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A pilot survey in the Central Garhwal Himalayan region, India, assessed radon and thoron inhalation doses using RADUET, CR39 detectors during January to October 2013. Detectors were deployed for 95, 101, and 92 days in winter, summer, and in the rainy season respectively. Highest 222Rn concentration (260 ± 13 Bqm−3) was in cemented categories, followed by 170 ± 8 and 190 ± 10 Bqm−3 in wood-stone dwellings. Wood-mud categories had lower levels (116 ± 6 to 128 ± 8 Bqm−3). Despite significant 222Rn concentration, analysis of seasonal radiation exposures (EECTn and Feq) with short-lived decay products showed reduced doses in winter months ranging from 2.97 (± 0.31) to 6.91 (± 0.32) Bqm−3. [ABSTRACT FROM AUTHOR]

We investigate the γ d → d π + π - reaction for a study of a possible N Δ dibaryon state using a deuterium target with a magnetic spectrometer, Neutral Kaon Spectrometer 2 (NKS2), at Research Center for Electron Photon Science (ELPH), Tohoku University. The incident photon energy ranged from 0.78 to 1.08 GeV. Resonance-like structures were found at a mass of ∼ 2.15 GeV / c 2 with a width of ∼ 0.1 GeV / c 2 in the d π + and d π - invariant mass spectra. [ABSTRACT FROM AUTHOR]

The rudder force, including interference with a ship hull in large drifting conditions, is investigated in this study by captive model tests using a ship model with steering. In the tests, hydrodynamic forces acting on the ship, the rudder normal force, and propeller thrust are measured while changing the hull drift angle β in the range of - 180 ∘ ∼ 180 ∘ , which encompasses forward, lateral, and astern motion. The hull and rudder interaction coefficients, thrust deduction factor, inflow velocity to propeller, and inflow velocity to rudder are obtained in large drifting conditions using the measured hydrodynamic force data. The Maneuvering Model Group (MMG) model (Yasukawa and Yoshimura, 2015) is applicable for estimating the rudder force when the absolute value of β is smaller than 45 ∘ . In this region, the hydrodynamic force parameters for the inflow velocity to the rudder are nearly constant for any hull drift angle. However, in the region where the absolute value of β is greater than nearly 45 ∘ , the MMG model cannot be applied. For improving the formula for the longitudinal inflow velocity component to the rudder ( u R ), we propose a new formula that is applicable to any hull drift angle. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibitors (ICIs) show promising clinical activity in advanced cancers. However, the safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies (ANA) are unclear. Methods: 191 patients treated with nivolumab, pembrolizumab, atezolizumab, or durvalumab for unresectable advanced cancers between September 2014 and December 2018 were identified retrospectively. Patients were divided into positive (ANA titers ≥ 1:160) and negative ANA groups (ANA titers < 1:160). Development of immune-related adverse events (irAEs), the overall response rate (ORR), and disease control rate (DCR) were monitored. Results: Positive ANA titers were seen in 9 out of 191 patients. Four patients in the positive ANA group and 69 patients in the negative group developed irAEs of any grade without a significant difference between the groups. The development of endocrine, pulmonary, and cutaneous irAEs was not significant, whereas positive ANA was significantly higher in patients who developed colitis (2/9) than in patients who did not (3/182, P = 0.0002). DCR in the positive and negative ANA group was 37.5% and 67.5%, respectively, and was not statistically significant, but had better efficacy in patients without ANA (P = 0.08). ANA-related autoimmune diseases such as SLE, Sjögren's syndrome, MCTD, scleroderma, dermatomyositis, and polymyositis was not induced in either group. However, one patient with preexisting dermatomyositis had a flare up after initiation of atezolizumab. Conclusion: Further studies to identify predictive factors for the development of irAEs are required to provide relevant patient care and maximize the therapeutic benefits of ICIs. [ABSTRACT FROM AUTHOR]

