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Background/Aims During endoscopy, white spots (WS) are sometimes observed around benign or malignant colorectal tumors; however, few reports have investigated WS, and their significance remains unknown. Therefore, we investigated the significance of WS from clinical and pathological viewpoints and evaluated its usefulness in endoscopic diagnosis. Methods Clinical data of patients with lesions diagnosed as epithelial tumors from January 1, 2019, to December 31, 2020, were analyzed (n=3,869). We also performed a clinicopathological analysis of adenomas or carcinomas treated with endoscopic resection (n=759). Subsequently, detailed pathological observations of the WS were performed. Results The positivity rates for WS were 9.3% (3,869 lesions including advanced cancer and non-adenoma/carcinoma) and 25% (759 lesions limited to adenoma and early carcinoma). Analysis of 759 lesions showed that the WS-positive lesion group had a higher proportion of cancer cases and larger tumor diameters than the WS-negative group. Multiple logistic analysis revealed the following three statistically significant risk factors for carcinogenesis: positive WS, flat lesions, and tumor diameter ≥5 mm. Pathological analysis revealed that WS were macrophages that phagocytosed fat and mucus and were white primarily because of fat. Conclusions WS are cancer-related findings and can become a new criterion for endoscopic resection in the future.

Background/Aims Vedolizumab (VDZ) is a gut-selective agent with a favorable safety profile. We aimed to assess the feasibility of elective switch from other advanced therapies to VDZ and subsequent live-attenuated vaccination while continuing VDZ in patients with inflammatory bowel diseases (IBD). Methods We measured antibody titers specific for measles, rubella, mumps, and varicella viruses in IBD patients under immunosuppressive therapy. Those with negative titers and without vaccination history were judged unimmunized. Patients were administered vaccines while continuing VDZ or switched to VDZ if receiving other advanced therapies and then administered vaccines. Co-primary outcomes were the rate of maintaining disease severity after vaccination and the rate without vaccine-induced infection. Results Among 107 unimmunized patients, 37 agreed to receive live-attenuated vaccines while continuing VDZ (17 patients) or after switching to VDZ (20 patients). In the 20 patients who electively switched to VDZ, disease severity was maintained except for 1 patient who developed intestinal infection. After 54 weeks, 18 patients (90%) continued to receive VDZ, excluding 2 patients who reverted to their originally administered biologics. In all 37 patients administered live-attenuated vaccines under VDZ treatment, disease severity was maintained after vaccination. Antibody titers became positive or equivocal in 34 patients (91.9%). There were no cases of vaccine-induced infection during a median observation period of 121 weeks. Conclusions While live-attenuated vaccines are contraindicated under immunosuppressive therapy, they may be safely administered while receiving VDZ immunotherapy. Switching from other advanced therapies to VDZ and subsequently receiving live-attenuated vaccines may be a safe alternative in unimmunized patients.

Abstract Background and Aim The number of older patients with ulcerative colitis is increasing; however, limited data exist regarding the differences between elderly‐ and non‐elderly‐onset ulcerative colitis. We aimed to compare the clinical practice and course of elderly‐onset ulcerative colitis with those of non‐elderly‐onset ulcerative colitis. Methods We selected older patients with ulcerative colitis and divided them into the elderly‐ and non‐elderly‐onset ulcerative colitis groups according to their age at onset. We compared the cumulative systemic steroid‐free, molecular targeting drug‐free, and surgery‐free rates between the two groups. We performed a multivariate analysis to identify the clinical factors related to systemic steroid administration, the use of molecular targeting drugs, surgery, and death. Results We collected data of 2669 and 277 elderly and non‐elderly‐onset ulcerative colitis patients, respectively. The cumulative systemic steroid‐free rate of elderly‐onset ulcerative colitis was significantly lower than that of non‐elderly‐onset ulcerative colitis. However, no difference was observed in the cumulative molecular targeting drugs and surgery‐free rates between the two groups. Elderly‐onset ulcerative colitis significantly increased the risk of systemic steroid administration and death but not the use of molecular targeting drugs and surgery. Conclusion The disease severity of ulcerative colitis and clinical practice may not differ between the elderly‐ and non‐elderly‐onset groups. However, elderly‐onset ulcerative colitis was associated with increased mortality risk. Thus, we need to pay attention to the patients' condition and appropriate timing of surgery for patients with elderly‐onset ulcerative colitis.

A novel oxylipin, okeanoate (1), was isolated from the Okinawan cyanobacterium Okeania hirsuta. The structure of 1 was elucidated based on spectroscopic data including 1D and 2D NMR, as well as high-resolution mass spectrometry. This is the first oxylipin with a dimethylsulfonium moiety in the middle of the hydrocarbon chain.

