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Supplementary Figures S1-S5. Figure S1: Kinase selectivity of alectinib, vandetanib, cabozantinib, sorafenib, sunitinib, and ponatinib against several kinases including RET. Figure S2: Effect of crizotinib or LDK378 against Ba/F3 cells expressing KIF5B-RET. Figure S3: Effects of alectinib on the expression levels of phospho-ERK, ERK, and BIM in Ba/F3 cells expressing KIF5B-RET. Figure S4: Structures of RET, RET V804L, and V804M with alectinib and vandetanib. Figure S5: X-ray structure of crizotinib with ROS1 and 3D models of alectinib and LDK378 on ROS1.

The sigmoid septum has been generally evaluated subjectively and qualitatively, without detailed examination of its diversity, impact on the morphology of the left ventricular outflow tract (LVOT), and anatomical background.We enrolled 100 patients without any background cardiac diseases (67.5 ± 12.8 years old; 43% women) who underwent cardiac computed tomography. Basal septal morphology was evaluated using antero-superior and medial bulging angles (bidirectional angulation of the basal septum relative to the LVOT). The eccentricity index of the LVOT, area narrowing ratio (LVOT/virtual basal ring area), aortic-to-left ventricular axial angle (angulation of the aortic root relative to the left ventricle), and wedged height (non-coronary aortic sinus to inferior epicardium distance) were also quantified.The antero-superior bulging, medial bulging, aortic-to-left ventricular axial angles, LVOT eccentricity index, area narrowing ratio, and wedged height were 76° ± 17°, 166° ± 27°, 127° ± 9°, 1.8 ± 0.5, 1.0 ± 0.2, and 41.2 ± 9.1 mm, respectively. Both bulging angles were correlated with each other and contributed to the narrowing and deformation of the LVOT. Angulated aortic root was not correlated with either bidirectional septal bulge or LVOT narrowing. Clockwise rotation of the aortic root rotation was an independent predictor of prominent antero-superior septal bulge. Deeper aortic wedging was a common independent predictor of bidirectional septal bulge.The extent of septal bulge varies in normal hearts. Along with deep aortic wedging, the bidirectional bulge of the basal septum deforms and narrows the LVOT without affecting the virtual basal ring morphology.

Detailed 3-dimensional analysis of mitral annular disjunction was undertaken in 3 comparative cases of mitral valve prolapse. A case of Barlow disease showed extensive disjunction, whereas cases of fibroelastic deficiency and forme fruste demonstrated less extensive disjunction. Considering the current controversies surrounding disjunction, these observations call for detailed research in the future. (Level of Difficulty: Advanced.), Central Illustration

Background A computational model demonstrated that atrial fibrillation (AF) rotors could be distributed in patchy late-gadolinium enhancement (LGE) areas and play an important role in AF drivers. However, this was not validated in humans. Objective The purpose of this study was to evaluate the LGE area properties of AF rotors in patients with persistent AF. Methods A total of 287 segments in 15 patients with persistent AF (longstanding persistent AF in 9 patients) that underwent AF ablation were assessed. Non-passively activated areas (NPAs), where rotational activation (AF rotor) was frequently observed, were detected by the novel real-time phase mapping (ExTRa Mapping). The properties of the LGE areas were assessed using the LGE heterogeneity, and the density was assessed by the entropy (LGE-entropy) and volume ratio of the enhancement voxel (LGE-volume ratio), respectively. Results NPAs were found in 61 (21%) of 287 segments and were mostly found around the pulmonary vein antrum. A receiver operating characteristic curve analysis yielded an optimal cutoff value of 5.7 and 10% for the LGE-entropy and LGE-volume ratio, respectively. The incidence of NPAs was significantly higher at segments with an LGE-entropy of >5.7 and LGE-volume ratio of >10% than at the other segments (38 [30%] of 126 vs. 23 [14%] of 161 segments, p = 0.001). No NPAs were found at segments with an LGE-volume ratio of >50% regardless of the LGE-entropy. Of 5 patients with AF recurrence, NPAs outside the PV antrum were not ablated in 3 patients and the remaining NPAs were ablated, but their LGE-entropy and LGE-volume ratio were low. Conclusion AF rotors are mostly distributed in relatively weak and much more heterogenous LGE areas. This article is protected by copyright. All rights reserved.

