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Despite recent advances in asthma treatments, the search for novel therapies remains necessary because there are still patients with recurrent asthma exacerbations and poor responses to the existing treatments. Since group 2 innate lymphoid cells (ILC2) play a pivotal role in asthma by triggering and exacerbating type 2 inflammation, controlling ILC2s function is key to combating severe asthma. Mucosal-associated invariant T (MAIT) cells are innate-like T cells abundant in humans and are activated both in a T cell receptor-dependent and -independent manner. MAIT cells are composed of MAIT1 and MAIT17 based on the expression of transcription factors T-bet and RORγt, respectively. MAIT cells play pivotal roles in host defense against pathogens and in tissue repair and are essential for the maintenance of immunity and hemostasis. Our recent studies revealed that MAIT cells inhibit both ILC2 proliferation and functions in a mouse model of airway inflammation. MAIT cells may alleviate airway inflammation in two ways, by promoting airway epithelial cell barrier repair and by repressing ILC2s. Therefore, reagents that promote MAIT cell-mediated suppression of ILC2 proliferation and function, or designer MAIT cells (genetically engineered to suppress ILC2s or promote repair of airway damage), may be effective therapeutic agents for severe asthma.

Blau syndrome (BS), is an autoinflammatory granulomatosis disease characterized by a distinct triad of skin, joint, and eye disorders similar to those of sarcoidosis, but the lung involvement frequently observed in sarcoidosis are rare. Granulomas from patients with BS displayed a distinct morphology indicating an exuberant chronic inflammatory response. Patients with BS may have granulomatous lung lesions, which require early diagnosis. To determine whether therapeutic intervention is needed for lung lesions, examining transbronchial lung cryobiopsy specimens and accumulating cases of BS with lung involvement could be contributed to improving BS management in the future.

Systemic administration of corticosteroids is used in the treatment of chronic eosinophilic pneumonia (CEP). However, in patients with CEP as well as other comorbidities, the adverse effects of corticosteroids should be minimized as much as possible. A 71-year-old woman was presented with aggravating asthma with CEP and sinusitis, and she had uncompensated liver cirrhosis (LC) with a Child-Pugh score of 7. Initial treatment with a low dose of oral corticosteroids (OCSs) in combination with tezepelumab, an anti-thymic stromal lymphopoietin (TSLP) antibody, resulted in rapid improvement of asthma and CEP without deteriorating LC. Sinusitis also improved after ceasing OCS. This case suggested that tezepelumab may be useful as a treatment option for patients with CEP, especially those with liver dysfunction.

Abstract This study investigated the utility of periostin, a matricellular protein, as a prognostic biomarker in patients with idiopathic pulmonary fibrosis (IPF) who received nintedanib. Monomeric and total periostin levels were measured by enzyme-linked immunosorbent assay in 87 eligible patients who participated in a multicenter prospective study. Forty-three antifibrotic drug-naive patients with IPF described in previous studies were set as historical controls. Monomeric and total periostin levels were not significantly associated with the change in forced vital capacity (FVC) or diffusing capacity of the lungs for carbon monoxide (DLCO) during any follow-up period. Higher monomeric and total periostin levels were independent risk factors for overall survival in the Cox proportional hazard model. In the analysis of nintedanib effectiveness, higher binarized monomeric periostin levels were associated with more favorable suppressive effects on decreased vital capacity (VC) and DLCO in the treatment group compared with historical controls. Higher binarized levels of total periostin were associated with more favorable suppressive effects on decreased DLCO but not VC. In conclusion, higher periostin levels were independently associated with survival and better therapeutic effectiveness in patients with IPF treated with nintedanib. Periostin assessments may contribute to determining therapeutic strategies for patients with IPF.

A 58-year-old man who had inhaled acetylene while welding 2 and 4 days previously and subsequently developed cough, dyspnea, and fever was referred by his general practitioner. A computed tomography scan showed diffuse ground-glass opacities in both lungs, and bronchoalveolar lavage fluid showed an increased proportion of eosinophils (25 %). Acute eosinophilic pneumonia (AEP) was diagnosed. Inhalation of acetylene was considered to be the most likely cause of AEP. Respiratory symptoms improved rapidly with intravenous corticosteroids. This is a rare case of AEP caused by inhalation of acetylene.

A 76-year-old woman was diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma by upper gastrointestinal endoscopy. She underwent further investigation for concomitant bilateral pleural effusions and right pulmonary consolidation. MALT lymphoma with the t(11; 18)(q21; q21) translocation and API2-MALT1 were detected in pleural fluid. Lymphoma was not histopathologically diagnosed by lung biopsies, but the same translocation was identified in bronchial lavage. MALT lymphoma is often difficult to diagnose by bronchoscopy because of only mild dysplasia. However, present report on using chromosomal translocation analysis from bronchial lavage indicates that such testing may serve as a useful diagnostic adjunct in MALT lymphoma with lung involvement.

Fibrosing interstitial lung diseases (FILDs), e.g., due to idiopathic pulmonary fibrosis (IPF), are chronic progressive diseases with a poor prognosis. The management of these diseases is challenging and focuses mainly on the suppression of progression with anti-fibrotic drugs. Therefore, novel FILD treatments are needed. In recent years, cell-based therapy with various stem cells has been investigated for FILD, and the use of mesenchymal stem cells (MSCs) has been widely reported and clinical studies are also ongoing. Induced pluripotent stem cells (iPSCs) have also been reported to have an anti-fibrotic effect in FILD; however, these have not been as well studied as MSCs in terms of the mechanisms and side effects. While MSCs show a potent anti-fibrotic effect, the possibility of quality differences between donors and a stable supply in the case of donor shortage or reduced proliferative capacity after cell passaging needs to be considered. The application of iPSC-derived cells has the potential to overcome these problems and may lead to consistent quality of the cell product and stable product supply. This review provides an overview of iPSCs and FILD, followed by the current status of cell-based therapy for FILD, and then discusses the possibilities and perspectives of FILD therapy with iPSC-derived cells.