Contrast-enhanced sonography (CEUS) is a very important diagnostic imaging tool in clinical settings. However, it is associated with possible artifacts, such as B-mode US-related artifacts. Sufficient knowledge of US physics and these artifacts is indispensable to avoid the misinterpretation of CEUS images. This review aims to explain the basic physics of CEUS and the associated artifacts and to provide some examples to avoid them. This review includes problems related to the frame rate, scanning modes, and various artifacts encountered in daily CEUS examinations. Artifacts in CEUS can be divided into two groups: (1) B-mode US-related artifacts, which form the background of the CEUS image, and (2) artifacts that are specifically related to the CEUS method. The former includes refraction, reflection, reverberation (multiple reflections), attenuation, mirror image, and range-ambiguity artifacts. In the former case, the knowledge of B-mode US is sufficient to read the displayed artifactual image. Thus, in this group, the most useful artifact avoidance strategy is to use the reference B-mode image, which allows for a simultaneous comparison between the CEUS and B-mode images. In the latter case, CEUS-specific artifacts include microbubble destruction artifacts, prolonged heterogeneous accumulation artifacts, and CEUS-related posterior echo enhancement; these require an understanding of the mechanism of their appearance in CEUS images for correct image interpretation. Thus, in this group, the most useful artifact avoidance strategy is to confirm the phenomenon’s instability by changing the examination conditions, including the frequency, depth, and other parameters.

We present observations of the gamma-ray binary PSR B1259-63/LS 2883 with the Atacama Large Millimeter/submillimeter Array (ALMA) at Band 3 (97 GHz), Band 6 (233 GHz), and Band 7 (343 GHz). PSR B1259-63/LS 2883 consists of a pulsar in a highly eccentric orbit around a massive companion star, with the pulsar passing through the circumstellar disk near periastron. Our new data were obtained over several epochs, ranging from −61 to +29 days from the periastron passage in 2024. We report an increase in flux in all bands near the periastron. The significant change in Band 3 flux suggests synchrotron emission from the interaction between the pulsar wind and the stellar wind or disk. The Band 6 flux shows an increase around periastron and a transition from thermal emission from the circumstellar disk to synchrotron emission. The Band 7 observation +24 days after periastron shows a brightening, suggesting that the pulsar's passage through the disk does not result in its immediate destruction. We discuss the implications of these results for the interaction between the pulsar wind and the circumstellar disk, such as the possible disk expansion after periastron.

Conclusion: Our findings support the safe and effective use of EBD for both ileal and colonic strictures associated with CD. The clinical practice and safety outcomes of EBD for CD-related strictures were comparable to those for strictures stemming from other etiologies.

The Event Horizon Telescope observed the horizon-scale synchrotron emission region around the Galactic center supermassive black hole, Sagittarius A* (Sgr A*), in 2017. These observations revealed a bright, thick ring morphology with a diameter of 51.8 ± 2.3 μ as and modest azimuthal brightness asymmetry, consistent with the expected appearance of a black hole with mass M ≈ 4 × 10 ^6 M _⊙ . From these observations, we present the first resolved linear and circular polarimetric images of Sgr A*. The linear polarization images demonstrate that the emission ring is highly polarized, exhibiting a prominent spiral electric vector polarization angle pattern with a peak fractional polarization of ∼40% in the western portion of the ring. The circular polarization images feature a modestly (∼5%–10%) polarized dipole structure along the emission ring, with negative circular polarization in the western region and positive circular polarization in the eastern region, although our methods exhibit stronger disagreement than for linear polarization. We analyze the data using multiple independent imaging and modeling methods, each of which is validated using a standardized suite of synthetic data sets. While the detailed spatial distribution of the linear polarization along the ring remains uncertain owing to the intrinsic variability of the source, the spiraling polarization structure is robust to methodological choices. The degree and orientation of the linear polarization provide stringent constraints for the black hole and its surrounding magnetic fields, which we discuss in an accompanying publication.

In a companion paper, we present the first spatially resolved polarized image of Sagittarius A* on event horizon scales, captured using the Event Horizon Telescope, a global very long baseline interferometric array operating at a wavelength of 1.3 mm. Here we interpret this image using both simple analytic models and numerical general relativistic magnetohydrodynamic (GRMHD) simulations. The large spatially resolved linear polarization fraction (24%–28%, peaking at ∼40%) is the most stringent constraint on parameter space, disfavoring models that are too Faraday depolarized. Similar to our studies of M87*, polarimetric constraints reinforce a preference for GRMHD models with dynamically important magnetic fields. Although the spiral morphology of the polarization pattern is known to constrain the spin and inclination angle, the time-variable rotation measure (RM) of Sgr A* (equivalent to ≈46° ± 12° rotation at 228 GHz) limits its present utility as a constraint. If we attribute the RM to internal Faraday rotation, then the motion of accreting material is inferred to be counterclockwise, contrary to inferences based on historical polarized flares, and no model satisfies all polarimetric and total intensity constraints. On the other hand, if we attribute the mean RM to an external Faraday screen, then the motion of accreting material is inferred to be clockwise, and one model passes all applied total intensity and polarimetric constraints: a model with strong magnetic fields, a spin parameter of 0.94, and an inclination of 150°. We discuss how future 345 GHz and dynamical imaging will mitigate our present uncertainties and provide additional constraints on the black hole and its accretion flow.

