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The stress corrosion cracking (SCC) susceptibility in supercritical pressurized water (SCPW) was investigated for the candidate structural steels of advanced fusion and fission nuclear system, which are SUS316L austenitic steel, F82H ferritic–martensitic steel and SOC-16 oxide dispersion strengthened (ODS) ferritic steel. In order to evaluate the susceptibility to SCC with those materials, slow strain rate test (SSRT) was carried out at 773 K, under a pressure of 25 MPa of SCPW with deaerated condition. High temperature tensile test in vacuum at 773 K was also performed to compare the deformation and fracture behavior between corrosive environment of SCPW and non-corrosive environment. Although SUS316L showed a change in the fracture mode in the deaerated SCPW from an entire ductile fracture at higher strain rate to a mixed mode of ductile and brittle fracture at lower one, the fracture mode of ODS steel and F82H was not changed in the tested strain rate range. Both the IGSCC and TGSCC were observed in SUS316L. And F82H steel suffered from much severer oxidation than SUS316L and SOC-16.

The effect of grain orientation, heat-treatment temperature and test temperature on the mechanical properties of tungsten (W), which vary depending on plastic working and fabrication process, was investigated by mechanical testing of tensile or bending. Heavily worked W samples (1.5–2.0 mm in the final thickness) exhibit degradation of fracture strength due to recrystallization embrittlement after heat-treatment at 1240 °C (temperature of diffusion bonding between W and a candidate material of the Fe base support structure). On the other hand, W samples with lower thickness reduction rates do not suffer degradation of fracture strength after heating up to around 1300 °C, and show somewhat higher fracture strength by heat-treatment below 1300 °C than the samples in the as-received state. The observed behavior is a reflection of recovery of dislocations introduced by plastic working. High temperature tensile testing of ITER grade W with an anisotropic grain structure and S-TUN with an equiaxed grain structure revealed that both W grades exhibit plastic elongation at temperatures higher than 200 °C with essentially the same temperature dependence of yield strength, which is relatively insensitive to grain orientation in the structure at 200–1300 °C.

F82H-IEA and its EB-weld joint were irradiated at 573 and 773 K up to 9.6 dpa and the irradiation effect on its mechanical properties and microstructure were investigated. A hardness profile across the weld joint before irradiation showed the hardness in transformed region (TR) was high and especially that in the edge of TR was the highest (high hardness region: HHR) compared to base metal (BM). These hardness distribution was correspond to grain size distribution. After irradiation, hardening in HHR was small compared to other region in the sample. In tensile test, the amount of hardening in yield strength and ultimate tensile strength of F82H EB-weld joint was almost similar to that of F82H-IEA but the fracture position of EB-weld joint was at the boundary of TR and BM. Therefore, the TR/BM boundary is the structural weak point in F82H EB-weld joint after irradiation. As the plastic instability was observed, the dislocation channeling deformation can be expected though the dislocation channel was not observed in this study.

The next generation of light water reactors, resource renewable BWR (RBWR), which can be burned trans uranium (TRU) is currently under development at Hitachi. The RBWR requires a high flux of fast neutron for efficient burning of the TRU, which is four times as large as that of the ABWR. Therefore, structural materials require both a high resistance to corrosion and to irradiation. In this study, oxide dispersion strengthened austenitic stainless steels (ODS-ASUS) with high corrosion resistance have been developed. The objective of this research is to evaluate irradiation resistance and SCC susceptibility in a simulated reactor water environment for the ODS-ASUS. The materials were irradiated with 6.4 MeV Fe3+ at 673 K up to 8.0 dpa using the DuET facility at Kyoto University. The creviced bent beam (CBB) test is conducted to assess the SCC susceptibility in the hot water, 288 °C, 8 MPa with a dissolved oxygen of 8 ppm.

Immunohistochemical investigation of aquaporin (AQP)1 and AQP3 was performed in human skin wounds obtained from forensic autopsy cases. A total of 55 human skin wounds of different postinfliction intervals were collected as follows: group I, 0–3 days (n = 16); II, 4–7 days (n = 11); III, 9–14 days (n = 16); and IV, 17–21 days (n = 12). In uninjured skin samples, AQP1 and AQP3 could be slightly detected in dermal vessels and keratinocytes, respectively. The percentage of AQP1+ vessels and the number of AQP3+ keratinocytes were apparently elevated in accordance with wound ages. The number of AQP3+ keratinocytes was distinctly evident in groups II and III. Morphometrically, both AQP1+ vessel area and AQP3+ cell number were markedly increased in group II, compared with other three groups. With regard to forensic safety, AQP1+ vessel area of over 5% would imply wound ages of 4–12 days. Moreover, the positive area of > 15% would suggest wound age of 7–10 days. Especially, most samples of skin wounds aged 5–10 days except for only one sample (a 10-day-old wound) showed AQP3+ cell number of > 300, and the remaining other samples had that of 300 would indicate wound ages of 5–10 days. Collectively, immunohistochemical analyses of AQP1 and AQP3 in human skin wounds would support the objective accuracy of wound age determination.

In forensic practices, it is often difficult to determine wound vitality in compression marks of the neck with naked eyes. AQP1 and AQP3 are the major water channels associated with skin. Thus, we immunohistochemically examined the expression of AQP1 and AQP3 in neck skin samples to discuss their forensic applicability to determination of the wound vitality. Skin samples were obtained from 56 neck compression cases (hanging, 35 cases; strangulation, 21 cases). The intact skin from the same individual was taken as a control. Although AQP1 was immnunostained in dermal capillaries in both the neck compression marks and intact skin samples, there was no significant difference in the magnitude of AQP1 expression between both groups. On the contrary, AQP3-positive signals could be faintly detected in uninjured skin samples, and the positive signals seemed more intense in the keratinocytes in compression regions. Morphometrical analyses revealed that the ratio of AQP3-expressed keratinocytes was significantly enhanced in neck compression regions, compared with control groups. From the viewpoints of forensic pathology, immunohistochemical detection of AQP3 in the neck skin can be considered a valuable marker to diagnose the trace of antemortem compression.

