Co-generation of palladium nanoparticles and phosphate supported on metal-organic frameworks as hydrogenation catalysts.

In this study, we demonstrated the direct synthesis of sodium dihydrogen phosphate (PA) containing palladium nanoparticles (PdNPs) supported on a metal-organic framework (MOF). The resulting composite containing PA molecules coexisting with PdNPs demonstrated improved hydrogenation catalytic performance compared to the composites without PA.

Decreased Interoceptive Awareness as a Risk Factor for Moderate to Severe Pain in Japanese Full-Time Workers: A Longitudinal Cohort Study.

Interoceptive awareness, the conscious perception of internal bodily states, is a key construct of mind-body interaction. Decreases in interoceptive awareness, as measured by the Multidimensional Assessment of Interoceptive Awareness (MAIA), are found in chronic pain patients. In this study, we explored whether a specific aspect of interoceptive awareness is a risk for the onset and chronicity of pain. A longitudinal cohort study was conducted in 2018 and 2020 among a sample of full-time workers in an industrial manufacturing company in Japan. Participants completed a questionnaire on pain intensity, MAIA, exercise habits, kinesiophobia, psychological distress and work stress. Principal component analyses using the MAIA identified two principal components: self-control and emotional stability. Low emotional stability was associated with the prevalence of moderate to severe pain in 2020 among people with mild or no pain in 2018 (p < 0.01). Lack of exercise habits were associated with the prevalence of moderate to severe pain in 2020 among people with pain in 2018 (p < 0.01). Furthermore, exercise habits were associated with reduction in kinesiophobia among people with moderate to severe pain in 2018 (p = 0.047). Overall, these findings indicate that low emotional stability may be a risk for the onset of moderate to severe pain; lack of exercise habits may sustain kinesiophobia and be a risk for the chronicity of pain.

Direct generation of polypyrrole-coated palladium nanoparticles inside a metal-organic framework for a semihydrogenation catalyst.

Herein, the direct synthesis of polypyrrole (PPy)-coated palladium nanoparticles (PdNPs) inside a metal-organic framework (MIL-101) was successfully demonstrated. Owing to the PPy coating of PdNPs, the resulting composites exhibited higher semihydrogenation capability (selectivity: up to 96%) than the analog composite without PPy coating.

Two-Dimensional Metal-Organic Framework-Based Cellular Scaffolds with High Protein Adsorption, Retention, and Replenishment Capabilities.

Metal-organic frameworks (MOFs) are porous materials with adsorption, storage, and separation capabilities due to their high specific surface areas and large pore volumes. MOFs are thus used in biomedical applications, and MOF nanoparticles have been widely studied as nanocarriers for drug delivery systems. Several research groups recently reported that specific MOF nanoparticles can adsorb and retain proteins, suggesting to us that MOF nanoparticles may have advantages as novel cell culture scaffolds. However, MOF nanoparticles cannot be used as two-dimensional scaffolds for cells. We therefore established a bottom-up technique to construct two-dimensional MOFs [MIL-53 (Al)] on polymer films. The developed two-dimensional MIL-53 (Al) film [fMIL-53 (Al)] exhibited high serum protein adsorption, retention, and replenishment capabilities as compared to conventional cell culture scaffolds. ß-Galactosidase, used as a model protein, adsorbed on fMIL-53 (Al) exhibited original enzymatic activity, indicating that proteins are not denatured during the adsorption process. The viability of mouse myoblast cells (C2C12) cultured on fMIL-53 (Al) was 100%, indicating the cell compatibility of fMIL-53 (Al). Importantly, C2C12 cells cultured on serum protein-preadsorbed fMIL-53 (Al) exhibited excellent long-term adhesion, morphology, and proliferation even in a medium lacking serum proteins, demonstrating an important advantage of fMIL-53 (Al) as a cell culture scaffold, given that conventional cell culture scaffolds typically require a serum-containing medium to support stable cell adhesion and proliferation. To our knowledge, this is the first report regarding the application of MOFs as cell culture scaffolds and will serve as a starting point for studying two- and three-dimensional MOF-based cellular scaffolds for cell culture systems and for in vitro and in vivo tissue engineering.

Clinical and virological outcomes with baloxavir compared with oseltamivir in pediatric patients aged 6 to < 12 years with influenza: an open-label, randomized, active-controlled trial protocol.