Abstract Marine microplastics are one of the global environmental issues. The present study examined whether rubber tips of artificial sports fields could be marine microplastics. We observed the migration of rubber tips from the artificial turf field to the surrounding ditch connected to sewer pipes and then examined the ingestion of rubber tips using the goldfish Carassius auratus. The rubber tips found in sediments in the ditch suggest that the rubber tips could be sent to the river and released into the ocean. The goldfish ingested rubber tips with or without fish feed, and rubber tips were found in the intestine. However, the fish discharged the rubber tips within 48 h after ingestion. These results indicate that ingestion of the rubber tips was not accidental but an active behavior. Therefore, artificial turf sports fields could be a source of marine microplastics and may cause hazardous effects on wild fishes through ingestion.

A GaN-on-diamond structure is the most promising candidate for improving the heat dissipation efficiency of GaN-based power devices. Room-temperature bonding of GaN and diamond is an efficient technique for fabricating this structure. However, it is extremely difficult to polish diamond to an average roughness (Ra) below 0.4 nm, especially for polycrystalline diamond. In this work, Room-temperature bonding of GaN and rough-surfaced diamond with a SiC layer was successfully achieved by a surface-activated bonding (SAB) method. The diamond surface’s initial Ra value was 0.768 nm, but after deposition of the SiC layer, the Ra decreased to 0.365 nm. The SiC layer formed at the as-bonded GaN/diamond interface was amorphous, with a thickness of about 7 nm. After annealing at 1000-°C, the amorphous SiC layer became polycrystalline, and its thickness increased to approximately 12 nm. These results indicate that the deposition of a SiC layer on diamond can efficiently lower the diamond surface’s roughness and thus facilitate room-temperature bonding.

Abstract Background We conducted a phase II study of carboplatin plus nab‐paclitaxel for the treatment of small cell lung cancer (SCLC) after the failure of a prior standard chemotherapy containing platinum, etoposide, irinotecan, and amrubicin if indicated. Patients with interstitial pneumonia complications were included in the study. Methods Patients received 100 mg/m2 of nab‐paclitaxel weekly (on days 1, 8, and 15) and an AUC 5 of carboplatin on day 1. The study treatment was repeated every 3 weeks until disease progression or the appearance of unacceptable toxicities. The primary endpoint was the objective response rate. Results A total of 21 patients were enrolled, all of whom were eligible for inclusion in the analysis. Twelve patients had pre‐existing interstitial pneumonia. The overall response rate was 19.0% (90% confidence interval [CI]: 6.8%–38.4%). The lower limit of the 90% CI for the response rate did not exceed the prespecified threshold value of 10%. Among the 12 patients with pre‐existing interstitial pneumonia, the response rate was 25%. The median progression‐free survival time was 2.5 months (95% CI: 1.5–3.4 months), and the median survival time was 5.1 months (95% CI: 2.1–8.1 months). Two patients developed interstitial lung disease; both of these patients had pre‐existing interstitial pneumonia. One of the patients died from interstitial lung disease. Conclusion Combination chemotherapy with carboplatin plus nab‐paclitaxel for recurrent SCLC had a modest activity, although the primary study endpoint was not met. Further investigation of this regimen for patients with recurrent SCLC and interstitial pneumonia is warranted.

A new technique of diamond and InGaP room temperature bonding in atmospheric air is reported. Diamond substrate cleaned with H2SO4/H2O2 mixture solution is bonded to InGaP exposed after removing the GaAs layer by the H2SO4/H2O2/H2O mixture solution. The bonding interface is free from interfacial voids and mechanical cracks. An atomic intermixing layer with a thickness of about 8 nm is formed at the bonding interface, which is composed of C, In, Ga, P, and O atoms. After annealing at 400 °C, no exfoliation occurred along the bonding interface. An increase of about 2 nm in the thickness of the atomic intermixing layer is observed, which plays a role in alleviating the thermal stress caused by the difference of the thermal expansion coefficient between diamond and InGaP. The bonding interface demonstrates high thermal stability to device fabrication processes. This bonding method has a large potential for bonding large diameter diamond and semiconductor materials.

Mucosal-associated invariant T (MAIT) cells, a blossoming member of the innate-like T cells, play a pivotal role in host defense through engaging the mucosal immunity. Although it has been suggested that MAIT cells are somehow implicated in the allergic airway inflammation mediated by group 2 innate lymphoid cells (ILC2s) such as asthma, the precise role(s) of MAIT cells in such inflammation has remained elusive. To explore the possible roles of MAIT cells in the inflammation, we examined whether MAIT cells suppressed the production of T helper (Th) 2 and inflammatory cytokines from ILC2s, and constrained the proliferation of ILC2s, both of which are prerequisite for airway inflammation. Given that laboratory mice are poor at MAIT cells, a novel mouse line rich in MAIT cells was used. We found that mice rich in MAIT cells showed alleviated airway inflammation as evidenced by reduced infiltration of the immune cells and hyperplasia in goblet cells in the lung concomitant with compromised production of Th2 and inflammatory cytokines, while wild type mice exhibited severe inflammation upon challenge with the fungal extracts. In vitro coculture experiments using purified ILC2s and MAIT cells unrevealed that cytokine-stimulated MAIT cells suppressed ILC2s to produce the cytokines as well as to proliferate most likely via production of IFN-γ. Furthermore, reconstitution of the allergic airway inflammation in the highly immunocompromised mice showed that ILC2-mediated inflammation was alleviated in mice that received MAIT cells along with ILC2s. We concluded that MAIT cells played a crucial role in suppressing the cytokine-producing capacity of ILC2s and ILC2 proliferation, that ultimately led to decrease in the allergic airway inflammation.The results open up a novel therapeutic horizon in ILC2-mediated inflammatory diseases by modulating MAIT cell activity.