Autoimmune gastritis is immune-mediated gastritis that destroys the oxyntic mucosa. Autoimmune hepatitis is an inflammatory liver disease caused by an autoimmune reaction. These diseases share similar pathogeneses as organ-specific autoimmune disorders; however, cases involving both diseases are quite rare and scarcely reported. Herein, we report a patient with concurrent autoimmune gastritis and hepatitis who developed enlargement of hyperplastic polyps and progression of gastric atrophy. The patient was a 79-year-old female referred to our hospital for the treatment of hyperplastic polyps detected on a follow-up upper gastrointestinal endoscopy. The patient’s previous upper gastrointestinal endoscopy from 3 years prior revealed small hyperplastic polyps and no mucosal atrophy. However, the current upper gastrointestinal endoscopy revealed three 10-mm red polyps, severe mucosal atrophy in the corpus, and mild atrophy in the antral area. In addition, biopsy samples from the gastric body revealed decreased parietal cells and diffuse lymphocytic infiltration of the deep mucosa. Further, chromogranin A-positive endocrine cell micronests and enterochromaffin-like cell hyperplasia were detected. After confirming the diagnosis of autoimmune gastritis, endoscopic mucosal resection was performed for all the polyps, which were histopathologically diagnosed as hyperplastic polyps without malignancy. Therefore, clinicians should consider autoimmune gastritis for enlarged hyperplastic polyps and gastric atrophy progression.

Introduction: Limited data exist regarding the prevalence and clinical practice involving generic drugs and biosimilars for treating ulcerative colitis (UC) in Japan. We aimed to clarify the clinical usage of these generic drugs and biosimilars for UC treatment in Japan using a nationwide database. Methods: We collected data from 30,675 UC cases, along with their prescriptions for both generic drugs or biosimilars and their original counterparts, using a medical claim database provided by DeSC Healthcare, Inc. We calculated the prescription and penetration rates of generic drugs and biosimilars and demonstrated the transition of these rates. Additionally, the cumulative retention rates between infliximab originator and biosimilar were compared using the Kaplan-Meier method. Results: The prescription rate of generic mesalazine increased from approximately 10% in 2015 to over 30% in 2021. Although the prescription rate of generic molecular targeting drugs (MTDs) also increased from approximately 0.15% in 2014 to 2.5% in 2021, the increment was lower than that of generic mesalazine. The penetration rates of generic 5-aminosalicylic acid and tacrolimus ranged from over 30% to approximately 50%. Infliximab biosimilar achieved an approximate 20% penetration rate, whereas adalimumab achieved

The physical quantity that directly controls the feedback of active galactic nuclei (AGNs) in elliptical galaxies remains to be determined. The discovery of molecular gas around the AGNs suggests that the gas is fueling the AGNs. Therefore, we analyze Atacama Large Millimeter/submillimeter Array data for the CO line ( J = 1–0, 2–1, 3–2) emission and estimate the mass of molecular gas within 500 pc of the center of 12 noncentral elliptical galaxies (NCEGs) and 10 of the brightest cluster galaxies. We find that the mass ( M _mol ∼ 10 ^5 –10 ^9 M _☉ ) is correlated with the jet power of their AGNs, which is represented by ${P}_{\mathrm{cav}}\approx 4.1\times {10}^{42}{({M}_{\mathrm{mol}}/{10}^{7}\ {M}_{\odot })}^{1.3}\mathrm{erg}\ {{\rm{s}}}^{-1}$ , although NCEGs alone do not show the correlation. We also find that M _mol is correlated with the AGN continuum luminosities at ∼1.4 GHz ( L _1.4 ) and ∼100–300 GHz ( L _con ). Since P _cav reflects galactic-scale, long-term AGN activity, while the continuum luminosities reflect local (≲500 pc), short-term AGN activity, our results suggest that AGN activity depends on the amount of gas, regardless of its timescale. On the other hand, we cannot find a clear correlation between the mass of the black holes in the AGNs ( M _BH ) and P _cav . This suggests that M _mol , rather than M _BH , is the main factor controlling AGN activity. We confirm that the origin of the continuum emission from the AGNs at ∼1.4–300 GHz is mostly synchrotron radiation.

We present the kinematics of the parsec-scale jet in 3C 84 from 2003 November to 2022 June observed with the Very Long Baseline Array at 43 GHz. We find that the C3 component, a bright feature at the termination region of the jet component ejected from the core in 2003, has maintained a nearly constant apparent velocity of 0.259 ± 0.003 c over the period covered by observations. We observe the emergence of four new subcomponents from C3, each exhibiting apparent speeds higher than that of C3. Notably, the last two subcomponents exhibit apparent superluminal motion, with the fastest component showing an apparent speed of 1.22 ± 0.14 c . Our analysis suggests that a change in viewing angle alone cannot account for the fast apparent speeds of the new subcomponents, indicating that they are intrinsically faster than C3. We identify jet precession (or reorientation), a jet–cloud collision, and magnetic reconnection as possible physical mechanisms responsible for the ejection of the new subcomponents.