BACKGROUND: Children with influenza virus infections are prone to complications and are common sources of influenza transmission. Baloxavir marboxil inhibits cap-dependent endonuclease and was approved for influenza treatment in adolescent, adult, and pediatric patients in Japan. The miniSTONE-2 study included pediatric patients with influenza (1 to < 12 years) and demonstrated similar median times to alleviation of signs and symptoms of influenza with a single dose of baloxavir granules (weight < 20 kg: 2 mg/kg, ≥ 20 kg: 40 mg) and oseltamivir. Although the baloxavir dose in miniSTONE-2 was higher than the Japanese-approved dose, baloxavir exposure in miniSTONE-2 was similar to Japanese pediatric patients who receive the Japanese-approved dose. This study will be the first randomized active-controlled study in pediatric patients with influenza using the Japanese-approved dose of baloxavir. METHODS: This is a multicenter, open-label, randomized, active-controlled trial in which 200 Japanese subjects aged 6 to < 12 years with influenza virus infection are randomly allocated (2:1) to a single dose of baloxavir at the approved dose in Japan (weight ≥ 10 to < 20 kg: 10 mg, ≥ 20 to < 40 kg: 20 mg, ≥ 40 kg: 40 mg) or oseltamivir twice daily for 5 days. The primary clinical endpoint is the time to illness alleviation of influenza, from administration of baloxavir or oseltamivir until the following criteria were met and sustained for at least 21.5 h (24 h-10%): cough and nasal discharge/nasal congestion rated as absent or mild axillary body temperature < 37.5 °C. The primary analysis population is the intention-to-treat infected population, which includes all pediatric subjects who receive at least one dose of study drug and have confirmed influenza virus infection by reverse transcription-polymerase chain reaction. The safety population includes all subjects who receive at least one dose of study drug. DISCUSSION: No comparative studies have been conducted to confirm the efficacy and safety of baloxavir versus a comparator in pediatric patients with influenza infection in Japan. The outcomes from this trial will provide evidence on the efficacy and safety of baloxavir as an antiviral treatment option for Japanese pediatric patients with influenza infection. Trial registration Japan Registry of Clinical Trials: jRCTs011200011. Registered November 2020. ( https://rctportal.niph.go.jp/en/ ).

Adaptation of the Compensatory Stepping Response Following Predictable and Unpredictable Perturbation Training.

BACKGROUND: Effective training of the backward step response could be beneficial to improve postural stability and prevent falls. Unpredicted perturbation-based balance training (PBT), widely known as compensatory-step training, may enhance the fear of falling and the patterns of postural muscle co-contraction. Contrastingly, PBT with predictable direction or both direction and timing would suppress the fear and the co-contraction patterns during training, but the efficacy of predictable PBT for unpredictable perturbations is still unknown. OBJECTIVE: To compare the adaptation effects of compensatory-step training with and without predictable perturbations on backward stepping against unpredictable perturbations. METHODS: Thirty-three healthy young adults were randomly assigned to one of the following step training groups: Unpredicted, Predicted, and Self-initiated. In training sessions, participants were perturbed to induce a compensatory step with (Predicted group) or without (Unpredicted group) knowledge of the perturbation's direction or while knowing both the direction and timing of the perturbation (Self-initiated group). In test sessions (pre- and post-training), participants were instructed to recover their postural stability in response to an unpredicted perturbation. The margin of stability (MOS), center of mass (COM) shift, and step characteristics were measured during a backward step in both test and training sessions. RESULTS: All three groups showed a significant increase in the step length and velocity in the post-training sessions compared to those in the pre-training sessions. Moreover, in the Unpredicted and Predicted groups, but not in the Self-initiated group, the MOS at step contact was significantly increased following the training session. In addition, the Self-initiated group showed a significant increase in COM shift at 50 ms after slip onset during training compared to the Unpredicted and Predicted groups. CONCLUSION: Unpredicted and predicted PBT improve step characteristics during backward stepping against unpredictable perturbations. Moreover, the unpredictable PBT and PBT with direction-predictable perturbations enhance the feedback postural control reflected as the postural stability at step contact.

Association of work performance and interoceptive awareness of 'body trusting' in an occupational setting: a cross-sectional study.

