogen atmosphere. Several samples obtained after different milling times were systematically examined to get fundamental information about the structures and hydrogen concentrations. After the expansion of the graphite interlayer, the long-range ordering of the interlayer disappears continuously with increasing milling time. The hydrogen concentration reaches up to 7.4 mass % (CH0.95) after milling for 80 h. Judging from the radial distribution function determined by the neutron diffraction measurement, there are two types of deuterium coordinations: deuterium atoms in the graphite interlayers and that with the CDx covalent bonds, respectively.

Oncostatin M (OSM) is a member of the interleukin-6 (IL6)-related cytokine subfamily that includes IL6, IL11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor and cardiotrophin-1. While human OSM has been characterized and the bovine OSM gene was recently cloned, the murine counterpart had not been identified. Here we describe molecular cloning of murine OSM as an immediate early gene induced by a subset of cytokines including IL2, IL3 and erythropoietin (EPO) in myeloid and lymphoid cell lines. The induction kinetics of OSM are rapid and transient, reaching a maximal level within 30-60 min and decreasing thereafter. Induction of OSM depends on the signals generated by the membrane-proximal region of the EPO receptor as well as that of the beta chain of the IL3/GM-CSF receptor, which activate JAK2 and STAT5. About 100 bases upstream of the transcription initiation site of the OSM gene contains a possible STAT5 binding site which is essential for IL2, IL3 and EPO-dependent promoter activity of the OSM gene. Expression of STAT5 and the EPO receptor in COS cells conferred EPO-dependent activation of the OSM promoter. Moreover, the mutant IL2 receptor lacking the ability to activate STAT5 induced c-myc but failed to induce OSM. Thus OSM is one of the common targets of a subset of cytokines that activate STAT5. The murine OSM gene is located near to the LIF gene, expressed at high levels in bone marrow and possesses similar biological activity to human OSM. Identification of murine OSM as a cytokine-inducible immediate early gene provides a new insight into the physiological function of this unique cytokine.

A criterion for the onset of a slug flow in a horizontal duct is derived theoretically. A potential flow analysis is carried out by considering waves of finite amplitude. The stability criterion is obtained by introducing the wave deformation limit and the “most dangerous wave” concept in the stability analysis. The present theoretical criterion for slug formation shows very good agreement with a large number of experimental data and with some empirical correlations.

Abstract A method for simulating strong ground motion for a large earthquake based on synthetic Green's function is presented. We use the synthetic motions of a small event as Green's functions instead of observed records of small events. Ground motions from small events are calculated using a hybrid scheme combining deterministic and stochastic approaches. The long-period motions from the small events are deterministically calculated using the 3D finite-difference method, whereas the high-frequency motions from them are stochastically simulated using Boore's method. The small-event motions are synthesized summing the long-period and short-period motions after passing them through a pair of matched filters to follow the omega-squared source model. We call the resultant time series “hybrid Green's functions” (HGF). Ground motions from a large earthquake are simulated by following the empirical Green's function (EGF) method. We demonstrate the effectiveness of the method at simulating ground motion from the 1995 Hyogo-ken Nanbu earthquake (Mw 6.9).

Two desorption peaks of hydrogen molecule (mass number=2), starting at about 600 and 950 K, respectively, are observed in thermal desorption mass spectroscopy of nanostructured graphite mechanically milled for 80 h under hydrogen atmosphere. It follows from a combined analysis of thermal desorption mass spectroscopy and thermogravimetry, that ∼6 mass % of hydrogen (corresponding to 80% of the total amount of hydrogen) is desorbed at the first desorption peak as a mixture of pure hydrogen and hydrocarbons. Below the temperature of the second desorption peak, at which recrystallization related desorption occurs, nanostructured graphite is expected to retain its specific defective structures mainly with carbon dangling bonds as suitable trapping sites for hydrogen storage. The formation process of the nanostructures during milling under hydrogen atmosphere is also discussed on the basis of the profile of Raman spectroscopy.