We present X-ray polarimetry observations from the Imaging X-ray Polarimetry Explorer (IXPE) of three low spectral peak and one intermediate spectral peak blazars, namely 3C 273, 3C 279, 3C 454.3, and S5 0716+714. For none of these objects was IXPE able to detect X-ray polarization at the 3 σ level. However, we placed upper limits on the polarization degree at ∼10%–30%. The undetected polarizations favor models where the X-ray band is dominated by unpolarized photons upscattered by relativistic electrons in the jets of blazars, although hadronic models are not completely eliminated. We discuss the X-ray polarization upper limits in the context of our contemporaneous multiwavelength polarization campaigns.

The first very long baseline interferometry (VLBI) detections at 870 μ m wavelength (345 GHz frequency) are reported, achieving the highest diffraction-limited angular resolution yet obtained from the surface of the Earth and the highest-frequency example of the VLBI technique to date. These include strong detections for multiple sources observed on intercontinental baselines between telescopes in Chile, Hawaii, and Spain, obtained during observations in 2018 October. The longest-baseline detections approach 11 G λ , corresponding to an angular resolution, or fringe spacing, of 19 μ as. The Allan deviation of the visibility phase at 870 μ m is comparable to that at 1.3 mm on the relevant integration timescales between 2 and 100 s. The detections confirm that the sensitivity and signal chain stability of stations in the Event Horizon Telescope (EHT) array are suitable for VLBI observations at 870 μ m. Operation at this short wavelength, combined with anticipated enhancements of the EHT, will lead to a unique high angular resolution instrument for black hole studies, capable of resolving the event horizons of supermassive black holes in both space and time.

Event Horizon Telescope (EHT) observations have revealed a bright ring of emission around the supermassive black hole at the center of the M87 galaxy. EHT images in linear polarization have further identified a coherent spiral pattern around the black hole, produced from ordered magnetic fields threading the emitting plasma. Here we present the first analysis of circular polarization using EHT data, acquired in 2017, which can potentially provide additional insights into the magnetic fields and plasma composition near the black hole. Interferometric closure quantities provide convincing evidence for the presence of circularly polarized emission on event-horizon scales. We produce images of the circular polarization using both traditional and newly developed methods. All methods find a moderate level of resolved circular polarization across the image (〈∣ v ∣〉 < 3.7%), consistent with the low image-integrated circular polarization fraction measured by the Atacama Large Millimeter/submillimeter Array (∣ v _int ∣ < 1%). Despite this broad agreement, the methods show substantial variation in the morphology of the circularly polarized emission, indicating that our conclusions are strongly dependent on the imaging assumptions because of the limited baseline coverage, uncertain telescope gain calibration, and weakly polarized signal. We include this upper limit in an updated comparison to general relativistic magnetohydrodynamic simulation models. This analysis reinforces the previously reported preference for magnetically arrested accretion flow models. We find that most simulations naturally produce a low level of circular polarization consistent with our upper limit and that Faraday conversion is likely the dominant production mechanism for circular polarization at 230 GHz in M87*.

The Event Horizon Telescope (EHT) is a millimeter very long baseline interferometry (VLBI) array that has imaged the apparent shadows of the supermassive black holes M87* and Sagittarius A*. Polarimetric data from these observations contain a wealth of information on the black hole and accretion flow properties. In this work, we develop polarimetric geometric modeling methods for mm-VLBI data, focusing on approaches that fit data products with differing degrees of invariance to broad classes of calibration errors. We establish a fitting procedure using a polarimetric “m-ring” model to approximate the image structure near a black hole. By fitting this model to synthetic EHT data from general relativistic magnetohydrodynamic models, we show that the linear and circular polarization structure can be successfully approximated with relatively few model parameters. We then fit this model to EHT observations of M87* taken in 2017. In total intensity and linear polarization, the m-ring fits are consistent with previous results from imaging methods. In circular polarization, the m-ring fits indicate the presence of event-horizon-scale circular polarization structure, with a persistent dipolar asymmetry and orientation across several days. The same structure was recovered independently of observing band, used data products, and model assumptions. Despite this broad agreement, imaging methods do not produce similarly consistent results. Our circular polarization results, which imposed additional assumptions on the source structure, should thus be interpreted with some caution. Polarimetric geometric modeling provides a useful and powerful method to constrain the properties of horizon-scale polarized emission, particularly for sparse arrays like the EHT.