Pulmonary fibrosis is a life-threatening disease that has been attributed to several causes. Specifically, vascular injury is thought to be involved in the pathogenesis of fibrosis. The effects of the antifibrotic drug pirfenidone on angiogenesis have not been fully elucidated. This study aimed to investigate the effects of pirfenidone in human lung fibroblast–endothelial cell co-culture network formation and to analyze the underlying molecular mechanisms. Human lung fibroblasts were co-cultured with human umbilical vein endothelial cells to establish a co-culture network cell sheet. The influence of pirfenidone was evaluated for protective effect on the endothelial network in cell sheets stimulated with transforming growth factor β (TGF-β). Results indicated that TGF-β disrupted the network formation. Pirfenidone and Y27632 (Rho-associated coiled-coil containing protein kinase [Rho-kinase or ROCK] inhibitor) protected against the TGF-β–induced endothelial network disruption. TGF-β activated Rho-kinase signaling in cells composing the co-culture cell sheet, whereas pirfenidone and Y27632 inhibited these effects. In conclusion, TGF-β–induced Rho-kinase activation and disrupted endothelial network formation. Pirfenidone suppressed TGF-β–induced Rho-kinase activity in cell sheets, thereby enabling vascular endothelial cells networks to be preserved in the cell sheets. These findings suggest that pirfenidone has potential vascular network–preserving effect via inhibiting Rho-kinase activity in vascular injury, which is a precursor to pulmonary fibrosis.

Three-dimensional distribution of arsenic (As) dopants at Σ3{111}, Σ9{221}, Σ9{114}, and Σ9{111}/{115} grain boundaries (GBs) in silicon (Si) is examined by correlative analytical methods using atom probe tomography (APT) combined with low-temperature focused ion beam (LT-FIB), scanning transmission electron microscopy, and ab initio calculations. Σ3{111} GBs, consisting of only 6-membered rings with small bond distortions, do not exhibit an apparent As segregation. Meanwhile, it is hypothesized that As atoms would segregate at 5-membered rings in the other GBs via anisotropic bond distortions spontaneously introduced so as to lower the donor level, as Jahn-Teller distortions. In addition, APT combined with LT-FIB suggests preferential As segregation around stretched $$\left\langle {1\overline 1 0} \right\rangle $$ bonds reconstructed in Σ9{114} and Σ9{111}/{115} GBs, that are inevitably introduced in the $$\left\langle {1\overline 1 0} \right\rangle $$ tilt GBs with the tilt angle larger than 70.5°. It is hypothesized that As atoms would form As dimers at stretched $$\left\langle {1\overline 1 0} \right\rangle $$ bonds and the adjacent $$\langle 111\rangle $$ bonds, due to the tendency of As with five valence electrons to form a three-coordinated configuration, which is efficiently attained by an As dimer of a long length. This work provides important insights into As segregation at GBs; it is mainly determined by electronic interactions depending on the characteristics of valence electrons of As atoms, as well as on local bond distortions at GBs, via anisotropic bond distortions and dimerization.

Introduction: Vascular endothelial cell disorders are closely related to cardiovascular disease (CVD) and pulmonary diseases. Abnormal lipid metabolism in the endothelium leads to changes in cell signalling, and the expression of genes related to immunity and inflammation. It is therefore important to investigate the pathophysiology of vascular endothelial disorders in terms of lipid metabolism, using a disease model of endothelium. Methods: Human induced pluripotent stem cell-derived endothelial cells (iECs) were cultured on a matrigel to form an iEC network. Lipids in the iEC network were investigated by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) imaging mass spectrometry (IMS) analysis. Ion fragments obtained by mass spectrometry were analysed using an infusion method, involving precursor ion scanning with fragment ion. Results: The MALDI TOF IMS analysis revealed co-localized intensity of peaks at m/z 592.1 and 593.1 in the iEC network. Tandem mass spectrometry (MS/MS) analysis by MALDI-imaging, in conjunction with precursor ion scanning using an infusion method with lipid extracts, identified that these precursor ions were lysophosphatidylcholine (LPC) (22:5) and its isotype. Conclusion: The MALDI-imaging analysis showed that LPC (22:5) was abundant in an iEC network. As an in vitro test model for disease and potential therapy, present analysis methods using MALDI-imaging combined with, for example, mesenchymal stem cells (MSC) to a disease derived iEC network may be useful in revealing the changes in the amount and distribution of lipids under various stimuli.

This study explored expectations regarding aging among a diverse cohort of undergraduates in Japan. A concurrent mixed methods design was employed with online administration of the Expectations Regarding Aging scale (ERA-12), and open-format and demographic questions among 133 culturally diverse undergraduates in Tokyo. Independent samples t-tests, one-way analysis of variance (ANOVA), descriptive sta­tistics, and thematic analysis were used to explore the data. ERA-12 scores and physical and cognitive function subscale results revealed negative perceptions about the aging process, while scores on the mental health subscale were significantly higher and positive. No significant differences emerged based on gender or cultural background. Qualitative data anal­ysis revealed student awareness of lifestyle influences on health in later life, concerns about current health and risk factors, and potential to tran­scend negative physical changes by finding meaning in other aspects of life. Understanding expectations regarding aging among younger cohorts may inform gerontological education and public health promotion to sup­port a life course approach to healthy aging.

