Search

This study conducted fundamental research to develop a more effective BNCT targeting cancer stem cells. We constructed plasmids that induced the overexpression of L-type amino acid transporter 1 (LAT1) tagged with tdTomato on the cytoplasmic membranes of CD133 expressing cancer cells. After transfection of the plasmids into a glioblastoma cell line (T98G), several clones overexpressing LAT1-tdTomato in the hypoxic microenvironment of the spheroids formed from each clone were obtained. Confocal laser microscopic observation confirmed that signals from LAT1-tdTomato overlapped with immunofluorescence signals from the second antibody binding to CD133 in the hypoxic microenvironment of the spheroids. As CD133-positive cells in the hypoxic microenvironment of T98G spheroids have cancer stem cell characteristics, LAT1 seems to be selectively overexpressed in cancer stem cell-like cells. An RI tracer method showed that cells overexpressing LAT1-tdTomato in the hypoxic microenvironment of spheroids incorporate 14C-BPA much more than cells that do not overexpress LAT1-tdTomato. Neutron radiation experiments showed a more significant regression in spheroids formed with clones than in spheroids formed with parental cells when spheroids were treated with 10BPA. These results suggest that BNCT combined with gene therapy targeting cancer stem cells is more effective in glioblastoma therapy.

Katsunori Yogo,1 Masaki Misawa,2 Morihito Shimizu,2 Hidetoshi Shimizu,3 Tomoki Kitagawa,3 Ryoichi Hirayama,4 Hiromichi Ishiyama,5 Takako Furukawa,1 Hiroshi Yasuda6 1Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan; 2Health and Medical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki, Japan; 3Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan; 4National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba-shi, Chiba, Japan; 5Graduate School of Medical Science, Kitasato University, Sagamihara, Kanagawa, Japan; 6Department of Radiation Biophysics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, JapanCorrespondence: Katsunori YogoNagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-Ku, Nagoya, Aichi 461-8673, JapanTel +81 52 719 1103Fax +81 52 719 3172Email yogo@met.nagoya-u.ac.jpPurpose: Gold nanoparticles (AuNPs) are candidate radiosensitizers for medium-energy photon treatment, such as γ-ray radiation in high-dose-rate (HDR) brachytherapy. However, high AuNP concentrations are required for sufficient dose enhancement for clinical applications. Here, we investigated the effect of positively (+) charged AuNP radiosensitization of plasmid DNA damage induced by 192Ir γ-rays, and compared it with that of negatively (−) charged AuNPs.Methods: We observed DNA breaks and reactive oxygen species (ROS) generation in the presence of AuNPs at low concentrations. pBR322 plasmid DNA exposed to 64 ng/mL AuNPs was irradiated with 192Ir γ-rays via HDR brachytherapy. DNA breaks were detected by observing the changes in the form of the plasmid and quantified by agarose gel electrophoresis. The ROS generated by the AuNPs were measured with the fluorescent probe sensitive to ROS. The effects of positively (+) and negatively (−) charged AuNPs were compared to study the effect of surface charge on dose enhancement.Results: +AuNPs at lower concentrations promoted a comparable level of radiosensitization by producing both single-stranded breaks (SSBs) and double-stranded breaks (DSBs) than those used in cell assays and Monte Carlo simulation experiments. The dose enhancement factor (DEF) for +AuNPs was 1.3 ± 0.2 for SSBs and 1.5 ± 0.4 for DSBs. The ability of +AuNPs to augment plasmid DNA damage is due to enhanced ROS generation. While −AuNPs generated similar ROS levels, they did not cause significant DNA damage. Thus, dose enhancement using low concentrations of +AuNPs presumably occurred via DNA binding or increasing local +AuNP concentration around the DNA.Conclusion: +AuNPs at low concentrations displayed stronger radiosensitization compared to −AuNPs. Combining +AuNPs with 192Ir γ-rays in HDR brachytherapy is a candidate method for improving clinical outcomes. Future development of cancer cell-specific +AuNPs would allow their wider application for HDR brachytherapy.Keywords: gold nanoparticles, high-dose-rate brachytherapy, DNA damage, radiosensitization, 192Ir γ-rays, positively charged nanoparticles