The optimal immunosuppressive therapy for elderly patients with ulcerative colitis (UC) remains unclear. We aimed to evaluate clinical practice and prognosis in elderly patients with UC through comparing between those with elderly-onset UC (EOUC) and those with long-standing elderly UC (LEUC). In this retrospective single-center cohort study, we evaluated elderly patients with UC aged = 60 in August 2022 through collecting medical record data from the time of diagnosis of UC until August 2022. The patients were divided into two groups based on age at disease onset: EOUC (age at onset, = 60 years) and LEUC (age at onset, < 60 years). We assessed the cumulative rates of systemic steroid and molecular targeted drug (MTD) initiation, and colectomy. We enrolled 97 eligible patients (EOUC group, n = 30; LEUC group, n = 67). The cumulative rates of initiating systemic steroid (46% vs. 22% at 1 year, respectively; P = 0.002) and MTD (17% vs. 5% at 1 year, respectively; P = 0.002) were higher in the EOUC group than in the LEUC group. In multivariate analysis, elderly onset was significantly associated with systemic steroid (hazard ratio [HR] 2.74, 95% confidence interval [CI] 1.43-5.29; P = 0.003) and MTD (HR 2.76, 95% CI 1.30-5.87; P = 0.008) initiation. Cumulative colectomy rates did not differ significantly between the two groups. Patients with EOUC were initiated on systemic steroids and MTDs sooner following disease onset than patients with LEUC. Our findings suggest rapid progression and refractoriness in patients with EOUC. [ABSTRACT FROM AUTHOR]

When a building is reconstructed, many existing piles that support the building are removed. After removing large-diameter piles, the holes are backfilled with various materials. In this study, vertical loading model tests were conducted for the case where a newly constructed pile overlaps clayey backfill columns whose properties differ from those of the surrounding sandy soil. The influence of the variation of the unconfined compressive strength of clayey soil backfill on the shaft resistance of a pile was investigated. The results indicated that the process of soil failure up to the maximum pile shaft resistance varies with the strength of the clayey soil backfill. The maximum shaft resistance of the pile was calculated based on the failure criteria of the soil and the cavity expansion theory, and the strength effect of the clayey soil backfill was estimated. For the pile shaft resistance overlapping partially clayey backfill columns in sandy soil to be equal to the pile shaft resistance in a homogeneous sandy soil, the shear strength of the clayey soil backfill must be higher than the pile shaft resistance in a homogeneous sandy soil. [ABSTRACT FROM AUTHOR]

Abstract Introduction Our previous clinical studies have demonstrated the short-term efficacy and safety of the sirolimus gel for patients with tuberous sclerosis complex (TSC). However, long-term clinical evidence is lacking. Our objective was to assess the safety and efficacy of long-term treatment with the sirolimus gel for the skin lesions of TSC patients. Methods We conducted a multicenter, open-label, uncontrolled clinical trial in 94 Japanese patients with TSC. Patients applied the 0.2% sirolimus gel on their face or head twice daily for > 52 weeks (maximum 136 weeks for safety). The safety endpoints were the rate of adverse event (AE)-caused discontinuation (primary endpoint) and the incidence of AEs. The efficacy endpoint was the response rate of angiofibromas, cephalic plaques, and hypomelanotic macules. Results Among 94 enrolled patients (mean age, 21 years; range 3–53 years), the rate of AE-caused discontinuation was 2.1% (2/94 patients). Although application site irritation and dry skin occurred relatively frequently, none of the drug-related AEs were serious; most of the drug-related AEs resolved rapidly. The major drug-related AEs (≥ 5% in incidence) were application site irritation (30.9%), dry skin (27.7%), acne (20.2%), eye irritation (8.5%), pruritus (8.5%), erythema (7.4%), dermatitis acneiform (6.4%), and dermatitis contact (5.3%). The response rates of angiofibromas, cephalic plaques, and hypomelanotic macules were 78.2% [95% confidence interval (CI) 68.0–86.3%], 66.7% (95% CI 51.1–80.0%), and 72.2% (95% CI 46.5–90.3%), respectively. Conclusions The gel was well tolerated for a long time by patients with TSC involving facial skin lesions and continued to be effective. Trial Registration ClinicalTrials.gov identifier: NCT02634931.

Abalone viscera, which accounts for more than 20% of body weight, is typically discarded. With increases in abalone aquaculture production, novel uses for abalone viscera are needed. Here, we evaluated the effects of abalone viscera fermented with Lactiplantibacillus pentosus SN001 on angiotensin-converting enzyme (ACE) activity and blood pressure elevation in spontaneously hypertensive rats. The fermented product significantly reduced systolic blood pressure compared with the control. There were no significant differences in blood glucose, triglyceride, total cholesterol, or high-density lipoprotein cholesterol levels; alanine aminotransferase activity; and aspartate aminotransferase activity between the fermented product and control groups. Uracil was isolated and identified from the fermented product. Uracil may be the active component. Overall, L. pentosus SN001-fermented abalone viscera showed sustained inhibitory effects on blood pressure elevation but did not alter blood components after long-term intake. These results provide insights into the safety of L. pentosus SN001-fermented abalone viscera as a food product.

We present here the East Asia to Italy Nearly Global VLBI (EATING VLBI) project. How this project started and the evolution of the international collaboration between Korean, Japanese, and Italian researchers to study compact sources with VLBI observations is reported. Problems related to the synchronization of the very different arrays and technical details of the telescopes involved are presented and discussed. The relatively high observation frequency (22 and 43 GHz) and the long baselines between Italy and East Asia produced high-resolution images. We present example images to demonstrate the typical performance of the EATING VLBI array. The results attracted international researchers and the collaboration is growing, now including Chinese and Russian stations. New in progress projects are discussed and future possibilities with a larger number of telescopes and a better frequency coverage are briefly discussed herein.