Background Inflammation, such as that associated with intermediate CD14++ CD16+ monocytes and atrial structural remodeling (SRM), may be important in the recurrence of atrial fibrillation (AF) after catheter ablation. However, the relationship between the intermediate CD14++ CD16+ monocytes, SRM, and AF recurrence is unclear. Methods Twenty-four patients with AF were enrolled. The proportion of intermediate monocytes (PIM) was assessed before ablation by flow cytometry. As a surrogate marker of SRM, the volume ratio (VR) of signal intensity greater than 1 standard deviation on late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) was calculated. We investigated whether PIM correlated with SRM on LGE-MRI and determined the optimal cutoff value for predicting AF recurrence. Results Univariate analysis revealed positive correlations between PIM and BNP with SRM (PIM: r = .593, p = .002; BNP: r = .567, p = .004). Multivariable analysis revealed that PIM was independently associated with VR on LGE-MRI (β = .522; p = .033). The finding of an area under the receiver operating characteristic curve of 0.750 revealed that a VR ≥ 13.3% on LGE-MRI as the optimal cutoff value to predict AF recurrence with 80% sensitivity and 71% specificity, which was associated with PIM ≥ 10.0%. Conclusion Intermediate monocytes were significantly positively correlated with SRM. PIM ≥ 10% was associated with a VR ≥ 13.3% on LGE-MRI, which predicted AF recurrence after catheter ablation.

BACKGROUND: A computer simulation model has demonstrated that an atrial fibrillation (AF) driver can be attached to heterogeneous fibrosis assessed by late gadolinium enhancement magnetic resonance imaging (LGE-MRI). However, it has not been well elucidated in patients with persistent AF. The aim of this study was to investigate whether radiofrequency (RF) applications in the fragmented LGE area (FLA) could terminate AF or convert it to atrial tachycardia (AT) and improve the rhythm outcome. METHODS: A total of 31 consecutive persistent AF patients with FLAs were enrolled (FLA ablation group, mean age: 69 ± 8 years, mean left atrial diameter: 42 ± 6 mm). A favorable response was defined as direct AF termination or AT conversion during RF applications at the FLA. The rhythm outcome was compared between the FLA ablation group and FLA burden-matched pulmonary vein isolation (PVI) group. RESULTS: Favorable responses were found in 15 (48%) of 31 patients in the FLA group (AF termination in 7, AT conversion in 8 patients), but not in the PVI group. AF recurrence at 12 months follow-up was significantly less in the FLA ablation group than in the PVI group (4 [13%] vs. 12 [39%] of 31 patients, log-rank p=0.023). In patients with a favorable response, AT recurred in 1 (7%) of 15 patients but AF did not. CONCLUSIONS: FLA ablation could terminate AF or convert it to AT in half of the patients. No AF recurrence was documented in patients with a favorable response. This article is protected by copyright. All rights reserved.

Background Atrial inflammation plays an important role in initiating atrial fibrosis, which could perpetuate atrial fibrillation (AF). However, the method of visualization of atrial inflammation has not been established. We sought to investigate whether the intensive atrial inflammation caused by cryoballoon ablation (CBA) could be detected by positron emission tomography/ magnetic resonance imaging (PET/MRI) and whether the atrial inflammation could be associated with consequent fibrosis. Methods A total of 10 paroxysmal atrial fibrillation patients after CBA were enrolled. To detect and quantify intensive atrial inflammation, PET/MRI was performed to assess regional 18F‐fluorodeoxyglucose (18F‐FDG) uptake one day after the CBA, and the standardized uptake values (SUV) max were compared between the pulmonary vein (PV) antrum where CBA could be applied and the healthy left atrial (LA) wall where CBA could not be applied. Furthermore, the atrial inflammation one day after the procedure and atrial fibrosis areas one month after the procedure were three‐dimensionally quantified by PET/MRI and late‐gadolinium enhancement magnetic resonance imaging (LGE‐MRI), respectively. Results The mean SUV max at the PV antrum was significantly higher than that on the healthy LA wall (2.12 ± 0.35 vs 1.73 ± 0.30, P = .00021). The volume of the atrial inflammation strongly correlated with that of the atrial fibrosis (r = .94 [.76‐.99], P = .00006). Conclusions The atrial inflammation after CBA could be detected by PET/MRI. CBA‐induced atrial inflammation was strongly associated with consequent lesion maturation., Atrial inflammation plays an important role in initiating atrial fibrosis, which could perpetuate atrial fibrillation (AF).This study demonstrated the feasibility of the PET/MRI visualizing inflammation in the left atrium.

