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We herein report a 74-year-old man who developed Lambert-Eaton myasthenic syndrome (LEMS) during atezolizumab treatment for extensive-stage small-cell lung cancer. He was started on maintenance immunotherapy with atezolizumab every three weeks after four cycles of atezolizumab plus carboplatin plus etoposide combination therapy. After 13 cycles of maintenance atezolizumab therapy, he complained of muscular weakness and fatigue. Findings from a nerve conduction study and positive findings for anti-P/Q-type voltage-gated calcium channel antibody resulted in a diagnosis of LEMS. This was a rare case of LEMS as a neurological immune-related adverse event induced by atezolizumab therapy.

形態: カラー図版あり, Physical characteristics: Original contains color illustrations, Accepted: 2019-08-26, 資料番号: PA2010049000

Tension-compression fatigue tests were performed on two types of Ni-based superalloy 718 with different microstructures, to which small artificial defects of various shapes and sizes were introduced. Similar tests were also conducted on hydrogen-charged specimens with defects, with a solute hydrogen content ranging from 26.3 to 91.0 mass ppm. In the non-charged specimens in particular, the fatigue strength susceptibility to defects varied significantly according to the type of microstructural morphology, i.e., a smaller grain size made the alloy more vulnerable to defects. The fatigue limit as a small-crack threshold was successfully predicted using the √area parameter model. Depending on the size of defects, the fatigue limit was calculated in relation to three phases: (i) harmless-defect regime, (ii) small-crack regime and (iii) large-crack regime. Such a classification enabled comprehensive fatigue limit evaluation in a wide array of defects, taking into consideration (a) the defect size over a range of small crack and large crack and (b) the characteristics of the matrix represented by grain size and hardness. In addition, the effect of defects and hydrogen on fatigue strength will be comprehensively discussed, based on a series of experimental results.

Fatigue crack growth (FCG) tests were performed with two types of metastable austenitic stainless steels having different austenite phase stabilities under hydrogen-precharged conditions (internal hydrogen) and in gaseous hydrogen environments (external hydrogen). The materials showed a peculiarly slower FCG rate with internal hydrogen than with external hydrogen even though the hydrogen concentration was much higher under the internal hydrogen conditions. The results are interpreted in terms of hydrogen-modified plastic deformation character comprising inhibited cross-slipping or enhanced deformation twinning in combination with the sequence of hydrogen penetration and strain-induced α′ martensite formation in the local region surrounding the fatigue crack tip.

Accepted: 2020-06-11, 資料番号: PA2110038000

The impact of hydrogen on crack-tip plastic-zone development was revisited via a novel approach, utilizing the measurement of fatigue crack-growth retardation in a medium-strength martensitic steel after a single overloading in laboratory air and in 90-MPa-hydrogen gas. The plastic zone can be characterized according to the crack-propagation length for reverting from the retardation caused by plasticity-induced crack-closure ascribed to overloading (overloading-affected, crack-growth distance). Hydrogen sharpened the shape of overloaded crack-tip and suppressed the extension of the severely-deformed zone in the crack proximity. Besides, it enhanced frequent crack-tip branching, giving rise to a slower crack growth rate than the in-air situation at the initial stage of retardation. However, no change in the overloading-affected, crack-growth distance was detected between the in-air and hydrogen-gas conditions. Ultimately, hydrogen barely altered the overall plastic-zone size.

The peculiar temperature dependence of hydrogen-enhanced fatigue crack growth (HEFCG) of low-carbon steel in hydrogen gas was successfully interpreted in terms of ‘trap-site occupancy’ of hydrogen. HEFCG decreased with increasing temperature in hydrogen gas at 0.7 MPa and 298 to 423 K due to lower occupancy of trap sites at higher temperatures. In hydrogen gas at 90 MPa, HEFCG was insensitive to the temperature because most of the trap sites were occupied by hydrogen, regardless of the temperature. Trap sites with a binding energy of 47 kJ/mol, corresponding approximately to the dislocation core, dominated the temperature dependence of HEFCG.

Hydrogen-assisted fatigue crack growth (HAFCG) in pure iron at a relatively low stress intensity range exhibits brittle-like intergranular (IG) fracture, while the macroscopic crack acceleration is not significant. The present study focuses on the mechanism of IG fracture in terms of the microscopic deformation structures near the crack propagation paths. We found that the IG fracture is attributed to hydrogen-enhanced dislocation structure evolution and subsequent microvoid formation along the grain boundaries. The impact of such IG cracking on the macroscopic fatigue crack growth (FCG) acceleration is evaluated according to the dependency of IG fracture tendency on the hydrogen gas pressure during testing. It is demonstrated for the first time that increased hydrogen pressure results in a larger fraction of IG fracture and correspondingly faster FCG. On the other hand, the gaseous hydrogen environment also has a positive role in decelerating the FCG rate relative to air due to the absence of oxygen and water vapor. The macroscopic crack propagation rate in hydrogen gas is eventually determined by the competition between the said positive and negative influences.

