Environmental radioactive contamination caused by the Fukushima Dai-ichi Nuclear Power Plant accident has aroused great concern regarding a possible increase in the incidence of childhood thyroid ...cancer. The ultrasound examinations were conducted immediately after the accident as part of the Fukushima Health Management Survey (FHMS), which is divided into the preliminary baseline survey (PBLS) and the full-scale survey (FSS). Some of their outcomes are reported regularly and made available to the public. We have detailed measurements of the air-dose rates and radioactive elements in soil in many places all over the Fukushima prefecture. To study the dose-response relationship, we begin with the assumption that the external and internal doses are correlated with the air-dose rate and the amount of
I in soil, respectively. We then investigate the relationship between these estimated doses and the PBLS and FSS thyroid cancer cases. Our analysis shows that the dose-response curve with the FSS data clearly differs from that with the PBLS data. Finally, we consider the potential mitigating effects of evacuation from highly contaminated areas in both external and internal exposure scenarios.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Notch signaling is often and aberrantly activated by hypoxia during tumor progression; however, the exact pathological role of hypoxia-induced Notch signaling in tumor metastasis is as yet poorly ...understood. In this study, we aimed to define the mechanism of Notch-ligand activation by hypoxia in both primary tumor and bone stromal cells in the metastatic niche and to clarify their roles in tumor progression. We have analyzed the expression profiles of various Notch ligands in 779 breast cancer patients in GEO database and found that the expression of Jagged2 among all five ligands is most significantly correlated with the overall- and metastasis-free survival of breast cancer patients. The results of our immunohistochemical (IHC) analysis for Jagged2 in 61 clinical samples also revealed that both Jagged2 and Notch signaling were strongly upregulated at the hypoxic invasive front. Activation of Jagged2 by hypoxia in tumor cells induced EMT and also promoted cell survival in vitro. Notably, a γ-secretase inhibitor significantly blocked Notch-mediated invasion and survival under hypoxia by promoting expression of E-cadherin and inhibiting Akt phosphorylation. Importantly, Jagged2 was also found to be upregulated in bone marrow stroma under hypoxia and promoted the growth of cancer stem-like cells by activating their Notch signaling. Therefore, hypoxia-induced Jagged2 activation in both tumor invasive front and normal bone stroma has a critical role in tumor progression and metastasis, and Jagged2 is considered to be a valuable prognostic marker and may serve as a novel therapeutic target for metastatic breast cancer.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Signals through Kit receptor tyrosine kinase are essential for development of erythrocytes, melanocytes, germ cells, mast cells and interstitial cells of Cajal (ICCs). Mice and rats with a double ...gene dose of loss-of-function mutations of Kit show depletion of these cells. Although human homozygotes with loss-of-function mutations of Kit have not been reported, gain-of-function mutations of Kit result in development of tumors from mast cells, germ cells and ICCs in humans. The ICC tumors are called gastrointestinal stromal tumors (GISTs), and GISTs are a good target for the Kit inhibitor imatinib mesylate. The interrelationship between the type of Kit gain-of-function mutations and the therapeutic effect of imatinib mesylate has been well characterized in GISTs. Kit is interesting from both a biological and clinical view-point.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
Specific components of the intestinal microbiota are capable of influencing immune responses such that a mutualistic relationship is established. In mice, colonization with segmented filamentous ...bacteria (SFB) induces T-helper-17 (Th17) cell differentiation in the intestine, yet the effector functions of interleukin (IL)-17A in response to SFB remain incompletely understood. Here we report that colonization of mice with SFB-containing microbiota induced IL-17A- and CXCR2-dependent recruitment of neutrophils to the ileum. This response required adaptive immunity, as Rag-deficient mice colonized with SFB-containing microbiota failed to induce IL-17A, CXCL1 and CXCL2, and displayed defective neutrophil recruitment to the ileum. Interestingly, neutrophil depletion in wild-type mice resulted in significantly augmented Th17 responses and SFB expansion, which correlated with impaired expression of IL-22 and antimicrobial peptides. These data provide novel insight into a dynamic IL-17A-CXCR2-neutrophil axis during acute SFB colonization and demonstrate a central role for neutrophils in limiting SFB expansion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
NAD⁺ (oxidized form of NAD:nicotinamide adenine dinucleotide)–reducing soluble NiFe-hydrogenase (SH) is phylogenetically related to NADH (reduced form of NAD⁺):quinone oxidoreductase (complex I), but ...the geometrical arrangements of the subunits and Fe–S clusters are unclear. Here, we describe the crystal structures of SH in the oxidized and reduced states. The cluster arrangement is similar to that of complex I, but the subunits orientation is not, which supports the hypothesis that subunits evolved as prebuilt modules. The oxidized active site includes a six-coordinate Ni, which is unprecedented for hydrogenases, whose coordination geometry would prevent O₂ from approaching. In the reduced state showing the normal active site structure without a physiological electron acceptor, the flavin mononucleotide cofactor is dissociated, which may be caused by the oxidation state change of nearby Fe–S clusters and may suppress production of reactive oxygen species.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