We have previously shown that the oral administration of the small molecule hPTHR1 agonist PCO371 and its lead compound, 1 (CH5447240) results in PTH-like calcemic and hypophostemic activity in thyroparathyroidectomized rats. However, 1 was converted to a reactive metabolite in a human liver microsome assay. In this article, we report on the modification path that led to an enhancement of PTHR1 agonistic activity and reduction in the formation of a reactive metabolite to result in a potent, selective, and orally active PTHR1 agonist 1-(3,5-dimethyl-4-(2-((4-oxo-2-(4-(trifluoromethoxy)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-8-yl)sulfonyl)ethyl)phenyl)-5,5-dimethylimidazolidine-2,4-dione (PCO371, 16c). This compound is currently being evaluated in a phase 1 clinical study for the treatment of hypoparathyroidism.

We investigated whether novobiocin is useful for elucidating the contribution of breast cancer resistance protein (Bcrp) to intestinal absorption without affecting the activities of P-glycoprotein (P-gp), cytochrome P450 (CYP) 3 A and hepatic organic anion transporting polypeptide (Oatp) in rats.To determine the effects of novobiocin on Bcrp, P-gp, CYP3A and Oatp activities, we used sulfasalazine, fexofenadine, bosentan and midazolam, respectively, as probe substrates. Each substrate was orally or intravenously administered to rats 15 min after oral novobiocin administration at a dose of 3 mg/kg.Pre-treatment with novobiocin significantly increased the area under the plasma concentration-time curve and the peak plasma concentration of sulfasalazine after oral administration by 3.2- and 5.9-fold, respectively, in rats, whereas its systemic clearance following intravenous dosing was not influenced. These results indicate that novobiocin selectively inhibits intestinal Bcrp-mediated efflux with limited effects on extra-intestinal Bcrp activity.In addition, novobiocin pre-treatment did not significantly alter the pharmacokinetic parameters of orally administered fexofenadine and midazolam or intravenously administered bosentan, suggesting that the effects of novobiocin on other processes were negligible.These findings demonstrate that novobiocin permits estimating the net contribution of Bcrp to intestinal absorption of drug candidates.

Background: Some of atrial fibrillation (AF) drivers are found in normal/mild late-gadolinium enhancement (LGE) areas, as well as moderate ones. The atrial wall thickness (AWT) has been reported to be important as a possible AF substrate. However, the AWT and degree of LGEs as an AF substrate has not been fully validated in humans. Objective: The purpose of this study was to evaluate the impact of the AWT in normal/mild LGE areas on AF drivers. Methods: A total of 287 segments in 15 persistent AF patients were assessed. AF drivers were defined as non-passively activated areas (NPAs), where rotational activation was frequently observed, and were detected by the novel real-time phase mapping (ExTRa Mapping), mild LGE areas were defined as areas with a volume ratio of the enhancement voxel of 0% to

Background: Some of atrial fibrillation (AF) drivers are found in lesser late-gadolinium enhancement (LGE) areas, as well as heterogenous ones. The atrial wall thickness (AWT) has been reported to be important as a possible AF substrate. However, the AWT and degree of LGEs as an AF substrate has not been fully validated in humans. Objective: The purpose of this study was to evaluate the impact of the AWT in lesser LGE areas on AF drivers. Methods: A total of 287 segments in 15 persistent AF patients were assessed. AF drivers were defined as non-passively activated areas (NPAs), where rotational activation was frequently observed, and were detected by the novel real-time phase mapping (ExTRa Mapping). Lesser LGE areas were defined as areas with a volume ratio of the enhancement voxel of

The purpose of this study is to examine the interrelationships among value co-creation, switching costs (SC), and customer share (CS) in both business-to-business (B2B) and business-to-consumer (B2...