Idiopathic pulmonary fibrosis (IPF) is a representative disease that causes fibrosis of the lungs. Its pathogenesis is thought to be characterized by sustained injury to alveolar epithelial cells and the resultant abnormal tissue repair, but it has not been fully elucidated. IPF is currently difficult to cure and is known to follow a chronic progressive course, with the patient’s survival period estimated at about three years. The disease occasionally exacerbates acutely, leading to a fatal outcome. In recent years, it has become evident that lipid metabolism is involved in the fibrosis of lungs, and various reports have been made at the cellular level as well as at the organic level. The balance among eicosanoids, sphingolipids, and lipid composition has been reported to be involved in fibrosis, with particularly close attention being paid to a bioactive lipid “lysophosphatidic acid (LPA)” and its pathway. LPA signals are found in a wide variety of cells, including alveolar epithelial cells, vascular endothelial cells, and fibroblasts, and have been reported to intensify pulmonary fibrosis via LPA receptors. For instance, in alveolar epithelial cells, LPA signals reportedly induce mitochondrial dysfunction, leading to epithelial damage, or induce the transcription of profibrotic cytokines. Based on these mechanisms, LPA receptor inhibitors and the metabolic enzymes involved in LPA formation are now considered targets for developing novel means of IPF treatment. Advances in basic research on the relationships between fibrosis and lipid metabolism are opening the path to new therapies targeting lipid metabolism in the treatment of IPF.

Abstract StarD7 facilitates phosphatidylcholine (PC) transfer to mitochondria, and is essential for mitochondrial homeostasis. However, the molecular mechanism for PC transfer by protein remains poorly understood. Herein, we describe a putative novel transmembrane (TM) domain C-terminal to the mitochondria-targeting signal (MTS) sequence at the N-terminus of StarD7. The mature form of StarD7 is integrated and/or associated onto the outer leaflet of the outer mitochondrial membrane (OMM) in HEPA-1 and HepG2 cells. A truncated form of StarD7 lacking the TM domain is distributed in the inner space of the mitochondria, and cannot reverse mitochondrial abnormalities, such as complex formation and PC content, when re-expressed in StarD7-KO HEPA-1 cells. Re-expression of wild StarD7 can compensate these mitochondrial functions of StarD7-KO HEPA-1 cells. The precursor form of StarD7 is cleaved between Met76 and Ala77, and Ala77 and Ala78 in the TM domain to produce the mature form. These results suggest that StarD7 is anchored onto the OMM through its N-terminal TM domain, and the C-terminal START domain may extend into the cytoplasm and shuttle PC between the ER and OMM at the ER-mitochondria contact sites.

Abstract Background Intelectin-1 (ITLN-1) is secreted by intestinal goblet cells and detectable in blood. Its expression is increased in IL-13-overexpressing mouse airways. However, its expression and function in human airways is poorly understood. Methods Distal and proximal bronchial epithelial cells (BECs) were isolated from bronchoscopic brushings of disease control (D-CON), COPD, inhaled corticosteroid-treated asthma (ST-Asthma) and inhaled corticosteroid-naïve asthma (SN-Asthma) patients. ITLN-1 mRNA expression in freshly isolated BECs, primary cultured BECs with or without IL-13 and inhibition effects of mometasone furoate (MF) were investigated by quantitative real-time PCR (qPCR). Correlations between ITLN-1 mRNA and Type-2 related parameters (e.g. FeNO, IgE, iNOS, CCL26, periostin and DPP4 mRNA) were analyzed. ITLN-1 protein distribution in asthmatic airway tissue was assessed by immunohistochemistry. Bronchial alveolar lavage (BAL) and serum ITLN-1 protein were measured by ELISA. The effect of recombinant human (rh) ITLN-1 on stimulated production of CXCL10 and phospho(p)-STAT1 expression examined in lung fibroblasts. Results ITLN-1 mRNA was expressed in freshly isolated BECs and was correlated with Type-2 related parameters. ITLN-1 protein was increased in goblet cells in SN-Asthmatics and increased in SN-Asthmatic BAL fluid. There were no any differences in serum ITLN-1 concentration between ST and SN-Asthma. IL-13 enhanced ITLN-1 expression and inhibited by MF from BECs in vitro, while rhITLN-1 inhibited CXCL10 production and p-STAT1 expression in HFL-1 cells. Conclusion ITLN-1 is induced by IL-13 and expressed mainly in goblet cells in untreated asthma where its levels correlate with known Type-2 related parameters. Further, ITLN-1 inhibits Type-1 chemokine expression.

Background and aims In many countries, early detection and diagnosis of autism spectrum disorder is largely dependent on parents’ initial concern with early symptoms of autism spectrum disorder. Previous research on parental perceptions of the autism spectrum disorder diagnostic process indicates that parental satisfaction may be due to either the timing of the diagnostic notification or the provision of post-diagnostic support. The objective of this research is to study the diagnostic notification process and its impact on parents who are informed of their young child’s diagnosis before they notice a problem and whose child undergoes early intervention therapy. Methods Eighty parents of preschool children diagnosed and undergoing early intervention for autism were surveyed to examine their experience of the diagnostic disclosure process. Results Of 68 respondents, 39 (58.2%) approved of the timing of diagnostic notification, while 10 of 13 dissatisfied respondents indicated that the diagnosis was communicated too late. However, there was no correlation between a higher degree of parental satisfaction with the diagnostic notification process and earlier timing of notification. Conclusions Although it is preferable to communicate a diagnosis of childhood autism as soon as possible, findings suggest that a highly individualized approach, allowing a degree of latitude in the timing of notification, may be permissible, depending on the individual case and parental readiness to receive the diagnosis. Implications Findings have clinical implications related to the concept of optimality of diagnostic disclosure as related to the diagnostic notification process, though later notification tends to lead to more dissatisfaction.