Blazars are a class of jet-dominated active galactic nuclei with a typical double-humped spectral energy distribution. It is of common consensus that the synchrotron emission is responsible for the low frequency peak, while the origin of the high frequency hump is still debated. The analysis of X-rays and their polarization can provide a valuable tool to understand the physical mechanisms responsible for the origin of high-energy emission of blazars. We report the first observations of BL Lacertae (BL Lac) performed with the Imaging X-ray Polarimetry Explorer, from which an upper limit to the polarization degree Π _X < 12.6% was found in the 2–8 keV band. We contemporaneously measured the polarization in radio, infrared, and optical wavelengths. Our multiwavelength polarization analysis disfavors a significant contribution of proton-synchrotron radiation to the X-ray emission at these epochs. Instead, it supports a leptonic origin for the X-ray emission in BL Lac.

Interpretation of resolved polarized images of black holes by the Event Horizon Telescope (EHT) requires predictions of the polarized emission observable by an Earth-based instrument for a particular model of the black hole accretion system. Such predictions are generated by general relativistic radiative transfer (GRRT) codes, which integrate the equations of polarized radiative transfer in curved spacetime. A selection of ray-tracing GRRT codes used within the EHT Collaboration is evaluated for accuracy and consistency in producing a selection of test images, demonstrating that the various methods and implementations of radiative transfer calculations are highly consistent. When imaging an analytic accretion model, we find that all codes produce images similar within a pixel-wise normalized mean squared error (NMSE) of 0.012 in the worst case. When imaging a snapshot from a cell-based magnetohydrodynamic simulation, we find all test images to be similar within NMSEs of 0.02, 0.04, 0.04, and 0.12 in Stokes I , Q , U , and V , respectively. We additionally find the values of several image metrics relevant to published EHT results to be in agreement to much better precision than measurement uncertainties.

We report on the observations of the quasar NRAO 530 with the Event Horizon Telescope (EHT) on 2017 April 5−7, when NRAO 530 was used as a calibrator for the EHT observations of Sagittarius A*. At z = 0.902, this is the most distant object imaged by the EHT so far. We reconstruct the first images of the source at 230 GHz, at an unprecedented angular resolution of ∼20 μ as, both in total intensity and in linear polarization (LP). We do not detect source variability, allowing us to represent the whole data set with static images. The images reveal a bright feature located on the southern end of the jet, which we associate with the core. The feature is linearly polarized, with a fractional polarization of ∼5%–8%, and it has a substructure consisting of two components. Their observed brightness temperature suggests that the energy density of the jet is dominated by the magnetic field. The jet extends over 60 μ as along a position angle ∼ −28°. It includes two features with orthogonal directions of polarization (electric vector position angle), parallel and perpendicular to the jet axis, consistent with a helical structure of the magnetic field in the jet. The outermost feature has a particularly high degree of LP, suggestive of a nearly uniform magnetic field. Future EHT observations will probe the variability of the jet structure on microarcsecond scales, while simultaneous multiwavelength monitoring will provide insight into the high-energy emission origin.

The Atacama Large Millimeter/submillimeter Array high-frequency long-baseline campaign in 2019 (HF-LBC-2019) was arranged to undertake band 9 (690 GHz) and 10 (850 GHz) observations using the longest 16 km baselines in order to explore calibration feasibility and imaging capabilities. Observations were arranged using close calibrators between 0° and 4° from the target point-source quasars (QSOs) to also explore subtle effects of calibrator separation angle. A total of 13 observations were made, five using standard in-band observations and eight using the band-to-band (B2B) observing mode, where phase solutions are transferred from a lower frequency band. At bands 9 and 10, image angular resolutions as high as 7 and 5 mas were achieved, respectively. Both in-band and B2B experiments were successful in imaging the target QSOs but with varying degrees of quality. Target image coherence varied between 0.14 and 0.79, driven by the calibrator separation angle and effectiveness of phase referencing despite observing in correct stability conditions. We conclude that the phase rms conditions and calibrator selection, specifically separation angle from the target, must carefully be considered prior to observing in order to minimize imaging defects. For bands 9 and 10, in order to achieve a coherence >0.7 such that the image structure and source flux can be regarded as suitably accurate, a 1° separated calibrator should be used while the phase rms over the phase switching cycle time should ideally be

In order to investigate the far-infrared excess detected from the western hot spot of the radio galaxy Pictor A with the Herschel observatory, submillimeter photometry is performed with the Atacama Compact Array (ACA) of the Atacama Large Millimeter/submillimeter Array at Band 8 with the reference frequency of 405 GHz. A submillimeter source is discovered at the radio peak of the hot spot. Because the 405 GHz flux density of the source, 80.7 ± 3.1 mJy, agrees with the extrapolation of the synchrotron radio spectrum, the far-infrared excess is suggested to exhibit no major contribution at the ACA band. In contrast, by subtracting the power-law spectrum tightly constrained by the radio and ACA data, the significance of the excess in the Herschel band is well confirmed. No diffuse submillimeter emission is detected within the ACA field of view, and thus, the excess is ascribed to the western hot spot itself. In comparison to the previous estimate based on the Herschel data, the relative contribution of the far-infrared excess is reduced by a factor of ∼1.5. The spectrum of the excess below the far-infrared band is determined to be harder than that of the diffusive shock acceleration. This strengthens the previous interpretation that the excess originates via the magnetic turbulence in the substructures within the hot spot. The ACA data are utilized to evaluate the magnetic field strength of the excess and of diffuse radio structure associated with the hot spot.