In this study, we examined whether the cancer cell-killing effects of boron neutron capture therapy (BNCT) are enhanced by manipulating the expression levels of l-type amino acid transporter 1 (LAT1) of human cancer cells, which transports boronophenylalanine into cells. We transfected pCMV/LAT1-GFP plasmids into a T98G glioblastoma cell line and selected several clones. Confocal laser microscopic observation was performed to confirm the stable overexpression of LAT1 in the plasma membranes of the clones. Western blot was used to analyze the cellular accumulation of LAT1 protein in the clones. Relative intracellular uptake of boronophenylalanine (BPA) was determined by measuring the radioactivity of 14C-BPA using a radioactive iodine (RI) tracer method. Sensitivity to neutron and gamma (γ)-ray fluences generated by a research reactor facility at Kyoto University was assayed using colony formation assay. Green fluorescent protein (GFP)-tagged LAT1 was observed in the plasma membranes of the LAT1-overexpressing clones and the cellular accumulation of GFP-tagged LAT1 was largely increased in these clones. Intracellular uptake of BPA was 1.5-5.0 times greater among the clones than that in a control clone. The LAT1-overexpressing clones and transiently LAT1-lipofected T98G cells showed clearly enhanced sensitivity to neutron and γ-ray fluences compared to the control clone when they were treated with 10BPA. The sensitivity of cancer cells to the fluences was well correlated with the expression level of LAT1 in the cells and the level of BPA uptake. These results suggest that overexpression of LAT1 in cancer cells results in enhanced anticancer effects of BNCT, and BNCT combined with gene therapy is beneficial for tumors with low LAT1 expression.

Gold nanoparticles (Au-NPs) have attracted attention as a promising sensitizer owing to their high atomic number (Z), and because they are considered fully multifunctional, they are preferred over other metal nanoparticles. Cold atmospheric plasma (CAP) has also recently gained attention, especially for cancer treatment, by inducing apoptosis through the formation of reactive oxygen species (ROS). In this study, the activity of different sized Au-NPs with helium-based CAP (He-CAP) was analyzed, and the underlying mechanism was investigated. Treating cells with only small Au-NPs (2 nm) significantly enhanced He-CAP-induced apoptosis. In comparison, 40 nm and 100 nm Au-NPs failed to enhance cell death. Mechanistically, the synergistic enhancement was due to 2 nm Au-NPs-induced decrease in intracellular glutathione, which led to the generation of intracellular ROS. He-CAP markedly induced ROS generation in an aqueous medium; however, treatment with He-CAP alone did not induce intracellular ROS formation. In contrast, the combined treatment significantly enhanced the intracellular formation of superoxide (O2• −) and hydroxyl radical (•OH). These findings indicate the potential therapeutic use of Au-NPs in combination with CAP and further clarify the role of Au-NPs in He-CAP-aided therapies.

Traditional tissue-engineered cartilage applied in clinical practice consists of cell suspensions or gel-form materials for which it is difficult to maintain their shapes. Although biodegradable polymer scaffolds are used for shape retention, deformation after transplantation can occur. Here, we showed that periostin (PN), which is abundantly expressed in fibrous tissues, contributes to the maturation and shape retention of tissue-engineered cartilage through conformational changes in collagen molecules. The tissue-engineered cartilage transplanted in an environment lacking PN exhibited irregular shapes, while transplants originating from chondrocytes lacking PN showed limited regeneration. In the in vitro assay, PN added to the culture medium of chondrocytes failed to show any effects, while the 3D culture embedded within the collagen gel premixed with PN (10 μg/mL) enhanced chondrogenesis. The PN-mediated collagen structure enhanced the mechanical strength of the surrounding fibrous tissues and activated chondrocyte extracellular signaling by interstitial fibrous tissues.

Currently, no standardized method for measuring intrahepatic fat density via conventional computed tomography (CT) exists.We aim to quantify intrahepatic fat density via material decomposition analysis using rapid kilovolt peak-switching dual-energy (RSDE) CT.Homogenized porcine liver and fat (lard) were mixed in various ratios to produce phantoms for fat density verification. The actual fat density was measured on the basis of the phantom volume and weight, and these measurements were used as reference densities. The fat and liver mass attenuation coefficients, which were used as the material basis pairs, were employed in the material decomposition analysis. Then, the measured fat density of each phantom was compared with the reference densities.For fat content differences exceeding 2%, the measured fat density for the phantoms became statistically significant (p 0.01). The correlation between the reference densities and RSDE-measured fat densities was reasonably high (R 0.9997); this indicates the validity of this analysis method.Intrahepatic fat density can be measured using the mass attenuation coefficients of fat and liver in a material decomposition analysis. Given the knowledge of the accuracy and the limitations found in this study, our method can quantitatively evaluate fat density.