The aim of this study is to provide a quantification of the internal pressure contribution to the SSRT properties of H-charged Type-316L steel tested in air at room temperature. Considering pre-existing penny-shaped voids, the transient pressure build-up has been simulated as well as its impact on the void growth by preforming JIc calculations. Several void distributions (size and spacing) have been considered. Simulations have concluded that there was no impact of the internal pressure on the void growth, regardless the void distribution since the effective pressure was on the order of 1 MPa during the SSRT test. Even if fast hydrogen diffusion related to dislocation pipe-diffusion has been assessed as a conservative case, the impact on void growth was barely imperceptible (or significantly low). The effect of internal pressure has been experimentally verified via the following conditions: (I) non-charged in vacuum; (II) H-charged in vacuum; (III) H-charged in 115-MPa nitrogen gas; (IV) non-charged in 115-MPa nitrogen gas. As a result, the relative reduction in area (RRA) was 0.84 for (II), 0.88 for (III), and 1.01 for (IV), respectively. The difference in void morphology of the H-charged specimens did not depend on the presence of external pressure. These experimental results demonstrate that the internal pressure had no effect on the tensile ductility and void morphology of the H-charged specimen.

Hydrogen-induced ductility loss and related fracture morphologies are comprehensively discussed in consideration of the hydrogen distribution in a specimen with external and internal hydrogen by using 300-series austenitic stainless steels (Types 304, 316, 316L), high-strength austenitic stainless steels (HP160, XM-19), precipitation-hardened iron-based super alloy (A286), low-alloy Cr-Mo steel (JIS-SCM435), and low-carbon steel (JIS-SM490B). External hydrogen is realized by a non-charged specimen tested in high-pressure gaseous hydrogen, and internal hydrogen is realized by a hydrogen-charged specimen tested in air or inert gas. Fracture morphologies obtained by slow-strain-rate tensile tests (SSRT) of the materials with external or internal hydrogen could be comprehensively categorized into five types: hydrogen-induced successive crack growth, ordinary void formation, small-sized void formation related to the void sheet, large-sized void formation, and facet formation. The mechanisms of hydrogen embrittlement are broadly classified into hydrogen-enhanced decohesion (HEDE) and hydrogen-enhanced localized plasticity (HELP). In the HEDE model, hydrogen weakens interatomic bonds, whereas in the HELP model, hydrogen enhances localized slip deformations. Although various fracture morphologies are produced by external or internal hydrogen, these morphologies can be explained by the HELP model rather than by the HEDE model.

The effects of external and internal hydrogen on the slow-strain-rate tensile (SSRT) properties at room temperature were studied for ten types of solution-treated austenitic stainless steels containing a small amount of additive elements. The hydrogen diffusivity and solubility of the steels were measured with high-pressure hydrogen gas. The remarkable tensile-ductility loss observed in the SSRT tests was attributed to hydrogen-induced successive crack growth (HISCG) and was successfully quantified according to the nickel-equivalent content (Nieq), which represents the stability of the austenitic phase. The relative reduction in area (RRA) of the steels with a larger Nieq was influenced by the hydrogen distribution, whereas that of the steels with a smaller Nieq was not. This unique trend was interpreted with regard to the hydrogen distribution and fracture morphology (HISCG or microvoid coalescence).

We employed X-ray diffraction using collimated X-rays to quantitatively evaluate the local hydrogen concentration behavior in metals. Hydrogen concentrating around a crack tip significantly accelerates crack propagation, i.e., hydrogen embrittlement. In order to clarify the mechanism leading to this, the local hydrogen concentration behavior, i.e., at a crack tip, was evaluated by numerical analysis and experimental measurements. Although thermal desorption analysis can be used to evaluate the total hydrogen content in metals, it cannot be applied to local areas. Microprint methods, which use chemical reactions between hydrogen and coated elements cannot quantitatively evaluate the hydrogen content. The present study takes account of hydrogen-induced strain, and X-ray diffraction in a confined area was employed to detect variations in lattice spacing before and after hydrogen charging. Using X-ray diffraction applied to a small area, we demonstrate that the hydrogen concentrates in the vicinity of the crack, i.e., at the elastic–plastic boundary.