Mesenteric ischemia is an infrequent, but potentially dangerous, complication of aortic or mesenteric artery dissection. Severe mesenteric ischemia presenting as a malperfusion syndrome, caused by aortic dissection or isolated mesenteric dissection, should be treated immediately by central aortic repair or angioplasty. However, treatment of non-critical, symptomatic mesenteric ischemia without narrowing true lumen of the aorta or localized mesenteric artery dissection was difficult. We treated two distinctly different cases of non-critical, symptomatic mesenteric ischemia superior mesenteric artery ischemia needing intensive care and mesenteric blood flow was determined by quantification with cine-phase contrast magnetic resonance imaging.

Background: Atrial fibrosis and inflammation play important roles in perpetuating and initiating atrial fibrillation (AF). Although the fibrotic area can be visualized as a delayed enhancement area on late gadolinium enhancement magnetic resonance imaging (LGE-MRI), atrial inflammation has not yet been visualized on any imaging modality. We describe the protocol for a feasibility study to visualize atrial inflammation on positron emission tomography/MRI (PET/MRI). Methods and Results: This is a single-arm, prospective, open-label proof-of concept trial, involving AF patients after cryoballoon ablation (CBA). A total of 30 paroxysmal AF patients will be enrolled and undergo simultaneous PET/MRI for the assessment of regional 18F-fluorodeoxyglucose (18F-FDG) uptake 1 day after the CBA. Furthermore, LGE-MRI will be performed before CBA, and at 1 and 4 weeks after assessing the regional LGE area. The main outcome measures will be (1) the feasibility of imaging inflammation in the left atrium on PET/MRI; and (2) the safety of the intervention. Conclusions: There are few data on the visualization of atrial inflammation using PET/MRI. Establishing the visualization methodology will contribute to elucidating the fundamental histopathologic findings of the progress to fibrosis, and to the planning and execution of a larger definitive trial to test the usefulness of PET/MRI.

In this study, we conducted vehicle experiments and a numerical simulation based on a simple algorithm inspired by the bio-sonar system of bats to investigate how the behavioral strategy employed b...

Purpose To retrospectively assess the repeatability of physiological F-18 labeled fluorodeoxyglucose (FDG) uptake in the skin on positron emission tomography/magnetic resonance imaging (PET/MRI) and explore its regional distribution and relationship with sex and age. Methods Out of 562 examinations with normal FDG distribution on whole-body PET/MRI, 74 repeated examinations were evaluated to assess the repeatability and regional distribution of physiological skin uptake. Furthermore, 224 examinations were evaluated to compare differences in the uptake due to sex and age. Skin segmentation on PET was performed as body-surface contouring on an MR-based attenuation correction map using an off-line reconstruction software. Bland–Altman plots were created for the repeatability assessment. Kruskal–Wallis test was performed to compare the maximum standardized uptake value (SUVmax) with regional distribution, age, and sex. Results The limits of agreement for the difference in SUVmean and SUVmax of the skin were less than 30%. The highest SUVmax was observed in the face (3.09±1.04), followed by the scalp (2.07±0.53). The SUVmax in the face of boys aged 0–9 years and 10–20 years (1.33±0.64 and 2.05±1.00, respectively) and girls aged 0–9 years (0.98±0.38) was significantly lower than that of men aged ≥20 years and girls aged ≥10 years (p Conclusion PET/MRI enabled the quantitative analysis of skin FDG uptake with repeatability. The degree of physiological FDG uptake in the skin was the highest in the face and varied between sexes. Although attention to differences in body habitus between age groups is needed, skin FDG uptake also depended on age.