In cartilage regenerative medicine, autologous chondrocyte implantation (ACI) has been applied clinically for partial defects of joint cartilage or nasal augmentation. To make treatment with ACI more effective and prevalent, modalities to evaluate the quality of transplanted constructs noninvasively are necessary. In this study, we compared the efficacy of several noninvasive modalities for evaluating the maturation of tissue-engineered auricular cartilage containing a biodegradable polymer scaffold. We first transplanted tissue-engineered cartilage consisting of human auricular chondrocytes, atelocollagen gel, and a poly-l-lactic acid (PLLA) porous scaffold subcutaneously into the back of athymic nude rats. Eight weeks after transplantation, the rats were examined by magnetic resonance imaging (MRI), X-ray, and ultrasound as noninvasive modalities. Then, the excised constructs were examined by histological and biochemical analysis including toluidine blue (TB) staining, glycosaminoglycans content, and enzyme-linked immunosorbent assay of type II collagen. Among the modalities examined, transverse relaxation time (T2) and apparent diffusion coefficient of MRI showed quite a high correlation with histological and biochemical results, suggesting that these can effectively detect the maturation of tissue-engineered auricular cartilage. Since these noninvasive modalities would realize time-course analysis of the maturation of tissue-engineered auricular cartilage, this study provides a substantial insight for improving the quality of tissue-engineered cartilage, leading to improvement of the quality and technique in cartilage regenerative medicine.

In order to achieve a nanometer-scale resolution in an x-ray microscopy system, a Gabor-type hologram was produced by eliminating the zero-order term of the object diffraction pattern. In this system, a Fresnel zone plate was used for strong illumination of an object, and the zero-order diffraction was physically eliminated by a center stop. An accurate phase plate of π / 2 in the Zernike method was numerically created, and the phase-contrast image was realized. The theoretical resolution was 19.8 nm. We proved that a gold nanocube with a size of 50 nm can be reconstructed with the predicted resolution.

The speed of sound (SOS) of a longitudinal wave propagating in the living body reflects the tissue properties and is expected as a promising evaluation index for detection of disease, diagnosis and monitoring. However, in general, the interpretation of SOS is complex, because it is influenced mostly by compressibility and multiple factors. In this study, as a study for the interpretation of SOS, the SOS of cartilage was measured in vivo by using a fusion of ultrasound and magnetic resonance imaging (MRI), and the correlations between the SOS and other quantities were investigated. In summary, as a possible interpretation of SOS of cartilage tissue used in this study, it was suggested that the SOS was partly related to water content.

Diffusion-magnetic resonance elastography (dMRE) is an emerging practical technique that can acquire diffusion magnetic resonance imaging and MRE simultaneously. However, a signal loss attributable to intravoxel phase dispersion (IVPD) interferes with the calculation of the apparent diffusion coefficient (ADC). This study presents an approach to dMRE that reduces the influence of IVPD by introducing a new pulse sequence. The existing and proposed techniques were performed using a phantom comprising five rods with different elasticities at 60 Hz vibration to investigate the accuracy of previous and proposed dMRE techniques. The measures of ADC and stiffness, obtained by using both dMRE techniques, were compared with conventional spin-echo (SE) diffusion and SE-MRE. Then, we evaluated those differences by using the mean of absolute differences (MAD) in each rod within the phantom. The results of the MAD of the stiffness from both dMRE techniques showed almost no difference. In contrast, the value of the ADC MAD (MAD ≒ 0.16 × 10−3 mm2/s), obtained in the soft region within the phantom with the previous dMRE technique, was large. This value was about 2.7 times that of the value produced by the proposed dMRE technique. This difference must reflect the degree of influence of IVPD in both techniques. These results demonstrate that our dMRE technique is a robust method for addressing the signal loss attributable to IVPD.

In this work, the application of an undecimated wavelet transformation together with digital interferometric contrast to improve the resulting reconstructions in a digital hard X-ray Gabor holographic microscope is shown. Specifically, the starlet transform is used together with digital Zernike contrast. With this contrast, the results show that only a small set of scales from the hologram are, in effect, useful, and it is possible to enhance the details of the reconstruction.

