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The system of equations describing motion of compressible viscoelastic fluids is considered in a one dimensional half space under the outflow boundary condition. We investigate the existence and stability of stationary solutions. It is shown that the stationary solution exists for large Mach number and small number of propagation speed of elastic wave. We next show that the stationary solution is asymptotically stable, provided that the initial perturbation is sufficiently small.

Aims: This study aimed to evaluate the geometrical accuracy of atlas-based auto-segmentation (ABAS), deformable image registration (DIR), and deep learning auto-segmentation (DLAS) in adaptive radiotherapy (ART) for head-and-neck cancer (HNC). Subjects and Methods: Seventeen patients who underwent replanning for ART were retrospectively studied, and delineated contours on their replanning computed tomography (CT2) images were delineated. For DIR, the planning CT image (CT1) of the evaluated patients was utilized. In contrast, ABAS was performed using an atlas dataset comprising 30 patients who were not part of the evaluated group. DLAS was trained with 143 patients from different patients from the evaluated patients. The ABAS model was improved, and a modified ABAS (mABAS) was created by adding the evaluated patients’ own CT1 to the atlas datasets of ABAS (number of patients of the atlas dataset, 31). The geometrical accuracy of DIR, DLAS, ABAS, and mABAS was evaluated. Results: The Dice similarity coefficient in DIR was the highest, at >0.8 at all organs at risk. The mABAS was delineated slightly more accurately than the standard ABAS. There was no significant difference between ABAS and DLAS in delineation accuracy. DIR had the lowest Hausdorff distance (HD) value (within 10 mm). The HD values in ABAS, mABAS, and DLAS were within 16 mm. Conclusions: DIR delineation is the most geometrically accurate ART for HNC.

A recent report on the detection of very-high-energy gamma rays from V4641 Sagittarii (V4641 Sgr) up to ≈0.8 PeV has made it the second confirmed “PeVatron” microquasar. Here we report on the observation of V4641 Sgr with X-Ray Imaging and Spectroscopy Mission (XRISM) in 2024 September. Thanks to the large field of view and low background, the CCD imager Xtend successfully detected for the first time X-ray extended emission around V4641 Sgr with a significance of ≳4.5 σ and >10 σ based on our imaging and spectral analysis, respectively. The spatial extent is estimated to have a radius of 7′ ± 3′ (13 ± 5 pc at a distance of 6.2 kpc) assuming a Gaussian-like radial distribution, which suggests that the particle acceleration site is within ~10 pc of the microquasar. If the X-ray morphology traces the diffusion of accelerated electrons, this spatial extent can be explained by either an enhanced magnetic field (∼80 μ G) or a suppressed diffusion coefficient (∼10 ^27 cm ^2 s ^−1 at 100 TeV). The integrated X-ray flux, (4–6) × 10 ^−12 erg s ^−1 cm ^−2 (2–10 keV), would require a magnetic field strength higher than the Galactic mean (≳8 μ G) if the diffuse X-ray emission originates from synchrotron radiation and the gamma-ray emission is predominantly hadronic. If the X-rays are of thermal origin, the measured extension, temperature, and plasma density can be explained by a jet with a luminosity of ∼2 × 10 ^39 erg s ^−1 , which is comparable to the Eddington luminosity of this system.

The X-ray binary system Cygnus X-3 (4U 2030+40, V1521 Cyg) is luminous but enigmatic owing to the high intervening absorption. High-resolution X-ray spectroscopy uniquely probes the dynamics of the photoionized gas in the system. In this Letter, we report on an observation of Cyg X-3 with the XRISM/Resolve spectrometer, which provides unprecedented spectral resolution and sensitivity in the 2–10 keV band. We detect multiple kinematic and ionization components in absorption and emission whose superposition leads to complex line profiles, including strong P Cygni profiles on resonance lines. The prominent Fe xxv He α and Fe xxvi Ly α emission complexes are clearly resolved into their characteristic fine-structure transitions. Self-consistent photoionization modeling allows us to disentangle the absorption and emission components and measure the Doppler velocity of these components as a function of binary orbital phase. We find a significantly higher velocity amplitude for the emission lines than for the absorption lines. The absorption lines generally appear blueshifted by ∼−500–600 km s ^−1 . We show that the wind decomposes naturally into a relatively smooth and large-scale component, perhaps associated with the background wind itself, plus a turbulent, denser structure located close to the compact object in its orbit.