Background:A thorough understanding of the anatomy of the aortic valve is necessary for aortic valve-sparing surgery. Normal valvar dimensions and their relationships in the living heart, however, have yet to be fully investigated in a 3-dimensional fashion. Methods and Results: In total, 123 consecutive patients (66±12 years, Men 63%) who underwent coronary computed tomographic angiography were enrolled. Mid-diastolic morphology of the aortic roots, including height of the interleaflet triangles, geometric height, free margin length of each leaflet, effective height, and coaptation length were measured using multiplanar reconstruction images. Average height of the interleaflet triangle, geometric height, free margin length, effective height, and the coaptation length were 17.3±1.8, 14.7±1.3, 32.6±3.6, 8.6±1.4, and 3.2±0.8 mm, respectively. The right coronary aortic leaflet displayed the longest free margin length and shortest geometric height. Geometric height, free margin length, and effective height showed positive correlations with aortic root dimensions. Coaptation length, however, remained constant regardless of aortic root dimensions. Conclusions: Diversities, as well as characteristic relationships among each value involving the aortic root, were identified using living-heart datasets. The aortic leaflets demonstrated compensatory elongation along with aortic root dilatation to maintain constant coaptation length. These measurements will serve as the standard value for revealing the underlying mechanism of aortic regurgitation to plan optimal aortic valve-sparing surgery.

Birds often hold important positions in the food webs of ecosystems. As a result, interactions between birds and their prey have attracted attention not only in ecology, but also in fields like agriculture and conservation. Avian food resources are well researched in Japan, however there is no database critically reviewing molluscs as a food resource for birds. Here, we present a new database reviewing dietary information for all Japanese bird species. In addition to addressing general diet categories and specific food habits for each bird, we include detailed data on the molluscan prey observed for all species that consume them. The information within this database was collected through intense literary review to provide a complete look at bird species historically present around the country. We also include new information on snail species found in the upper digestive tract of harvested wild birds. This database is publicly available in the Zenodo repository. The information should aid research around the Japanese archipelago, especially projects involving birds or molluscs., Measurement(s) Distribution • endemicity • species status • habitat • diet • information of molluscan prey Technology Type(s) digital curation Sample Characteristic - Organism Aves • Mollusca Sample Characteristic - Environment sea • fresh water • terrestrial biome Sample Characteristic - Location Japan Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.13296275

For improvement of energy conversion efficiency, a sound wave is superimposed with a loudspeaker to the working fluid in the stack. By using this method the work-flow generation of the stack was enhanced. To analyze this enhancement mechanism, the thickness of the boundary layer and the heat exchange area in the stack are calculated from the viewpoint of the heat exchange circumstance. The effect of the heat exchange circumstance on the particle displacement and thermal flow is investigated. As a result, it is confirmed that the superimposed sound wave improves the heat exchange circumstance and then the thermoacoustic phenomenon is enhanced.

The influence of an external sound applied to a loop-tube type thermoacoustic system on the energy conversion efficiency is experimentally examined. The investigation is carried out by studying the effect of a loudspeaker (SP) set as an external sound source. As a result, it is found that the location of the SP affects the sound field in the system and that the amount of energy generated increases or decreases. The increasing or decreasing effect differs depending on the location of the SP. Furthermore, it is confirmed that, provided the SP is located near the particle velocity node, the sound energy can be increased by more than the input power to the SP without changing the sound field in the tube. From these results it can be confirmed that, similar to a straight-tube type thermoacoustic system, the energy conversion efficiency can be enhanced by locating the SP at a suitable position even in a loop-tube type system without end surfaces.

Background: A computational model demonstrated that atrial fibrillation (AF) rotors could be distributed in patchy fibrotic tissue and play an important role in AF drivers. However, this was not validated in humans. Objective: The purpose of this study was to evaluate the fibrotic tissue properties of AF rotors in patients with persistent AF. Methods: A total of 287 segments in 15 patients with persistent AF (longstanding persistent AF in 9 patients) that underwent AF ablation were assessed. Non-passively activated areas (NPAs), where rotational activation (AF rotor) was frequently observed, were detected by the novel real-time phase mapping (ExTRa Mapping). Atrial fibrosis was detected by late-gadolinium enhancement magnetic resonance imaging (LGE-MRI), and the fibrotic heterogeneity and density were assessed by the entropy (LGE-entropy) and volume ratio of the enhancement voxel (LGE-volume ratio), respectively. Results: NPAs were found in 61 (21%) of 287 segments and were mostly found around the pulmonary vein antrum. A receiver operating characteristic curve analysis yielded an optimal cutoff value of 5.7 and 10% for the LGE-entropy and LGE-volume ratio, respectively. The incidence of NPAs was significantly higher at segments with an LGE-entropy of >5.7 and LGE-volume ratio of >10% than at the other segments (38 [30%] of 126 vs. 23 [14%] of 161 segments, p = 0.001). No NPAs were found at segments with an LGE-volume ratio of >50% regardless of the LGE-entropy. Conclusion: AF rotors are mostly distributed in relatively weak and much more heterogenous fibrotic tissue.