The influences of internal and external hydrogen on the tensile ductility loss and fracture behaviors of a precipitation-hardened Ni-based superalloy 718 were investigated via slow strain rate tensile (SSRT) testing under hydrogen pre-charged conditions (internal hydrogen) or in gaseous hydrogen environments (external hydrogen) . Severe degradation of tensile ductility was confirmed both in internal and external hydrogen conditions, and the degree of such degradation became more significant with increasing hydrogen content or hydrogen gas pressures. Moreover, the loss of tensile ductility was more pronounced in internal hydrogen conditions than external hydrogen environments. In association with such degradation of macroscopic tensile ductility, hydrogen also altered fracture mode from ductile microvoid coalescence to some brittle appearances. Whereas typical intergranular fracture combined with a decent fraction of quasi-cleavage fracture appeared on the fracture surface formed in external hydrogen environments, several types of unique faceted characteristics were found on the fracture surfaces in internal hydrogen conditions. The detailed observation of the mid-sectioned lateral surfaces of post-mortem samples successfully revealed that the observed distinctions consisted of the fracture along grain boundaries and {111} crystallographic planes including annealing twin boundaries, besides the frequency of the cracking along twin boundaries evidently increased at higher hydrogen concentration. On the basis of the series of experimental results, the initiation and propagation mechanisms of those hydrogen-induced cracks are discussed in terms of hydrogen distribution, intrinsic deformation character of the material itself as well as the alteration of plastic deformation mode caused by dissolved hydrogen.

The effect of hydrogen on the deformation and fracture behavior in pure Cu, pure Ni and Cu–Ni alloy was studied via tensile tests of H-charged, smooth and circumferentially-notched specimens at room temperature (RT) and 77 K. Hydrogen-diffusion properties were determined by the desorption method. To obtain a uniform hydrogen concentration in the H-charged specimens, specimens were exposed to 100-MPa hydrogen gas at 543 K for 200 h, based on the determined hydrogen diffusivity. In tensile tests of smooth pure Ni and Cu–Ni alloy specimens at RT, common hydrogen effects were detected, namely, an increase in yield and flow stresses — a hardening effect; and a ductility loss that was accompanied by a change in fracture surface from ductile to brittle feature — an embrittling effect. With regard to the embrittling effect, the pure Ni and Cu–Ni alloy showed different fracture-surface morphologies at RT; the pure Ni showed an intergranular (IG) surface and the Cu–Ni alloy surface was flat. However, a number of IG cracks were detected beneath the fracture surfaces on the smooth Cu-Ni alloy. The tensile tests of the H-charged smooth specimens at 77 K yielded an IG surface for the pure Ni and a ductile fracture surface with dimples in the Cu–Ni alloy. In contrast, tensile tests of the H-charged, notched specimens at RT demonstrated clear IG fractures for the pure Ni and Cu–Ni alloy. These facts indicate that IG cracking was the first step in the embrittling process for the pure Ni and Cu–Ni alloy, and IG cracking was accompanied by a large plastic deformation that formed the flat surface (unclear IG surface) for the smooth Cu–Ni alloy. Considering that the HE of both pure Ni and Cu–Ni alloy was related to IG cracking, possible mechanisms were discussed and tensile tests performed at 77 K suggested two possibilities: (I) interaction between hydrogen-moving dislocation is more important in the HE process of the Cu-Ni alloy compared to the pure Ni; (II) hydrogen transportation towards grain boundaries are required to cause the IG fracture in the Cu-Ni alloy.

Hydrogen energy is a possible solution for storage in the future. The resistance of packaging materials such as stainless steels has to be guaranteed for a possible use of these materials as containers for highly pressurized hydrogen. The effect of hydrogen charging on the nucleation and growth of microdamage in two different austenitic stainless steels AISI316 and AISI316L was studied using in situ tensile tests in synchrotron X-ray tomography. Information about damage nucleation, void growth and void shape were obtained. AISI316 was found to be more sensitive to hydrogen compared to AISI316L in terms of ductility loss. It was measured that void nucleation and growth are not affected by hydrogen charging. The effect of hydrogen was however found to change the morphology of nucleated voids from spherical cavities to micro-cracks being oriented perpendicular to the tensile axis.

Elasto-plastic fracture toughness tests of a commercially pure iron were performed in air and in hydrogen gas at two different pressures. Some unique characteristics of hydrogen-enhanced cracking were exhibited at both the macroscopic and microscopic length scales, based on the observation of fracture surface, fracture plane, plasticity distribution and dislocation structure. The possible mechanisms responsible for the hydrogen-induced degradation of fracture toughness are discussed.

Hydrogen-assisted, fatigue crack-growth in pure iron within a low stress-intensity range was ascribed to the emergence of intergranular fracture, the significance of which was emphasized by increased hydrogen-gas pressure, while conversely mitigated by an elevation of test temperature. Based on conventional thermodynamic theory, a single parameter, GB hydrogen-coverage (θx), was used to derive a systematic, unified evaluation of such a complex reliance on the dual environmental variables. Furthermore, post-mortem microscopic analyses of the crack-wake deformation microstructures were employed to elucidate the contribution of dislocation activity regarding the triggering of IG fracture, which also varied significantly with the alteration of θx.

