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The intrinsic value of an action refers to the inherent sense that experiencing a behavior is enjoyable even if it has no explicit outcome. Previous research has suggested that a common valuation mechanism within the reward network may be responsible for processing the intrinsic value of achieving both the outcome and external rewards. However, how the intrinsic value of action is neurally represented remains unknown. We hypothesized that the intrinsic value of action is determined by an action-outcome contingency indicating the behavior is controllable and that the outcome of the action can be evaluated by this feedback. Consequently, the reward network should be activated, reflecting the generation of the intrinsic value of action. To test this hypothesis, we conducted a functional magnetic resonance imaging (fMRI) investigation of a stopwatch game in which the action-outcome contingency was manipulated. This experiment involved 36 healthy volunteers and four versions of a stopwatch game that manipulated controllability (the feeling that participants were controlling the stopwatch themselves) and outcome (a signal allowing participants to see the result of their action). A free-choice experiment was administered after the fMRI to explore preference levels for each game. The results showed that the stopwatch game with the action-outcome contingency evoked a greater degree of enjoyment because the participants chose this condition over those that lacked such a contingency. The ventral striatum and midbrain were activated only when action-outcome contingency was present. Thus, the intrinsic value of action was represented by an increase in ventral striatal and midbrain activation.

Purpose The assessment of retinal nerve fiber layer defects (RNFLDs) is a useful part of glaucoma care. Here, we obtained en-face images of retinal layers below the inner limiting membrane (ILM) with swept source-optical coherence tomography (SS-OCT), and measured RNFLD angle with new software. Methods This study included 105 eyes of 105 normal tension glaucoma (NTG) patients (age, 59.8 ± 13.2). Exclusion criteria were best-corrected visual acuity 28 mm, non-glaucoma ocular disease, and systemic disease affecting the visual field. We obtained 12 x 9 mm 3D volume scans centered on the macula with SS-OCT (DRI OCT-1, Topcon), and from these scans, created 3 averaged en-face images, each comprising 7 horizontal en-face images (total thickness: 18.2 μm). We labeled these averaged images, according to their depth below the ILM, as en-face images 1 (shallowest), 2 (middle) and 3 (deepest). In each image, a circle was drawn centered on the disc, with a radius of half the distance between the centers of the disc and macula. The investigator marked points where the edge of the RNFLD intersected this circle, and RNFLD angle (RNFLDA) was calculated with new software. Finally, we analyzed the association between RNFLDA, cpRNFLT, weighted RGC count (wrgc) and Humphrey field analyzer (HFA)-measured mean deviation (MD) and hemifield total deviation (TD), both overall and in each hemifield. Results En-face image 2 had the highest interclass reproducibility for measuring RNFLDA (intra-rater intraclass correlation coefficient (ICC): 0.988, inter-rater ICC: 0.962). The correlation coefficients with RNFLDA were: HFA MD, -0.60; superior TD, -0.73; inferior TD, -0.69; overall cpRNFLT, -0.27; superior hemifield cpRNFLT, -0.39; and inferior hemifield cpRNFLT, -0.53 (all p

The Master Curve approach using miniature C(T) specimens with 4 mm thickness is promising for directly determining the reference temperature of reactor pressure vessel (RPV) steels because they can be taken from the broken halves of the Charpy specimens used in the surveillance program to monitor neutron irradiation embrittlement. The relative dimensional tolerances of standard C(T) specimens are provided in the present ASTM E1921 standard; consequently, the absolute dimensional tolerances are stricter for smaller specimens. In this study, the effect of the tolerances of key dimensions on the elastic–plastic equivalent stress intensity factor derived from the J-integral, KJ, was calculated using three-dimensional finite-element analysis. Even if the dimensional tolerances for the miniature C(T) specimens based on the present standard were mitigated in some degree (as examples, the tolerance of specimen thickness of ±0.08 mm was mitigated to ±0.1 mm; and the tolerance of specimen width of ±0.04 mm was mitigated to ±0.1 mm), the variations of KJ and the reference temperature were negligibly small. Furthermore, the use of the mitigated dimensional tolerances with adequate accuracy for evaluating the fracture toughness was ascertained.

In petrochemical and nuclear power plants, inner surface of components, such as pressure vessels and piping, which are made of carbon steels or low-alloy steels, is often cladded by austenitic stainless steels to improve the corrosion resistance of those components. In the evaluation of a crack postulated near the inner surface of cladded components, the following two different kinds of cracks are often assumed: One is a surface crack penetrated through cladding and the other is a subsurface crack under cladding. In order to evaluate the structural integrity of those components in a rational manner, it is important to investigate the crack propagation behavior. In particular, it should be evaluated whether a subsurface crack penetrates through cladding or is arrested at the interface between cladding and base metal. In this study, ductile crack propagation analysis for a subsurface elliptical crack in cladded plates was performed using elastic-plastic XFEM, which can model the crack independent of finite elements.