We present an analysis of the first two XRISM/Resolve spectra of the well-known Seyfert-1.5 active galactic nucleus (AGN) in NGC 4151, obtained in 2023 December. Our work focuses on the nature of the narrow Fe K _α emission line at 6.4 keV, the strongest and most common X-ray line observed in AGN. The total line is found to consist of three components. Even the narrowest component of the line is resolved with evident Fe K _α _,1 (6.404 keV) and K _α _,2 (6.391 keV) contributions in a 2:1 flux ratio, fully consistent with neutral gas with negligible bulk velocity. Subject to the limitations of our models, the narrowest and intermediate-width components are consistent with emission from optically thin gas, suggesting that they arise in a disk atmosphere and/or wind. Modeling the three line components in terms of Keplerian broadening, they are readily associated with (1) the inner wall of the “torus,” (2) the innermost optical “broad-line region” (or “X-ray BLR”), and (3) a region with a radius of r ≃ 100 GM / c ^2 that may signal a warp in the accretion disk. Viable alternative explanations of the broadest component include a fast-wind component and/or scattering; however, we find evidence of variability in the narrow Fe K _α line complex on timescales consistent with small radii. The best-fit models are statistically superior to simple Voigt functions, but when fit with Voigt profiles the time-averaged lines are consistent with a projected velocity broadening of FWHM $\,=\,{1600}_{-200}^{+400}\,\mathrm{km}\,{{\rm{s}}}^{-1}$ . Overall, the resolution and sensitivity of XRISM show that the narrow Fe K line in AGN is an effective probe of all key parts of the accretion flow, as it is currently understood. We discuss the implications of these findings for our understanding of AGN accretion, future studies with XRISM, and X-ray-based black hole mass measurements.

Summary: Lymphocyte trafficking requires fine-tuning of chemokine-mediated cell migration. This process depends on cytoskeletal dynamics and polarity, but its regulation remains elusive. We quantitatively measured cell polarity and revealed critical roles performed by integrin activator Rap1 in this process, independent of substrate adhesion. Rap1-deficient naive T cells exhibited impaired abilities to reorganize the actin cytoskeleton into pseudopods and actomyosin-rich uropods. Rap1-GTPase activating proteins (GAPs), Rasa3 and Sipa1, maintained an unpolarized shape; deletion of these GAPs spontaneously induced cell polarization, indicative of the polarizing effect of Rap1. Rap1 activation required F-actin scaffolds, and stimulated RhoA activation and actomyosin contractility at the rear. Furthermore, talin1 acted on Rap1 downstream effectors to promote actomyosin contractility in the uropod, which occurred independently of substrate adhesion and talin1 binding to integrins. These findings indicate that Rap1 signaling to RhoA and talin1 regulates chemokine-stimulated lymphocyte polarization and chemotaxis in a manner independent of adhesion.

Abstract We established a multi-institution model (big model) of knowledge-based treatment planning with over 500 treatment plans from five institutions in volumetric modulated arc therapy (VMAT) for prostate cancer. This study aimed to clarify the efficacy of using a large number of registered treatment plans for sharing the big model. The big model was created with 561 clinically approved VMAT plans for prostate cancer from five institutions (A: 150, B: 153, C: 49, D: 60, and E: 149) with different planning strategies. The dosimetric parameters of planning target volume (PTV), rectum, and bladder for two validation VMAT plans generated with the big model were compared with those from each institutional model (single-institution model). The goodness-of-fit of regression lines (R2 and χ2 values) and ratios of the outliers of Cook’s distance (CD) > 4.0, modified Z-score (mZ) > 3.5, studentized residual (SR) > 3.0, and areal difference of estimate (dA) > 3.0 for regression scatter plots in the big model and single-institution model were also evaluated. The mean ± standard deviation (SD) of dosimetric parameters were as follows (big model vs. single-institution model): 79.0 ± 1.6 vs. 78.7 ± 0.5 (D50) and 0.13 ± 0.06 vs. 0.13 ± 0.07 (Homogeneity Index) for the PTV; 6.6 ± 4.0 vs. 8.4 ± 3.6 (V90) and 32.4 ± 3.8 vs. 46.6 ± 15.4 (V50) for the rectum; and 13.8 ± 1.8 vs. 13.3 ± 4.3 (V90) and 39.9 ± 2.0 vs. 38.4 ± 5.2 (V50) for the bladder. The R2 values in the big model were 0.251 and 0.755 for rectum and bladder, respectively, which were comparable to those from each institution model. The respective χ2 values in the big model were 1.009 and 1.002, which were closer to 1.0 than those from each institution model. The ratios of the outliers in the big model were also comparable to those from each institution model. The big model could generate a comparable VMAT plan quality compared with each single-institution model and therefore could possibly be shared with other institutions.