Hydrogen-assisted fatigue crack growth in gaseous environment was comparatively examined at room temperature (RT) and 423 K, based on analysis of the deformation structure evolution around crack-wakes using scanning electron microscopy techniques. In hydrogen-gas at RT, the propagating crack displayed weakly-evolved dislocation arrangement, accompanied by a significant acceleration of fatigue crack growth. However, in hydrogen-gas at 423 K, the crack-wake plasticity was well-evolved and analogous to that observed in an inert environment. This apparent recovery of deformation micro structure coincided with suppressed crack growth acceleration, the rationale for which can be interpreted by the trapping/de-trapping equilibrium between hydrogen and dislocations.

Hydrogen effect on fatigue performance of commercially pure BCC iron has been studied with a combination of various electron microscopy techniques. The fatigue crack growth (FCG) in gaseous hydrogen was found to consist of two regimes corresponding to a slightly accelerated regime at relatively low stress intensity factor range, ΔK, (Stage I) and the highly accelerated regime at relatively high ΔK (Stage II). These regimes were manifested by the intergranular and quasicleavage types of fractures respectively. Scanning electron microscopy (SEM) observations demonstrated an increase in plastic deformation around the crack wake in the Stage I, but considerably lower amount of plasticity around the crack path in the Stage II. Transmission electron microscopy (TEM) results identified dislocation cell structure immediately beneath the fracture surface of the Stage I sample, and dislocation tangles in the Stage II sample corresponding to fracture at high and low plastic strain amplitudes respectively.

In order to elucidate the temperature dependence of hydrogen-enhanced fatigue crack growth (FCG), the FCG test was performed on low-alloy Cr-Mo steel JIS-SCM435 according to ASTM E647 using compact tension (CT) specimen under 0.1–95 MPa hydrogen-gas at temperature ranging from room temperature (298 K) to 423 K. The obtained results were interpreted according to trap site occupancy under thermal equilibrium state. The FCG was significantly accelerated at RT under hydrogen-gas, that its maximum acceleration rate of the FCG was 15 at the pressure of 95 MPa at the temperature of 298 K. The hydrogen-enhanced FCG was mitigated due to temperature elevation for all pressure conditions. The trap site with binding energy of 44 kJ/mol dominated the temperature dependence of hydrogen-enhanced FCG, corresponding approximately to binding energy of dislocation core. The trap site (dislocation) occupancy is decreased with the temperature elevation, resulting in the mitigation of the FCG acceleration. On the basis of the obtained results, when the occupancy becomes higher at lower temperature, e.g. 298 K, hydrogen-enhanced FCG becomes more pronounced. The lower occupancy at higher temperature does the opposite.

A new model for hydrogen-assisted fatigue crack growth (HAFCG) in BCC iron under a gaseous hydrogen environment has been established based on various methods of observation, i.e., electron backscatter diffraction (EBSD), electron channeling contrast imaging (ECCI) and transmission electron microscopy (TEM), to elucidate the precise mechanism of HAFCG. The FCG in gaseous hydrogen showed two distinguishing regimes corresponding to the unaccelerated regime at a relatively low stress intensity factor range, ΔK, and the accelerated regime at a relatively high ΔK. The fracture surface in the unaccelerated regime was covered by ductile transgranular and intergranular features, while mainly quasi-cleavage features were observed in the accelerated regime. The EBSD and ECCI results demonstrated considerably lower amounts of plastic deformation, i.e., less plasticity, around the crack path in the accelerated regime. The TEM results confirmed that the dislocation structure immediately beneath the crack in the accelerated regime showed significantly lower development and that the fracture surface in the quasi-cleavage regions was parallel to the {100} plane. These observations suggest that the HAFCG in pure iron may be attributed to “less plasticity” rather than “localized plasticity” around the crack tip.

Hydrogen effect on fatigue performance at relatively high values of stress intensity factor range, ΔK, of pure BCC iron has been studied with a combination of various electron microscopy techniques. Hydrogen-assisted fatigue crack growth rate is manifested by a change of fracture features at the fracture surface from ductile transgranular in air to quasi-cleavage in hydrogen gas. Grain reference orientation deviation (GROD) analysis has shown a dramatic suppression of plastic deformation around the crack wake in samples fatigued in hydrogen. These results were verified by preparing site-specific specimens from different fracture features by using Focused Ion Beam (FIB) technique and observing them with Transmission Electron Microscope (TEM). The FIB lamella taken from the sample fatigued in air was decorated with dislocation cell structure indicating high amount of plasticity, while the lamella taken from the quasi-cleavage surface of the sample fatigued in hydrogen revealed a distribution of dislocation tangles which corresponds to smaller plastic strain amplitude involved at the point of fracture. These results show that a combination of critical hydrogen concentration and critical stress during fatigue crack growth at high ΔK values triggers cleavage-like fracture due to reduction of cohesive force between matrix atoms.