The Master Curve approach is a powerful tool to evaluate material-specific fracture toughness of ferritic steels, such as RPV steels, using a limited number of specimens. However, preparing a sufficient number of standard fracture toughness test specimens is difficult for irradiated RPV steels of existing surveillance programs. Utilization of miniature specimens that can be machined from broken halves of standard Charpy specimens is a possible solution to address this issue. CRIEPI has been working on the test technique utilizing a miniature C(T) (Mini-C(T)) specimens, whose dimensions are 4 × 10 × 9.6 mm (0.16 inch thickness specimen). The basic applicability of the Mini-C(T) Master Curve approach has been confirmed [1] for the base metals of typical Japanese RPV steels. International round robin tests confirmed the reproducibility of fracture toughness data obtained by Mini-C(T) specimens [2–4]. Ensuring the applicability of the Mini-C(T) Master Curve approach to weld metals and heat affected zone materials is of great importance to meet the future demand from the RPV surveillance programs for over 40 or 60 years’ reactor operation. For a weld metal deposit, we verified that valid reference temperature, To, can be estimated using the Mini-C(T) specimens and the statistics of the fracture toughness data [5] show good conformity to the assumption of the Master Curve method [6]. In the present paper, fracture toughness of a weld joint, which consists of two different heats of RPV plate material was examined. Five sets of Mini-C(T) specimens taken from two base metals, their heat affected zones (HAZ) and weld metal deposit, were subjected to the fracture toughness test. 0.5T-C(T) specimens taken from similar locations were also subjected to the fracture toughness tests to investigate specimen size effect. All the Mini-C(T) data sets taken from base metal, HAZ and weld metal were eligible for the determination of valid To with each 12 to 16 Mini-C(T) specimens. The relevance of the specimen size correction in the Master Curve method was confirmed for two base metals and a weld metal. The fracture toughness data for HAZ materials gave a reasonable agreement with the specific Weibull distribution assumed in the Master Curve method. Nevertheless, To values of four data sets of HAZ materials, including two Mini-C(T) datasets and two 0.5T-C(T) datasets, showed larger variation than that of the base metals or the weld metal. The crack initiation sites of HAZ specimens were all within so-called fine grain HAZ. However the HAZ width near the crack initiation site was dependent on the individual specimens. Higher fracture toughness tended to be gained from the specimens with narrower HAZ width. The resulting To values for HAZ material were close to or lower than that for base metals. The results suggest that the HAZ material gives equivalent or higher fracture toughness than in base metals.

Introduction Despite the proven benefits of thrombolytic therapy with tissue plasminogen activator (t-PA) for peripheral thromboembolism, perfusion failure frequently occurs, particularly in arterial circulation. We evaluated how the modification of fibrinolytic activity affects thrombus formation under flow and static conditions. Materials and methods t-PA-treated human whole-blood samples (n = 6) were perfused over a microchip coated with collagen and tissue thromboplastin at different shear rates, and thrombus formation was quantified by measuring flow pressure changes. For comparison, rotational thromboelastometry (ROTEM) was used to evaluate fibrinolytic activity under static conditions. Results At a shear rate of 240 s − 1 , t-PA (200–800 IU/ml) concentration-dependently delayed capillary occlusion, whereas at 600 s − 1 , capillary occlusion was significantly faster and t-PA had limited effects, even at a supra-pharmacological concentration (800 IU/ml). In contrast, 200 IU/ml t-PA efficiently prevented clot formation in the ROTEM assay. The combined treatment of blood with a specific PAI-1 inhibitor (PAI-039) moderately enhanced the efficacy of t-PA, but only under flow conditions. In addition, 1:1-diluted blood samples of PAI-1-deficient (−/−) mice showed a significant delay of capillary occlusion at 240 s − 1 , compared with those from wild-type mice (1.55 fold; P Conclusions The present results suggest that the anti-thrombotic efficacy of t-PA is sensitive to arterial shear flow, and that PAI-1 secreted from activated platelets plays an essential role in thrombolytic resistance.

Acute ischemic stroke (AIS) is a major cause of morbidity and mortality in the aging population worldwide. Alteplase, a recombinant tissue plasminogen activator, is the only Food and Drug Administration-approved thrombolytic agent for the treatment of AIS. Only 2–5% of patients with stroke receive thrombolytic treatment, mainly due to delay in reaching the hospital. Edaravone is a free radical scavenger marketed in Japan to treat patients with AIS, who present within 24 h of the onset of symptoms. When used in combination with alteplase, edaravone may have three useful effects: enhancement of early recanalization, inhibition of alteplase-induced hemorrhagic transformation and extension of the therapeutic time window for alteplase. This is the first review of the literature evaluating the clinical efficacy of edaravone, aiming to clarify whether edaravone should be further evaluated for clinical use worldwide. This review covers both clinical and experimental studies conducted between 1994 and 2012. Edaravone is a potentially useful neurovascular protective agent, used in combination with thrombolytic agents to treat >15 million patients devastated by stroke worldwide annually. Additional clinical studies are necessary to verify the efficacy of edaravone when used in combination with a thrombolytic agent.

The authors evaluated dermal phototoxicity using the world smallest minipig (MMPig: Microminipig). MMPigs were administered 100 mg/kg ciprofloxacin hydrochloride with an infusion pump. The dorsal area of each animal was irradiated with ultraviolet-A irradiation. The left dorsal skin was irradiated at intensities of 5, 10, 15, and 20 J/cm2, and the right dorsal back skin was set as a nonirradiated site. Gross and histopathological examinations were conducted before irradiation and from 1 to 72 hr after irradiation. Initial changes in the skin were necrosis of the basal and/or prickle cell layer and cellular infiltration from 24 hr after irradiation. Vesicle formation observed from 48 hr after irradiation was considered similar to bullous eruptions, a known side effect of fluoroquinolones in humans. Therefore, the authors suggest that the MMPig may be a useful experimental animal model for dermal phototoxicity studies.