We developed a facile one-pot fabrication process for magnetic iron oxide–calcium phosphate (IO–CaP) composite nanoparticles via coprecipitation in labile supersaturated CaP solutions containing IO nanocrystals. All the source solutions used were clinically approved for injection, including water and magnetic IO nanocrystals (ferucarbotran, used as a negative magnetic resonance imaging (MRI) contrast agent). This ensured that the resulting nanoparticles were pathogen- and endotoxin-free. The dispersants used were clinically approved heparin sodium (heparin) or adenosine triphosphate disodium hydrate (ATP), which were added to the IO-containing labile supersaturated CaP solutions. Both heparin and ATP coprecipitated with CaP and ferucarbotran to form heparin- and ATP-modified IO–CaP nanoparticles, respectively, with a hydrodynamic diameter of a few hundred nanometers. Both the resulting nanoparticles exhibited relatively large negative zeta potentials, caused by the negatively charged functional groups in heparin and ATP, which improved the particle dispersibility when compared to non-modified IO–CaP nanoparticles. The heparin-modified IO–CaP nanoparticles were effectively ingested by murine macrophages (RAW264.7) without showing significant cytotoxicity but barely ingested by non-phagocytotic human umbilical vein endothelial cells, indicating the potential of these nanoparticles for targeted delivery to macrophages. The heparin-modified IO–CaP nanoparticles exhibited a negative contrast enhancing ability for MRI. Our results show that IO–CaP nanoparticles have potential as delivery and MRI contrast agents for macrophages.

In this paper, we show how the starlet transform can be used to process holograms from a digital Gabor holographic microscope. The starlet transform is an undecimated wavelet transform with the property that when performing reconstruction, we only need to add all scales without the use of a synthesis filter bank. When the starlet transform is applied to a hologram, we divide the hologram into a certain number of scales, process them separately, and propagate each one using a numerical diffraction method. After diffraction propagation, we perform processing on complex amplitudes that correspond to individual scales. With the aforementioned procedure, it is possible to reduce the background and effects of parasitic fringes caused by high coherence of a laser, enhance the contrast, and reduce the effects of the twin image. Experimental results confirming the method are presented.

To reduce particulate matter (PM) including soot in diesel exhaust gas, a diesel particulate filter (DPF) has been developed. Since it is difficult to observe the phenomena in a DPF experimentally, we have conducted a lattice Boltzmann simulation. In this study, we simulated the flow in a metallic filter. An X-ray computed tomography (CT) technique was applied to obtain its inner structure. The processes of soot deposition and oxidation were included for a continuously regenerating diesel filter. By comparing experimental data, a parameter of soot deposition probability in the numerical model was determined.

We propose a differential interference contrast method for cells using hard x-ray Gabor holography and knife-edge filtering in the spatial frequency domain, without relying on beam shearing. A phase object is holographically recorded and reconstructed by computer. Interference between the wavefronts of zeroth order weighted by ejπ/2 in the positive frequency region produces a dark image. Similarly, interference between the wavefronts of the zeroth order weighted by ej3π/2 in the negative frequency region produces a bright image. By adding these two intensity distributions, good quality phase-contrast images of 8-μm-diameter polystyrene beads and human HeLa cells were obtained.

The interface area between the bubble and emulsion phases in a fluidized catalyst bed is one of the important parameters used to analyze and design the fluidized bed reactor. We used a fast-scanning X-ray CT system to observe the bubble shape and structure. We then obtained the transient 2-dimensional cross sectional gas-phase distribution in a fluidized catalyst bed. Using image-processing techniques, pseudo 3-dimensional images of the bubbles were reconstructed. The bubble structure was studied based on the 3-dimensional images and the previously obtained results in a 2-dimensional fluidized bed. It was found that the bubble shape was not spherical but complicated, and that the bubbles ascending in a fluidized catalyst bed consisted of some smaller bubbles.