In this paper, it has been demonstrated that compressive residual stress induced by cavitation peening which is one of the mechanical surface modification techniques can reduce invasion of the surface of austenitic stainless steel by hydrogen. Cavitation peening was done with employing a cavitating jet in air. The specimens were prepared with different processing time of cavitation peening. Then, stress measurement was performed using an X-ray diffraction analysis. After that, the surface was charged with hydrogen employing a cathodic charging method. Hydrogen content was evaluated by a thermal desorption analysis using a gas chromatography. From the obtained results, hydrogen content was reduced along with increase in compressive residual stress at surface. In particular hydrogen content became to 15% at processing time of 2 s/mm introducing compressive residual stress of 378 MPa. In short, cavitation peening can drastically prevent invasion by hydrogen.

Slow-strain rate tensile (SSRT) tests on various metals having γ-Fe phase; Type 304 and 316L stainless steels, HP160 high strength stainless steel, and A286 Fe-based super alloy were conducted in external hydrogen and with internal hydrogen. The external hydrogen indicates non-charged specimens tested in high-pressure hydrogen-gas environment, whereas the internal hydrogen indicates hydrogen-charged specimens, with uniform distribution of hydrogen, tested in inert gas. The hydrogen distribution was calculated based on the measured hydrogen diffusivity and solubility. The fracture morphologies were observed by scanning electron microscopy (SEM). For Types 304, 316L, and HP160, the relative reduction in area (RRA) of the steels was successfully reproduced by the nickel equivalent, Nieq, showing the higher Nieq, the lager RRA. Furthermore, at a low Nieq, the RRA of the steel with external hydrogen was nearly equal to that with internal hydrogen. In contrast, at a high Nieq, the RRA of the steel with internal hydrogen was slightly degraded by hydrogen, RRA ≈ 0.8, whereas that in external hydrogen was not degraded, RRA ≈ 1. For A286, despite a high Nieq, the RRA of the alloy with internal hydrogen was significantly degraded by hydrogen, RRA ≈ 0.5. The fracture morphologies were categorized into four types: quasi-cleavage fracture associated with hydrogen-assisted surface cracks; ordinary void formation with no hydrogen effect; small-void formation associated with void sheet enhanced by hydrogen; facet formation induced by hydrogen. These categorized morphologies could be interpreted in terms of hydrogen distribution (internal or external hydrogen), austenitic stability (a low or high Nieq), and microstructure (solution or precipitation-hardened treatment).

The paper presents the hydrogen-entry, tensile, and fatigue properties of a precipitation-hardened martensitic stainless steel, JIS-SUS630, with a newly developed coating, whose thickness ranges from 10 to 20 μm. The newly developed coating consists of alumina, aluminum, and ferroaluminum, and has an excellent resistance to hydrogen entry in 100-MPa hydrogen gas at 270°C. The hydrogen entry in the coated specimen occurred under a diffusion-controlled process and the effective hydrogen diffusivity was approximately one thousandth of that of the base steel. Although the hydrogen diffusivity of JIS-SUS630 was two orders of magnitude larger than that of JIS-SUS304, the effective hydrogen diffusivity of the coated JIS-SUS630 was nearly equal to that of the coated SUS304. In our previous study with secondary-mass ion spectroscopy (SIMS), the coating’s excellent resistance to hydrogen entry was attributed to interfacial hydrogen trapping between the aluminum and ferroaluminum layers. The experimental result obtained in this study suggested that the excellent resistance to hydrogen entry demonstrated by the developed coating can be attributed to the reduction in the permeation area induced by the interfacial trapping of hydrogen. The tensile tests of a smooth, round-bar specimen and fatigue tests of a circumferentially notched specimen with exposure to 100-MPa hydrogen gas at 270°C were performed in air at room temperature (RT). The test results showed that the tensile and fatigue properties of the coated specimens were not degraded by hydrogen exposure, whereas those for the non-coated specimens were significantly degraded. Hydrogen-pressure cycle tests of the coated, tubular specimens with an inner notch were also carried out with 95-MPa hydrogen gas at 85°C, demonstrating that the fatigue life of the tubular specimen was improved by the developed coating.