Osteoblastomas are benign bone tumors that produce prostaglandin and promote inflammation. The aim of the present study was to describe the clinical and radiological characteristics of a pediatric osteoblastoma case over an 8-month postoperative follow-up. The case involved an 11-year-old female patient with normal somatic development, presenting with a chief complaint of sleep disturbance. The patient had no spontaneous pain or other readily evident possible causes. Magnetic resonance imaging (MRI) revealed a neoplastic lesion in the sacrum, with peritumoral edema. Intraoperative fast-frozen biopsy raised the suspicion of osteosarcoma. However, the final diagnosis was osteoblastoma and a second operation was performed for total resection. The edematous peritumoral bone and muscle tissues were preserved. Following total removal of the tumor, the sleep disturbance resolved. Eight months after the surgery, MRI revealed no recurrence of the tumor and reduction of the peritumoral edema. On immunohistochemical examination, cyclooxygenase (COX)-1 and COX-2 were strongly positive, indicating that the tumor activated the arachidonic acid metabolic pathway and produced prostaglandin. The inflammatory process subsequently promoted the development of peritumoral edema and induced the sleep disturbance.

Endothelial progenitor cells (EPCs), a newly identified cell type, are bone marrow-derived progenitor cells that co-express stem cell markers and Flk-1 (one of the receptors for vascular endothelial growth factor). In this study, double-color immunofluorescence analysis was performed using anti-CD34 and anti-Flk-1 antibodies in order to examine the time-dependent intrathrombotic appearance of EPCs, using the thrombi of DVT model mice with different thrombus ages (1–21 days). In thrombus cross-section specimens with an age of less than 3 days, CD34+/Flk-1+ EPCs were not detected. EPCs were initially observed in wounds aged 5 days, and their number was increased in thrombi with the advance of thrombus ages. The number of EPCs was the largest in the 10-day thrombus. Moreover, all 15 samples aged 7–14 days had an EPC number of more than 10, and, in 9 of them, the number of intrathrombotic EPCs was over 20. In contrast, in all thrombus samples aged 21 days, the number of intrathrombotic EPCs was less than 20. However, in three of them, the intrathrombotic EPC number was ≥ 10. These observations suggested that an intrathrombotic EPC number exceeding 20 would indicate a thrombus age of approximately 7–14 days.

In forensic pathology, the novel molecular biomarkers as well as innovative devices and techniques are always explored for the correct diagnosis of the cause of death, postmortem intervals, wound ages, and so on. In wound age determination, application techniques, and target cells and molecules are main elements. Bone marrow-derived cells such as fibrocytes and endothelial progenitor cells can contribute to skin wound healing, thus implying that those cells would be candidate cells for wound age determination. Analyses of aquaporins that are water channels in mammals would be helpful for the differential diagnosis of saltwater and freshwater drowning. Circadian rhythm is well controlled by the time-dependent expression of “clock genes”, indicating that analyses of the biological clock would be powerful methods for the estimation of the time of death. Postmortem computed tomography (PMCT) has rapidly and widely spread, and assists forensic autopsy. Actually, it is unnecessary to mention that the advancement of molecular and imaging innovations is able to contribute to the progress of forensic pathology.

Several fatal cases of bodybuilders, following a myocardial infarction after long exposure to androgenic-anabolic steroids (AAS), are reported. In recent years, evidence has emerged of cases of heart failure related to AAS consumption, with no signs of coronary or aorta atherosclerosis. This study aims to further investigate the pathogenesis of the ventricular AAS-related remodeling performing immunohistochemistry (IHC). In order to examine innate immunity activity and myocytes and endothelial cell apoptosis, IHC analyses were performed on heart tissue of two cases of bodybuilders who died after years of supratherapeutic use of metelonone and nandrolone and where no atherosclerosis or thrombosis were found, using the following antibodies: anti-CD68, anti-iNOS, anti-CD163, anti-CD 15, anti-CD8, anti-CD4, anti-HIF1 α, and in situ TUNEL staining. Results confirm the experimental findings of recent research that, in the absence of other pathological factors, if intensive training is combined with AAS abuse, myocytes and endothelial cells undergo apoptotic alterations. The absence of inflammatory reactions and the presence of an increased number of M2 macrophages in the areas of fibrotic remodeling confirm that the fibrotic changes in the heart are apoptosis-related and not necrosis-related. In conclusion, the study indicates that, in very young subjects with chronic hypoxia-related alterations of the heart, signs of a heart failure in the other organs and a history of AAS abuse, death can be ascribed to progressive heart failure due to the direct apoptotic cardiac and endothelial changes produced by AAS.

Inborn errors of bile acid synthesis are rare genetic disorders that can present as neonatal cholestasis and fat-soluble vitamin deficiency. Though rare, these diseases account for some patients with cholestasis of unknown etiology. Seven known defects of bile acid synthesis occur in children. These defects may be categorized as deficiencies in activity of enzymes catalyzing reactions affecting the steroid nucleus or the side chain. Defects in reactions involving the steroid nucleus include cholesterol 7α-hydroxylase deficiency, 3β-hydroxysteroid-Δ5-C27-steroid dehydrogenase/isomerase deficiency, Δ4-3-oxosteroid 5β-reductase deficiency, and oxysterol 7α-hydroxylase deficiency. Defects in reactions involving side-chain modification are sterol 27-hydroxylase deficiency, α-methyl-CoA racemase deficiency, disorders of peroxisomal β-oxidation, bile acid-CoA: amino acid N-acyltransferase deficiency, and bile acid-CoA ligase deficiency. Cholesterol 7α-hydroxylase deficiency and disorders of peroxisomal β-oxidation are not considered here, since cholesterol 7α-hydroxylase deficiency is not known to occur in children and disorders of peroxisomal β-oxidation represent disease of peroxisomes. When identified early, many patients with inborn errors of bile acid synthesis have a favorable clinical response to oral primary bile acid therapy. These inborn errors characteristically result in elevated serum bilirubin and aminotransferase concentrations but produce no abnormalities of serum γ-glutamyltransferase or of total bile acid concentrations detectable by enzymatic methods. Screening for inborn errors of bile acid synthesis using fast atom bombardment ionization mass spectrometry, gas chromatography-mass spectroscopy, and liquid chromatography-electrospray ionization tandem mass spectrometry is useful. Genetic analysis is available for a definitive diagnosis. Disorders of bile acid synthesis account for some 2–3% of screened cases of cholestatic liver disease in infants and children.

