Combinatorial Measurement of CDKN1A/p21 and KIF20A Expression for Discrimination of DNA Damage-Induced Clastogenicity

In vitro mammalian cytogenetic tests detect chromosomal aberrations and are used for testing the genotoxicity of compounds. This study aimed to identify a supportive genomic biomarker could minimize the risk of misjudgments and aid appropriate decision making in genotoxicity testing. Human lymphoblastoid TK6 cells were treated with each of six DNA damage-inducing genotoxins (clastogens) or two genotoxins that do not cause DNA damage. Cells were exposed to each compound for 4 h, and gene expression was comprehensively examined using Affymetrix U133A microarrays. Toxicogenomic analysis revealed characteristic alterations in the expression of genes included in cyclin-dependent kinase inhibitor 1A (CDKN1A/p21)-centered network. The majority of genes included in this network were upregulated on treatment with DNA damage-inducing clastogens. The network, however, also included kinesin family member 20A (KIF20A) downregulated by treatment with all the DNA damage-inducing clastogens. Downregulation of KIF20A expression was successfully confirmed using additional DNA damage-inducing clastogens. Our analysis also demonstrated that nucleic acid constituents falsely downregulated the expression of KIF20A, possibly via p16 activation, independently of the CDKN1A signaling pathway. Our results indicate the potential of KIF20A as a supportive biomarker for clastogenicity judgment and possible mechanisms involved in KIF20A downregulation in DNA damage and non-DNA damage signaling networks.     

DISPERSION OF GAS AND LIQUID IN BUBBLE COLUMNS OF HOMOGENEOUS BUBBLE FLOW REGIME

Mean gas holdup, lateral distribution of gas holdup and axial mixing of gas and liquid were measured in bubble columns of 12 and 19cm i.d. The lateral distribution of gas holdup was strongly dependent on the flow regimes in the column. The axial mixing of liquid in the homogeneous bubble flow regime was much smaller than that in the heterogeneous bubble flow regime, and was not expressed by existing correlations. The axial mixing of liquid in the homogeneous bubble flow and the intermediate flow regime was simulated with a flow model based on the lateral distribution of buoyancy force and the effective viscosity. The axial mixing of gas was larger than that of liquid.     

Sintering Kinetics at Constant Rates of Heating: Effect of Al2O3 on the Initial Sintering Stage of Fine Zirconia Powder

The sinterabilities of fine zirconia powders including 5 mass% Y₂O₃ were investigated, with emphasis on the effect of Al₂O₃ at the initial sintering stage. The shrinkage of powder compact was measured under constant rates of heating (CRH). The powder compact including a small amount of Al₂O₃ increased the densification rate with elevating temperature. The activation energies at the initial stage of sintering were determined by analyzing the densification curves. The activation energy of powder compact including Al₂O₃ was lower than that of a powder compact without Al₂O₃. The diffusion mechanisms at the initial sintering stage were determined using the new analytical equation applied for CRH techniques. This analysis exhibited that Al₂O₃ included in a powder compact changed the diffusion mechanism from grain boundary to volume diffusions (VD). Therefore, it is concluded that the effect of Al₂O₃ enhanced the densification rate because of decrease in the activation energy of VD at the initial sintering stage.     

Significant Roles of Regulatory T Cells and Myeloid Derived Suppressor Cells in Hepatitis B Virus Persistent Infection and Hepatitis B Virus-Related HCCs

The adaptive immune system, including type1 helper T cells (Th1 cells), cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs), plays an important role in the control of hepatitis B virus (HBV). On the other hand, regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs) suppress the immune reaction in HBV and hepatocellular carcinoma (HCC). Excessive activation of immune suppressive cells could contribute to the persistent infection of HBV and the progression of HCC. The frequency and/or function of Tregs could affect the natural course in chronic hepatitis B patients and the treatment response. In addition to the suppressive function of MDSCs, MDSCs could affect the induction and function of Tregs. Therefore, we should understand in detail the mechanism by which Tregs and MDSCs are induced to control HBV persistent infection and HBV-related HCC. Immune suppressive cells, including Tregs and MDSCs, contribute to the difficulty in inducing an effective immune response for HBV persistent infection and HBV-related HCC. In this review, we focus on the Tregs and MDSCs that could be potential targets for immune therapy of chronic hepatitis B and HBV-related HCC.     

Formation of Sm2+ lons in Sol-Gel-Derived Glasses of the System Na2 O-Al2O3-SiO2

Samarium ions (Sm²⁺) incorporated into aluminosilicate glasses by a sol-gel process showed persistent spectral hole burning at room temperature. Gels of the system Na₂O-Al₂O₃SiO₂ synthesized by the hydrolysis of Si(OC₂H₅)₄, Al(OC₄H₉)₃, CH₃ COONa, and SmCl₃·6H₂O were heated in air at 500°C, then reacted with H₂ gas to form Sm²⁺ ions. Whereas Al³⁺ ions effectively dispersed the Sm³⁺ ions in the glass structure, Na⁺ ions were not effective. The Al₂O₃-SiO₂ glasses proved appropriate for reacting the Sm³⁺ ions with H₂ gas and exhibited the intense photoluminescence of Sm²⁺ ions. The reaction of Sm³⁺ ions with H₂ in the Al₂O₂-SiO₂ glasses was determined by first-order kinetics, and the activation energy equaled 95 kJ/mol. At 800°C, the maximum photoluminescence of the Sm²⁺ ions was achieved within 20 min.     