Background Asthmatic cough is often refractory to standard treatments such as inhaled corticosteroids (ICS) and long-acting β 2 agonists (LABA). Tiotropium may modulate cough reflex sensitivity of acute viral cough, but its efficacy in asthmatic cough remains unknown. Objective To evaluate whether tiotropium improves cough and cough reflex sensitivity in patients with asthma refractory to ICS/LABA. Methods Seventeen consecutive patients with asthma with chronic cough despite the use of ICS/LABA (13 women; 43.4 ± 19.0 years; average ICS dose, 651 ± 189 μg/d; fluticasone equivalent) were additionally treated with tiotropium (5 μg/d) for 4 to 8 weeks to examine its effects on pulmonary function and capsaicin cough reflex sensitivity (cough thresholds C2 and C5). Cough severity, cough-specific quality of life, and asthma control were also evaluated using cough visual analog scales (VASs), the Japanese version of Leicester Cough Questionnaire (J-LCQ), and Asthma Control Test (ACT), respectively. Patients with an improved cough VAS score of 15 mm or more were considered responders to tiotropium. Results Tiotropium significantly improved cough VAS, J-LCQ, and ACT scores, but not FEV 1 . Changes in cough VAS score correlated with those in C2 ( r = −0.58; P = .03), C5 ( r = −0.58; P = .03), and ACT scores ( r = −0.62; P = .02), but not in FEV 1 in the overall patients. When analyses were confined to the 11 responders, tiotropium significantly improved capsaicin cough reflex sensitivity within the subgroup (C2: P = .01 and C5: P = .02) and versus the nonresponders (C2: P = .004 and C5: P = .02). Conclusion Tiotropium may alleviate asthmatic cough refractory to ICS/LABA by modulating cough reflex sensitivity but not through bronchodilation.

In the context of the fatigue life design of components, particularly those destined for use in hydrogen refuelling stations and fuel cell vehicles, it is important to understand the hydrogen-induced, fatigue crack growth (FCG) acceleration in steels. As such, the mechanisms for acceleration and its influencing factors are reviewed and discussed in this paper, with a special focus on the peculiar frequency dependence of the hydrogen-induced FCG acceleration. Further, this frequency dependence is debated by introducing some potentially responsible elements, along with new experimental data obtained by the authors. This article is part of the themed issue ‘The challenges of hydrogen and metals’.

Background: Despite the close linkage between rhinitis, chronic rhinosinusitis (CRS) and asthma, relevant biomarkers of both upper and lower airway inflammation are rare. Methods: Patients with asthma (without upper airway disease [UAD; n = 24], with rhinitis [n = 25], CRS [n = 24], and nasal polyps [n = 2]), isolated rhinitis (n = 13), isolated CRS (n = 13), and 10 healthy controls were prospectively recruited. Fractional exhaled nitric oxide (NO) levels at 50 mL/s (FeNO50), nasal NO levels, Lund–Macay-scores of sinus computed tomography and an asthma control questionnaire (ACQ) were evaluated. Results: Asthma was associated with higher FeNO50 levels irrespective of the UAD category. FeNO50 levels were higher in asthmatics with CRS (median: 54.0 ppb) than those with rhinitis (35.2 ppb, p = 0.02) and those without UAD (34.3 ppb, p = 0.002). Nasal NO levels were higher in rhinitis patients than other UAD categories, irrespective of the asthma concomitance. Nasal NO levels were higher in asthmatics ...

In order to study the influence of hydrogen on plastic deformation behavior in the vicinity of the fatigue crack-tip in a pure iron, a multi-scale observation technique was employed, comprising electron channeling contrast imaging (ECCI), electron back-scattered diffraction (EBSD) and transmission electron microscopy (TEM). The analyses successfully demonstrated that hydrogen greatly reduces the dislocation structure evolution around the fracture path and localizes the plastic flow in the crack-tip region. Such clear evidence can reinforce the existing model in which this type of localized plasticity contributes to crack-growth acceleration in metals in hydrogen atmosphere, which has not yet been experimentally elucidated.

The objective of this study is to evaluate the effect of hydrogen on the micro-and macro-strain of austenitic stainless steel using X-ray diffraction. When hydrogen is trapped in lattice sites, it can affect both the micro-and macro-strain. The micro-strain was evaluated through fitting profiles to measured X-ray diffraction profile using a fundamental parameter method. The macro-strain, i.e., the residual stress, was evaluated by a 2D method using a two-dimensional PSPC. The experimental samples were charged with hydrogen by a cathodic charging method. The results revealed that the induced residual stress was equi-biaxial and compressive, and that the micro-strain increased. Both of these varied rapidly with increasing hydrogen charging time. Saturation occurred at a compressive stress of around 130 MPa. On reaching saturation, the hydrogen charging was terminated and desorption of hydrogen began at room temperature. Then, the strains decreased and the compressive stress reverted, ultimately, to a tensile stress of 180 MPa. Martensitic transformation occurred due to hydrogen charging and this had a significant effect on the X-ray diffraction profile.