The concentrations of transition-metal impurities in a photovoltaic-grade multicrystalline silicon ingot have been measured by neutron activation analysis. The results show that the concentrations of Fe, Co, and Cu are determined by segregation from the liquid-to-solid phase in the central regions of the ingot. This produces high concentrations near the top of the ingot, which subsequently diffuse back into the ingot during cooling. The extent of this back diffusion is shown to correlate to the diffusivity of the impurities. Near the bottom, the concentrations are higher again due to solid-state diffusion from the crucible after crystallization has occurred. Measurement of the interstitial Fe concentration along the ingot shows that the vast majority of the Fe is precipitated during ingot growth. Further analysis suggests that this precipitation occurs mostly through segregation to extrinsic defects at high temperature rather than through solubility-limit-driven precipitation during ingot cooling.

Formaldehyde is an aliphatic monoaldehyde and is a highly reactive environmental human carcinogen. Whereas humans are continuously exposed to exogenous formaldehyde, this reactive aldehyde is a naturally occurring biological compound that is present in human plasma at concentrations ranging from 13 to 97 micromol/L. It has been well documented that DNA-protein crosslinks (DPC) likely play an important role with regard to the genotoxicity and carcinogenicity of formaldehyde. However, little is known about which DNA damage response pathways are essential for cells to counteract formaldehyde. In the present study, we first assessed the DNA damage response to plasma levels of formaldehyde using chicken DT40 cells with targeted mutations in various DNA repair genes. Here, we show that the hypersensitivity to formaldehyde is detected in DT40 mutants deficient in the BRCA/FANC pathway, homologous recombination, or translesion DNA synthesis. In addition, FANCD2-deficient DT40 cells are hypersensitive to acetaldehyde, but not to acrolein, crotonaldehyde, glyoxal, and methylglyoxal. Human cells deficient in FANCC and FANCG are also hypersensitive to plasma levels of formaldehyde. These results indicate that the BRCA/FANC pathway is essential to counteract DPCs caused by aliphatic monoaldehydes. Based on the results obtained in the present study, we are currently proposing that endogenous formaldehyde might have an effect on highly proliferating cells, such as bone marrow cells, as well as an etiology of cancer in Fanconi anemia patients.

We introduce a generalized method for simulating strong ground motion from large earthquakes by summing subevent records to follow the ?2 law. The original idea of the method is based on a constant stress parameter between the target event and the subevent. It is applicable to a case where both events have a different stress drop after some manipulation. However, the simulation for a very large earthquake from a small event with this method has inevitably some deficiencies of spectral amplitudes in the intermediate frequency range deviating f`rom the ?2 model, although the high and low frequency motions match the scaling. We improve the simulation algorithm so as not to make spectral sags, introducing self-similar distribution of subfaults with different sizes in the fault plane, so-called fractal composite faulting model. We show successful simulations for intermediate-sized earthquakes (MJMA = 5.0, 6.0 and 6.1), the large aftershocks of the 1983 Akita-Oki earthquake. using the records of smaller aftershocks (MJMA = 3.9 and 5.0) as an empirical Green's function. Further, we attempted to estimate strong ground motion for the 1946 Nankai earthquake with Mw 8.2, using the records of a MJMA 5.1 earthquake occurring near the source region of the mainshock. We found that strong ground motions simulated for the fractal composite faulting model with two asperities radiating significantly high frequency motions matched well the observed data such as the near-field displacement record, the source spectrum estimated from the teleseismic record, and the seismic intensity distribution during the 1946 Nankai earthquake.