Stroke is a major cause of mortality and disability worldwide. During the past three decades, major advances have occurred in secondary prevention, which have demonstrated the broader potential for the prevention of stroke. Risk factors for stroke include previous stroke or transient ischemic attack, hypertension, high blood cholesterol and diabetes. Proven secondary prevention strategies are anti-platelet agents, antihypertensive drugs, statins and glycemic control. In the present review, we evaluated the secondary prevention of stroke in light of clinical studies and discuss new pleiotropic effects beyond the original effects and emerging clinical evidence, with a focus on the effect of optimal oral pharmacotherapy.

Adults seem to have greater difficulties than children in acquiring a second language (L2) because of the alleged “window of opportunity” around puberty. Postpuberty Japanese participants learned a new English rule with simplex sentences during one month of instruction, and then they were tested on “uninstructed complex sentences” as well as “instructed simplex sentences.” The behavioral data show that they can acquire more knowledge than is instructed, suggesting the interweaving of nature (universal principles of grammar, UG) and nurture (instruction) in L2 acquisition. The comparison in the “uninstructed complex sentences” between post-instruction and pre-instruction using functional magnetic resonance imaging reveals a significant activation in Broca's area. Thus, this study provides new insight into Broca's area, where nature and nurture cooperate to produce L2 learners' rich linguistic knowledge. It also shows neural plasticity of adult L2 acquisition, arguing against a critical period hypothesis, at least in the domain of UG.

Atherosclerotic lesions were observed in male and ovariectomized female Microminipig (MMP) fed a high fat and cholesterol diet with sodium cholate (HFCD/SC) for 3 months. HFCD/SC induced hypercholesterolemia accompanied by an increase in serum total cholesterol (T-Cho), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and cholesterol ester (CE). Unlike the mouse or rabbit, a dominant LDL-C fraction in the intact MMP, similar to that in humans, was observed by serum lipoprotein analysis. HFCD/SC increased body weight gain. At the end of the experiment, computed tomography scans of conscious animals showed that HFCD/SC had decreased liver attenuation values (Hounsfield unit) and increased subcutaneous and abdominal fat, suggesting the induction of fatty liver and obesity. HFCD/SC induced atherosclerotic lesions in systemic arteries, including the external and internal iliac arteries, abdominal aorta, coronary artery, and cerebral arterial circle. Atherosclerosis and pathological findings induced by HFCD/SC in MMP were similar to those in humans. The MMP is a potentially suitable tool for investigating human atherosclerosis. Keywords:: atherosclerosis, cholesterol, diet, life-style, Microminipig

Nosocomial infections caused by microbial opportunistic infections or microbial biofilms may occur during hospitalization and increase patient morbidity, mortality and health care costs. Artificial antibiotic agents were initially used to prevent infection; however, the high prevalence of nosocomial infections has resulted in their excessive use, which has led to microbial resistance to these agents. The increase in microbial resistance to antibiotics and the development of antibiotic agents may be the cause of the production of other microbial resistance. Thus, natural compounds that have no adverse side effects would be a preferred treatment modality. Recently, the monosaccharide 1,5-anhydro-D-fructose (1,5-AF), a natural plant compound derived from starch, has been found to have multifunctional properties, including antioxidant, antiplatelet aggregation by thrombin and anti-inflammatory activities. The results of the present study demonstrate that 1,5-AF suppressed the growth of coagulase-negative staphylococci on the hands as well as the growth of Staphylococcus epidermidis, which is a cause of opportunistic infections. Furthermore, 1,5-AF suppressed biofilm formation by the methicillin-resistant Staphylococcus aureus. In conclusion, 1,5-AF is a natural compound that may be effective in preventing nosocomial infections, without causing adverse side effects.

The fracture toughness Master Curve gives a universal relationship between the median of fracture toughness and temperature in the ductile-brittle transition temperature region of ferritic steels such as reactor pressure vessel (RPV) steels. Considering the possible application of the Master Curve method coexistent with the present surveillance program for operating RPVs, the utilization of miniature specimens is quite important for efficient determination of the Master Curve from limited volume of the materials of concern. In this study, fracture toughness tests were conducted for typical Japanese RPV steels using the miniature C(T) specimens with the thickness of 4 mm following the procedure of the ASTM standard. The results showed that the differences in test temperature, evaluation method, and specimen size did not affect the Master Curves, and the fracture toughness indexed by the reference temperature, To, obtained from miniature C(T) specimens were consistent with those obtained from standard and larger C(T) specimens.

Historically, clinical outcomes following spinal cord injury (SCI) have been dismal. Severe SCI leads to devastating neurological deficits, and there is no treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. To address all the issues associated with SCI, a multidisciplinary approach is required, as it is unlikely that a single approach, such as surgical intervention, pharmacotherapy or cellular transplantation, will suffice. High mobility group box 1 (HMGB1) is an inflammatory cytokine. Various studies have shown that HMGB1 plays a critical role in SCI and that inhibition of HMGB1 release may be a novel therapeutic target for SCI and may support spinal cord repair. In addition, HMGB1 has been associated with graft rejection in the early phase. Therefore, HMGB1 may be a promising therapeutic target for SCI transplant patients. We hypothesize that inhibition of HMGB1 release rescues patients with SCI. Taken together, our findings suggest that anti-HMGB1 monoclonal antibodies or short hairpin RNA-mediated HMGB1 could be administered for spinal cord repair in SCI patients.