Recently, a repair method by bonding patch plates is being applied to corroded steel structures. However, one of the issues of patch plate bonding repair is the brittle debonding of the patch plates. Generally, when the delamination of the patch plates occurs, the composite effect acting between the steel members and patch plates abruptly decreases. Therefore, to prevent the brittle debonding of the patch plates, a repair method combining an adhesive and stud bolts is proposed. Till date, tensile and compressive tests have been performed for the proposed method. In this study, plate bending tests were conducted to verify the effectiveness of this method under bending conditions. Furthermore, two types of epoxy resin-based adhesives were prepared to evaluate the effectiveness of the proposed method with different adhesive properties. The test results show that the proposed method is able to prevent the brittle debonding of the patch plates in the case of both epoxy resins. [ABSTRACT FROM AUTHOR]

In steel members strengthened by carbon-fiber reinforced polymer (CFRP) plates, the thermal stresses are introduced in the steel members, the CFRP plates and the adhesive layers when temperature changes because the linear thermal expansion coefficients of steel and CFRP are mismatched. As so far, the authors proposed a technique to reduce the thermal stress in steel members strengthened by CFRP plates, which involves bonding aluminum alloy plates with CFRP plates. In the proposed method, the thermal stress in steel member can be reduced so that there are negligible levels of stress in steel member when the cross sectional areas of CFRP and aluminum plates are designed to correspond to the coefficient of thermal expansion of steel, even though the thermal stresses are introduced in the CFRP and aluminum plates. In this study, to confirm the maintaining the thermal stress reduction in steel member by proposed method, thermal stress measurement in steel plate strengthened by CFRP and aluminum plates was carried out about 21 months. In this research, the thermal stress introduced in the steel plate strengthened by CFRP plates was also measured. Furthermore, to assume the thermal shear and normal (peel) stresses in adhesive layers, FE analysis with plane stress element was employed. As the result, it was shown the thermal stresses in steel plate with CFRP plate were able to calculate by using composite theory and measured temperature. Furthermore, in steel plate strengthened by CFRP and aluminum plates, the thermal stress introduced in steel plate was negligible-small through the all-season. It was found the thermal stresses in steel plate with CFRP plates as well as CFRP and aluminum plates were also estimated by using composite theory and measured temperature. In the steel plate strengthened by CFRP and aluminum plates, the thermal shear and normal stresses in adhesive layer glued to steel plate become smaller than that in the conventional CFRP bonded specimen. However, the shear stress in adhesive layers between CFRP and aluminum plates in proposed method was higher than the thermal stress in adhesive layers between CFRP plates in conventional method. [ABSTRACT FROM AUTHOR]

Genetic characteristics of four wild (Mie, Fukui, Shimane and Nagasaki) and five cultured populations (selectively bred for 12 years with an origin of Ehime population) of the Japanese pearl oyster, Pinctada fucata martensii, were evaluated by using AFLP markers. Six primer pairs generated 1019 loci in total, among which 45.2-55.1 % was polymorphic among populations. Although there was no significant difference in gene diversity between wild (0.170-0.174) and cultured (0.158-0.173) populations, genetic relatedness in cultured populations (0.316-0.450) was about three times higher than that in wild populations (0.110-0.165). In addition, genetic differentiation was about twenty times larger in cultured populations (Nei's distance: 0.0111) than in wild populations (Nei's distance: 0.0005). These results mean that selective breeding can cause marked inbreeding as well as large genetic differentiation among cultured populations in a short period. On the other hand, it was suggested that genetic homogenization in the wild, probably due to a large-scale transport of cultured oysters, had progressed in the sea around Japan. In conclusion, it is necessary to prevent inbreeding by the reconsideration of the style of selective breeding in cultured populations, while the escape of gametes or spats of cultured strains in the wild should be avoided for the preservation of genetic characteristics in native populations of P. f. martensii. [ABSTRACT FROM AUTHOR]

We used a generalized linear model (GLM) to investigate environmental characteristics of capture sites of the invasive small Indian mongoose ( Herpestes auropunctatus) on Amami Island, Japan. Data were collected from 2002 to 2011, from an area with the lowest mongoose density. Data on capture levels and environmental factors were obtained within 1 × 1 km grid cells. In addition, we developed an evaluation map that predicts the occurrence of mongooses throughout the island by extrapolating the 2011 results, in which the last mongoose appearance was confirmed. We found that environmental characteristics of capture sites drastically changed during the final stage of the eradication project. From 2002 to 2010, mongooses were captured in grid cells with many gentle ridges. In 2011, when mongoose density became exceedingly low, mongooses seem to have survived in the grid cells with abundant steep ridges, where it was difficult to establish traps. Therefore, environmental factors affected capture levels and the density of the mongoose population. The evaluation map predicts that mongooses could survive on the southwest and southeast island peninsulas. This evaluation map will be helpful in allocating limited labor and financial resources toward the most effective capture strategies. This study suggests that an analysis of pest management data is an important step in the eradication of mongooses. Our results can contribute to long-term projects in invasive pest management not only for the mongoose population on Amami Island, but also for other invasive species globally. [ABSTRACT FROM AUTHOR]