Diffusion bonding was employed to join oxide-dispersion-strengthened ferritic/martensitic steel under uniaxial hydrostatic pressure using a high vacuum hot press, and the microstructure and tensile properties of the joints were investigated. 9Cr oxide dispersion strengthened (ODS) steel was successfully diffusion bonded at 1150 °C for 1 h to migrate a residual bonding interface. Following heat treatment, including normalising at 1050 °C and tempering at 800 °C for 1 h, comparable results without inclusions or micro-voids at the bonding interface, or degradation in the base metal were achieved. Transmission electron microscopy (TEM) observation revealed that the nano-oxide particles in the bonding region were uniformly distributed in the matrix. At room temperature, the joint had nearly the same tensile properties with that of the base metal. The tensile strength of the joint region at elevated temperatures was comparable with that of the base metal. The total elongation of the joint region decreased slightly, but reached 80% of the base metal at 700 °C, and a ductile fracture occurred far from the bonding interface. Therefore, it is considered that diffusion bonding with a phase transformation can be a very useful joining method for fabricating components in next-generation nuclear systems using 9Cr ODS ferritic/martensitic steel.

For the purpose of arranging reference alloys available for various characterization efforts by Japanese fusion research groups, fabrication of reference 9Cr and 12Cr-ODS steels have been carried out with similar manufacturing processes followed by various characterizations. The fabrication proceeded with powder mixing, MA, encapsulation into mild steel cases, hot extrusion and hot forging, followed by final heat treatments. Each alloy was extruded into three bars. The characterization included chemical composition analysis, SEM and TEM microstructural observations, hardness tests, tensile tests at RT and 973 K, and relatively short-term thermal creep tests at 973 K. Room temperature hardness for 9Cr-ODS was larger than 12Cr-ODS, the former showing large increase when annealing temperature exceeded 1200 K and the latter showing no significant change with annealing temperature. Tensile strength of 9Cr-ODS was significantly larger than that of 12Cr-ODS at RT but comparable at 973 K. 9Cr-ODS showed longer and shorter creep rupture time than 12Cr-ODS at high and low stress levels, respectively. The mechanism of the difference in creep properties of the two alloys was discussed.

Bonding of oxide dispersion strengthened (ODS) steels to non-ODS reduced activation ferritic/martensitic (RAFM) steels is essential to their application to blanket systems. In the present study, a diffusion-bonded joint of the candidate 9Cr-ODS steel and JLF-1 RAFM steel was fabricated using hot isostatic pressing (HIP). The effect of post-bond heat treatments (PBHTs) was studied by hardness measurement and microstructural analysis. The results indicated that, after normalization and tempering (N&T), the hardness and microstructures of 9Cr-ODS and JLF-1 base metals recovered to levels similar to those before HIP. However, a soft region was observed across the bonding interfaces for all specimens containing the as-HIPed condition and those after PBHTs. This was due to coarser micro-carbides (M3C in as-HIPed condition and M23C6 in N&T conditions) near the interfaces than in the base metals for both 9Cr-ODS and JLF-1. Energy Dispersive X-ray Spectroscopy (EDS) analysis confirmed that carbon, tungsten, and chromium in the matrix near the interfaces are transferred to the micro-carbides, making them coarser there. Ti diffused from the 9Cr-ODS side to the JLF-1 side forming Ti-rich carbides after tempering, especially at high temperature to 1073 K.

Cavity evolutions in a normalized and tempered martensitic steel (TMS) and two nanostructured ferritic alloys (NFA) under Fe3+ and He+ dual ion beam irradiations (DII) at 500 °C and 650 °C were characterized. The irradiation conditions encompass a wide range of displacement per atom damage (dpa), He and He/dpa. The 500 °C DII produced damage and He levels of ≈10–47 dpa and ≈400–2000 appm, respectively. Transmission electron microscopy (TEM) showed that DII of a 8Cr TMS, at 500 °C to up to 60 dpa and 2100 appm He, produced a moderate density of non-uniformly distributed cavities with bimodal sizes ranging from ≈1 nm He bubbles to ≈20 nm faceted voids, and swelling ≈0.44%. In contrast, the same irradiation conditions produced only small ≈1.3 nm diameter bubbles and swelling of ≈0.05% in the NFA MA957. Similar bubble distributions were observed in MA957 and a developmental NFA DII at 650 °C up to ≈80 dpa and ≈3900 appm He. These results demonstrate the outstanding He management capability of the oxide nano-features in the NFA. The various data trends are shown as a function of dpa, He, He/dpa and He*dpa.

In the present study, interfacial microstructures and hardness distributions of W-coated ODS steels as plasma facing structural materials were investigated. A vacuum plasma spraying (VPS) technique was employed to fabricate a W layer on the surface of the ODS ferritic steel substrates. The microstructural observations revealed that the VPS-W has very fine grains aligned toward the spraying direction, and a favorable interface between W and ODS ferritic steels by a mechanical inter-locking without an intermetallic layer. However, crack-type defects were found in VPS-W. Because a brittle inter-diffused layer does not exist at the joint interface, the hardness was gradually distributed in the joint region. After neutron irradiation, irradiation hardening significantly occurred in the VPS-W. However, the hardening of VPS-W was less than that of bulk W irradiated at 773 K. Thus, the VPS is considered to be one of the promising ways to join dissimilar materials between W and ODS steels, which can avoid the formation of an interfacial intermetallic layer and create favorable irradiation hardening resistance on the W coated layer.

The friction stir welding (FSW) method was used to form joints in an oxide dispersion strengthened (ODS) steel with tool rotation speeds ranging from 250 rpm to 400 rpm to investigate the effect of rotation speed of the tool on the mechanical properties and microstructure of the joints. The hardness of the stirred zone (SZ) of the ODS steel joints was reduced after welding at all rotation speeds because of recrystallization induced by the heat generated during the FSW process. The recrystallization was accompanied by a change in the grain morphology from elongated grains to isotropic grains. The sizes of recrystallized grains increased with increasing rotation speed of the tool. Oxide particles, however, were slightly coarsened by the FSW process, and there was no systematic relationship between the particle size and the rotation speed. The hardness of the SZ of ODS steel joints followed the Hall–Petch relationship. Tensile tests of the FSW ODS steel joints revealed that the change in the ultimate tensile strength is similar to the change in the hardness, suggesting that the joint strength was reduced by grain growth but not by degradation of the fracture strength.