OBJECTIVES: Work performance has been known to be influenced by both psychological stress (mind) and physical conditions (body). The aim of this study was to investigate the association between work performance and 'body trusting', which is a dimension of interoceptive awareness representing mind-body interactions. METHODS: A cross-sectional study was conducted among a sample of workers in an industrial manufacturing company in Japan. Participants were assessed with a self-reported questionnaire including evaluations of work performance, body trusting, psychological distress, pain persistence, workplace and home stressors, and workaholism. Participants' sociodemographic, health and lifestyle characteristics were collected from their annual health check data. The association between work performance and body trusting was examined using multivariable regression analyses in the overall sample and in a subsample of people with pain. RESULTS: A total of 349 workers participated in the study. A significant association between work performance and body trusting was observed, with higher body trusting representing higher work performance. The association was significant after controlling for psychological distress, workplace and home stress, workaholism and participants' characteristics (p<0.001). Compared with people without pain (n=126, 36.1%), people with pain (n=223, 63.9%) showed less body trusting, which was associated with decreased work performance after controlling for pain-related variables (p<0.001). CONCLUSIONS: Workers with higher body trusting showed higher work performance, even after controlling for various influencing factors. Body trusting may be an important target to promote work performance and to prevent loss of performance induced by health problems.

Inhibited autonomy for promoting physical health: qualitative analysis of narratives from persons living with severe mental illness.

BACKGROUND: Autonomy is a key factor in the reduction of inequitable physical healthcare among people with severe mental illness compared with the general population.AimsTo clarify the critical mechanism underlying autonomy in physical health promotion based on the perspectives of people with severe mental illness. METHOD: We employed a conventional content analysis of narrative data from the Healthy Active Lives in Japan (HeAL Japan) workshop meetings. RESULTS: 'Inhibited autonomy' was extracted as a central component and shaped by the users' experiences, both in a healthcare setting and in real life. This component emerged based on the lack of an empowerment mechanism in psychiatric services. CONCLUSIONS: A barrier to the encouragement of autonomy in physical health promotion was found in current psychiatric services. An effective strategy should be explored to foster an empowerment mechanism in psychiatric and mental health services.Declaration of interestNone.

The course of chronic and delayed onset of mental illness and the risk for suicidal ideation after the Great East Japan Earthquake of 2011: A community-based longitudinal study.

This study investigated how the course of a mental illness is distributed and evaluated the risk factors and suicidality of chronic and delayed onset mental illness after the Great East Japan Earthquake. The first, second, and third waves of this study were conducted in 2012, 2013, and 2014, respectively. Psychological distress, suicidal ideation, and socio-demographics were assessed by a self-report questionnaire for affected residents (N = 1473; 768 females, 52.1%; average age = 66.3 years, ranged from 20 to 89 years). Prevalence of mental illness was 10.0%, 14.7%, and 11.8% in the first, second, and third waves, respectively. Prevalence of mental illness for three years was found to be 21.4% and of remission, chronic, and delayed-onset course was 5.0% (2.9-7.1%), 3.6% (1.6-5.8%), and 6.2% (4.2-8.4%), respectively. Psychological distress and serious damage to their homes in the first wave predicted chronic course. Psychological distress in the first wave, living at temporary housing, and unemployment in the third wave increased risk for delayed onset. Among the participants, 9.8% reported suicidal ideation. Chronic or delayed onset course showed a higher risk of suicidal ideation. Many residents, who showed high risk of suicidality, still suffer from mental illness requiring housing, occupation, and psychological support.

Adaptation effects in static postural control by providing simultaneous visual feedback of center of pressure and center of gravity.