We are planning test experiments of fundamental symmetries based on the intrinsic properties of francium. It is expected that the laser cooling and trapping of francium will produce precision measurements. The pilot experiment using rubidium was performed with the goal of francium trapping. The ion beam generated with a francium ion source was investigated using a Wien filter. Each piece of equipment still must be studied in more detail, and the equipment should be upgraded in order to trap radioactive atoms. [ABSTRACT FROM AUTHOR]

A laser cooled heavy atom is one of the candidates to search for the permanent electric dipole moment (EDM) of the electron due to the enhancement mechanism and its long coherence time. The laser cooled francium (Fr) factory has been constructed to perform the electron EDM search at the Cyclotron and Radioisotope Center, Tohoku University. The present status of Fr production and the EDM measurement system is presented. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infection induces chronic inflammation that contributes to gastric tumorigenesis. Tumor necrosis factor (TNF-α) is a proinflammatory cytokine, and polymorphism in the TNF-α gene increases the risk of gastric cancer. We herein investigated the role of TNF-α in gastric tumorigenesis using Gan mouse model, which recapitulates human gastric cancer development. We crossed Gan mice with TNF-α (Tnf) or TNF-α receptor TNFR1 (Tnfrsf1a) knockout mice to generate Tnf−/− Gan and Tnfrsf1a−/− Gan mice, respectively, and examined their tumor phenotypes. Notably, both Tnf−/− Gan mice and Tnfrsf1a−/− Gan mice showed similar, significant suppression of gastric tumor growth compared with control Tnf+/+ or Tnfrsf1a+/+ Gan mice. These results indicate that TNF-α signaling through TNFR1 is important for gastric tumor development. Bone marrow (BM) transplantation experiments showed that TNF-α expressed by BM-derived cells (BMDCs) stimulates the TNFR1 on BMDCs by an autocrine or paracrine manner, which is important for gastric tumor promotion. Moreover, the microarray analysis and colony formation assay indicated that NADPH oxidase organizer 1 (Noxo1) and Gna14 are induced in tumor epithelial cells in a TNF-α-dependent manner, and have an important role in tumorigenicity and tumor-initiating cell property of gastric cancer cells. Accordingly, it is possible that the activation of TNF-α/TNFR1 signaling in the tumor microenvironment promotes gastric tumor development through induction of Noxo1 and Gna14, which contribute to maintaining the tumor cells in an undifferentiated state. The present results indicate that targeting the TNF-α/TNFR1 pathway may be an effective preventive or therapeutic strategy for gastric cancer. [ABSTRACT FROM AUTHOR]

Background:CD133 and CD44 are putative cancer stem cell (CSC) markers in colorectal cancer (CRC). However, their clinical significance is currently unclear. Here, we evaluated primary CRC cell isolates to determine the significance of several CSC markers, including CD133 and CD44, as predictors of tumourigenesis and prognosis.Methods:CD133- and CD44-positive cells from fresh clinical samples of 77 CRCs were selected by flow cytometric sorting and evaluated for tumourigenicity following subcutaneous transplantation into NOD/SCID mice. Cancer stem cell marker expression was examined in both xenografts and a complementary DNA library compiled from 167 CRC patient samples.Results:CD44+, CD133+ and CD133+CD44+ sub-populations were significantly more tumourigenic than the total cell population. The clinical samples expressed several transcript variants of CD44. Variant 2 was specifically overexpressed in both primary tumours and xenografts in comparison with the normal mucosa. A prognostic assay using qRT-PCR showed that the CD44v2high group (n=84, 5-year survival rate (5-OS): 0.74) had a significantly worse prognosis (P=0.041) than the CD44v2low group (n=83, 5-OS: 0.88).Conclusions:CD44 is an important CSC marker in CRC patients. Furthermore, CRC patients with high expression of CD44v2 have a poorer prognosis than patients with other CD44 variants. [ABSTRACT FROM AUTHOR]