In 2017 the Event Horizon Telescope (EHT) observed the supermassive black hole at the center of the Milky Way, Sagittarius A* (Sgr A*), at a frequency of 228.1 GHz ( λ = 1.3 mm). The fundamental physics tests that even a single pulsar orbiting Sgr A* would enable motivate searching for pulsars in EHT data sets. The high observing frequency means that pulsars—which typically exhibit steep emission spectra—are expected to be very faint. However, it also negates pulse scattering, an effect that could hinder pulsar detections in the Galactic center. Additionally, magnetars or a secondary inverse Compton emission could be stronger at millimeter wavelengths than at lower frequencies. We present a search for pulsars close to Sgr A* using the data from the three most sensitive stations in the EHT 2017 campaign: the Atacama Large Millimeter/submillimeter Array, the Large Millimeter Telescope, and the IRAM 30 m Telescope. We apply three detection methods based on Fourier-domain analysis, the fast folding algorithm, and single-pulse searches targeting both pulsars and burst-like transient emission. We use the simultaneity of the observations to confirm potential candidates. No new pulsars or significant bursts were found. Being the first pulsar search ever carried out at such high radio frequencies, we detail our analysis methods and give a detailed estimation of the sensitivity of the search. We conclude that the EHT 2017 observations are only sensitive to a small fraction (≲2.2%) of the pulsars that may exist close to Sgr A*, motivating further searches for fainter pulsars in the region.

Abalone viscera are typically discarded in the food industry. This study evaluated the potential use of abalone viscera as a functional food. After fermentation by lactic acid bacteria, namely Lactobacillus casei 001, abalone viscera exhibited the ability to inhibit angiotensin-converting enzyme (ACE) and suppressed blood pressure increases in healthy mice and spontaneously hypertensive rats. Purification and characterization of extracts derived from fermented abalone viscera showed that the active component was homarine, which exhibited strong, noncompetitive ACE-inhibitory capacity. Altogether, these findings suggest that abalone viscera fermented by lactic acid bacteria hold potential as functional food materials to manage blood pressure.

Sargassum horneri is a seaweed with antihypertensive properties. However, it is underutilized in some areas, and effective utilization methods are being sought. In this study, we prepared a fermented S. horneri using lactic acid bacteria Lactiplantibacillus pentosus SN001 and investigated its effective utilization by enhancing its antihypertensive effect. The ACE inhibitory activity of S. horneri ranged from 3.6% to a maximum of 63.3% after fermentation. In vivo studies using mice and spontaneously hypertensive rats (SHR) suggested an antihypertensive effect of fermented S. horneri. Purification and NMR analysis of the ACE inhibitory component in fermented S. horneri identified glycerol. Therefore, it is suggested that glycerol is responsible for the strong antihypertensive effect of fermented S. horneri. In conclusion, S. horneri is expected to be used as a dietary ingredient with enhanced antihypertensive effect by fermentation with L. pentosus SN001.

Aplysiatoxin and its derivatives have been isolated from marine cyanobacteria. The biosynthesis of their characteristic bicyclic skeletons from a linear polyketide intermediate has been proposed. Two polyketides, aplysiadione (1) and aplysiaenal (2), were isolated from the marine cyanobacterium Moorea producens (formerly Lyngbya majuscula) collected in the Okinawan coastal area. The polyketide chemical structures were elucidated from HR ESI-MS and NMR spectra. Aplysiadione (1) corresponds to a decarboxylated analog of the proposed biosynthetic intermediate of aplysiatoxins. Aplysiaenal (2) is a truncated analog of the linear intermediate. The isolation of aplysiadione (1) strongly supports the proposed ring formation mechanisms for the aplysiatoxins, and this compound is a rare example of a biosynthetic intermediate of polyketide secondary metabolites from marine cyanobacteria.

Hidakakombu (Saccharina angustata), commonly known as kelp, is an edible macroalgae mainly grown in the Hidaka region of Hokkaido. Hidakakombu is graded based on its shape and color. Low-grade Hidakakombu has low value and is distributed at a low price. It is desired to establish a method to add value to low-grade Hidakakombu. In this study, low-grade Hidakakombu was fermented by Lacticaseibacillus casei 001 to add value. Fermentation of Hidakaombu enhanced the inhibition of blood pressure elevation due to ACE inhibition. L. casei 001 in fermented Hidakakombu remained viable in simulated gastric and intestinal juices. The ACE inhibitory component in L. casei 001-fermented Hidakakombu was isolated from the fraction below 3 kDa using high-performance liquid chromatography. The purified amino acid was identified as D-Trp using nuclear magnetic resonance, mass spectroscopy, and optical rotation measurements. This is the first report on the ACE inhibitory activity of D-Trp in L. casei 001-fermented Hidakakombu. Hidakakombu fermented by L. casei 001 was shown to be a source of probiotics and functional components against hypertension. Therefore, fermentation by L. casei 001 was found to be an effective means of adding high value to low-grade Hidakombu.