Abstract The Technical Design for the COMET Phase-I experiment is presented in this paper. COMET is an experiment at J-PARC, Japan, which will search for neutrinoless conversion of muons into electrons in the field of an aluminum nucleus ($\mu$–$e$ conversion, $\mu^{-}N \rightarrow e^{-}N$); a lepton flavor-violating process. The experimental sensitivity goal for this process in the Phase-I experiment is $3.1\times10^{-15}$, or 90% upper limit of a branching ratio of $7\times 10^{-15}$, which is a factor of 100 improvement over the existing limit. The expected number of background events is 0.032. To achieve the target sensitivity and background level, the 3.2 kW 8 GeV proton beam from J-PARC will be used. Two types of detectors, CyDet and StrECAL, will be used for detecting the $\mu$–$e$ conversion events, and for measuring the beam-related background events in view of the Phase-II experiment, respectively. Results from simulation on signal and background estimations are also described.

PURPOSE: Survivin, a member of the inhibitor of apoptosis protein family, is an attractive target for cancer therapy. We have now investigated the effect of YM155, a small-molecule inhibitor of survivin expression, on the sensitivity of human non-small cell lung cancer (NSCLC) cell lines to gamma-radiation. EXPERIMENTAL DESIGN: The radiosensitizing effect of YM155 was evaluated on the basis of cell death, clonogenic survival, and progression of tumor xenografts. Radiation-induced DNA damage was evaluated on the basis of histone H2AX phosphorylation and foci formation. RESULTS: YM155 induced down-regulation of survivin expression in NSCLC cells in a concentration- and time-dependent manner. A clonogenic survival assay revealed that YM155 increased the sensitivity of NSCLC cells to gamma-radiation in vitro. The combination of YM155 and gamma-radiation induced synergistic increases both in the number of apoptotic cells and in the activity of caspase-3. Immunofluorescence analysis of histone gamma-H2AX also showed that YM155 delayed the repair of radiation-induced double-strand breaks in nuclear DNA. Finally, combination therapy with YM155 and gamma-radiation delayed the growth of NSCLC tumor xenografts in nude mice to a greater extent than did either treatment modality alone. CONCLUSIONS: These results suggest that YM155 sensitizes NSCLC cells to radiation both in vitro and in vivo, and that this effect of YM155 is likely attributable, at least in part, to the inhibition of DNA repair and enhancement of apoptosis that result from the down-regulation of survivin expression. Combined treatment with YM155 and radiation warrants investigation in clinical trials as a potential anticancer strategy.

We evaluate the clinical results of a form of tumor selective particle radiation known as boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma (NDGB) patients, especially in combination with X-ray treatment (XRT). Between 2002 and 2006, we treated 21 patients of NDGB with BNCT utilizing sodium borocaptate and boronophenylalanine simultaneously. The first 10 were treated with only BNCT (protocol 1), and the last 11 were treated with BNCT followed by XRT of 20 to 30 Gy (protocol 2) to reduce the possibility of local tumor recurrence. No chemotherapy was applied until tumor progression was observed. The patients treated with BNCT (protocol 1 plus 2) showed a significant survival prolongation compared with the institutional historical controls. BNCT also showed favorable results in correspondence with the RTOG- and EORTC-RPA subclasses. The median survival time (MST) was 15.6 months for protocols 1 and 2 together. For protocol 2, the MST was 23.5 months. The main causes of death were cerebrospinal fluid dissemination as well as local recurrence. Our modified BNCT protocol showed favorable results of patients with NDGB not only for those with good prognoses but also for those with poor prognoses.

Superb biological effectiveness and dose conformity represent a rationale for heavy-ion therapy, which has thus far achieved good cancer controllability while sparing critical normal organs. Immediately after irradiation, heavy ions produce dense ionization along their trajectories, cause irreparable clustered DNA damage, and alter cellular ultrastructure. These ions, as a consequence, inactivate cells more effectively with less cell-cycle and oxygen dependence than conventional photons. The modes of heavy ion-induced cell death/inactivation include apoptosis, necrosis, autophagy, premature senescence, accelerated differentiation, delayed reproductive death of progeny cells, and bystander cell death. This paper briefly reviews the current knowledge of the biological aspects of heavy-ion therapy, with emphasis on the authors' recent findings. The topics include (i) repair mechanisms of heavy ion-induced DNA damage, (ii) superior effects of heavy ions on radioresistant tumor cells (intratumor quiescent cell population, TP53-mutated and BCL2-overexpressing tumors), (iii) novel capacity of heavy ions in suppressing cancer metastasis and neoangiogenesis, and (iv) potential of heavy ions to induce secondary (especially breast) cancer.