The viscosities of molten InSb, GaSb, and $$\mathrm{{In}}_{{x}}\mathrm{{Ga}}_{1-{x}}\mathrm{{Sb}}$$ ( $$x=0.2$$ and 0.4) were measured as a function of temperature using an oscillating viscometer for fundamental understanding of the physical properties for fabricating high quality InGaSb multicomponent semiconductor crystals. The measured values showed good Arrhenius linearity for InSb, GaSb, and $$\mathrm{{In}}_{{x}}\mathrm{{Ga}}_{1-{x}}\mathrm{{Sb}}$$ samples. The absolute values of the viscosity for InSb and GaSb agreed with a previous study. Also, it is suggested that the absolute values of the viscosity among the compounds are quite similar, and the results can be associated with their crystal structures. [ABSTRACT FROM AUTHOR]

The precision of GPS/acoustic seafloor positioning was improved by introducing a hull-mounted onboard system in March 2008, which allows us to conduct acoustic ranging measurements with the vessel sailing along the pre-determined track lines, while the early system before 2008 could only adopt the uncontrollable drifting observation. The continuity of the positioning results due to the transition was first confirmed through the comparison between results from sailing and drifting observations conducted in parallel. Using the data acquired for about 3 years since 2008, the repeatability of the determined position for the sailing observation was evaluated to be about 2 cm in root mean squares in the horizontal component, significantly better than that for the early drifting observation. The improvement of positioning precision probably resulted from the improvement of geometric distribution of acoustic ranging data by controlling the track lines. It was also shown that the sailing observation allows to obtain reliable results with a smaller amount of data. Comparison between the results in different sea regions suggests that positioning precision is better in the region along the Nankai Trough than in the region along the Japan Trench, probably because of the complicated acoustic velocity structure of seawater often observed in the latter. Furthermore, the precision of height determination was also improved, which leads us to expect that vertical crustal movement will be detectable in the future through accumulation of data as well as further technology development. [ABSTRACT FROM AUTHOR]

Baryon spectroscopy is important to understand Quantum Chromodynamics at low energies. In this purpose, a series of π and η photoproduction experiments was carried out with an electro-magnetic calorimeter FOREST at Research Center for Electron Photon Science, Tohoku University. The incident tagged bremsstrahlung photon energy ranges from 550 to 1,150 MeV. The differential and total cross sections obtained for π and η photoproduction processes on the proton are consistent with the SAID and MAID calculations. The analysis of π and η photoproduction on the neutron is underway. [ABSTRACT FROM AUTHOR]

The total cross section has been measured for ω meson photoproduction on the proton for the center-of-mass energy $${\sqrt{s}}$$ ranging from 1.69 to 1.75 GeV. Including the subthreshold region of ω photoproduction, a set of about 40 data points has been obtained with a fine energy step of 1-2 MeV. The data set enables us to deduce the ω- N scattering length. [ABSTRACT FROM AUTHOR]

Double charged pion photoproductions from the deuteron have been studied at Research Center for Electron Photon Science (ELPH), Tohoku University. Tagged photon beams in an energy range of 0.67 ≤ E ≤ 1.08 GeV were impinged on the liquid deuteron target. Produced charged particles were observed with the Neutral Kaon Spectrometer2 (NKS2). The γ d → π π d process was clearly separated among the three charged tracks. We obtained the photon energy dependence of the normalized yields of this process. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on the significance of the growth factor receptor-binding protein 2 (Grb2) in myeloproliferative disease development.

A letter to the editor is presented in response to the article on the outcomes of allogeneic and autologous hematopoietic stem cell transplantation for peripheral T-cell lymphomas with central review of pathology.