DNA methylation is considered the primary epigenetic mechanism underlying the development of malignant melanoma. Since DNA methylation can be influenced by environmental factors, it is preferable to compare cancer and normal cells from the same patient. In order to compare the methylation status in melanoma tissues and melanocytes from the same individuals, we employed a novel epidermal sheet cultivation technique to isolate normal melanocytes from unaffected sites of melanoma patients. We also analyzed primary and metastatic melanoma samples, three commercially available melanocytes, and four melanoma cell lines. Cluster analysis of DNA methylation data classified freshly isolated melanomas and melanocytes into the same group, whereas the four melanoma cell lines were clustered together in a distant clade. Moreover, our analysis discovered methylation at several novel loci (KRTCAP3, AGAP2, ZNF490), in addition to those identified in previous studies (COL1A2, GPX3); however, the latter two were not observed in fresh melanoma samples. Subsequent studies revealed that NPM2 was hypermethylated and downregulated in melanomas, which was consistent with previous reports. In many normal melanocytes, NPM2 showed distinct immunohistochemical staining, while its expression was lost in malignant melanoma cells. In particular, intraepithelial lesions of malignant melanoma, an important challenge in clinical practice, could be distinguished from benign nevi. The present findings indicate the importance of using fresh melanoma samples, not melanoma cell lines and melanocytes in epigenetic studies. In addition, NPM2 immunoreactivity could be used to differentiate melanomas from normal melanocytes or benign disease.

Japanese scallops, Patinopecten yessoensis, were fed with the toxic dinoflagellate Dinophysis fortii to elucidate the relative magnitude of assimilation, accumulation, and metabolism of diarrhetic shellfish toxins (DSTs) and pectenotoxins (PTXs). Three individual scallops were separately exposed to cultured D. fortii for four days. The average cell number of D. fortii assimilated by each individual scallop was 7.7 × 105. Dinophysistoxin-1 (DTX1), pectenotoxin-2 (PTX2) and their metabolites were analyzed by liquid chromatography tandem mass spectrometry (LC/MS/MS) and the toxin content in individual tissues (digestive gland, adductor muscle, gill, gonad, mantle, and the others), feces and the seawater medium were quantified. Toxins were almost exclusively accumulated in the digestive gland with only low levels being detected in the gills, mantles, gonads, and adductor muscles. DTX1 and PTX2 were the dominant toxins in the D. fortii cells fed to the scallops, whereas the dominant toxins detected in the digestive gland of scallops were PTX6 and esterified acyl-O-DTX1 (DTX3). In other tissues PTX2 was the dominant toxin observed. The ratio of accumulated to assimilated toxins was 21%–39% and 7%–23% for PTXs and DTXs respectively. Approximately 54%–75% of PTX2 and 52%–70% of DTX1 assimilated by the scallops was directly excreted into the seawater mainly without metabolic transformation.

In this study, compressive loading tests of pile-overlapping backfilled soil were performed to investigate the effect of the dimensions and location of backfilled sand with different densities on the shaft resistance of the pile. The results showed that when the backfilled soil is dense sand, the shaft resistance is affected by the dimensions and location of the sand. The earth pressure at which the maximum value of the shaft resistance is reached is shown to be related to the distance from the outer surface of the pile to the outer edge of the backfilled sand (i.e., the width of the backfilled sand). Thereafter, a method was developed to evaluate the earth pressure related to the shaft resistance of the pile according to the width of the backfilled sand by dividing the sand into several segments in the circumferential direction. Based on these results, a calculation method was developed to calculate the maximum axial resistance of the pile considering various conditions (dimensions, location, and density) of the backfilled sand. [ABSTRACT FROM AUTHOR]

Cubozoan nematocyst venoms contain known cytolytic and hemolytic proteins, but small molecule components have not been previously reported from cubozoan venom. We screened nematocyst extracts of Alatina alata and Chironex yamaguchii by LC-MS for the presence of small molecule metabolites. Three isomeric compounds, cnidarins 4A (1), 4B (2), and 4C (3), were isolated from venom extracts and characterized by NMR and MS, which revealed their planar structure as cyclic γ-linked tetraglutamic acids. The full configurational assignments were established by syntheses of all six possible stereoisomers, comparison of spectral data and optical rotations, and stereochemical analysis of derivatized degradation products. Compounds 1−3 were subsequently detected by LC-MS in tissues of eight other cnidarian species. The most abundant of these compounds, cnidarin 4A (1), showed no mammalian cell toxicity or hemolytic activity, which may suggest a role for these cyclic tetraglutamates in nematocyst discharge.