The direct joining between AZ31B Mg alloy and MC Nylon 6 using friction lap welding (FLW) was performed over a wide range of welding parameters to clarify the effect of welding parameters on bubble ...formation for the purpose of obtaining high strength hybrid joints without bubbles. The volume of bubbles in the FLW joints was influenced by the amount of gases generated due to the pyrolysis of Nylon 6 and the amount of gases squeezed out of the joints during welding. An appropriate increase in welding speed, tool rotation rate and plunge depth can reduce the volume of bubbles. Strong FLW joint with area fraction of bubbles <8% was obtained after welding process optimisation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A novel formula of crosslinked polyvinyl alcohol (PVA) with glutaraldehyde (GTA), a tri-iodide complex, and glucono-δ-lactone (GDL) acid for gel dosimetry was investigated in the present study. The ...objectives of this study were to evaluate the formula's dose response properties through spectrophotometry and possible reusability by reannealing. After production, the gel samples were irradiated from 1 to 70 Gy of gamma-rays from a Cs-137 source with a constant dose rate of 0.857 Gy/min. Spectrum data were obtained using a UV-Vis spectrophotometer and analyses were done for dose linearity, dose sensitivity versus GTA concentration, and absorbance profile versus time. The resulting unirradiated gel samples were colorless and transparent, while the irradiated samples turned to a reddish-brown hue with a peak absorbance response at 490 nm. Dose linearity results indicated R2 values of 0.9, 0.986 and 0.8 for GTA concentrations of 7 mM, 15 mM and 30 mM, respectively. Moreover, dose sensitivity is higher for lower concentrations of GTA. Time progression results indicated that the absorbance decreases within one day after irradiation and increases subsequently. Through reannealing for 24 hours at 45°C in an oven, a colorless material with an absorbance value identical to the unirradiated samples was finally made for samples irradiated from 1 to 20 Gy, while the 70 Gy irradiated sample had a significant decrease in color and absorbance peak. This radiochromic gel dosimeter is promising and should be useful for 3D radiation dose assessments. Further investigation of the formula and preparation techniques are suggested for future experiments.
Used for both proton decay searches and neutrino physics, large water Cherenkov (WC) detectors have been very successful tools in particle physics. They are notable for their large masses and charged ...particle detection capabilities. While current WC detectors reconstruct charged particle tracks over a wide energy range, they cannot efficiently detect neutrons. Gadolinium (Gd) has the largest thermal neutron capture cross section of all stable nuclei and produces an 8 MeV gamma cascade that can be detected with high efficiency. Because of the many new physics opportunities that neutron tagging with a Gd salt dissolved in water would open up, a large-scale R&D program called EGADS was established to demonstrate this technique’s feasibility. EGADS features all the components of a WC detector, chiefly a 200-ton stainless steel water tank furnished with 240 photo-detectors, DAQ, and a water system that removes all impurities from water while keeping Gd in solution. In this paper we discuss the milestones towards demonstrating the feasibility of this novel technique, and the features of EGADS in detail.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The study of human fingernails as a possible dosimeter has continued to be of interest in the field of accident dosimetry because of its potential advantages. The present study aims to investigate ...the suitability of fingernails for the assessment of accidental exposure in medical facilities that use radiation for diagnosis or radiation therapy through the electron spin resonance (ESR) dosimetry technique. Relevant drying conditions, sample characteristics, and setup modifications were tested and compared among the samples of three different individuals. Results indicated that 1 h of sample drying inside a heat dryer sterilizer at 100 °C temperature showed good thermal stability of the ESR signals up to 30 days of postmeasurement. Another finding of this study was the effective approach in the signal stability for samples kept under vacuum storage condition with limited exposure to ambient light. While the samples from three different individuals showed unique dose–response curves after the X-ray irradiation, those were quite linear in the therapeutic dose range (up to 70 Gy). These results indicate that fingernails could be useful for the detection of unexpected significant exposure of patients and medical staff handling radiation or radiopharmaceuticals. Further investigations are desirable for standardization of the fingernail dosimetry in medical applications.
•A new setup modification for the fingernail ESR dosimetry was introduced.•Unique responses of fingernail ESR signals were found among three donors.•Fingernail ESR signals of each donor showed a good linearity of dose response up to 70 Gy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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