BACKGROUND: The benefit of visual feedback of the center of pressure (COP) on quiet standing is still debatable. This study aimed to investigate the adaptation effects of visual feedback training using both the COP and center of gravity (COG) during quiet standing. METHODS: Thirty-four healthy young adults were divided into three groups randomly (COP + COG, COP, and control groups). A force plate was used to calculate the coordinates of the COP in the anteroposterior (COPAP) and mediolateral (COPML) directions. A motion analysis system was used to calculate the coordinates of the center of mass (COM) in both directions (COMAP and COMML). The coordinates of the COG in the AP direction (COGAP) were obtained from the force plate signals. Augmented visual feedback was presented on a screen in the form of fluctuation circles in the vertical direction that moved upward as the COPAP and/or COGAP moved forward and vice versa. The COP + COG group received the real-time COPAP and COGAP feedback simultaneously, whereas the COP group received the real-time COPAP feedback only. The control group received no visual feedback. In the training session, the COP + COG group was required to maintain an even distance between the COPAP and COGAP and reduce the COGAP fluctuation, whereas the COP group was required to reduce the COPAP fluctuation while standing on a foam pad. In test sessions, participants were instructed to keep their standing posture as quiet as possible on the foam pad before (pre-session) and after (post-session) the training sessions. RESULTS: In the post-session, the velocity and root mean square of COMAP in the COP + COG group were lower than those in the control group. In addition, the absolute value of the sum of the COP - COM distances in the COP + COG group was lower than that in the COP group. Furthermore, positive correlations were found between the COMAP velocity and COP - COM parameters. CONCLUSIONS: The results suggest that the novel visual feedback training that incorporates the COPAP-COGAP interaction reduces postural sway better than the training using the COPAP alone during quiet standing. That is, even COPAP fluctuation around the COGAP would be effective in reducing the COMAP velocity.

Mental Health Problems in a Community After the Great East Japan Earthquake in 2011: A Systematic Review.

INTRODUCTION: On March 11, 2011, the Great East Japan Earthquake caused a tsunami and led to the collapse of the Fukushima-Daiichi Nuclear Power Plant, thus severely damaging the surrounding area. METHODS: A systematic review was conducted in March 2015 with the following objectives: (1) to clarify the type, severity, and prevalence of mental health problems in the areas affected by the disaster, (2) to investigate trends in mental health problems over time, (3) to reveal demographic and socio-environmental characteristics associated with the post-disaster risk for developing mental health problems, and (4) to examine the impact of this natural disaster on the mental health of people in Fukushima. RESULTS: Forty-two papers were included in this review. The reported prevalence of posttraumatic stress reaction exceeded 10% in all studies. While some longitudinal studies observed an improvement in posttraumatic stress reaction over time, none reported a decrease in depression. Most risk factors for mental health problems were related to resettlement of daily lives, preexisting illnesses, and social networks. Overall, the reported prevalence of posttraumatic stress reaction seemed to be higher in Fukushima than in other affected areas. CONCLUSION: Given that some mental health problems had not improved even two years after the disaster occurred, long-term mental health support is required for people in the affected area. Our finding that mental health problems seemed to be more severe in residents of Fukushima than among those in other areas suggests that residents in this prefecture require special care.

Genomewide identification of target genes of histone methyltransferase dG9a during Drosophila embryogenesis.

Post-translational modification of the histone plays important roles in epigenetic regulation of various biological processes. Among the identified histone methyltransferases (HMTases), G9a is a histone H3 Lys 9 (H3K9)-specific example active in euchromatic regions. Drosophila G9a (dG9a) has been reported to feature H3K9 dimethylation activity in vivo. Here, we show that the time required for hatching of a homozygous dG9a null mutant and heteroallelic combination of dG9a null mutants is delayed, suggesting that dG9a is at least partially responsible for progression of embryogenesis. Immunocytochemical analyses of the wild-type and the dG9a null mutant flies indicated that dG9a localizes in cytoplasm up to nuclear division cycle 7 where it is likely responsible for di-methylation of nucleosome-free H3K9. From cycles 8-11, dG9a moves into the nucleus and is responsible for di-methylating H3K9 in nucleosomes. RNA-sequence analysis utilizing early wild-type and dG9a mutant embryos showed that dG9a down-regulates expression of genes responsible for embryogenesis. RNA fluorescent in situ hybridization analysis further showed temporal and spatial expression patterns of these mRNAs did not significantly change in the dG9a mutant. These results indicate that dG9a controls transcription levels of some zygotic genes without changing temporal and spatial expression patterns of the transcripts of these genes.

[Primary Sjögren's syndrome with lymphocytic interstitial pneumonia, autoimmune hemolytic anemia and an endobronchial amyloid nodule].