We have demonstrated that it is possible to reproducibly quantify hydrogen concentration in the SiN layer of a SiO2/SiN/SiO2 (ONO) stack structure using ultraviolet laser-assisted atom probe tomography (APT). The concentration of hydrogen atoms detected using APT increased gradually during the analysis, which could be explained by the effect of hydrogen adsorption from residual gas in the vacuum chamber onto the specimen surface. The amount of adsorbed hydrogen in the SiN layer was estimated by analyzing another SiN layer with an extremely low hydrogen concentration (

The research discussed in this paper proposed a control method that imparts equivalent friction to electronic power steering (EPS) systems in order to improve the steering feel. In order to impart friction stably, the proposed method uses motor torque rather than mechanical elements to impart friction. First, the effect of friction on the steering system was considered theoretically using simple harmonic motion models, and it was demonstrated theoretically that steering responsiveness could be increased by imparting appropriate friction force to the steering system. Based on the results of this analysis, a target value for equivalent friction force to be imparted by means of EPS control system was formulated. A method of linear approximation of the friction force necessary to realize equivalent friction force based on this target value was proposed. The method was applied in an actual vehicle, and the EPS system configuration necessary for the desired effect to be obtained was examined. It was considered that a system configuration incorporating a steering torque sensor with high torsional rigidity would be necessary, and a control method for imparting equivalent friction force was proposed. Finally, the effectiveness of the proposed method was verified in simulations using a vehicle model and in tests involving an actual vehicle. The vehicle model simulations demonstrated that the application of the proposed method increased steering responsiveness. The vehicle tests verified that the proposed method made it possible to obtain a stable steering feel, and was also effective in improving steering feel.

In this paper, we focused on the fact that the ease of driving changed according to torsional rigidity of the electric power steering system for the purpose of the improvement in control performance of vehicle. First, the influence on transfer characteristics from a steering angle(steering wheel) to front wheel angle(front tires) by torsional rigidity was considered theoretically. As a result, it turned out that a front wheel angle was determined by not only a steering angle but also the influence of the dynamic state of vehicle, and it was shown that the influence of the dynamic state of vehicle can be shut by making steering torsional rigidity into high torsional rigidity. Next, the validity of a theoretical verification was confirmed through numerical simulation of steering correction at the time of a disturbance input. Finally, the lower limit value of torsional rigidity for practical use of a high torsional rigidity steering was determined.

Airway inflammation is accompanied by infiltration of inflammatory cells and an abnormal response of airway smooth muscle. These cells secrete chemokines and express the cell surface chemokine receptors that play an important role in the migration and degranulation of inflammatory cells. Omalizumab is a monoclonal antibody directed against immunoglobulin E, and its blocking of IgE signaling not only reduces inflammatory cell infiltration mediated by the Th2 immune response but also inhibits other immune responses. The chemokine CCL15 is influenced by omalizumab, and the source of CCL15 has been reported to be airway smooth muscle cells and basophils. CCL15 binds to its receptor CCR1, which has been reported to be expressed by various inflammatory cells and also by airway smooth muscle cells. Therefore, CCL15/CCR1 signaling could be a target for the treatment of asthma. We review the role of CCL15 in the pathogenesis of asthma and also discuss the influence of IgE-mediated immunomodulation via CCL15 and its receptor CCR1.

This study explored expectations regarding aging among a diverse cohort of undergraduates in Japan. A concurrent mixed methods design was employed with online administration of the Expectations Regarding Aging scale (ERA-12), and open-format and demographic questions among 133 culturally diverse undergraduates in Tokyo. Independent samples t-tests, one-way analysis of variance (ANOVA), descriptive statistics, and thematic analysis were used to explore the data. ERA-12 scores and physical and cognitive function subscale results revealed negative perceptions about the aging process, while scores on the mental health subscale were significantly higher and positive. No significant differences emerged based on gender or cultural background. Qualitative data analysis revealed student awareness of lifestyle influences on health in later life, concerns about current health and risk factors, and potential to transcend negative physical changes by finding meaning in other aspects of life. Understanding expectations regarding aging among younger cohorts may inform gerontological education and public health promotion to support a life course approach to healthy aging. [ABSTRACT FROM AUTHOR]

Graphite-reinforced 5083 aluminum matrix composites were successfully fabricated via friction stir processing. The graphite-reinforced aluminum alloy sheet sintered at 550°C in a vacuum atmosphere was applied as a reinforcement. Grain refinement and many minute aluminum carbides (Al4C3) were observed in the composites fabricated. The tensile strength of the composites fabricated with the 550°C sintered sheets considerably increased by 64 percent, and the sliding wear characteristics of the composites were appreciably improved compared with that of the base material. [ABSTRACT FROM AUTHOR]