In order to determine the effect of hydrogen on the local yield stress near the surface of austenitic stainless steel, an indentation test combined with inverse problem analysis was employed. For austenitic stainless steel, the indentation test is an effective method since the hydrogen is distributed near to the surface because of its high solubility and low diffusion coefficient. Although uniaxial tensile tests can also provide useful data, greater variations in the mechanical properties due to the presence of hydrogen can be detected through indentation tests. In this study, Secondary Ion Mass Spectrometry (SIMS) was used to measure hydrogen depth profiles in order to establish the relationships between the hydrogen absorption depth and the effects due to hydrogen evaluated using the indentation test. The results showed that the yield stress doubled due to hydrogen absorption and then reverted to its initial state due to hydrogen desorption at room temperature. Also, hardening due to the presence of hydrogen, which was determined using an indentation test, was found to be dependent on the relationship between the plastic deformation depth and the hydrogen absorption depth.

In order to clarify the contribution of dislocation‒hydrogen interaction on the hydrogen embrittlement (HE) of pure Ni and of Cu‒55 wt% Ni binary alloy, slow strain rate tensile (SSRT) tests were conducted at room temperature (RT) and at 77 K on hydrogen-precharged specimens. Regarding the SSRT test at RT, hydrogen increased the flow stress and induced intergranular fracture in both pure Ni and Cu–Ni alloy. Furthermore, based on scanning transmission electron microscopy investigations, it was suggested that the evolution of dislocation structures had been enhanced by hydrogen, but only in the case of pure Ni. At 77 K, the ductility of pure Ni was degraded by hydrogen, whereas that of Cu–Ni alloy was not. The difference in temperature dependence of the dislocation‒hydrogen interaction between pure Ni and Cu–Ni alloy was discussed, based on the previously proposed HE mechanisms.

Three effects of hydrogen have been reported on an austenitic stainless steel (Type-316L), a Cr-Mo steel (JIS-SCM435) and a carbon steel (JIS-SGP) during slow strain rate tensile (SSRT) tests performed in air on H-charged, smooth round-bar specimens. Two H-charging conditions were considered: exposure to 100-MPa hydrogen gas (270 °C, 200 h for Type-316L), and immersion in a NH4SCN solution (40 °C, 48 h for other steels). Modifications of the micro-void coalescence (MVC) mechanism were observed for each steel: decrease of dimple size (Type-316L), increase of dimple size (JIS-SGP), and formation of quasi-cleavage (QC) surfaces (JIS-SCM435). To clarify the contribution of the hydrogen-induced cracking (HIC) mechanism to these failures, the pressure build-up in preexisting cavities and its impact on the material strength was simulated by finite difference method (FDM) and finite element method (FEM). The failure criterion was defined based upon the elastoplastic fracture mechanics parameter: J-integral. For Type-316L, no effect of internal pressure on the fracture was expected. For JIS-SCM435 and JIS-SGP, although an effect of internal pressure exists, its relatively low value cannot lead to failure. SSRT tests were performed on Type-316L under the following conditions: (I) non-charged in vacuum; (II) H-charged in vacuum; (III) H-charged in 115 MPa nitrogen gas; (IV) non-charged in 115 MPa nitrogen gas. The experimental results successfully supported the simulation-based conclusions.

Objectives In this study, we investigated whether single nucleotide polymorphisms (SNPs) in folylpoly-γ-glutamate synthase (FPGS), which catalyzes the polyglutamation of pemetrexed (PEM), is related to FPGS expression and the response to PEM in non-small cell lung cancer (NSCLC). Materials and methods We first examined FPGS protein expressions according to FPGS SNPs genotype groups in 15 lung adenocarcinoma cell lines. Next, 101 non-squamous NSCLC patients treated with PEM and platinum drugs were classified into FPGS SNP genotype groups to investigate the relation between FPGS SNP genotypes and treatment outcome. Results When the 15 adenocarcinoma cell lines were classified into FPGS SNP 2572C > T genotype groups, we found that the FPGS protein expression was significantly higher in the CC genotype group than in the TT + CT genotype group (p = 0.0022). In contrast, there was no significant difference in FPGS expression when another FPGS SNP was analyzed. We also examined the FPGS SNP 2572C > T genotype in 101 non-squamous NSCLC patients treated with PEM and platinum drugs. Among these 101 patients, response rate was significantly higher in the CC genotype group than in the TT + CT genotype group (p = 0.0034). When we examined the patients treated with PEM, platinum drugs and Bev, almost all (29/33) were classified into the TT + CT genotype group. The response rate, progression-free survival, and over-all survival were all significantly better in the patients of the TT + CT genotype group who also received Bev than in those who did not receive Bev (p = 0.034, 0.021, 0.018, respectively). Conclusion FPGS SNP 2572C > T is a predictive marker of the efficacy of PEM and platinum drugs for NSCLC.