A 73-year-old woman was admitted to our hospital for examination of anemia, dry feeling of oral and eyes with chest abnormal shadow in October, 1999. Chest radiograph showed interstitial shadows difference and CT showed small nodular opacities in both lung fields. Laboratory examination showed direct Coombs test was positive, and the serum levels of indirect bilirubin and haptoglobin were elevated. Anti-SS-A antibody and anti-SS-B antibody were positive with hypergammaglobulinemia. The serum levels of SP-D and KL-6 were elevated. Lip biopsy showed atrophy and lymphocyte infiltration of the salivary glands. According to these findings, she was diagnosed as primary Sjögren's syndrome with autoimmune hemolytic anemia. In addition, bronchoscopic examination showed an endobronchial polyp in the right B8, and the biopsy specimen showed AL type amyloid deposits. In order to obtain pathological diagnosis of lung lesions, we performed lung biopsy by video-assisted thoracoscopic surgery. The biopsy specimen showed severe infiltration of lymphocytes and the plasma cells around peribronchiole with lymphoepithelial lesions, suggesting malignant lymphoma. However, immunohistochemistry did not show monoclonal profile and Southern blot hybridization assay demonstrated no rearrangement of JH gene. Lung lesions were diagnosed as lymphocytic interstitial pneumonia due to Sjögren's syndrome. Steroid therapy was performed and followed by improvement of anemia and pulmonary lesions. Malignant lymphoma has not been involved for eight years after a diagnosis.

Endocytosis of E-cadherin regulated by Rac and Cdc42 small G proteins through IQGAP1 and actin filaments.

E-cadherin is a key cell-cell adhesion molecule at adherens junctions (AJs) and undergoes endocytosis when AJs are disrupted by the action of extracellular signals. To elucidate the mechanism of this endocytosis, we developed here a new cell-free assay system for this reaction using the AJ-enriched fraction from rat liver. We found here that non-trans-interacting, but not trans-interacting, E-cadherin underwent endocytosis in a clathrin-dependent manner. The endocytosis of trans-interacting E-cadherin was inhibited by Rac and Cdc42 small G proteins, which were activated by trans-interacting E-cadherin or trans-interacting nectins, which are known to induce the formation of AJs in cooperation with E-cadherin. This inhibition was mediated by reorganization of the actin cytoskeleton by Rac and Cdc42 through IQGAP1, an actin filament-binding protein and a downstream target of Rac and Cdc42. These results indicate the important role of the Rac/Cdc42-IQGAP1 system in the dynamic organization and maintenance of the E-cadherin-based AJs.

Regulation of SNAREs by tomosyn and ROCK: implication in extension and retraction of neurites.

Extension of neurites requires the SNARE-dependent fusion of plasmalemmal precursor vesicles with the plasma membrane of growth cones. Here, we show that tomosyn localizes at the palm of growth cones and inhibits the fusion of the vesicles there, thus promoting transport of the vesicles to the plasma membrane of the leading edges of growth cones. Tomosyn localizes because ROCK activated by Rho small G protein phosphorylates syntaxin-1, which increases the affinity of syntaxin-1 for tomosyn and forms a stable complex with tomosyn, resulting in inhibition of the formation of the SNARE complex. In retraction of neurites, tomosyn localizes all over the edges of the neurites and inhibits fusion of the vesicles with the plasma membrane. Thus, tomosyn demarcates the plasma membrane by binding to syntaxin-1 phosphorylated by ROCK, and thereby regulates extension and retraction of neurites.

Elevated serum surfactant protein A and D in a case of acute eosinophilic pneumonia.

A 29-year-old man was admitted to our hospital because of fever elevation, dry cough, malaise, skin eruption, and dyspnea with hypoxemia. His serum levels of surfactant protein (SP) -A and SP-D were markedly high, but serum KL-6 was not. He was diagnosed as acute eosinophilic pneumonia (AEP) on the basis of CT imaging, bronchoalveolar lavage findings and the clinical course. He showed good response to steroid therapy and serum levels of SP-A and SP-D returned to almost normal levels. Our experience suggested that serum SP-A and SP-D might be helpful markers for monitoring the clinical course in AEP.

[Two younger male patients with rapidly progressing pulmonary pleomorphic carcinoma].