[Introduction] The number of prior studies has reported that mental health problems related to Japanese school teachers have increased sharply during the last two decades, and have become a severe problem for school administration, as well as Japanese society. Therefore, this study is to develop a high school teacher-specific version of four stress-related scales, and to examine the hypothesis, based on the school stress model that stressors, self-efficacy, and coping predict teachers stress reactions. [Methods] The sample of this study included 368 Japanese high school teachers (248 male and 120 female, mean age =42.2, SD=8.2). The participants voluntarily responded to a questionnaire survey that was composed of items in the teacher-specific stressor scale, the self-Efficacy scale, the coping scale, and the stress reaction scale. Exploratory factor analyses, confirmatory factor analyses, and reliability analyses were conducted to develop the four original scales・ The hierarchical regression analyses were performed to confirm the relationships between the four scales.【Results】 The results of exploratory factor analyses indicated that the Stressor Scale, the Self-Efficacy Scale, the Coping Scale, and the Stress Reaction Scale consisted of two factors. All the subscales had satisfactory internal consistency as indicated by Cronbach's alpha reliabilities, and fit indices of structural validities. The results of hierarchical regression analyses indicated that gender, stressors, self-efficacy, and coping, predicted stress reactions. Contrary to the hypothesis of this study, both approach and avoidance coping were associated with higher stress levels. Moreover, there was a limited impact of self-efficacy on the relationship between the stressor and the stress reaction, whereas coping failed to moderate the impact of stressors on stress reactions. 【Conclusion】 These results suggest that mental health interventions for reducing teachers' stress burden should focus on addressing the causes of stress, as well as enhancing the teachers' self-efficacy. Furthermore, more targeted support is needed for female teachers given their reports of elevated stress levels. [ABSTRACT FROM AUTHOR]

Population aging may increase chronic disease prevalence in Japan without widespread health behavior change. Walking and sitting are common behaviors that are amenable to intervention. This study examined age-related variations in daily walking and sitting time among middle-aged and older Japanese who live in urban areas. An online survey including validatedmeasureswas administered with a representative sample of 4,000 middle-aged and older adults from five large cities. Walking time showed a significant association with age, and the oldest cohortwalked 25%more per day compared to those in early middle age, F (3, 3996) = 8.04, p < .001. Sitting time showed a significant decline with age, F (3, 3996) = 3.83, p < .001, although gender differences were evident among the oldest cohorts. Early middle age (45-54 years) appears to be associated with lesswalking and more sitting time in Japan. This study has implications for healthy aging and successful transitions to retirement in Japan. Occupational and environmental interventions are recommended to facilitate increases in activity and reductions in sedentary behavior. [ABSTRACT FROM AUTHOR]

To evaluate dislocations induced by neutron irradiation, we developed a weak-beam scanning transmission electron microscopy (WB-STEM) system by installing a novel beam selector, an annular detector, a high-speed CCD camera and an imaging filter in the camera chamber of a spherical aberration-corrected transmission electron microscope. The capabilities of the WB-STEM with respect to wide-view imaging, real-time diffraction monitoring and multi-contrast imaging are demonstrated using typical reactor pressure vessel steel that had been used in an European nuclear reactor for 30 years as a surveillance test piece with a fluence of 1.09 × 1020 neutronscm-2. The quantitatively measured size distribution (average loop size = 3.6 ± 2.1 nm), number density of the dislocation loops (3.6 × 1022m-3) and dislocation density (7.8 × 1013mm-3) were carefully compared with the values obtained via conventional weak-beam transmission electron microscopy studies. In addition, cluster analysis using atom probe tomography (APT) further demonstrated the potential of the WB-STEM for correlative electron tomography/APT experiments. [ABSTRACT FROM AUTHOR]

Using the atom probe tomography, transmission electron microscopy, and ab initio calculations, we investigate the three-dimensional distributions of oxygen atoms segregating at the typical large-angle grain boundaries (GBs) (Σ3{111}, Σ9{221}, Σ9{114}, Σ9{111}/{115}, and Σ27{552} in Czochralski-grown silicon ingots. Oxygen atoms with a covalent radius that is larger than half of the silicon's radius would segregate at bond-centered positions under tensile stresses above about 2 GPa, so as to attain a more stable bonding network by reducing the local stresses. The number of oxygen atoms segregating in a unit GB area NGB (in atoms/nm2) is hypothesized to be proportional to both the number of the tensilely-stressed positions in a unit boundary area nbc and the average concentration of oxygen atoms around the boundary [Oi] (in at. %) with NGB∼50nbc[Oi]. This indicates that the probability of oxygen atoms at the segregation positions would be, on average, fifty times larger than in bond-centered positions in defect-free regions. [ABSTRACT FROM AUTHOR]

Three-dimensional distribution of impurity atoms was determined at functional ∑5{013} and smallangle grain boundaries (GBs) in as-grown mono-like silicon crystals by atom probe tomography combined with transmission electron microscopy, and it was correlated with the recombination activity of those GBs, CGB, revealed by photoluminescence imaging. Nickel (Ni), copper (Cu), and oxygen atoms preferentially segregated at the GBs on which arrays of dislocations existed, while those atoms scarcely segregated at ∑5{013} GBs free from dislocations. Silicides containing Ni and Cu about 5nm in size and oxides about 1 nm in size were formed along the dislocation arrays on those GBs. The number of segregating impurity atoms per unit GB area for Ni and that for Cu, NNi and NCu, were in a trade-off correlation with that for oxygen, NO, as a function of CGB, while the sum of those numbers was almost constant irrespective of the GB character, CGB, and the dislocation density on GBs. CGB would be explained as a linear combination of those numbers: CGB (in %) ~400(0.38NO+NNi+NCu) (in atoms/nm²). The GB segregation of oxygen atoms would be better for solar cells, rather than that of metal impurities, from a viewpoint of the conversion efficiency of solar cells. [ABSTRACT FROM AUTHOR]