Stress corrosion cracking (SCC) susceptibility was investigated by means of steady strain rate tests for a 15Cr–4Al–2W oxide dispersion strengthened (ODS) ferritic steel in supercritical pressurized water (SCPW) dissolved with different hydrogen (DH) and dissolved oxygen (DO) contents. All the specimens exhibit ductile fracture mode, regardless of the strain rate. The effect of DH and DO on the fracture behavior is negligible. Small cracks were observed at necking region but most of the cracks were identified as “corrosion layer cracking” by cross-sectional observation. The ODS ferritic steel shows no susceptibility to SCC in SCPW at this experimental conditions.

The nanoparticles in an Al-alloyed high-Cr oxide dispersion strengthened (ODS) ferritic steel with Hf addition, i.e., SOC-16 (Fe-15Cr-2W-0.1Ti-4Al-0.62Hf-0.35Y2O3), have been examined by transmission electron microscopy (TEM) and high resolution transmission electron microscopy (HRTEM). Relative to an Al-alloyed high-Cr ODS ferritic steel without Hf addition, i.e., SOC-9 (Fe-15.5Cr-2W-0.1Ti-4Al-0.35Y2O3), the dispersion morphology and coherency of the oxide nanoparticles in SOC-16 were significantly improved. Almost all the small nanoparticles (diameter 10 nm) were also mainly identified as cubic Y2Hf2O7 oxides with the anion-deficient fluorite structure. The results presented here are compared with those of SOC-9 with a brief discussion of the underlying mechanisms of the unusual thermal and irradiation stabilities of the oxides as well as the superior strength, excellent irradiation tolerance and extraordinary corrosion resistance of SOC-16.

Joint strengthening of oxide dispersion strengthened (ODS) martensitic steel has been attained by a transient liquid phase (TLP) bonding utilizing a newly developed ODS insert foil. The ODS insert foil (Fe–9Cr–2W–0.2Ti–0.35Y 2 O 3 –0.5C–3B–2Si) was fabricated using mechanical alloying and a spark plasma sintering method. Compared to conventional TLP bonding with a non-ODS insert foil (Fe–0.5C–3B–2Si), the microstructure of the melted zone consists of finer grains in the joint with the newly developed ODS insert material, and the grain size is almost one third of that in the conventional insert material. This increases the hardness by ΔHv = 100 in the region of the joints. Oxide particles that are coherent to the ferritic matrix in the ODS insert foil could be responsible for the grain refinement, which is explained in terms of enhanced nucleation of consolidation matrix at the oxide particles.

A δ-Zr-hydride was irradiated with 6.4 MeV Fe3+ ions to clarify the relationship between hardening and microstructural changes of bulk Zr-hydrides under neutron irradiation. Irradiation hardening was measured by nanoindentation tests. Transmission electron microscope cross-sectional observations showed that the deformation mechanism of the δ-Zr-hydride was both slip and twinning. Dislocation loops were observed in the irradiated hydride matrix. These irradiation-induced defects make slip deformation difficult and consequently promote the twin deformation of δ-Zr-hydride. This work is a continuation of the previous our work (J. Nucl. Mater. 419 (2011) 366–370) focused upon e-Zr-hydride and we discuss a comparison between the two Zr-hydrides.

Nano-bubble dispersion strengthened (N-BDS) Fe was made from Fe and polymethylmethacrylate (PMMA) powder and irradiated by 6.4 MeV Fe 3+ ions to investigate the cavity strengthening and the bubble to void evolution. The bubbles accelerated the irradiation-induced cavity growth. The hardness of the N-BDS Fe was 500 MPa higher than that of unalloyed Fe and the hardness increased by irradiation, while that of unalloyed Fe did not increase. Cavity is probably the origin of the irradiation hardening of N-BDS Fe.

Fracture toughness data was obtained for reduced-activation ferritic (RAF) steels with different sizes of specimens (1 compact tension(CT), 1/2 CT and 1/4 CT) using the master curve (MC) method in the transition temperature region. Considering the size adjustment by ASTM E1921, effects of specimen size on the fracture toughness are not observed and the reference temperature (T0) is around 164 K which is similar to those (154 K) of other previous studies. However, the data are not well represented by a MC, showing a rather large number of data below the lower boundary curve. Our proposed new MC was derived within the framework of the ASTM E1921 standard to apply the MC method to F82H steel. This new MC analysis can be applied to RAF steels to estimate T0 with a better description of the data scatter in the transition temperature region of fracture toughness than that of the conventional MC analysis.

Several types of reduced activation ferritic/martensitic (RAFM) steel have been developed over the past 30 years in China, Europe, India, Japan, Russia and the USA for application in ITER test blanket modules (TBMs) and future fusion DEMO and power reactors. The progress has been particularly important during the past few years with evaluation of mechanical properties of these steels before and after irradiation and in contact with different cooling media. This paper presents recent RAFM steel results obtained in ITER partner countries in relation to different TBM and DEMO options. (C) 2012 Elsevier B. V. All rights reserved.

Ion irradiations with 6.4 MeV Fe 3+ were performed on pure-Fe, Fe–1 at.% Cr, Fe–1 at.% Mn, and Fe–1 at.% Ni to a nominal damage of 1 dpa, at a damage rate of 1 × 10 −4 dpa/s, at irradiation temperatures of 473, 563, and 673 K. After irradiations at 473 and 563 K, Fe–1Mn and Fe–1Ni showed significant irradiation hardening, which was due to irradiation induced dislocation loops in high density. In pure-Fe, the dislocation loops were localized in the vicinity of dislocations, while those in Fe alloys were distributed rather homogeneously. This can be interpreted in terms of the interaction between alloying element and dislocation strain field. Irradiation at 673 K resulted in the formation of voids in pure-Fe, Fe–1Cr, and Fe–1Mn. We found that chromium suppressed void swelling.