Chemical reaction kinetics dataset of Cs-I-B-Mo-O-H system for evaluation of fission product chemistry under LWR severe accident conditions

In order to improve LWR source term under severe accident conditions, the first version of a fission product chemistry database named ‘ECUME’ was developed. The ECUME is intended to include several datasets of major chemical reactions and their effective kinetic constants for representative severe accident sequences. It is expected that the ECUME can serve as a fundamental basis from which fission product chemical models can be elaborated for use in the severe accident analysis codes. The implemented chemical reactions in the first version were those for representative gas species in Cs-I-B-Mo-O-H system from 300 to 3000 K. The chemical reaction kinetic constants were evaluated from either literature data or calculated values using ab-initio calculations. The sample chemical reaction calculation using the presently constructed dataset showed meaningful kinetics effects at 1000 K. Comparison of the chemical equilibrium compositions by using the dataset with those by chemical equilibrium calculations has shown rather good consistency for the representative Cs-I-B-Mo-O-H species. From these results, it was concluded that the present dataset should be useful to evaluate fission product chemistry in Cs-I-B-Mo-O-H system under LWR severe accident conditions, where kinetics effects should be considered.     

Corrosion characteristics of reduced activation ferritic steel, JLF-1 (8.92Cr–2W) in molten salts Flibe and Flinak

Static corrosion tests were performed in molten salts, LiF–BeF₂ (Flibe) and LiF–NaF–KF (Flinak), at 500 °C and 600 °C for 1000 h. The purpose is to investigate the corrosion characteristics of reduced activation ferritic steels, JLF-1 (8.92Cr–2W) in the fluids. The concentration of hydrogen fluoride (HF) in the fluids was measured by slurry pH titration method before and after the exposure. The HF concentration determined the fluoridation potential. The corrosion was mainly caused by dissolution of Fe and Cr into the fluids due to fluoridation and/or electrochemical corrosion. Carbon on the surface might be dissolved into the fluids due to the corrosion, and this resulted to the decrease of carbide on the surface. The corrosion depth of the JLF-1 specimen, which was obtained from the weight losses, was 0.637 μm in Flibe at 600 °C and 6.73 μm in Flinak at 600 °C.     

Effects of EDTA saturated with Ca2+ (Ca-EDTA) on pig,bovine and mouse oocytes at the germinal vesicle stage during maturation culture and the involvement of chelation of Zn2+ in pronuclear formation induction by Ca-EDTA

EDTA saturated with Ca(2+), Fe(3+) or Cu(2+) can induce parthenogenetic activation of pig oocytes at the germinal vesicle stage, whereas EDTA saturated with Zn(2+), which is unable to chelate Zn(2+), does not, indicating that chelation of Zn(2+) with EDTA saturated with Ca(2+) (Ca-EDTA) in maturing pig oocytes plays a pivotal role in the induction of parthenogenetic activation of oocytes. In the present study, the involvement of Zn(2+) chelation in the induction of parthenogenetic activation of pig oocytes at the germinal vesicle stage was confirmed first by examining the effects of concomitant addition of Zn(2+), Cu(2+) or Ni(2+) at various concentrations together with 1 mmol Ca-EDTA l(-1) to the maturation medium. The titration experiments revealed that the pronuclear formation induced by 1 mmol Ca-EDTA l(-1) was completely inhibited by the addition of > 30 micromol Zn(2+) l(-1) to the medium, but not by the addition of Cu(2+) and Ni(2+) at any concentration examined. Second, bovine and mouse oocytes at the germinal vesicle stage were cultured in medium with or without 1 mmol Ca-EDTA l(-1) for 48 h to examine the effects of Ca-EDTA treatment on these oocytes during maturation culture. Most (70-86%) of the bovine oocytes that underwent germinal vesicle breakdown matured to the MII stage via the MI phase, regardless of whether Ca-EDTA was present for the first 24 h of culture. However, 61% of oocytes that had been cultured with Ca-EDTA for 48 h formed a pronucleus without a second polar body, whereas oocytes cultured in the absence of Ca-EDTA were not observed to form a pronucleus at any time during culture. However, even when mouse oocytes at the germinal vesicle stage were cultured for up to 48 h in maturation medium containing Ca-EDTA, pronuclear formation was not observed. Finally, when bovine oocytes that had been cultured with 1 mmol Ca-EDTA l(-1) for 48 h from the germinal vesicle stage were cultured further in medium without Ca-EDTA that was supplemented with 5% fetal calf serum, only 26% of the oocytes developed to the cleaved stage, and none could develop further.     

Flame-spread probability and local interactive effects in randomly arranged fuel-droplet arrays in microgravity

We investigated the flame-spread characteristics of randomly arranged fuel-droplet arrays in microgravity. Flame-spread probability was calculated based on a percolation model with the flame-spread-limit distance of evenly-spaced n-decane droplet arrays in microgravity. Flame-spread probability depends on the occupation fraction of droplets in a lattice and rapidly increases with the occupation fraction. The local flame-spread-limit distance of unevenly-spaced n-decane droplet arrays was experimentally investigated in microgravity. The droplets were arranged in a straight line at uneven intervals. The local flame-spread-limit distance of the unevenly-spaced droplet arrays depended on the droplet arrangement and increased from the flame-spread-limit distance of the evenly-spaced droplet arrays due to interactive effects. The flame-spread probability considering the increase in local flame-spread-limit distance is larger than that without it.