Rap1-GTPase activates integrins and plays an indispensable role in lymphocyte trafficking, but the importance of Rap1 inactivation in this process remains unknown. Here we identified the Rap1-inactivating proteins Rasa3 and Sipa1 as critical regulators of lymphocyte trafficking. The loss of Rasa3 and Sipa1 in T cells induced spontaneous Rap1 activation and adhesion. As a consequence, T cells deficient in Rasa3 and Sipa1 were trapped in the lung due to firm attachment to capillary beds, while administration of LFA1 antibodies or loss of talin1 or Rap1 rescued lung sequestration. Unexpectedly, mutant T cells exhibited normal extravasation into lymph nodes, fast interstitial migration, even greater chemotactic responses to chemokines and sphingosine-1-phosphate, and entrance into lymphatic sinuses but severely delayed exit: mutant T cells retained high motility in lymphatic sinuses and frequently returned to the lymph node parenchyma, resulting in defective egress. These results reveal the critical trafficking processes that require Rap1 inactivation.

Summary: Bidirectional control of integrin activation plays crucial roles in cell adhesive behaviors, but how integrins are specifically regulated by inside-out and outside-in signaling has not been fully understood. Here, we report distinct bidirectional regulation of major lymphocyte homing receptors LFA1 and α4β7 in primary T cells. A small increase of Rap1 activation in L-selectin-mediated tether/rolling was boosted by the outside-in signaling from ICAM1-interacting LFA1 through subsecond, simultaneous activation of Rap1 GTPase and talin1, but not kindlin-3, resulting in increased capture and slowing. In contrast, none of them were required for tether/rolling by α4β7 on MAdCAM1. High Rap1 activation with chemokines or the loss of Rap1-inactivating proteins Rasa3 and Sipa1 increased talin1/kindlin-3-dependent arrest with high-affinity binding of LFA1 to membrane-anchored ICAM1. However, despite increased affinity of α4β7, activated Rap1 severely suppressed adhesion on MAdCAM1 under shear flow, indicating the critical importance of a sequential outside-in/inside-out signaling for α4β7.

Hard X-ray-selected samples of active galactic nuclei (AGN) provide one of the cleanest views of supermassive black hole accretion but are biased against objects obscured by Compton-thick gas column densities of N _H > 10 ^24 cm ^−2 . To tackle this issue, we present the NuSTAR Local AGN N _H Distribution Survey (NuLANDS)—a legacy sample of 122 nearby ( z < 0.044) AGN primarily selected to have warm infrared colors from IRAS between 25 and 60 μ m. We show that optically classified Type 1 and 2 AGN in NuLANDS are indistinguishable in terms of optical [O iii ] line flux and mid-to-far-infrared AGN continuum bolometric indicators, as expected from an isotropically selected AGN sample, while Type 2 AGN are deficient in terms of their observed hard X-ray flux. By testing many X-ray spectroscopic models, we show the measured line-of-sight column density varies on average by ∼1.4 orders of magnitude depending on the obscurer geometry. To circumvent such issues, we propagate the uncertainties per source into the parent column density distribution, finding a directly measured Compton-thick fraction of 35% ± 9%. By construction, our sample will miss sources affected by severe narrow-line reddening, and thus segregates sources dominated by small-scale nuclear obscuration from large-scale host-galaxy obscuration. This bias implies an even higher intrinsic obscured AGN fraction may be possible, although tests for additional biases arising from our infrared selection find no strong effects on the measured column density distribution. NuLANDS thus holds potential as an optimized sample for future follow-up with current and next-generation instruments aiming to study the local AGN population in an isotropic manner.