The deuterium (D) retention for Vacuum Plasma Spray (VPS)–tungsten (W)/F82H was studied using two different implantation methods, namely D plasma exposure and D2+ implantation. The D retention for polished VPS–W/F82H after plasma exposure was found to be reduced compared to that for polycrystalline tungsten. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations indicated that porous structures around grain boundaries and the interface between VPS–W layers would be potential D diffusion paths, leading to low D retention. In the case of D2+ implantation, the shape of D2 TDS spectrum was almost the same as that for D plasma-exposed VPS–W/F82H; however, the D retention was quite high for unpolished VPS–W/F82H, indicating that most of D was trapped by the oxide layer, which was produced by the VPS process. The reduction of surface area due to the polishing process also reduces D retention for VPS–W/F82H. These results indicate that controlling the surface chemical states is important for the reduction of tritium retention for future fusion reactors.

The irradiation hardening behavior of reduced-activation ferritic steels after single Fe-ion beam irradiation and dual-ion (Fe ion and He ion) beam irradiation experiments was investigated with nanoindentation tests. The ion-irradiation experiments were conducted at 563 K with 6.4 MeV Fe3+ ions up to 3 dpa at a 600 nm depth from the irradiated surface. Furthermore, these experiments were conducted with and without simultaneous energy-degraded 1 MeV He+ ions up to 300 appm. The materials used were F82H, F82H + 1Ni, and F82H + 2Ni to investigate the effect of Ni addition on the irradiation hardening behavior. The measured nanoindentation hardness was converted to the bulk-equivalent hardness based on a combination of the Nix–Gao model to explain the indentation size effect and the composite hardness model to explain the softer substrate effect of the nonirradiated region beyond the irradiated depth range. It is clearly shown that the Ni addition enhances the irradiation hardening of F82H. The bulk-equivalent hardness is compared with the experimentally obtained Vickers hardness of F82H steels after neutron irradiation. The effect of simultaneously implanted helium on the irradiation hardening is negligible in the investigated irradiation conditions.

The oxidation of six oxide dispersion strengthened (ODS) ferritic alloys was investigated at 1050 °C in air up to 200 h. Al plays the dominant role in improving the oxidation resistance of the ODS alloys. Cr and Y are of importance in forming the stable Al2O3 scale. To produce the dense alumina layer with enhanced adherence to the metal substrate, the concentrations of Al and Cr should be larger than 2 and 14 wt.%, respectively.

Out-of-pile high-temperature reaction tests are carried out on the diffusion couples between U–Zr fuel and ODS ferritic steels, in which the concentrations of Cr and Al were systematically changed for improvement of corrosion resistance. The results show that the Al addition to ODS ferritic steel considerably improves the compatibility between U–Zr fuel and the ODS steel. The threshold temperature for reaction layer formation is roughly 50 K higher in the Al-containing ODS ferritic steels than in the steels without Al addition for the testing time up to 900 min. The compatibility improvement mechanism by Al addition is discussed from the viewpoint of activity change. The activity calculation results obtained using general thermodynamic data indicate the possibility that stabilization of the intact α-Zr layer by Al addition is the main mechanism and occupation of steel lattice sites by Al that does not easily diffuse into γ-U–Zr also partly contributes to suppression of the inter-diffusion.

Elucidation of the one-dimensional (1-D) motion of dislocation loops is important for describing the microstructural development of materials under irradiation. In this study, the effect of Mn on radiation-induced microstructure evolution in body-centered cubic Fe was experimentally investigated by focusing on the migration of dislocation loops. Pure Fe and Fe–1.4Mn alloy were irradiated with Fe3+ ions to introduce dislocation loops. In pure Fe, inhomogeneous distribution of loops in the vicinity of the residual dislocation was observed. However, in Fe–1.4Mn, isolated dislocation loops were homogeneously distributed in a high number density. In situ transmission electron microscopy during annealing revealed that 1-D motion of dislocation loops occurred in pure Fe at 623 K, while 1-D motion of dislocation loops occurred minimally in Fe–1.4Mn annealed at temperatures below 773 K. These results indicate that 1-D motion of dislocation loops play a key role in producing the differences in the microstructures between pure Fe and Fe–1.4Mn. In pure Fe, dislocation loops were mobile and trapped in the strain field of a dislocation, leading to the formation of loop decoration of dislocations. However, in Fe–1.4Mn, dislocation loops were less mobile and dislocation loops were homogeneously formed in high density in the matrix. The migration of dislocation loops by Mn solute is strongly suggested as one of the key mechanisms of microstructure development in irradiated Fe–Mn alloy.

The influence of nickel on the neutron irradiation embrittlement of Ni-Mo-Cr reactor pressure vessel (RPV) steels was investigated using alloys containing nickel in the range of 0.9–3.5 wt%. In all investigated alloys, the neutron irradiation with two dose conditions of 4.5 × 1019 neutron/cm2 at 290 °C and 9.0 × 1019 neutron/cm2 at 290 °C, respectively, increased the hardness and ductile-to-brittle transition temperature (DBTT). However, the increases of the hardness and DBTT resulting from the neutron irradiation were primarily affected by the irradiation dose that is closely related to the generation of irradiation defects, but not by the nickel content. In addition, a linear relationship between the changes in the hardness and DBTT subjected to the irradiation was confirmed. These results demonstrate that increasing the nickel content up to 3.5 wt% does not have a harmful effect on the irradiation embrittlement of Ni-Mo-Cr reactor pressure vessel (RPV) steels.

D retention in a VPS W coated V alloy (V–4Cr–4Ti, NIFS Heat 2) was investigated by an ion beam irradiation with a HiFIT device. Irradiation temperature changed from 473 K to 773 K and ion fluence was 1024 m−2. In addition, during ion irradiation atmospheric pressure was 0.5 mTorr. It was found that ambient gas absorption was the dominant process for D retention. Ion irradiation could enhance gas absorption probably due to surface modification (oxide layer removal) and could produce ion induced trapping sites. Although these ion induced processes can be avoided by W coating layers, D retention is still significant for VPS-W coated V alloy. D trapping could be done mainly in V-alloy and its mechanisms could be related to some intrinsic defects in V alloy and formation of titanium hydride at elevated temperature.