Human memory systems contain self-monitoring mechanisms for evaluating their progress. People can change their learning strategy on the basis of confidence in their performance at that time. However, it has not been fully understood how the brain is engaged in reliable rating of confidence in past recognition memory performance. We measured the brain activity by fMRI while healthy subjects performed a visual short-term recognition memory test and then rated their confidence in their answers as high, middle, or low. As shown previously, their behavioral performance in the confidence rating widely varied; some showed a positive confidence-recognition correlation (i.e., "rate reliably") while others did not. Among brain regions showing greater activity during rating their confidence relative to during a control, non-metamemory task (discriminating brightness of words), only a posterior-dorsal part of the right frontopolar cortex exhibited higher activity as the confidence level better correlated with actual recognition memory performance. These results suggest that activation in the right frontopolar cortex is key to a reliable, retrospective rating of confidence in short-term recognition memory performance.

Vascular endothelial growth factor A (VEGF-A) is a prominent growth factor for both angiogenesis and lymphangiogenesis. Recent studies have shown the importance of VEGF-A in enhancing the growth of lymphatic endothelial cells in lymph nodes (LNs) and the migration of dendritic cells into LNs. VEGF-A is produced in inflamed tissues and/or in draining LNs, where B cells are a possible source of this growth factor. To study the effect of B cell-derived VEGF-A, we created transgenic mice (CD19Cre/hVEGF-Afl) that express human VEGF-A specifically in B cells. We found that the human VEGF-A produced by B cells not only induced lymphangiogenesis in LNs, but also induced the expansion of LNs and the development of high endothelial venules. Contrary to our expectation, we observed a significant decrease in the Ag-specific Ab production postimmunization with OVA and in the proinflammatory cytokine production postinoculation with LPS in these mice. Our findings suggest immunomodulatory effects of VEGF-A: B cell-derived VEGF-A promotes both lymphangiogenesis and angiogenesis within LNs, but then suppresses certain aspects of the ensuing immune responses.

Conventional finite element method is continually used for the flaw evaluation of pipe structures to investigate the fitness-for-service for power plant components, however, it is generally time consuming to make a model of specific crack configuration. The consideration of a propagating surface crack is further accentuated since the crack propagation behavior along the crack front is implicitly affected by the distribution of the crack driving force along the crack front. The authors developed a system to conduct crack propagation analysis by use of the three-dimensional elastic-plastic extended finite element method. It was applied to simulate ductile crack propagation of circumferentially surface cracks in pipe structures and could realize the simultaneous calculation of the J-integral and the consequent ductile crack propagation. Both the crack extension and the possible change of crack shape were evaluated by the developed system.

Aquaporin-4 (AQP4) plays a role in the generation of post-ischemic edema. Pharmacological modulation of AQP4 function may thus provide a novel therapeutic strategy for the treatment of stroke, tumor-associated edema, epilepsy, traumatic brain injury, and other disorders of the central nervous system (CNS) associated with altered brain water balance. Edaravone, a free radical scavenger, is used for the treatment of acute ischemic stroke (AIS) in Japan. In this study, edaravone significantly reduced the infarct area and improved the neurological deficit scores at 24 h after reperfusion in a rat transient focal ischemia model. Furthermore, edaravone markedly reduced AQP4 immunoreactivity and protein levels in the cerebral infarct area. In light of observations that edaravone specifically inhibited AQP4 in a rat transient focal ischemia model, we propose that edaravone might reduce cerebral edema through the inhibition of AQP4 expression following cerebral infarction.

Lipopolysaccharide (LPS) stimulates macrophages by activating NF-kappaB, which contributes to the release of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. 1,5-Anhydro-D-fructose (1,5-AF), a monosaccharide formed from starch and glycogen, exhibits anti-oxidant activity and enhances insulin secretion. This study examined the effects of 1,5-AF on LPS-induced inflammatory reactions and elucidated its molecular mechanisms. Before LPS challenge, mice were pretreated with 1,5-AF (38.5 mg/kg). We found that 1,5-AF pretreatment attenuated cytokine release into the serum, including TNF-alpha, IL-6 and macrophage chemoattractant protein (MCP)-1. Furthermore, pretreatment with 1,5-AF (500 microg/ml) attenuated cytokine release, and 1,5-AF directly inhibited the nuclear translocalization of the NF-kappaB p65 subunit in LPS-stimulated murine macrophage-like RAW264.7 cells. This inhibition was responsible for decreased LPS-induced phosphorylation on Ser536 of the NF-kappaB p65 subunit, which is a posttranslational modification involved in the non-canonical pathway. Collectively, these findings indicate that the anti-inflammatory activity of 1,5-AF occurs via inactivation of NF-kappaB.