We have demonstrated that it is possible to reproducibly quantify hydrogen concentration in the SiN layer of a SiO2/SiN/SiO2 (ONO) stack structure using ultraviolet laser-assisted atom probe tomography (APT). The concentration of hydrogen atoms detected using APT increased gradually during the analysis, which could be explained by the effect of hydrogen adsorption from residual gas in the vacuum chamber onto the specimen surface. The amount of adsorbed hydrogen in the SiN layer was estimated by analyzing another SiN layer with an extremely low hydrogen concentration (<0.2 at. %). Thus, by subtracting the concentration of adsorbed hydrogen, the actual hydrogen concentration in the SiN layer was quantified as approximately 1.0 at. %. This result was consistent with that obtained by elastic recoil detection analysis (ERDA), which confirmed the accuracy of the APT quantification. The present results indicate that APT enables the imaging of the three-dimensional distribution of hydrogen atoms in actual devices at a sub-nanometer scale. [ABSTRACT FROM AUTHOR]

Background: Type 2 helper T-cell cytokines including IL-13 play a central role in the pathogenesis of bronchial asthma (BA). During the course of our research, our attention was drawn to dipeptidyl peptidase-4 (DPP4) as one of the molecules that were induced from bronchial epithelial cells (BECs) by IL-13 stimulation. DPP4 could become a new biomarker or therapeutic target. The aim of this study was to investigate the expression of DPP4 in the asthmatic airway, and its role in the pathophysiology of asthma.Methods: BECs were isolated from patients with inhaled corticosteroid-treated asthma (stBA) and inhaled corticosteroid-naïve asthma (snBA) using bronchoscopy. DPP4 mRNA expression in freshly isolated BECs and primary cultured BECs with or without IL-13 stimulation was investigated by microarray analysis and quantitative real-time PCR (qPCR). The distribution of DPP4 protein was determined by immunostaining of transbronchial lung biopsy specimens from asthma patients. The effect of recombinant human (rh) DPP4 on the proliferation of lung fibroblasts (HFL-1) and bronchial smooth muscle cells (BSMCs) was examined, as well as its effect on the production of fibronectin (FN).Results: DPP4 mRNA was strongly expressed in freshly isolated BECs in snBA, and its expression was significantly enhanced by IL-13 stimulation. DPP4 mRNA expression in BECs of snBA significantly correlated with exhaled nitric oxide. Biopsied tissues of the asthmatic airway revealed strong expression of DPP4 protein in BECs from snBA subjects. rhDPP4 stimulated the proliferation of HFL-1 and BSMCs, and it also enhanced production of FN from these airway cells.Conclusion: DPP4 may be involved in the pathologic features of asthmatic airway inflammation and cell proliferation and FN production. [ABSTRACT FROM AUTHOR]

Three-dimensional distribution of oxygen atoms at small-angle tilt boundaries (SATBs) in Czochralski-grown p-type silicon ingots was investigated by atom probe tomography combined with transmission electron microscopy. Oxygen gettering along edge dislocations composing SATBs, post crystal growth, was observed. The gettering ability of SATBs would depend both on the dislocation strain and on the dislocation density. Oxygen atoms would agglomerate in the atomic sites under the tensile hydrostatic stress larger than about 2.0GPa induced by the dislocations. It was suggested that the density of the atomic sites, depending on the tilt angle of SATBs, determined the gettering ability of SATBs. [ABSTRACT FROM AUTHOR]

Background: Pulmonary alveolar proteinosis (PAP) is a rare disease occurred by idiopathic (autoimmune) or secondary to particle inhalation. The in-air microparticle induced X-ray emission (in-air micro-PIXE) system performs elemental analysis of materials by irradiation with a proton microbeam, and allows visualization of the spatial distribution and quantitation of various elements with very low background noise. The aim of this study was to assess the secondary PAP due to inhalation of harmful particles by employing in-air micro-PIXE analysis for particles and intracellular iron in parafin-embedded lung tissue specimens obtained from a PAP patient comparing with normal lung tissue from a non-PAP patient. The iron inside alveolar macrophages was stained with Berlin blue, and its distribution was compared with that on micro-PIXE images.Results: The elements composing particles and their locations in the PAP specimens could be identified by in-air micro-PIXE analysis, with magnesium (Mg), aluminum (Al), silicon (Si), phosphorus (P), sulfur (S), scandium (Sc), potassium (K), calcium (Ca), titanium (Ti), chromium (Cr), copper (Cu), manganase (Mn), iron (Fe), and zinc (Zn) being detected. Si was the major component of the particles. Serial sections stained by Berlin blue revealed accumulation of sideromacrophages that had phagocytosed the particles. The intracellular iron content of alveolar macrophage from the surfactant-rich area in PAP was higher than normal lung tissue in control lung by both in-air micro-PIXE analysis and Berlin blue staining.Conclusion: The present study demonstrated the efficacy of in-air micro-PIXE for analyzing the distribution and composition of lung particles. The intracellular iron content of single cells was determined by simultaneous two-dimensional and elemental analysis of paraffin-embedded lung tissue sections. The results suggest that secondary PAP is associated with exposure to inhaled particles and accumulation of iron in alveolar macrophages. [ABSTRACT FROM AUTHOR]

The Adacolumn is an adsorptive-type extracorporeal device, which is filled with cellulose diacetate beads that selectively adsorb granulocytes and monocytes. Patients with severe persistent asthma experience highly variable continuous symptoms and severe exacerbations in spite of medication based on inhaled glucocorticosteroids. Granulocyte and monocyte adsorption apheresis using extracorporeal circulation through the Adacolumn was performed in nine patients with severe persistent asthma. The extracorporeal circulation through the Adacolumn was performed once a week for 5 weeks. We were able to perform this therapy without any severe adverse effects in all patients, although one patient complained of general fatigue just after the circulations. In six of the nine patients, the increase in peak expiratory flow (PEF) was more than 50 mL/min. The average increase in morning PEF was 23.3% while that in the evening PEF was 26.4% after the therapy. This therapy was not harmful for patients with severe persistent asthma. A placebo-controlled study will be desired to evaluate the efficacy of this nonpharmacological strategy accurately. [ABSTRACT FROM AUTHOR]