High density W coatings on reduced activation ferritic martensitic steel (RAF/M) have been produced by Vacuum Plasma Spraying technique (VPS) and heat flux experiments on them have been carried out to evaluate their possibility as a plasma-facing armor in a fusion device. In addition, quantitative analyses of temperature profile and thermal stress have been carried out using the finite element analysis (FEA) to evaluate its thermal properties. No cracks or exfoliation has been formed by steady state and cyclic heat loading experiments under heat loading at 700 °C of surface temperature. In addition, stress distribution and maximum stress between interface of VPS-W and RAF/M have been obtained by FEA. On the other hand, exfoliation has occurred at interlayer of VPS-W coatings near the interface between VPS-W and RAF/M at 1300 °C of surface temperature by cyclic heat loading.

We immunohistochemically examined the expression of IFNγ, TNFα, and TNF receptor p55 (TNF-Rp55) in a stasis-induced venous thrombus murine model. IFNγ(+), TNFα(+), and TNF-Rp55(+) cells could be first detected 7, 3, and 3 days after inferior vena cava (IVC) ligation. Thereafter, the numbers of these positive cells increased with time after IVC ligation. Double-color immunofluorescence analyses demonstrated that each molecule was expressed by intrathrombotic macrophages. In all samples with postligation intervals of 7 days or less, IFNγ/macrophage ratio (IFNγ/Mϕ), TNFα/macrophage ratio (TNFα/Mϕ), and TNF-Rp55/macrophage ratio (TNF-Rp55/Mϕ) were0.2,0.2, and0.4, respectively. In contrast, IFNγ/Mϕ and TNFα/Mϕ were greater than 0.2 and 0.3 at ≥10 days after the IVC ligation, respectively. These observations suggested that IFNγ/Mϕ ratios of0.2 and TNFα/Mϕ ratios of0.3 indicated thrombus age of ≥10 days. Moreover, TNF-Rp55/Mϕ ratios of0.7 strongly suggested thrombus age of14 days. The present study demonstrated that the immunohistochemical detection of IFNγ, TNFα, and TNF-Rp55 was suitable to estimate the age of venous thrombi. However, the variation in TNF-Rp55/Mϕ ratios is wider than those of the other two markers. Thus, IFNγ and TNFα could be more practical markers.

A method for the determination of conjugated and unconjugated 3β-hydroxy-Δ 5 -bile acids and related bile acids in human urine and serum has been developed using high-performance liquid chromatography–electrospray ionization-tandem mass spectrometry. Calibration curves for the bile acids were linear over the range of 10–2000 pmol/mL, and the detection limit was less than 4 pmol/mL for all bile acids using selected reaction monitoring analysis. The bile acids in urine and serum samples from two patients with severe cholestatic liver disease were measured by this analytical method. Glycine-conjugated 3β-hydroxy-Δ 5 -bile acid 3-sulfates were determined to be the major bile acids in the urine and serum from patients with a 3β-hydroxy-Δ 5 -C 27 -steriod dehydrogenase/isomerase deficiency or dysfunction.

1Department of Materials Science and Engineering, Hokkaido University, Sapporo 060-8628, Japan 2National Institute of Fusion Science, Department of Helical Plasma Research, National Institute for Fusion Science, Toki 509-5292, Japan 3Institute of Advanced Energy, Kyoto University, Uji 611-0011, Japan 4Department of Mechanical Engineering, University of California, Santa Barbara, CA 93106, USA 5Oak Ridge National Laboratory, P. O. Box 2008, Oak Ridge, TN 37831-6138, USA

A diffusion bonding (DB) technique to reduce thermal expansion coefficient mismatch between tungsten (W) and oxide dispersion strengthened ferritic steel (ODS-FS) was developed by applying a vanadium (V) alloy as an insert material. In order to suppress · phase precipitation at the interface, DB of ODS-FS and V­4Cr­4Ti was carried out by introducing a Ti insert as a diffusion barrier between V­4Cr­4Ti and ODS-FS, and examined feasibility of W/V/Ti/ODS-FS joint for application to fusion reactor components by comparing the three-point bending strength and microstructure between the joints with and without a Ti diffusion barrier layer. It is shown that the fracture strength of the joint without a Ti insert was decreased by 25% after aging at 700°C for 100h, but that with a Ti insert shows no change after the aging treatment up to 1000h. The result indicates that the introduction of a Ti insert leads to the prevention of the formation of · phase during aging and resultant control of the degradation of the bonding strength. [doi:10.2320/matertrans.MG201213]

A method has been developed for the measurement of transport activities in membrane vesicles obtained from Sf9 cells for 3β-hydroxy-Δ(5)-bile acids by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Calibration curves for the bile acids were linear over the range of 10 to 2000 pmol/mL, and the detection limit was less than 1 pmol/mL for 3β-hydroxy-Δ(5)-bile acids using selected reaction monitoring analysis. The analytical method was applied to measurements of transport activities in membrane vesicles obtained from human multidrug resistance-associated protein 2-, 3-, and human bile salt export pump-expressing Sf9 cells for conjugated 3β-hydroxy-Δ(5)-bile acids. The present study demonstrated that human multidrug resistance-associated protein 3 vesicles accepted conjugated 3β-hydroxy-Δ(5)-bile acids along with common bile acids such as glycocholic acid and taurolithocholic acid 3-sulfate.

Irradiation hardening and microstructural change of the brazed-joint of W and oxide dispersion strengthened ferritic steel (ODS-FS) was investigated by nano-indentation hardness test and transmission electron microscopy after ion irradiation with 6.4MeV Fe 3+ ions at 500°C up to 10dpa. Dual-beam irradiation of Fe 3+ ions and energy-degraded 1MeV He + ion was also carried out. A considerable irradiation hardening occurred in the W base metal where dislocation loops and nano-scaled voids or He-bubbles were observed. Dual-beam irradiation enhanced the hardening. No significant hardening was observed in ODS-FS. The hardness of insert material was reduced after irradiation, which is due to the recovery of dislocations generated during joining process. [doi:10.2320/matertrans.MG201212] (Received October 19, 2012; Accepted December 17, 2012; Published February 16, 2013)

Summary Foxp3 controls the development and function of regulatory T (Treg) cells, but it remains elusive how Foxp3 functions in vivo. Here, we established mouse models harboring three unique missense Foxp3 mutations that were identified in patients with the autoimmune disease IPEX. The I363V and R397W mutations were loss-of-function mutations, causing multi-organ inflammation by globally compromising Treg cell physiology. By contrast, the A384T mutation induced a distinctive tissue-restricted inflammation by specifically impairing the ability of Treg cells to compete with pathogenic T cells in certain non-lymphoid tissues. Mechanistically, repressed BATF expression contributed to these A384T effects. At the molecular level, the A384T mutation altered Foxp3 interactions with its specific target genes including Batf by broadening its DNA-binding specificity. Our findings identify BATF as a critical regulator of tissue Treg cells and suggest that sequence-specific perturbations of Foxp3-DNA interactions can influence specific facets of Treg cell physiology and the immunopathologies they regulate.