Aims: The ability to suppress soil nitrification through the release of nitrification inhibitors from plant roots is termed 'biological nitrification inhibition' (BNI). Here, we aimed at the quantification and characterization of the BNI function in sorghum that includes inhibitor production, their chemical identity, functionality and factors regulating their release. Methods: Sorghum was grown in solution culture and root exudate was collected using aerated NHCl solutions. A bioluminescence assay using recombinant Nitrosomonas europaea was employed to determine the BNI activity. Activity-guided chromatographic fractionation was used to isolate biological nitrification inhibitors (BNIs). The chemical structure was analyzed using NMR and mass spectrometry; pH-stat systems were deployed to analyze the role of rhizosphere pH on BNIs release. Results: Sorghum roots released two categories of BNIs: hydrophilic- and hydrophobic-BNIs. The release rates for hydrophilic- and hydrophobic- BNIs ranged from 10 to 25 ATU g root dwt. d. Addition of hydrophilic BNIs (10 ATU g soil) significantly inhibited soil nitrification (40 % inhibition) during a 30-d incubation test. Two BNI compounds isolated are: sakuranetin (ED 0.6 μM; isolated from hydrophilic-BNIs fraction) and sorgoleone (ED 13.0 μM; isolated from hydrophobic-BNIs fraction), which inhibited Nitrosomonas by blocking AMO and HAO enzymatic pathways. The BNIs release required the presence of NH in the root environment and the stimulatory effect of NH lasted 24 h. Unlike the hydrophobic-BNIs, the release of hydrophilic-BNIs declined at a rhizosphere pH >5.0; nearly 80 % of hydrophilic-BNI release was suppressed at pH ≥7.0. The released hydrophilic-BNIs were functionally stable within a pH range of 5.0 to 9.0. Sakuranetin showed a stronger inhibitory activity (ED 0.2 μM) than methyl 3-(4-hydroxyphenyl) propionate (MHPP) (ED 100 μM) (isolated from hydrophilic-BNIs fraction) in the in vitro culture-bioassay, but the activity was non-functional and ineffective in the soil-assay. Conclusions: There is an urgent need to identify sorghum genetic stocks with high potential to release functional-BNIs for suppressing nitrification and to improve nitrogen use efficiency in sorghum-based production systems. [ABSTRACT FROM AUTHOR]

We present the full $\mathcal{O}(\alpha)$ electroweak radiative corrections to the process $e^{+}e^{-} \rightarrow t \bar{t} \gamma$ at the International Linear Collider (ILC). The computation is performed with the help of the GRACE-Loop system. We present the total cross-section and the top quark forward-backward asymmetry ( A) as a function of the center-of-mass energy and compare them with the process $e^{+}e^{-} \rightarrow t \bar{t}$. We find that the value of A in $t \bar{t} \gamma$ production is larger than A in $t\bar{t}$ production. It is an important result for the measurement of the top quark forward-backward asymmetry at the ILC. Applying a structure function method, we also subtract the QED correction to gain the genuine weak correction in both the α scheme and the G scheme ( $\delta_{W}^{G_{\mu}}$). We obtain numerical values for $\delta_{W}^{G_{\mu}}$ which are changing from 2 % to −24 % when we vary the center-of-mass energy from 360 GeV to 1 TeV. [ABSTRACT FROM AUTHOR]

Aims and background: The ability to suppress soil nitrification through the release of nitrification inhibitors from plant roots is termed 'biological nitrification inhibition' (BNI). Earlier, we reported that sorghum roots release higher BNI-activity when grown with NH, but not with NO as N source. Also for BNI release, rhizosphere pH of <5.0 is needed; beyond this, a negative effect on BNI release was observed with nearly 80% loss of BNI activity at pH >7.0. This study is aimed at understanding the inter-functional relationships associated with NH uptake, rhizosphere-pH and plasma membrane H-ATPase (PM H-ATPase) activity in regulating the release of BNIs (biological nitrification inhibitors) from sorghum roots. Methods: Sorghum was grown hydroponically and root exudates were collected from intact plants using a pH-stat system to separate the secondary acidification effects by NH uptake on BNIs release. A recombinant luminescent Nitrosomonas europaea bioassay was used to determine BNI-activity. Root plasma membrane was isolated using a two-phase partitioning system. Hydrolytic H-ATPase activity was determined. Split-root system setup was deployed to understand the localized responses to NH, H-ATPase-stimulator (fusicoccin) or H-ATPase-inhibitor (vanadates) on BNI release by sorghum. Results: Presence of NH in the rhizosphere stimulated the expression of H-ATPase activity and enhanced the release of BNIs from sorghum roots. Fusicoccin, which stimulates H-ATPase activity, also stimulated BNIs release in the absence of NH; vanadate, which suppresses H-ATPase activity, also suppressed the release of BNIs. NH levels (in rhizosphere) positively influenced BNIs release and root H-ATPase activity in the concentration range of 0-1.0 mM, indicating a close relationship between BNI release and root H-ATPase activity with a possible involvement of carrier-mediated transport for the release of BNIs in sorghum. Conclusion: Our results suggest that NH uptake, PM H-ATPase activity, and rhizosphere acidification are functionally inter-connected with BNI release in sorghum. Such knowledge is critical to gain insights into why BNI function is more effective in light-textured, mildly acidic soils compared to other soil types. [ABSTRACT FROM AUTHOR]