For a development of deep tumor treatment in photodynamic therapy, a feasibility of novel radiosensitizers induced by x-ray was investigated. The sensitizers are designed to generate reactive oxygen species (ROS) inside or outside the cell, possibly leading to damage exclusively on tumor cells and reservation of normal cells along the x-ray path. Taking note of the similarity in energy transfer mechanism in photocatalysts, scintillators, and particulate semiconductors, we chose TiO2, ZnS:Ag, CeF3, and quantum dots (CdTe and CdSe) in particulate form, which contain heavy atoms for efficient absorption of x-rays. A parameter study for x-ray operating conditions showed that in a typical scenario, photons with 20 to 170 keV energy are attenuated by 90% through the region of particle dispersed aqueous solution at varying concentration between 0.01 and 100 wt%. The amount of ROS generation under the exposure of polychromatic x-ray was measured using dihydroethidium reagent which detects an integrated amount of several species. Proportional increase in ROS generation to x-ray dose was observed for varying concentrations of TiO2, ZnS:Ag, CeF3, and CdSe quantum dot dispersions. Then, HeLa cells were mixed with aqueous solutions dispersed with sensitizing materials at a concentration of 3.0 mg/ml and were exposed to x-ray. Their survival fraction obtained by a cell proliferation reagent WST-1 immediately after the irradiation showed insignificant effects of sensitizing materials except at large doses. To enhance the sensitization effect, bio-conjugated CdSe quantum dots were internalized in the cytoplasm up to a concentration of 1.0 ng/ml. The cells were irradiated by x-ray up to 5 Gy, and their survival fraction was measured by the colony forming ability 9 days after irradiation. Survival fraction of the cells treated with quantum dots were less than those without quantum dots for all doses, suggesting that the colony forming ability is impaired by the internalized quantum dots.

Since diesel exhaust gas has more ambient air pollutants such as NOx and particulate matters (PM) including soot, the special treatment for exhaust emission standards is needed. Recently, a diesel particulate filter (DPF) has been developed to reduce PM in the after-treatment of exhaust gas. However, since the structure of the filter is small and complex, it is impossible to examine the phenomena inside the filter experimentally. In this study, we conduct fluid simulation in the diesel filter. We use the lattice Boltzmann method. The soot accumulation is considered to simulate the PM trap in the filter. For the wall-boundary in the simulation, the inner structure of the filter is obtained by a 3D-CT technique. Results show complex flow pattern in the diesel filter. Due to the soot accumulation, the velocity is changed and the pressure is increased. The pressure drop becomes larger as soot concentration at the inlet is higher.

In this study, we report on the potential use of platinum nanoparticles (Pt-NPs), a superoxide dismutase (SOD)/catalase mimetic antioxidant, in combination with 1MHz ultrasound (US) at an intensity of 0.4 W/cm(2), 10% duty factor, 100 Hz PRF, for 2 min. Apoptosis induction was assessed by DNA fragmentation assay, cell cycle analysis and Annexin V-FITC/PI staining. Cell killing was confirmed by cell counting and microscopic examination. The mitochondrial and Ca(2+)-dependent pathways were investigated. Caspase-8 expression and autophagy-related proteins were detected by spectrophotometry and western blot analysis, respectively. Intracellular reactive oxygen species (ROS) elevation was detected by flow cytometry, while extracellular free radical formation was assessed by electron paramagnetic resonance spin trapping spectrometry. The results showed that Pt-NPs exerted differential effects depending on their internalization. Pt-NPs functioned as potent free radical scavengers when added immediately before sonication while pre-treatment with Pt-NPs suppressed the induction of apoptosis as well as autophagy (AP), and resulted in enhanced cell killing. Dead cells displayed the features of pyknosis. The exact mode of cell death is still unclear. In conclusion, the results indicate that US-induced AP may contribute to cell survival post sonication. To our knowledge this is the first study to discuss autophagy as a pro-survival pathway in the context of US. The combination of Pt-NPs and US might be effective in cancer eradication.

It is important to evaluate the elasticity of tissue-engineered cartilage, for evaluating its structural strength. However, in vivo evaluation of tissue-engineered cartilage elasticity has not been established. On the other hand, since the speed of sound (SOS) is available for elasticity evaluation, we have proposed in vivo measurement method of SOS using ultrasound and MR images. This method determines the SOS based on the thickness measurement using the MR image and the time-of-flight (TOF) measurement using the ultrasound. In this study, this method was applied to the SOS measurement in tissue-engineered cartilage, and then relation between in vivo SOS and elasticity was investigated. As the result, in vivo SOS had a high correlation with Young's modulus. This result reveals that in vivo evaluation of tissue-engineered cartilage elasticity is available through in vivo SOS measurement.