Most studies on the frequency of autism have had methodological problems. Most notable of these have been differences in diagnostic criteria between studies, degree of cases overlooked by the initial screening, and type of measurement. This study aimed to replicate the first report on childhood autism to address cumulative incidence as well as prevalence, as defined in the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10) Diagnostic Criteria for Research. Here, the same methodological accuracy (exactness of a measurement to the true value) as the first study was used, but population size was four times larger to achieve greater precision (reduction of random error). A community-oriented system of early detection and early intervention for developmental disorders was established in the northern part of Yokohama, Japan. The city's routine health checkup for 18-month-old children served as the initial mass screening, and all facilities that provided child care services aimed to detect all cases of childhood autism and refer them to the Yokohama Rehabilitation Center. Cumulative incidence up to age 5 years was calculated for childhood autism among a birth cohort from four successive years (1988 to 1991). Cumulative incidence of childhood autism was 27.2 per 10 000. Cumulative incidences by sex were 38.4 per 10 000 in males, and 15.5 per 10 000 in females. The male:female ratio was 2.5:1. The proportions of children with high-functioning autism who had Binet IQs of 70 and over and those with Binet IQs of 85 and over were 25.3% and 13.7% respectively. Data on cumulative incidence of childhood autism derived from this study are the first to be drawn from an accurate, as well as precise, screening methodology. [ABSTRACT FROM AUTHOR]

Direct bonding of diamond and Cu was successfully conducted by the surface activated bonding method at room temperature. The structure of the diamond/Cu bonding interface was investigated by transmission electron microscopy and electron energy-loss spectroscopy. The effect of heat treatment temperature on the interface structure was also investigated. A 4-nm-thick damaged layer was formed at the as-bonded interface, and the damaged layer's thickness decreased with an annealing temperature rise. It was found that the atomic ratio of sp2 bonding in the bonding interface was larger than that of the diamond separated from the interface by approximately 50 nm, which indicates that the damaged layer was composed of amorphous carbon or graphite and diamond. After annealing at 700 °C, a composite layer about 2 nm thick was observed at the interface. There were no nano-voids or micro-cracks observed at the interface with annealing at a temperature as high as 700 °C. These results indicate that the diamond/Cu bonding interface has high thermal stability and can withstand the temperature rise of power devices during operation. [ABSTRACT FROM AUTHOR]

We have shown that the structural and compositional properties of semiconductor interfaces fabricated by surface activated bonding (SAB) would be modified during focused ion beam (FIB) processes operated at room temperature (RT), especially for wide band-gap materials, and such a modification can be suppressed by FIB processes operated at lower temperatures. During FIB processes operated at RT, SAB-fabricated Si/Si and GaAs/GaAs interfaces are amorphized along the interfaces, even at the internal locations deeper than the penetration depth of the FIB, and the impurity distribution across the interfaces is modified. This phenomenon is presumably due to the atomic diffusion assisted by the point defects that are introduced by FIB irradiation. By using FIB processes operated at −150 °C, the FIB-induced atomic diffusion would be ignored for Si/Si interfaces. Meanwhile, the diffusion would be still effective for GaAs/GaAs interfaces, presumably due to the effects of recombination-enhanced defect motion under FIB irradiation. [ABSTRACT FROM AUTHOR]

The effect of P or B predoping on As diffusion in polycrystalline Si was investigated by atom probe tomography. In all samples, a high concentration of As was found at grain boundaries, indicating that such boundaries are the main diffusion path. However, As grain-boundary diffusion was suppressed in the B-doped sample and enhanced in the P-doped sample. In a sample codoped with both P and B, As diffusion was somewhat enhanced, indicating competition between the effects of the two dopants. The results suggest that As grain-boundary diffusion can be controlled by varying the local concentration of P or B. [ABSTRACT FROM AUTHOR]

The successful formation of abrupt phosphorus (P) δ-doping profiles in germanium (Ge) is reported. When the P δ-doping layers were grown by molecular beam epitaxy (MBE) directly on Ge wafers whose surfaces had residual carbon impurities, more than a half the phosphorus atoms were confined successfully within a few nm of the initial doping position even after the growth of Ge capping layers on the top. On the other hand, the same P layers grown on Ge buffer layers that had much less carbon showed significantly broadened P concentration profiles. Current–voltage characteristics of Au/Ti/Ge capping/P δ-doping/n-Ge structures having the abrupt P δ-doping layers with carbon assistance showed excellent ohmic behaviors when P doses were higher than 1 × 1014 cm−2 and the capping layer thickness was as thin as 5 nm. Therefore, the insertion of carbon around the P doping layer is a useful way of realizing ultrashallow junctions in Ge. [ABSTRACT FROM AUTHOR]

The impact of carbon (C) co-implantation on boron (B) activation in crystalline silicon was investigated. The detailed distribution of B and C atoms and B activation ratios dependent on the C ion-implantation energies were examined based on three-dimensional spatial mappings of B and C obtained by atom probe tomography and from depth profiles of their concentrations from secondary ion mass spectrometry and depth profiles of carrier concentrations with spreading resistance measurements. At all C implantation energies (8, 15, and 30 keV), B out-diffusion during activation annealing was reduced, so that more B atoms were observed in the C co-implanted samples. The carrier concentration was decreased throughout the entire implanted region for C implantation energies of 15 and 30 keV, although it was only increased at greater depths for C co-implantation at 8 keV. Two different effects of C co-implantation, (I) reduction of B out-diffusion and (II) influence of B activation, were confirmed. [ABSTRACT FROM AUTHOR]