The purpose of this study was to formulate an algorithm for assessing sleep/waking from activity intensities measured with a waist-worn actigraphy, the Lifecorder PLUS (LC; Suzuken Co. Ltd., Nagoya, Japan), and to test the validity of the algorithm. The study consisted of 31 healthy subjects (M/F = 20/11, mean age 31.7 years) who underwent one night of simultaneous measurement of activity intensity by LC and polysomnography (PSG). A sleep(S)/wake(W) scoring algorithm based on a linear model was determined through discriminant analysis of activity intensities measured by LC over a total of 235 h and 56 min and the corresponding PSG-based S/W data. The formulated S/W scoring algorithm was then used to score S/W during the monitoring epochs (2 min each, 7078 epochs in total) for each subject. The mean agreement rate with the corresponding PSG-based S/W data was 86.9%, with a mean sensitivity (sleep detection) of 89.4% and mean specificity (wakefulness detection) of 58.2%. The agreement rates for the individual stages of sleep were 60.6% for Stage 1, 89.3% for Stage 2, 99.2% for Stage 3 + 4, and 90.1% for Stage REM. These results demonstrate that sleep/wake activity in young to middle-aged healthy subjects can be assessed with a reliability comparable to that of conventional actigraphy through LC waist actigraphy and the optimal S/W scoring algorithm.

We examined the somatotopical relationship between cortical activity and sensory stimulation of reflex areas in reflexology using functional magnetic resonance imaging. Three reflex areas on the left foot, relating to the eye, shoulder, and small intestine were stimulated during the experiment. A statistical analysis showed that reflexological stimulation of the foot reflex areas corresponding to the eye, shoulder, and small intestine activated not only the somatosensory areas corresponding to the foot, but also the somatosensory areas corresponding to the eye, shoulder, and small intestine or neighboring body parts. Thus, the findings showed that reflexological stimulation induced a somatosensory process corresponding to the stimulated reflex area and that a neuroimaging approach can be used to examine the basis of reflexology effects.

In the design assessment of fast reactor plant components, prevention of crack initiation from defect-free structures is a main concern. However, existence of initial defects such as weld defects cannot be entirely excluded and this potential cracks are to be evaluated to determine if initiated cracks do not lead to component failure instantly. Therefore, evaluation of structural integrity in the presence of crack-like defects is also important to complement the formal design assessment. The authors have been developing a guideline for assessing long-term structural integrity of fast reactor components using detailed inelastic analysis and nonlinear fracture mechanics. This guideline consists of two parts, evaluation of defect-free structures and flaw evaluation. In the latter, creep-fatigue is considered to be one of the most essential driving force for crack propagation at high operating temperature exceeding 500 °C. The uses of J-integral-type parameters (fatigue J-integral range and creep J-integral) are recommended to describe creep-fatigue crack propagation behavior in the guideline. This paper gives an outline of the simplified evaluation method for creep-fatigue crack propagation.

Numerous stress intensity factor solutions have been proposed so far depending on the objects of evaluation including the variations of structures, cracks, and applied loads. In applying the flaw evaluation methodology to components of nuclear power plants, the use of reliable stress intensity factor solutions is essential. In this study, cracked cylinders were focused on as one of the typical configurations in actual plants. Existing stress intensity factor solutions for cracked cylinders were reviewed, and the accuracy of these solutions was investigated thorough the comparison with each other. Specific solutions were then recommended for cylindrical structures. Approximate expressions were newly derived for axially through-wall cracked cylinder subjected to linear stress distribution and for circumferentially through-wall cracked cylinder subjected to bending to realize simple evaluation of stress intensity factor. Considering that the cylindrical structures are often replaced with flat plates in the evaluation of actual components, the propriety of the replacement was also studied.

The extended finite element method (X-FEM), which can model the domain without explicitly meshing the crack surface, can be used to perform stress analyses for solving fracture mechanics problems efficiently. In the present study, the principle of superposition is used to solve crack problems in conjunction with the X-FEM. In the proposed method, the surface load distributed on the crack surface, which is modeled implicitly by the interpolation functions with enrichment terms, is introduced to X-FEM analysis. Moreover, the energy release rate at the crack front is evaluated by the domain integral method with boundary integral terms for the surface load. The proposed method is verified through numerical analyses of two- and three-dimensional crack problems in linear fracture mechanics.

Considering a rational maintenance rule of Light Water Reactor piping, reliable flaw evaluation criteria are essential to determine how a detected flaw is detrimental to continuous plant operation. Ductile fracture is one of the dominanant failure modes to be considered for carbon steel piping, and can be analyzed by the elastic-plastic fracture mechanics. Some analytical efforts have been provided as flaw evaluation criteria using load correction factors such like the Z-factors in the JSME codes on fitness-for-service for nuclear power plants or the ASME boiler and pressure vessel code section XI. The present correction factors were conventionally determined taken conservatism and simplicity into account, however, the effect of internal pressure which would be an important factor under an actual plant condition was not adequately considered. Recently, a J-estimation scheme, “LBB. ENGC” for ductile fracture analysis of circumferentially through-wall-cracked pipes subject-ed to combined loading was newly developed to have a better prediction with more realistic manner. This method is explicitly incorporated the contribution of both bending and tension due to internal pressure by means of the scheme compatible with an arbitrary combined loading history. In this paper, the effect of internal pressure on the flaw evaluation criteria was investigated using the new J-estimation scheme. A correction factor based on the new J-estimation scheme was compared with the present correction factors, and the predictability of the current flaw evaluation criteria was quantitatively evaluated in consideration of internal pressure.