Inflammation has an important role in cancer development through various mechanisms. It has been shown that dysregulation of microRNAs (miRNAs) that function as oncogenes or tumor suppressors contributes to tumorigenesis. However, the relationship between inflammation and cancer-related miRNA expression in tumorigenesis has not yet been fully understood. Using K19-C2mE and Gan mouse models that develop gastritis and gastritis-associated tumors, respectively, we found that 21 miRNAs were upregulated, and that 29 miRNAs were downregulated in gastric tumors in an inflammation-dependent manner. Among these miRNAs, the expression of miR-7, a possible tumor suppressor, significantly decreased in both gastritis and gastric tumors. Moreover, the expression of miR-7 in human gastric cancer was inversely correlated with the levels of interleukin-1β and tumor necrosis factor-α, suggesting that miR-7 downregulation is related to the severity of inflammatory responses. In the normal mouse stomach, miR-7 expression was at a basal level in undifferentiated gastric epithelial cells, and was induced during differentiation. Moreover, transfection of a miR-7 precursor into gastric cancer cells suppressed cell proliferation and soft agar colony formation. These results suggest that suppression of miR-7 expression is important for maintaining the undifferentiated status of gastric epithelial cells, and thus contributes to gastric tumorigenesis. Although epigenetic changes were not found in the CpG islands around miR-7-1 of gastritis and gastric tumor cells, we found that activated macrophage-derived small molecule(s) (<3 kDa) are responsible for miR-7 repression in gastric cancer cells. Furthermore, the miR-7 expression level significantly decreased in the inflamed gastric mucosa of Helicobacter-infected mice, whereas it increased in the stomach of germfree K19-C2mE and Gan mice wherein inflammatory responses were suppressed. Taken together, these results indicate that downregulation of tumor suppressor miR-7 is a novel mechanism by which the inflammatory response promotes gastric tumorigenesis. [ABSTRACT FROM AUTHOR]

Radon and thoron concentration in the outdoor environment are affected by the magnitude of the exhalation rate that can vary diurnally and seasonally. This paper presents measurement results of radon and thoron exhalation rates and gamma-ray dose rate in different season at same location points in Gunma Prefecture Japan. Exhalation rates were measured by the MSZ instrument which is based on the accumulation method. Three measurement points Katashina Village, Midori City and Takasaki City were selected for measurement. Soil water saturation and soil temperature were measured to investigate their relationship with exhalation rate. The diurnal variation of exhalation rate may be correlated with soil temperature but no clear relationship was found between them. The gamma-ray dose rate do not vary significantly at the same places even in different season. The average radon exhalation rates were 11 ± 2, 2 ± 1, 5 ± 3 and 11 ± 4 mBq m s for spring, summer, autumn and winter, respectively. Those for thoron were 1,100 ± 100, 120 ± 30, 250 ± 80 and 860 ± 140 mBq m s. Thus there was a variation of radon and thoron exhalation rate with different seasons. The radon and thoron exhalation rates in the summer and autumn surveys are higher than those in the spring and winter surveys which were affected by rainfall. It indicates that water saturation is an influential factor for radon and thoron exhalation rates. [ABSTRACT FROM AUTHOR]

Liver cirrhosis patients generally progress to liver failure. To cure this progressive disease, we developed a novel cell therapy using bone marrow cells; autologous bone marrow cell infusion (ABMi) therapy. We previously described the possible action mechanism of ABMi therapy in the cirrhotic liver, and showed the timeline and results of clinical studies of ABMi therapy. We have also carried out other clinical studies using bone marrow cells and granulocyte colony-stimulating factor. Here, we report a new randomized clinical trial to evaluate the effects of ABMi therapy. However, ABMi therapy may not be possible in patients who are unable to undergo general anesthesia; therefore, we have started to develop a next-generation stem cell therapy using cultured mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