BACKGROUND Transmission and tomographic X-ray measurements are useful in assessing bone structures, but only a few studies have examined cartilage growth because of the poor contrast in conventional X-ray imaging. OBJECTIVE In this study, we attempted to use the linear attenuation coefficient (LAC) as a metric of tissue-engineered cartilage development, which would be useful in high-throughput screening of cartilage products. METHODS Assuming that the LAC is related to the amount of extracellular matrix (ECM) in terms of the density and its atomic components, we measured X-ray absorption through tissue-engineered cartilage constructs. Characteristic X-ray beams from a molybdenum microfocus X-ray tube were employed to avoid beam hardening. The correlation of the LAC with mechanical properties was analyzed for verification. RESULTS The LAC was higher for chondrocyte constructs and lower for fibroblast-dominant constructs and was consistent with the quantification of toluidine blue staining, which is a proof of ECM production. The LAC was positively correlated with the bending modulus but negatively correlated with the dynamic elastic modulus and stiffness, possibly because of the remaining scaffold. CONCLUSIONS The LAC has the potential to be used as a metric of development of tissue-engineered cartilage. However, the calcified regions should be excluded from analysis to avoid decreasing the correlation between the LAC and the amount of ECM.

Numerical simulation of gas-liquid two-phase flow is important for design of nuclear power systems. Conventional codes require experiments from laboratory scale to mock-up to obtain database for constitutive equations and verification. The aim of this study is to provide new simulation technique to substitute for a part of costly experiments. The extended two-fluid model developed by Hitachi, Ltd. was employed to treat inhomogeneous and intermittent two-phase flow behavior, which had been considered through constitutive equations. Validity of the new simulation code for complex two-phase flow was proved by comparison between calculated and experimental void fraction signals from two-phase flows in circular tubes, CCFL of a thick plate, and natural circulation of aerated pool in double cylinders. For measurement of instantaneous, multi-dimensional void fraction distributions, wire-mesh sensor techniques were employed for all test setups. It was found that the two-phase flow has higher orders of dynamics than initially expected, leading to development of robust analysis methods. The comparison was successful for well-structured flow patterns as slug flow, since the large diameter bubbles show low dimensional dynamics. It is also noted that an optimal delay time reconstruction method and a point correlation dimension method together were useful to increase the reliability of the analysis.

The nonlinear time series analysis of two-phase flow is difficult, and the analysis sometimes results subjectively. Using artificially generated quasiperiodic data and submerged nozzle pressure fluctuation, we showed that applying an optimal delay time reconstruction method and a point correlation dimension method together greatly improved the reliability of the analysis. In this paper, we analyze real two-phase flows time series : differential pressure and void fraction of slug and bubbly flow in a vertical pipe. The comparisons of estimated results and their statistical test results demonstrate the high reliability of the proposed analysis method.

In order to detect the disease and degeneration of cartilage early, evaluations of acoustic properties are expected, but the physical meaning should be clarified. On the other hand, we have proposed a multimodal method using ultrasound (US) and magnetic resonance (MR) images for in vivo SOS measurement. In this study, the method was applied for the tissue-engineered cartilage, and the SOS was compared with T1, T2, apparent diffusion coefficient (ADC), attenuation coefficient (ATT), and Young’s modulus (YM). All procedures were approved by the Animal Care and Use Committee of our institution. 12-week-old male rats were used, and five different types of tissue-engineered cartilage was subcutaneously implanted in the back of rat (n = 30). Under anesthesia, MR and US images including same cross-sections were acquired separately, by using a MR imager of 2 Tesla and a US device of 13 MHz. At this time, T1, T2, ADC were also measured. The SOS was determined by the thickness measurement using the MR image and the...

A new gas-liquid two-phase flow simulation method has been developed based on the extended two-fluid model, which has capabilities of both the two-fluid and the interface-tracking models. The VOF (Volume of Fluid) technique has been introduced for suitable interface calculations. Interfaces of free surface and large bubbles are calculated directly by solving transport of a steep void fraction gradient corresponding to interface, while averaged behavior of microscopic dispersed bubbles and droplets are calculated in the two-fluid model scheme. It is expected that the present method can treat effects of significant kinetic interaction between the phases directly without empirical correlations. The calculated propagation of wet front in a dam break problem is close to experimental data. The predicted flow patterns of complex gas-liquid two-phase flow in a flat tube are quite similar to observations with a video camera. The present simulation will be a useful tool for predictions of integral behavior of thermal-hydraulic phenomena in large-scale nuclear power plants.