To achieve a rational maintenance program for aged Light Water Reactor components, it is important to establish and to improve the flaw evaluation criteria. The current flaw evaluation criteria such as ASME Boiler and Pressure Vessel Code Section XI are focused on Class 1 piping which usually shows relatively higher toughness. On the other hand, flaw evaluation criteria suitable for Class 2, 3 piping with moderate-toughness are also required because some Class 2, 3 piping systems are as important to plant safety analysis as Class 1 piping. In this study, both analytical and experimental studies were conducted to provide the evaluation method of fracture loads for acceptance criteria for Class 2, 3 piping. Pipe fracture tests by four-point bending were conducted on circumferentially cracked carbon steel pipes with moderate-toughness. The Net-Section Collapse criterion overpredicted experimental maximum loads for through-wall-cracked pipes, which suggested the necessity of Z-factor. Three-dimensional finite element analysis and simplified analysis based on the reference stress method were conducted to complement the limited pipe fracture tests. It was ascertained that the reference stress method always gave moderately conservative fracture loads compared with the finite element analysis and pipe fracture tests as well. Z-factor for Class 2, 3 piping was then derived and formulated using the reference stress method. Z for Class 2, 3 piping was affected by radius-to-thickness ratio, and was higher than Z for Class 1 piping in the present codes.

Previously, we found that enteric lactoferrin (eLF) could reduce the visceral fat accumulation known to associate strongly with metabolic syndrome symptoms and consequently with an increased risk of atherosclerosis. In this study, the atherosclerosis-preventive potential of LF was assessed in a high-fat and high-cholesterol diet (HFCD)-induced hypercholesterolemia and atherosclerosis model using Microminipig™. Eight-week orally administered eLF remarkably reduced the HFCD-induced serum total and low-density lipoprotein cholesterol levels but not high-density lipoprotein cholesterol levels. A histological analysis of 15 arteries revealed that eLF systemically inhibited the development of atherosclerotic lesions. Pathway analysis using identified genes that characterized eLF administration in liver revealed significant changes in the steroid biosynthesis pathway (ssc00100) and all affected genes in this pathway were upregulated, suggesting that cholesterol synthesis inhibited by HFCD was recovered by eLF. In summary, eLF could potentially prevent the hypercholesterolemia and atherosclerosis through protecting homeostasis from HFCD-induced dysfunction of cholesterol metabolism.

GM2 gangliosidosis variant 0 (Sandhoff disease, SD) is a fatal, progressive, neurodegenerative lysosomal storage disease caused by simultaneous deficiencies of acid β-hexosaminidases A and B. Canine SD has so far been identified only in two purebreeds. In this article, we present the case of a 10 mo old, male dog of mixed breed that developed progressive neurological signs including ataxia, postural deficit, and visual deficits and finally died at the age of 21 mo. The dog was diagnosed with SD on the basis of the results of biochemical and histopathological analyses. This is the third report of canine SD and the first time it has been identified in a mixed breed.

Developing an extremely efficient packet inspection algorithm for lookup engines is important to realize a high throughput and a lower energy dissipation. Previously, we proposed a mismatch detection circuit that detects mismatches with a minimal amount of memory accesses. In the present paper, we propose a new lookup engine based on the combination of a mismatch detection circuit and a linked-list hash table. An experimental chip was fabricated in 40-nm 8-metal CMOS process technology. The chip operates at a frequency of 100 MHz under a power supply voltage of VDD=1.1 V. The throughput of 100 Mpacket/s (=51.2 Gb/s) is obtained at a frequency of 100 MHz, which is 3 times greater when compared to the 33 M Mpacket/s of a lookup engine without a mismatch detection circuit. The measured energy dissipation is 0.808 nJ/Search. The proposed lookup engine improves the packet inspection throughput and reduces energy dissipation.

The Master Curve approach for the fracture toughness evaluation is expected to be a powerful tool to ensure the reliability of long term used reactor pressure vessel (RPV) steels. In order to get sufficient number of data for the Master Curve approach coexistent with the present surveillance program for RPVs, the utilization of miniature specimens that can be taken from the broken halves of the surveillance Charpy specimens is important. CRIEPI has developed the test technique for the miniature C(T) specimens, whose dimensions are 4 × 10 × 9.6 mm, and has verified the basic applicability of the Master Curve approach by means of the miniature C(T) for the determination of the fracture toughness of typical Japanese RPV steel base metals [1]. A series of round robin tests on RPV steel base metals [2–4] demonstrated that the miniature C(T) specimen can be used for the determination of the reference temperature (To) with no specific difficulties in test techniques. The present paper addresses the applicability of the fracture toughness evaluation by the miniature C(T) specimens on a RPV weld metal with multi-layer weld bead structure. The distribution of the fracture toughness and the trend in fracture toughness change with temperature were confirmed to show a good agreement with the assumption of the Master Curve method [5]. Fracture surface of the specimens were in cleavage fracture mode regardless of the difference in fracture toughness level. The relevance of the specimen size correction in the Master Curve method was confirmed. The difference of To values were only in a few degrees Celsius between the data obtained with 0.5 inch-thickness C(T) specimens and the miniature C(T) specimens. The effect of local loss of constraint nearby the specimen side surface was examined by comparing with the datasets from the specimens with and without side grooves. The difference of To was only 3 degree centigrade and no remarkable effect of side grooving could be seen. From overall examination results, it was concluded that the miniature C(T) specimen can be used for the Master Curve evaluation of tested PRV weld metal.