Development of targeted therapy for hepatocellular carcinoma (HCC) remains a major challenge. We have recently identified an elevated expression of the fifth subunit of COP9 signalosome (CSN5) in early HCC as compared with dysplastic stage. In the present study, we explored the possibility of CSN5 being a potential therapeutic target for HCC. Our results show that CSN5 knockdown by small-interfering (si) RNA caused a strong induction of apoptosis and inhibition of cell-cycle progression in HCC cells in vitro. The down-regulation of CSN5 was sufficient to interfere with CSN function as evidenced by the accumulation of neddylated Cullin 1 and changes in the protein levels of CSN-controlled substrates SKP2, p53, p27 and nuclear factor-κB, albeit to a different degree depending on the HCC cell line, which could account for the CSN5 knockdown phenotype. The transcriptomic analysis of CSN5 knockdown signature showed that the anti-proliferative effect was driven by a common subset of molecular alterations including down-regulation of cyclin-dependent kinase 6 (CDK6) and integrin β1 (ITGB1), which were functionally interconnected with key oncogenic regulators MYC and TGFβ1 involved in the control of proliferation, apoptotic cell death and HCC progression. Consistent with microarray analysis, western blotting revealed that CSN5 depletion increased phosphorylation of Smad 2/3, key mediators of TGFβ1 signaling, decreased the protein levels of ITGB1, CDK6 and cyclin D1 and caused reduced expression of anti-apoptotic Bcl-2, while elevating the levels of pro-apoptotic Bak. A chemically modified variant of CSN5 siRNA was then selected for in vivo application based on the growth inhibitory effect and minimal induction of unwanted immune response. Systemic delivery of the CSN5 3/8 variant by stable-nucleic-acid-lipid particles significantly suppressed the tumor growth in Huh7-luc+ orthotopic xenograft model. Taken together, these results indicate that CSN5 has a pivotal role in HCC pathogenesis and maybe an attractive molecular target for systemic HCC therapy. [ABSTRACT FROM AUTHOR]

In spite of fundamental differences between plant and animal cells, it is remarkable that some cell death regulators that were identified to control cell death in metazoans can also function in plants. The fact that most of these proteins do not have structural homologs in plant genomes suggests that they may be targeting a highly conserved 'core' mechanism with conserved functions that is present in all eukaryotes. The ubiquitous Bax inhibitor-1 (BI-1) is a common cell death suppressor in eukaryotes that has provided a potential portal to this cell death core. In this review, we will update the current status of our understanding on the function and activities of this intriguing protein. Genetic, molecular and biochemical studies have so far suggested a consistent view that BI-1 is an endoplasmic reticulum (ER)-resident transmembrane protein that can interact with multiple partners to alter intracellular Ca2+ flux control and lipid dynamics. Functionally, the level of BI-1 protein has been hypothesized to have the role of a rheostat to regulate the threshold of ER-stress inducible cell death. Further, delineation of the cell death suppression mechanism by BI-1 should shed light on an ancient cell death core-control pathway in eukaryotes, as well as novel ways to improve stress tolerance. [ABSTRACT FROM AUTHOR]

Nowadays, artificial 'radon spa sources' for home baths are commercially available. Although these sources could give a potential radiation exposure to the users, few studies have been reported on their radiological measurements. In the present study, five types of radon spa sources were collected and their radiological characterization was investigated. The followings were estimated for these samples: (1) radon emanation coefficients (dry and water-saturated conditions), (2) surface γ-ray dose rate, (3) surface count rates for α- and β-rays, (4) activity concentrations of Ra, Th and K, and (5) concentrations of radon and thoron generated from the sources located in an air flow system. The activity concentrations were very high (except for one sample (named 'sample B'), although radon emanation coefficient was low compared with soil. This leads to high concentrations of radon/thoron generated from the sample. The maximum surface γ-ray dose rate was observed for sample A (2.7 μGy h). If people stay very close to the sample for a long time, the exposure might be significant. [ABSTRACT FROM AUTHOR]