BACKGROUND: We investigated the application of boron neutron capture therapy (BNCT) to suitable cancers other than glioblastoma and melanoma. Head and neck malignancies were consequently selected as adaptable cancers. We reported the clinical results of our first case treated and discussed several advantages to the application of BNCT to head and neck tumors. METHODS: The patient was a 48-year-old woman with recurrent submandibular gland cancer. We confirmed the p-boronophenylalanine (BPA)-accumulating capacity of the tumor by fluorine-18-labeled p-boronophenylalanine positron emission tomography ((18)F-BPA PET) before BNCT. The tumor/normal tissue boron concentration ratio was 2.9. The patient underwent a preirradiation CT scan for treatment planning performed using the "SERA" software program. The tumor was irradiated at the Kyoto University Research Reactor with epithermal neutrons 5 MW for 90 minutes. The tumor dose and normal tissue dose calculated ranged from 20.0 to 25.2 Gy and from 3.2 to 5.8 Gy, respectively. RESULTS: To date there has been continuous complete regression in the tumor and no acute and chronic complications for 1.5 years. CONCLUSIONS: Although only 1 patient has shown complete regression and additional long-term follow-up should be required to assess this treatment, we believe that head and neck tumors are suitable for BNCT and that such excellent results will have a great impact on patients in the near future.

Neutron diffraction measurements were made on single crystals of CsCuCl 3 . The sense of Cu 2+ ion helix was found from nuclear reflections to be predominantly right-handed. The magnetic reflection data could be interpreted satisfactorily by considering a triangular spin structure of helically modulated ferromagnetic chains: The magnetic moments lie in the c-plane and rotate by 5.1±0.1° along the chain or the c-axis, while the moments rotate by 120° in the c-plane. The magnitude of the magnetic moment is 0.58±0.01 µ B at 4.2 K. The critical exponent of the magnetization, β was found to be 0.358±0.015 around the Néel temperature, 10.70±0.05 K. We present a model that the helical modulation along the c-axis is caused by the antisymmetric exchange (Dzyaloshinsky-Moriya) interaction characteristic of the crystal symmetry of CsCuCl 3 . The model predicts a right-handed magnetic helix in the present case.

The Isua Supracrustal Belt, Greenland, of Early Archean age (3.81-3.70 Ga) represents the oldest crustal segment on Earth. Its complex lithology comprises an ophiolite-like unit and volcanic rocks reminiscent of boninites, which tie Isua supracrustals to an island arc environment. We here present zinc (Zn) isotope compositions measured on serpentinites and other rocks from the Isua supracrustal sequence and on serpentinites from modern ophiolites, midocean ridges, and the Mariana forearc. In stark contrast to modern midocean ridge and ophiolite serpentinites, Zn in Isua and Mariana serpentinites is markedly depleted in heavy isotopes with respect to the igneous average. Based on recent results of Zn isotope fractionation between coexisting species in solution, the Isua serpentinites were permeated by carbonate-rich, high-pH hydrothermal solutions at medium temperature (100-300 °C). Zinc isotopes therefore stand out as a pH meter for fossil hydrothermal solutions. The geochemical features of the Isua fluids resemble the interstitial fluids sampled in the mud volcano serpentinites of the Mariana forearc. The reduced character and the high pH inferred for these fluids make Archean serpentine mud volcanoes a particularly favorable setting for the early stabilization of amino acids.