Piping lines in nuclear power plants may experience multi-axial loads including tensile force, bending, and torsion moments during operation. There is a lack of guidance for failure evaluation of locally wall-thinned pipes under the multi-axial loads including torsion moment. The ASME B&PV Code Section XI Working Group is currently developing fully plastic failure evaluation procedures for pressurized piping items containing local wall thinning subjected to multi-axial loads. A failure estimation method for locally wall-thinned pipes subjected to multi-axial loads including torsion moment has been proposed through numerical analyses. In this study, in order to investigate the failure behavior of the pipes with local wall thinning subjected to multi-axial loads including the torsion, failure experiments were performed on 20 mm diameter carbon steel pipes with a local wall thinning. Based on the experimental results, the proposed failure estimation method is confirmed to be applicable to pipes with local wall thinning.

When a crack is detected in a piping line during in-service inspections, failure estimation method provided in ASME Boiler and Pressure Vessel Code Section XI or JSME Rules on Fitness-for-Service for Nuclear Power Plants can be applied to evaluate the structural integrity of the cracked pipe. The failure estimation method in the current codes accounts for the bending moment and axial force due to pressure. The torsion moment is not considered. Recently, analytical investigations have been carried out by several authors on the limit load of cracked pipes considering multi-axial loads including torsion and two failure estimation methods for multi-axial loads including torsion moment with different ranges of values have been proposed. In this study, to investigate the failure behavior of cracked pipes subjected to multi-axial loads including the torsion moment and to provide experimental support for the failure estimation methods, failure experiments were performed on 20 mm diameter stainless steel pipes with a circumferential surface crack or a through-wall crack under combined axial force and bending and torsion moments. Based on the experimental results, the proposed failure estimation methods were confirmed to be applicable to cracked pipes subjected to multi-axial loads.

The use of miniature C(T) specimens makes it possible for the direct determination of the reference temperature of reactor pressure vessel steels, because they can be taken from the broken halves of the Charpy specimens used for surveillance program to monitor neutron irradiation embrittlement. Fracture toughness tests using C(T) specimens usually need the measurement of load-line displacement, however, it is difficult to mount a clip gauge inside the miniature specimen due to the limitation of the specimen size. A pair of knife edges is machined at the front face of the miniature C(T) specimen to mount a clip gauge with razor blade tips, and the front-face displacement is translated to the load-line displacement. When front-face displacement measurements are made, the load-line displacement can be inferred by multiplying the measured values by the constant 0.73. This conversion factor has been simply derived from the assumption of the linear deformation around a supposed point of rotation. In this study, the conversion factor was directly evaluated by using a three-dimensional elastic-plastic finite element analysis for the miniature C(T) specimens, and the adequacy of the conversion factor was investigated.Copyright © 2015 by ASME

The aim of the present study was to consider the safety and efficacy of concurrent use of strontium-89 (Sr-89) with external beam radiotherapy (EBRT) for multiple bone metastases, including lesions that require urgent therapy. A retrospective review was performed of a consecutive series of patients who received Sr-89 for multiple bone metastases. Forty-five patients with multiple bone metastases received Sr-89 injection. Since 17 of the 45 patients had osteolytic bone lesions requiring emergent EBRT, they underwent concurrent use of Sr-89 with EBRT (concurrent group). The remaining 28 patients, none of whom had osteolytic lesions requiring urgent EBRT, were given Sr-89 injection only (singularity group). The injection of Sr-89 was to be given during EBRT, or on the day before the first day of EBRT. The dose of EBRT was 30 Gy in 10 fractions or 40 Gy in 20 fractions. Adverse events were evaluated according to hematological toxicity as measured by the Common Terminology Criteria for Adverse Events (V4.0). To assess efficacy, we checked changes in the pain scale and analgesic drug dosages, and the presence or absence of serious complications from bone metastases. Fifteen of 17 patients (88.2 %) in the concurrent group and 17 of 28 patients (60.7 %) in the singularity group reported bone pain relief. A statistically significant difference was found between the two groups, and severe complications (spinal cord compression and pathological fracture) from bone metastases could be prevented in all patients in the concurrent group. Severe hematological toxicity (grade 3 or higher) was not observed in the two groups. There was no statistical difference between the two groups. No one required additional intervention. The adverse events were tolerable. The results of our study suggest that concurrent use of Sr-89 with EBRT for multiple bone metastases can be performed safely if it is carried out with care, and that it may be an effective therapy in cases requiring emergency treatment.

The purpose of this study is to determine, by functional magnetic resonance imaging, how the activated regions of the brain change as a Japanese sentence is presented in a grammatically correct order. In this study, we presented constituents of a sentence to Japanese participants one by one at regular intervals. The results showed that the left lingual gyrus was significantly activated at the beginning of the sentence, then the left inferior frontal gyrus and left supplementary motor area, in the middle of the sentence, and the left inferior temporal gyrus, at the end of the sentence. We suggest that these brain areas are involved in sentence comprehension in this temporal order.