Deep vein thrombi are dissolved after fibrosis process along with an increase of thrombus age. Fibrocytes are circulating bone marrow-derived cells with mesenchymal features that potentially have a unique and critical function in fibrosis. In this study, a double-color immunofluorescence analysis was carried out by using anti-CD45 and anti-collagen type I antibodies to examine the time-dependent appearance of fibrocytes in the murine model of stasis-induced deep vein thrombosis. The thrombus ages were 1, 3, 5, 7, 10, 14, and 21 days. In a thrombus age of less than 5 days, CD45+ and collagen type I+ fibrocytes were never detected. The intrathrombotic fibrocytes were initially observed in thrombi aged 7 days, and their number increased with advances in thrombus age. In a quantitative morphometrical analysis, the average number of intrathrombotic fibrocytes was highest in 14-day-old thrombi, and all of the five samples aged 14 days had the fibrocyte number of more than 25, and in three out of them, the number of intrathrombotic fibrocytes was over 30. On the contrary, in all of thrombus samples with the postligation intervals of 10 and 21 days, the number of intrathrombotic fibrocytes was less than 25. These observations imply that thrombi containing fibrocytes are at least 7 days old and that a fibrocyte number exceeding 30 would indicate the thrombus age of approximately 14 days. Our observations indicate that the detection of fibrocytes could be useful for thrombus age determination.

In two Japanese infants with neonatal cholestasis, 3-oxo-Δ(4)-steroid 5β-reductase deficiency was diagnosed based on mutations of the SRD5B1 gene. Unusual bile acids such as elevated 3-oxo-Δ(4) bile acids were detected in their serum and urine by gas chromatography-mass spectrometry. We studied effects of oral chenodeoxycholic acid treatment.SRD5B1 gene analysis used peripheral lymphocyte genomic DNA. Diagnosis and treatment of these two patients were investigated retrospectively and prospectively investigated.With respect to SRD5B1, one patient was heterozygous (R266Q, a novel mutation) while the other was a compound heterozygote (G223E/R261C). Chenodeoxycholic acid treatment was effective in improving liver function and decreasing unusual bile acids such as 7α-hydroxy- and 7α,12α-dihydroxy-3-oxo-4-cholen-24-oic acids in serum and urine.Primary bile acid treatment using chenodeoxycholic acid was effective for these patients treated in early infancy before the late stage of chronic cholestatic liver dysfunction.

The chemotherapeutic agent cisplatin often causes severe renal dysfunction; however, the molecular mechanism causing renal injury remains unclear. In wild-type mice, intrarenal interferon (IFN)-γ gene expression was found to be enhanced while CD3(+) T cells and Ly-6G neutrophils were the main cellular source of IFN-γ following cisplatin injection. Compared to wild-type mice, cisplatin-treated IFN-γ-deficient (IFN-γ(-/-)) mice exhibited exaggerated histopathological changes with higher blood urea nitrogen and creatinine levels. Cisplatin-induced apoptosis was associated with enhanced caspase-3 activation in renal proximal tubular epithelial cells, with effects suppressed by IFN-γ resulting in increased cell viability. IFN-γ significantly reduced the levels of the autophagic markers LC3-II and p62, and enhanced cathepsin D expression in cisplatin-treated renal proximal tubule epithelial cells, implying that IFN-γ can accelerate autophagic flux. Tubular cell apoptosis was more evident with enhanced caspase-3 activation in IFN-γ-deficient compared to wild-type mice. Elevated intrarenal LC3-II and increased p62 accumulation were associated with reduced cathepsin D activation in IFN-γ-deficient mice, implying that the absence of IFN-γ suppressed autophagic flux. Thus, IFN-γ can accelerate autophagic flux by augmenting cathepsin D levels and reciprocally increasing the viability of renal tubular cells, thereby attenuating cisplatin-induced acute renal injury.

Background Inborn errors of bile acid synthesis are rare genetic disorders that can present with cholestatic liver disease. Recently we encountered 3 infants with neonatal cholestasis and excessive 3β-monohydroxy-Δ5-C24 bile acids in serum and urine. We investigated whether identification of 3β-hydroxy-5-cholestenoic acid and 27-hydroxycholesterol in serum and urine of cholestatic patients is necessary for diagnosis of primary oxysterol 7α-hydroxylase deficiency. Methods These 3 patients initially led us to suspected oxysterol 7α-hydroxylase deficiency. However, sequence analysis of genomic DNA resulted in diagnosis of 2 patients with oxysterol 7α-hydroxylase deficiency and 1 patient with 3β-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase deficiency. We examined identification of 3β-hydroxy-5-cholestenoic acid and 27-hydroxycholesterol by gas chromatography–mass spectrometry after diagnosis. Results Interestingly, we detected a peak for 3β-hydroxy-5-cholestenoic acid in serum and 27-hydroxycholesterol of the neutral sterol in urine from 2 patients who were diagnosed with primary oxysterol 7α-hydroxylase deficiency. Conclusion In evaluating infants with cholestasis and excessive 3β-monohydroxy-Δ5-C24 bile acids in infancy, one needs to conduct C24 bile acid analysis serially. Results can guide performance and interpretation of genomic DNA analysis. Moreover, identification of 3β-hydroxy-5-cholestenoic acid in serum and 27-hydroxycholesterol in urine is highly important for diagnosis of oxysterol 7α-hydroxylase deficiency as is genomic DNA analysis.