Although fluoroquinolones or other antibiotics are commonly used to prevent bacterial infections after hematopoietic cell transplantation (HCT), because of the growing presence of multidrug-resistant microorganisms, it is important to identify patients who are more likely to benefit from antibacterial prophylaxis. To evaluate risk factors for early bacterial infection after allogeneic HCT, we retrospectively analyzed clinical data for 112 consecutive adult patients with hematological malignancies who received transplants without any antibacterial prophylaxis. The cumulative incidence of bacterial infection at 30 days after transplantation was 16%. Among various pre-transplant factors, only high serum ferritin (>700 ng/mL, 47 patients) and high C-reactive protein (CRP) (>0.3 mg/dL, 28 patients) levels were significantly associated with the development of bacterial infection in a multivariate analysis (hazard ratio (95% confidence interval): ferritin, 4.00 (1.32-12.17); CRP, 3.64 (1.44-9.20)). In addition, septic shock and sepsis with organ failure were exclusively observed in patients who had high ferritin and/or high CRP levels. These results suggest that pretransplant serum ferritin and CRP levels can be useful markers for predicting the risk of early bacterial infection after allogeneic HCT. It may be prudent to limit antibacterial prophylaxis to patients with predefined risk factors to ensure the safety of HCT with the use of fewer antibiotics. [ABSTRACT FROM AUTHOR]

The development of cancer is due to the growth and proliferation of transformed normal cells. Recent evidence suggests that the nature of oncogenic stress and the state of the cell of origin critically affect both tumorigenic activity and tumor histological type. However, this mechanistic relationship in mesenchymal tumors is currently largely unexplored. To clarify these issues, we established a mouse osteosarcoma (OS) model through overexpression of c-MYC in bone marrow stromal cells (BMSCs) derived from Ink4a/Arf (−/−) mice. Single-cell cloning revealed that c-MYC-expressing BMSCs are composed of two distinctly different clones: highly tumorigenic cells, similar to bipotent-committed osteochondral progenitor cells, and low-tumorigenic tripotent cells, similar to mesenchymal stem cells (MSCs). It is noteworthy that both bipotent and tripotent cells were capable of generating histologically similar, lethal OS, suggesting that both committed progenitor cells and MSCs can become OS cells of origin. Shifting mesenchymal differentiation by depleting PPARγ in tripotent MSC-like cells and overexpressing PPARγ in bipotent cells affected cell proliferation and tumorigenic activity. Our findings indicate that differentiation potential has a key role in OS tumorigenic activity, and that the suppression of adipogenic ability is a critical factor for the development of OS. [ABSTRACT FROM AUTHOR]

Purpose: Triple-negative breast cancer (TNBC), a subtype of breast cancer that is oestrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) negative, has a poor prognosis. Although a correlation between E-cadherin expression level and outcome has been demonstrated among all types of breast cancer, little is known about the significance of E-cadherin expression levels in TNBC.Methods: A total of 574 patients who had undergone a resection of a primary breast cancer except for invasive lobular carcinomas were enrolled in this study. Expressions of ER, PR, HER2, and E-cadherin were assessed by immunohistochemistry. We examined the association between TNBC and other clinicopathological variables and evaluated the significance of the E-cadherin expression.Results: Among the 574 breast cancer cases, 123 (21.4%) revealed a triple-negative phenotype. Patients with TNBC experienced more frequent lymph node metastasis (P=0.024) and a poorer prognosis (P<0.001) in comparison with non-TNBC patients. Triple-negative breast cancer was an independent prognostic factor. Reduced levels of E-cadherin were observed in 238 (41.5%) of the 574 breast cancer cases. E-cadherin reduction was significantly frequent in cases of TNBC (P<0.001) and lymph node metastasis (P=0.032). Furthermore, in the 123 TNBC cases, the prognosis of patients with an E-cadherin-negative expression was significantly worse than that of E-cadherin-positive patients (P=0.0265), especially for those in clinical stage II (P=0.002). A multivariate logistic regression analysis showed a reduction of the E-cadherin expression to be an independent prognostic factor (P=0.046).Conclusion: E-cadherin expression may be a useful prognostic marker for classifying subgroups of TNBC. [ABSTRACT FROM AUTHOR]