Background: Computer simulation model demonstrated that atrial fibrillation (AF) driver attached to the patchy fibrosis assessed by late gadolinium enhancement magnetic resonance imaging (LGE-MRI). However, it has not been well elucidated in patients with persistent AF. The aim of this study is to investigate whether radiofrequency (RF) application on the patchy LGE site (PLS) could terminate AF or convert to atrial tachycardia (AT) and improve the rhythm outcome. Methods: A total of 31consecutive persistent AF patients with PLS were enrolled (PLS ablation group, mean age: 69 ± 8 years, mean left atrial diameter: 42 ± 6 mm). AF direct termination or AT conversion during RF application on the PLS were defined as favorable response. The rhythm outcome was compared between the PLS ablation group and the propensity matched conventional ablation group. Results: Favorable response was found in 15 (48%) of 31 patients (AF termination in 7, AT conversion in 8 patients). AF recurrence at 12 months follow-up was significantly less in the PLS group as compared to the control group (4 (13%) of 31 patients vs. 11 (35%) of 31 patients, log-rank p = 0.019). In patients with favorable response, AT recurred in 1 (7%) of 15 patients but AF. Conclusions: The PLS ablation could terminate AF or convert to AT in half of the patients and improve the rhythm outcome as compared to the conventional ablation. No AF recurrence was documented in patients with a favorable response.

Background Pulmonary vein isolation (PVI) lesions after cryoballoon ablation (CBA) are characterized as a wider and more continuous than that after conventional radiofrequency catheter ablation (RFCA) without the contact force (CF)-sensing technology. However, the impact on the lesion characteristics of ablation with a CF-sensing catheter has not been well discussed. We sought to assess the lesions using late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) and to compare the differences between the two groups (CB group vs. RF group). Methods A total of 30 consecutive patients who underwent PVI were enrolled (CB group, 18; RF group, 12). The RF applications were delivered with a target lesion size index (LSI) of 5. The PVI lesions were assessed by LGE-MRI 3 months after the PVI. The region around the PV was divided into eight segments: roof, anterior-superior, anterior carina, anterior inferior, bottom, posterior inferior, posterior carina, and posterior superior segment. The lesion width and visual gap of each segment were compared between the two groups. The visual gaps were defined as no-enhancement site of >4 mm. Results The mean LSI was 4.7 ± 0.7. The lesion width was significantly wider but the visual gaps were more frequently documented at the bottom segment of right PV in the CBA group (lesion width: 8.1 ± 2.2 vs. 6.3 ± 2.2 mm; p = .032; visual gap at the bottom segment or right PV: 39% vs. 0%; p = .016). Conclusions The PVI lesion was wider after CBA, while the visual gaps were fewer after RFCA with a CF-sensing catheter.

P-glycoprotein (P-gp) has been shown previously to contribute to the intestinal absorption of verapamil, diltiazem, tacrolimus, colchicine and indinavir in situ; however, its contribution in vivo is unknown. The present study aimed to evaluate the in vivo involvement of P-gp using elacridar as its inhibitor to distinguish the contribution of P-gp from cytochrome P450 (CYP) 3A. Fexofenadine (5 mg/kg) and buspirone (1 mg/kg) were used as probe substrates of P-gp and CYP3A, respectively. Each dual substrate (1 or 2 mg/kg) was orally administered to rats after elacridar pre-treatment (3 mg/kg). Additionally, verapamil, diltiazem or tacrolimus was orally co-administered with fexofenadine. Elacridar drastically increased the area under the plasma concentration–time curve (AUC0–t) of oral fexofenadine by 8.6-fold; however, it did not affect the AUC0–t of oral buspirone. Therefore, elacridar inhibited P-gp without affecting CYP3A. The absorption of oral verapamil, diltiazem and tacrolimus was not influenced by elacridar pre-treatment, and the increase in the AUC0–t of fexofenadine was approximately 3-fold when co-administered with each substrate; the minimal effect of elacridar was attributable to the limited contribution of P-gp but not to their self-inhibition against the transporter. Conversely, elacridar significantly increased the AUC0–t of colchicine (5.3-fold) and indinavir (2.0-fold), indicating that P-gp contributes to their absorption. Elacridar is useful for distinguishing the contribution of P-gp from CYP3A to the absorption of drugs in rats. The in vivo contribution of P-gp is minimal for high permeable compounds owing to their fraction absorbed of nearly 1.0.