We report a case of fatal intoxication caused by the ingestion of an organophosphate pesticide, methidathion (DMTP). An 80-year-old male was found dead in his bed. Forensic autopsy revealed no remarkable morphological changes. However, in a toxicological screening test, methidathion was qualitatively detected in extracts of stomach contents. Concentrations of methidathion (μg/g) in body fluids and organ tissues, determined by gas chromatography–mass spectrometry, were as follows; 66.2 in heart blood, 8.33 in peripheral blood, 8.80 in urine, 2000 in the brain (frontal lobe), 4800 in the left lung, 810 in the liver, 150 in the left kidney, and 64,000 in the stomach contents (total 1.9g). These results strongly suggested that the victim orally ingested methidathion. Additionally, xylene was determined in body fluids and organ tissues. From the toxicological data together with autopsy findings, the cause of his death was diagnosed as acute poisoning by an emulsion of methidathion.

The effectiveness of Al addition for improvement of the corrosion resistance of ODS steel in lead–bismuth eutectic (LBE) was investigated. Al-alloying surface treatment using a GESA facility was applied to 9Cr-ODS martensitic steel, and the corrosion resistance in stagnant LBE containing 10−6 wt% oxygen was subsequently examined. Corrosion resistance of ODS ferritic steels with high Cr content (14.7 wt%), containing 3.3–3.8 wt% Al and small amounts of Zr or Hf, was also examined. Al-alloying surface treated 9Cr-ODS martensitic steel was tested at 650 °C and ODS ferritic steels with high Cr content, containing 3.3–3.8 wt% Al and small amounts of Zr or Hf, were tested at 650 and 700 °C. The maximum exposure duration was 10,000 h. All tested materials showed good corrosion resistance under all test conditions. Both the Al-alloying surface treatment by the GESA facility and the Al addition to the matrix with small amounts of Zr or Hf effectively improved the compatibility of ODS steel with LBE at high temperatures.

Background Benign recurrent intrahepatic cholestasis type 1 (BRIC-1), a rare autosomal recessive disorder characterized by recurrent episodes of jaundice and pruritus, is caused by mutations in the ATP8B1 gene. Rifampicin has been reported to be an effective treatment of jaundice and pruritus in patients with BRIC. Proposed mechanisms of effect for rifampicin include enhancement of multidrug-resistance protein 2 expression, activation of the enzymes of uridine diphosphate glucuronosyltransferase 1A1 and cytochrome P450 3A4, and stimulation of 6α-hydroxylation of bile acids. Methods To confirm the diagnosis of BRIC-1 and demonstrate the effect of rifampicin treatment on bile acid metabolism, we analyzed the patient's ATP8B1 gene and bile acids in urine. Results We detected 2 heterozygous mutations in the ATP8B1 gene, and increasing amounts of unusual bile acids such as 1β-hydroxylated cholic acid, 2β-hydroxylated cholic acid, 4β-hydroxylated cholic acid, 6α-hydroxylated cholic acid, and hyocholic acid in urine during rifampicin treatment. Conclusions We diagnosed a jaundiced pediatric patient with BRIC-1 caused by 2 novel mutations (1226delA/2210delA) in the ATP8B1 gene. Rifampicin was effective in treating cholestasis. Results of urinary bile acid analyses during rifampicin treatment in this patient, suggested that rifampicin might stimulate 1β-, 2β-, and 4β-hydroxylation of bile acids in addition to 6α-hydroxylation.

Diffusion bonding techniques were employed to join high Cr oxide dispersion strengthened (ODS) ferritic steel (Fe–15Cr–2W–0.2Ti–0.35Y 2 O 3 ) and F82H steel under uni-axial hydrostatic pressure using a high vacuum hot press, and the microstructure and mechanical properties of the joints were investigated. The dissimilar joints were bonded by solid-state diffusion bonding (SSDB) and liquid phase diffusion bonding (LPDB). After bonding process, heat treatments were conducted to utilize the phase transformation of F82H steel for recovering the martensitic structure. Tensile tests with miniaturized specimens were carried out to investigate and compare the bonding strengths of each joint. Microstructure was observed for the bonding interface, and fracture mode was investigated after the tensile tests. LPDB joint of interfacial F82H steel fully recovered to martensite phase by post-joining heat treatments, while SSDB joint had ferrite phases at the interface even after heat treatment, which is considered to be due to decarburization of F82H steel during the bonding process. Therefore it is considered that the insert material plays a role as diffusion barrier of carbon during LPDB process. Microstructure observations and tensile tests of the joints revealed that the LPDB joints possess suitable tensile properties which are comparable to that of F82H steel. This indicates that LPDB is more promising method to bond ODS-FS and F82H steel than SSDB.

The synthesis of bile salts from cholesterol is a complex biochemical pathway involving at least 16 enzymes. Most inborn errors of bile acid biosynthesis result in excessive formation of intermediates and/or their metabolites that accumulate in blood and are excreted in part in urine. Early detection is important as oral therapy with bile acids results in improvement. In the past, these intermediates in bile acid biosynthesis have been detected in neonatal blood or urine by screening with FAB-MS followed by detailed characterization using GC-MS. Both methods have proved difficult to automate, and currently most laboratories screen candidate samples using LC-MS/MS. Here, we describe a new, simple and sensitive analytical method for the identification and characterization of 39 conjugated and unconjugated bile acids, including Δ(4)-3-oxo- and Δ(4,6)-3-oxo-bile acids (markers for Δ(4)-3-oxo-steroid 5β-reductase deficiency), using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). In this procedure a concentrated, desalted urinary sample (diluted with ethanol) is injected directly into the LC-ESI-MS/MS, operated with ESI and in the negative ion mode; quantification is obtained by selected reaction monitoring (SRM). To evaluate the performance of our new method, we compared it to a validated method using GC-MS, in the analysis of urine from two patients with genetically confirmed Δ(4)-3-oxo-steroid 5β-reductase deficiency as well as a third patient with an elevated concentration of abnormal conjugated and unconjugated Δ(4)-3-oxo-bile acids. The Δ(4)-3-oxo-bile acids concentration recovered in three patients with 5β-reductase deficiency were 48.8, 58.9, and 49.4 μmol/mmol creatinine, respectively by LC-ESI-MS/MS.