The behavior of a single bubble and a pair of bubbles under microgravity conditions has been investigated using the NASA-DC9 aircraft in order to understand the effects of various parameters and to control the bubble behavior in space. Silicone oil was used as the test liquid, and a nitrogen gas bubble was injected from the top wall under different experimental conditions. In an isothermal case, two different microgravity conditions were achieved by either fixing the experimental apparatus to the aircraft floor or freely floating the apparatus in the aircraft cabin. The bubble behavior was found to be clearly influenced by the quality of the microgravity environment, and variations of the bubble aspect ratio with the Bond number were presented. The results indicate that there is a critical Bond number of the order of 10−1 which determines the bubble shape deformation. In the free-floating experiments, a temperature gradient was imposed on the liquid around the bubble near the heated top wall. Marangoni convection was expected to occur around the bubble and the bubble behavior was studied under various temperature gradients. The bubble aspect ratio was found to decrease with an increase in the Marangoni number. A theoretical model for the relation between the Marangoni flow around the bubble and the aspect ratio is proposed based on simple assumptions. Visualization of Marangoni convection around the bubbles using the photochromic dye activation method was successfully performed. The aspect ratios predicted by the model agreed with the experimental results reasonably well. Direct measurements of surface velocity are, however, necessary to further evaluate the validity of the model.

高速X線CTスキャナを利用して触媒流動層の分散器より0.6mの高さにおいて気泡の断層画像を得た．流動層には内径46mm，高さ1.5mのアクリル樹脂製のカラムを使用した．空気を流動化ガスとし，空塔ガス速度0.01–0.07ms− 1の範囲で測定を行った．得られた断層画像を使用して気泡の境界部の解析を行った．エマルション相の空隙率が気泡界面付近でどのように変化するか調べた．また，気泡形状を考慮した界面積を求め，気泡長さから球状を仮定して求められる気泡の界面積との比較を行った．その結果，気泡形状を考慮した界面積は気泡を球状と仮定して推算される界面積よりもかなり大きくなることがわかった．

CdZnTe (CZT) detectors are promising detectors, which have many good characteristics such as room temperature operation, reasonable energy resolution, high-detection efficiency to gamma rays, etc. However, energy resolution of CZT is governed by poor mobilities of charge carriers. Many researchers have tried to solve this problem. Among them, a clustering method has been recently proposed which is based on a digital signal processing of preamplifier output waveforms. In this method, we can classify signals according to their shapes and independently treat different shapes. In this paper, we report a new clustering algorithm with adaptive shaping time. The obtained energy resolution for /sup 137/Cs was improved to 5.4-keV full width at half maximum (FWHM) by applying this method.

Since the speed of sound (SOS) reflects tissue characteristics and is expected as an evaluation index of elasticity and water content, the noninvasive measurement of SOS is eagerly anticipated. However, it is difficult to measure the SOS by using an ultrasound device alone. Therefore, we have presented a noninvasive measurement method of SOS using ultrasound (US) and magnetic resonance (MR) images. By this method, we determine the longitudinal SOS based on the thickness measurement using the MR image and the time of flight (TOF) measurement using the US image. The accuracy of SOS measurement is affected by the accuracy of image registration and the accuracy of thickness measurements in the MR and US images. In this study, we address the accuracy improvement in the latter thickness measurement, and present an image-processing-based method for improving the accuracy of thickness measurement. The method was investigated by using in vivo data obtained from a tissue-engineered cartilage implanted in the back of a rat, with an unclear boundary.

In this study, the mutual fusion of chondrocyte pellets was promoted in order to produce large-sized tissue-engineered cartilage with a three-dimensional (3D) shape. Five pellets of human auricular chondrocytes were first prepared, which were then incubated in an agarose mold. After 3 weeks of culture in matrix production-promoting medium under 5.78g/cm(2) compression, the tissue-engineered cartilage showed a sufficient mechanical strength. To confirm the usefulness of these methods, a transplantation experiment was performed using beagles. Tissue-engineered cartilage prepared with 50 pellets of beagle chondrocytes was transplanted subcutaneously into the cell-donor dog for 2 months. The tissue-engineered cartilage of the beagles maintained a rod-like shape, even after harvest. Histology showed fair cartilage regeneration. Furthermore, 20 pellets were made and placed on a beta-tricalcium phosphate prism, and this was then incubated within the agarose mold for 3 weeks. The construct was transplanted into a bone/cartilage defect in the cell-donor beagle. After 2 months, bone and cartilage regeneration was identified on micro-computed tomography and magnetic resonance imaging. This approach involving the fusion of small pellets into a large structure enabled the production of 3D tissue-engineered cartilage that was close to physiological cartilage tissue in property, without conventional polyper scaffolds.