Autonomous navigation is of great importance for service robots. Such robots need various technologies, especially localization, and mapping. In this paper, we focus on the localization problem. Commonly, to solve the localization problem, the creation of a map is needed. However, creating the map takes considerable time and costs. Therefore, one solution for indoor environment is to use architectural floor plans since buildings have own floor plans. If a robot can use them for localization, it enables users to cut the time and costs for creating the map from scratch. However, the floor plans sometimes do not match with a real building. Besides, sensor measurement sometimes contains objects such as a pedestrian, which are not contained in the floor plans. In this paper, we propose a localization algorithm with architectural floor plans that is robust to such inconsistencies. The algorithm estimates a robot coordinate by matching the floor plan with the point clouds obtained from depth images. Outliers derived from the inconsistencies in the point clouds are filtered with plane information from the depth images with the Generalized ICP framework. We tested our algorithm with floor plans in a real building and in a simulator as a case study. The results show that our algorithm can localize a robot with average more than twice accuracy compared to AMCL and be used for real-time applications.

The majority of aerosol data are obtained from daytime measurements, and there are few datasets available for studying nighttime aerosol characteristics. In order to estimate the aerosol optical depth (AOD) and the precipitable water vapor (PWV) during the nighttime using the moon as a light source, a sky radiometer (POM-02, Prede Ltd., Japan) was modified. The amplifier was adjusted so that POM-02 could measure lower levels of input irradiance. In order to track the moon based on the calculated values, a simplified formula was incorporated into the firmware. A new position sensor with a four-quadrant detector to adjust the tracking of the Sun and moon was also developed. The calibration constant, which is the sensor output for the extraterrestrial solar and lunar irradiance at the mean Earth–Sun distance, was determined by using the Langley method. The measurements for the Langley calibration were conducted at the National Oceanic and Atmospheric Administration/Mauna Loa Observatory (NOAA/MLO) from 28 September 2017 to 7 November 2017. By assuming that the correct reflectance is proportional to the reflectance estimated by the Robotic Lunar Observatory (ROLO) irradiance model, the calibration constant for the lunar direct irradiance was successfully determined using the Langley method. The ratio of the calibration constant for the moon to that of the Sun was often greater than 1; the value of the ratio was 0.95 to 1.18 in the visible and near-infrared wavelength regions. This indicates that the ROLO model often underestimates the reflectance. In addition, this ratio depended on the phase angle. In this study, this ratio was approximated by a quadratic equation of the phase angle. By using this approximation, the reflectance of the moon can be calculated to within an accuracy of 1 % or less. In order to validate the estimates of the AOD and PWV, continuous measurements with POM-02 were conducted at the Japan Meteorological Agency/Meteorological Research Institute (JMA/MRI) from January 2018 to May 2018, and the AOD and PWV were estimated. The results were compared with the AOD and PWV obtained by independent methods. The AOD was compared with that estimated by the National Institute for Environmental Studies (NIES) High Spectral Resolution Lidar measurements (wavelength: 532 nm), and the PWV was compared with the PWV obtained from a radiosonde and the Global Positioning System. In addition, the continuity of the AOD (PWV) before and after sunrise and sunset in Tsukuba was examined, and the AOD (PWV) of AERONET and that of POM-02 at MLO were compared. In the results, the daytime and nighttime AOD (PWV) measurements are shown to be statistically almost equivalent. The AODs (PWVs) during the daytime and nighttime for POM-02 are presumed to have the same degree of precision and accuracy within the measurement uncertainty.