The extended finite element method (X-FEM), which can model the domain without explicitly meshing the crack surface, can be used to perform stress analyses for efficiently solving fracture mechanics problems. In the present study, the constraint condition enforcement for X-FEM analysis considering symmetry is presented. Since the interpolation functions utilized in X-FEM analysis include the enrichment basis functions, the freedoms of the node on the symmetric plane should be constrained properly in the X-FEM model with symmetric conditions. Moreover, evaluation of the energy release rate by the domain integral method should be performed considering the symmetry conditions. In the present paper, the constraint conditions for three-dimensional X-FEM analysis considering symmetric conditions are summarized, and numerical examples using symmetric X-FEM models are shown. The proposed procedure can be used to perform efficient X-FEM analyses of practical fracture problems.

A 10-year-old, neutered male Labrador retriever presented with progressive left hind lameness. Ultrasonography revealed large, subcutaneous, ovoid cysts around the stifle joint. Radiographic and computed tomographic images revealed periosteal reaction of the distal femur. Magnetic resonance (MR) imaging showed a large cyst that was hypointense in T1-weighted images, hyperintense in T2-weighted images and had a thin lining that was enhanced by intravenous gadonium injection. The cyst communicated with the joint cavity and other small cysts around the joint. Histopathology of an excisional biopsy specimen led to diagnosis of ganglion cyst. This report provides MR images of a ganglion cyst in a canine stifle.

A stretched zone is formed as a result of blunting and stretching at the tip of the crack during the fracture process. Consequently, the fracture surface becomes fine and smooth. Paying attention to this characteristic, the authors proposed a new method to evaluate the stretched zone width quantitatively, based on the difference in the fracture surface roughness.To verify the validity of the proposed method, elastic-plastic fracture toughness tests were performed on compact tension specimens cut out of carbon steel pipes. After the fracture toughness tests, the stretched zone was observed with a high-resolution scanning electron microscope to measure the critical stretched zone width (SZWc) for stable crack initiation quantitatively. The critical stretched zone widths determined by the proposed method were compared with those reported in the references. The comparison led the conclusion that this method enabled us to measure SZWc quantitatively, which had been difficult to measure in the absence of skilled microscope operators. The method also showed the possibility to estimate the failure load from the fracture surface by using fracture mechanics parameters.

A locally bred, 12-year-old, intact female Satsuma dog presented with generalized alopecia. Erythema, crusts and desquamation were observed primarily on the truck. Papules and erosions were present in the pinnae, and there were multiple areas of skin necrosis on the right forelimb. The cutaneous lesions had not responded to treatment with systemic antibiotics and prednisolone. The dog also had progressive anemia. Babesia gibsoni was detected in the blood, and the dog was treated with antiprotozoal agents. The skin lesions and anemia improved, but relapsed after the treatment was discontinued. Histopathological examination of skin biopsies revealed findings suggestive of early leukocytoclastic vasculitis or ischemic vasculopathy.

The purpose of this study was to investigate human brain activity during the reading aloud of Japanese sentences using fMRI. Twenty-three right-handed normal Japanese subjects performed three reading tasks: covert reading of meaningful or meaningless sentences, and reading aloud of meaningful sentences. Areas in the bilateral frontal and temporal cortices were activated during the reading-aloud task compared with the covert reading task. In addition, activation of these brain areas showed significant positive correlation with the reading speed during the reading-aloud task. Our results indicate that bilateral frontal-temporal networks are involved in phonological processing during reading aloud.

Permanent pacemakers are commonly used in veterinary practice and can have a dramatic effect on the treatment of heart block. A Labrador Retriever dog suffering from exercise intolerance secondary to third degree atrioventricular block was treated with a new pacemaker system. A steroid-eluting screw-in type lead that has the advantage of being more fixed to the myocardial wall without increasing the pacing threshold was used. The heart rate was regulated with an acceleration sensing pacemaker generator that included several automatic modulation systems. Nineteen months after implantation, the dog has a normal level of activity. The present case suggests that this pacemaker design may offer important advantages for canine patients.

Acute myocardial ischemia was induced by occluding the LAD in Clawn miniature pigs. Eight pigs (group 1) were subjected to 6 h ischemia and nine pigs (group 2) were subjected to 20 min ischemia, followed by reperfusion for 340 min. Three animals of the group 1 died due to ventricular fibrillation after occlusion and in group 2, four animals died due to the arrhythmia after reperfusion. Though the ischemic area of group 2 (15.6% of the ventricle) was narrower than that of group 1 (21.7%), the survival rate was lower. We supposed that ischemia-reperfusion injuries were strongly connected with the hemodynamics of group 2. Clawn miniature pigs are useful experimental animals for myocardial ischemic researches.

Rheumatoid arthritis (RA) is one of the most critical articular diseases with synovial hyperplasia followed by impairment of quality of life. However, the mechanism(s) that regulates synovial cell outgrowth is not fully understood. To clarify its mechanism(s), we carried out immunoscreening by using antirheumatoid synovial cell antibody and identified and cloned “Synoviolin/Hrd1”, an E3 ubiquitin ligase. Synoviolin/Hrd1 was highly expressed in the rheumatoid synovium, and mice overexpressing this enzyme developed spontaneous arthropathy. Conversely,synoviolin/hrd1+/-mice were resistant to collagen-induced arthritis by enhanced apoptosis of synovial cells. We conclude that Synoviolin/Hrd1 is a novel causative factor for arthropathy by triggering synovial cell outgrowth through its antiapoptotic effects. Our findings provide a new pathogenetic model of RA and suggest that Synoviolin/Hrd1 could be targeted as a therapeutic strategy for RA.