The objective of this paper is to optimize the pitch at which the nozzle of a cavitating jet is scanned during peening. The evaluations of an effect of the pitch on overlapping treatment are done, firstly theoretically, by estimating the aggressive intensity of the jet based on a Gaussian distribution in order to uniformly and effectively treat the surface in applications such as cavitation peening and cleaning. Experimentally, cavitation peening was conducted with the nozzle scanned at various pitches. Striped patterns, due to the non-uniform treatment, were formed in aluminum when pitches of 6, 8, 10 or 12 mm were used, whereas with pitches of 2 and 4 mm the patterns were uniform. The compressive residual stress introduced into type 316L stainless steel by cavitation peening was approximately 380 and 400 MPa for pitches of 2 and 4 mm, respectively. From the viewpoint of not only the uniformity but also effective and efficient treatment, the optimum pitch for scanning was determined to be 4 mm, since this requires half the number of scans compared to 2 mm.

In order to demonstrate the effect that the compressive residual stress introduced by cavitation peening has on suppressing the invasion of the surface of steel by hydrogen, we examined the surface after hydrogen charging using a spherical indenter. It was demonstrated that hydrogen considerably hardens the surface of austenitic stainless steel by 35% and that the surface hardening induced by hydrogen was reduced with increasing compressive residual stress introduced by cavitation peening. Moreover, the surface hardness was restored to its initial state after two weeks due to hydrogen desorption from the charged surface. This shows that the hardening was caused by the invasion of the surface by hydrogen and that the introduction of compressive residual stress suppresses it.

Introduction Amrubicin is a promising agent in the treatment of lung cancer, but predictive biomarkers have not yet been described. NAD(P)H:quinone oxidoreductase 1 (NQO1) is an enzyme known to metabolize amrubicinol, the active metabolite of amrubicin, to an inactive compound. We examined the relationship between NQO1 and amrubicinol cytotoxicity. Methods Gene and protein expression of NQO1, amrubicinol cytotoxicity, and C609T single-nucleotide polymorphism of NQO1 were evaluated in 29 lung cancer cell lines: 14 small cell lung cancer (SCLC) and 15 non-SCLC (NSCLC). The involvement of NQO1 in amrubicinol cytotoxicity was evaluated by small interfering RNA against NQO1 . Results A significant inverse relationship between both gene and protein expression of NQO1 and amrubicinol cytotoxicity was found in all cell lines. Treatment with NQO1 small interfering RNA increased amrubicinol cytotoxicity and decreased NQO1 expression in both NSCLC and SCLC cells. Furthermore, cell lines genotyped homozygous for the 609T allele showed significantly lower NQO1 protein expression and higher sensitivity for amrubicinol than those with the other genotypes in both NSCLC and SCLC cells. Conclusions NQO1 expression is one of the major determinants for amrubicinol cytotoxicity, and C609T single-nucleotide polymorphism of NQO1 could be a predictive biomarker for response to amrubicin treatment.

In the use of hydrogen energy, the hydrogen embrittlement should be investigated, and it is necessary to improve reliability and safety of machine components which are used in hydrogen environment. The hydrogen sensitivity of material depends on material structure, defect and stress distribution. There is a possibility that the hydrogen invasion into material and the fatigue crack propagation with hydrogen embrittlement can be suppressed by introducing compressive residual stress by us- ing surface modification such as cavitation peening. The cavitation peening is a one of the peening technique, and enhancement of the fatigue strength of the mechanical components and structural materials by cavitation peening have been revealed. In this study, the austenite stainless steel JIS SUS316L with precrack were charged by a cathodic hydrogen charging method, and the fatigue test with and without hydrogen charge were conducted by a plate bending fatigue test. The results demonstrated that the fatigue crack propagation with hydrogen embrittlement can be greatly suppressed by cavitation peening.

The role of hydrogen on intergranular (IG) fracture in hydrogen-assisted fatigue crack growth (HAFCG) of a pure iron at low stress intensity was discussed in terms of the microscopic deformation structures near crack propagation paths. The main cause of IG fracture was assumed to be the hydrogen-enhanced dislocation structure evolution and subsequent microvoids formation along the grain boundaries. Additionally, the impact of such IG cracking on the macroscopic FCG rate was evaluated according to the dependency of IG fracture propensity on the hydrogen gas pressure. It was first demonstrated that the increased hydrogen pressure results in the larger area fraction of IG and corresponding faster FCG rate. Moreover, gaseous hydrogen environment also had a positive influence on the FCG rate due to the absence of oxygen and water vapor. The macroscopic crack propagation rate was controlled by the competition process of said positive and negative effects.