5-Aminolevulinic acid (ALA) is a precursor of the photosensitizer used in photodynamic therapy. It accumulates in tumor cells and subsequently metabolizes to protoporphyrin IX (PpIX), which generates singlet oxygen after light irradiation. PpIX enhances the generation of reactive oxygen species following physicochemical interactions with X-rays. ALA-based treatment using fractionated doses of irradiation suppressed tumor growth in a mouse melanoma model. To study the transcriptomic effects of PpIX, microarray analyses were conducted using HeLa cells with limited proliferation capacity. Based on the p-values (p &lt, 0.01), we selected genes showing altered expression in each treatment group with reference to the non-treatment (NT) group. We detected 290, 196 and 28 upregulated genes, as well as 203, 146 and 36 downregulated genes after a 6 h-long PpIX treatment (1 μg/mL) prior to 3 Gy X-ray irradiation (PpIX-XT), 3 Gy X-ray irradiation alone (XT) and PpIX treatment alone (PpIXT), respectively. Functional analysis revealed that a majority of the regulated genes in the XT and PpIX-XT groups were related to cell-cycle arrest. The XT and PpIX-XT groups differed in the quantity, but not in the quality of their gene expression. The combined effect of PpIX and X-ray irradiation sensitized HeLa cells to X-ray treatment.

We describe the numerical simulation results of bubble motion under gravity by the lattice Boltzmann method(LBM), which assumes that a fluid consists of mesoscopic fluid particles repeating collision and translation and a multiphase interface is reproduced in a self-organizing way by repulsive interaction between different kinds of particles. The purposes in this study are to examine the applicability of LBM to the numerical analysis of bubble motions, and to develop a three-dimensional version of the binary fluid model that introduces a free energy function. We included the buoyancy terms due to the density difference in the lattice Boltzmann equations, and simulated single- and two-bubble motions, setting flow conditions according to the Eotvos and Morton numbers. The two-dimensional results by LBM agree with those by the Volume of Fluid method based on the Navier-Stokes equations. The three-dimensional model possesses the surface tension satisfying the Laplace's law, and reproduces the motion of single...

A tournament clustering algorithm for treating pulse-height variation of detector signals related to the waveform change has been introduced. The algorithm does not need prior modeling of signals. The algorithm was applied to CdTe/CdZnTe detectors of 2 mm thick. Each classified spectrum was summed up to form a combined pulse-height spectrum using normalization factors obtained during a test run. The obtained energy resolution for 137Cs was improved to 13.1 keV FWHM. This method can be applied to any type of semiconductor detectors that exhibits great variation in individual signal waveforms. The classification results contain information on the signal collection process and can improve the effective performance of the detector.

This study describes the numerical simulations of two-phase fluid motions under gravity by the lattice Boltzmann method (LBM), in which the fluid motions result from collision and translation of mesoscopic particles and the interface interaction in multiphase fluids can be reproduced in a self-organizing way. Our aims are to examine the applicability of LBM to the numerical analysis of bubble motions in comparison with the two-dimensional results by the Volume Of Fluid (VOF) method based on the Navier–Stokes and the liquid-volume convective equations, and to develop the three-dimensional binary fluids model, consisting of two sets of distribution functions to represent the total fluid density and the density difference, which introduces the repulsive interaction consistent with a free energy function between fluid particles. We included the buoyancy terms due to the density difference between two phases in the lattice Boltzmann equations, and simulated the motions of single bubble and two bubbles rising in a duct, calculating the surface tension from the Laplace's law represented by the non-dimensional numbers, Eotvos and Morton numbers. In the two-dimensional simulations, the results by LBM agree with those by the VOF method. The three-dimensional simulation of two bubble interaction shows that the upper bubble takes a shape of skirt as the lower bubble approaches due to the wake formation, and they coalesce into a single bubble eventually. These results prove the validity of the buoyancy model proposed here and the applicability of LBM to the quantitative numerical analysis of two-phase fluid motions.