We report 2 cases of pulmonary pleomorphic carcinoma. The patient in case 1 was a 44-year-old man who was admitted to our hospital complaining of dry cough and dyspnea on exertion. Chest radiography and CT showed a huge tumor with left pleural effusion. Percutaneous biopsy suggested malignancy. As distant metastasis was not found and as cytological examination of pleural effusion gave a result of class II, we attempted to perform left pneumonectomy. However, we performed partial resection of the tumor because it had invaded the aorta, pulmonary artery, pericardium and pleura. The pathological diagnosis was pleomorphic carcinoma, p-T4 N2 M0. After the operation, we performed systemic chemotherapy, including cisplatin and irinotecanm with little effect (PD). The patient died of progression of the tumor. Case 2 was a 34-year-old man who was admitted to our hospital complaining of fever and general malaise. Chest radiography and CT showed a tumor in the left upper lobe. As no distant metastasis was found, we tried left upper lobectomy. However, we performed left upper segmentectomy and lymph node dissection because of invasion of the aorta and the chest wall, and because of hypersegmentation of the left upper lobe. Pathological diagnosis was pleomorphic carcinoma, p-T4 N0 M0. After the operation, the mediastinum was subjected to radiation therapy. However, a metastatic tumor was found in the pelvis after this radiation was given. We performed systemic chemotherapy with substances including cisplatin, gemcitabine and vinorelbine, but with little effect (PD). The patient died of peritonitis and pleuritis due to the recurrence and progression of the tumor. Both cases had rapidly growing neoplasms showing little sensitivity to chemotherapy or radiotherapy. Pulmonary pleomorphic carcinoma is suggested to be type of lung cancer with a poor prognosis when the tumor is not resected in the early stages.

High dose of inhaled fluticasone reduces high levels of urinary leukotriene E4 in the early morning in mild and moderate nocturnal asthma.

BACKGROUND: The circadian variation in urinary leukotriene E(4) (LTE(4)) excretion with a morning acrophase has recently been reported in nocturnal asthma (NA); however, the effects of inhaled corticosteroids (ICS) on this circadian rhythmicity of leukotriene (LT) in patients with NA are controversial. METHODS: We first measured peak expiratory flow (PEF), urinary LTE(4), 11-dehydro-thromboxane B(2) (TXB(2)), and creatinine levels six times every 4 h for 24 h in two groups: patients with mild-to-moderate, steroid-naive NA (n = 10, group A), and patients with severe NA treated with high-dose ICS (n = 10, group B). Next, group A patients received 2 weeks of treatment with 800 microg/d of inhaled fluticasone propionate (FP), and we compared the measured parameters before and after treatment. RESULTS: In group A, a circadian rhythm in urinary LTE(4) with peak levels at approximately 4 AM associated with reduced PEF was observed. Group B had suppression of urinary LTE(4) excretion and had no circadian rhythmicity, as seen in group A, despite a dip in PEF at 4 AM. A high dose of FP in group A significantly (p < 0.05) reduced LTE(4) levels and abolished the circadian rhythm, as well as improving PEF. We found no significant difference in the circadian rhythm of urinary 11-dehydro-TXB(2) between groups A and B, and high-dose FP partially decreased urinary 11-dehydro-TXB(2) levels but not significantly. CONCLUSIONS: A high-dose of ICS reduced urinary LTE(4) levels and abolished their circadian variation in patients with asthma, suggesting that LT might contribute to the mechanism of NA.

Increased airway vascularity in newly diagnosed asthma using a high-magnification bronchovideoscope.

Hypervascularity in the bronchial wall is part of airway remodeling, but has remained an ill-defined process in asthma pathogenesis. Previous morphologic assessment has been limited to biopsy specimens, and therefore a high-magnification bronchovideoscope (side-viewing type) was developed for less invasive examination of subepithelial vessels. We evaluated vascularity in the lower trachea, using this novel scope in 12 normal control subjects, 13 patients with chronic obstructive pulmonary disease, and 24 subjects with stable asthma; 8 were steroid naive with newly diagnosed asthma (Group A) and 16 had been treated with inhaled corticosteroids for more than 5 years (Group B). The redness of bronchial mucosa in patients with asthma observed by conventional fiberoptic bronchoscopy proved to be due to a fine vascular network. Morphometric measurements of subepithelial vessels showed that both vessel area density and vessel length density were significantly (p<0.0001) increased in subjects with asthma as compared with control subjects and patients with chronic obstructive pulmonary disease. The degree of increase in vessels did not differ between Group A and Group B. The increase in subepithelial vessels of the airway is present even in newly diagnosed asthma. This novel bronchovideoscope is useful for assessment of vessel network in the surface of the airway lumen in vivo.