We present a statistical study of 180 dust continuum sources identified in 33 massive cluster fields by the Atacama Large Millimeter/submillimeter Array Lensing Cluster Survey (ALCS) over a total of 133 arcmin ^2 area, homogeneously observed at 1.2 mm. ALCS enables us to detect extremely faint millimeter sources by lensing magnification, including near-infrared (NIR) dark objects showing no counterparts in existing Hubble Space Telescope and Spitzer images. The dust continuum sources belong to a blind sample ( N = 141) with signal-to-noise ratio (S/N) ≳ 5.0 (a purity of >0.99) or a secondary sample ( N = 39) with S/N = 4.0–5.0 screened by priors. With the blind sample, we securely derive 1.2 mm number counts down to ∼7 μ Jy, and find that the total integrated 1.2 mm flux is ${20.7}_{-6.5}^{+8.5}$ Jy deg ^−2 , resolving ≃80% of the cosmic infrared background light. The resolved fraction varies by a factor of 0.6–1.1 due to the completeness correction depending on the spatial size of the millimeter emission. We also derive infrared (IR) luminosity functions (LFs) at z = 0.6–7.5 with the $1/{V}_{\max }$ method, finding the redshift evolution of IR LFs characterized by positive luminosity and negative density evolution. The total (= UV + IR) cosmic star formation rate density (SFRD) at z > 4 is estimated to be ${161}_{-21}^{+25}$ % of the Madau and Dickinson measurements mostly based on rest-frame UV surveys. Although our general understanding of the cosmic SFRD is unlikely to change beyond a factor of 2, these results add to the weight of evidence for an additional (≈60%) SFRD component contributed by the faint millimeter population, including NIR-dark objects.

We perform a systematic, multiwavelength spectral energy distribution (SED) analysis of X-ray detected active galactic nuclei (AGNs) at z = 0.2–0.8 with Sloan Digital Sky Survey (SDSS) counterparts in the Stripe 82 region, consisting of 60 type 1 and 137 type 2 AGNs covering a 2–10 keV luminosity range of $41.6\lt \mathrm{log}\ {L}_{{\rm{x}}}\lt 44.7$ . The latest CIGALE code, where dusty polar components are included, is employed. To obtain reliable host and AGN parameters in type 1 AGNs, we utilize the image-decomposed optical SEDs of host galaxies by Li et al. based on the Subaru Hyper-Suprime Cam images. The mean ratio of black hole masses ( M _BH ) and stellar masses ( M _stellar ) of our X-ray detected type 1 AGN sample, $\mathrm{log}({M}_{\mathrm{BH}}/{M}_{\mathrm{stellar}})=-2.7\pm 0.5$ , is close to the local relation between BH and stellar masses as reported by Li et al. for SDSS quasars. This ratio is slightly lower than that found for more luminous ( $\mathrm{log}{L}_{\mathrm{bol}}\gt 45$ ) type 1 AGNs at z ∼ 1.5. This can be explained by the AGN luminosity dependence of $\mathrm{log}({M}_{\mathrm{BH}}/{M}_{\mathrm{stellar}})$ , which little evolves with redshift. We confirm the trend that the UV-to-X-ray slope ( α _OX ) or X-ray-to-bolometric correction factor ( κ _2–10 ) increases with AGN luminosity or Eddington ratio. We find that type 1 and type 2 AGNs with the same luminosity ranges share similar host stellar mass distributions, whereas type 2s tend to show smaller AGN luminosities than type 1s. This supports the luminosity-dependent (or Eddington-ratio-dependent) unified scheme.

We investigate the black hole mass function (BHMF) and Eddington-ratio distribution function (ERDF) of broad-line active galactic nuclei (AGNs) at z = 4, based on a sample of 52 quasars with i < 23.2 at 3.50 ≤ z ≤ 4.25 from the Hyper Suprime-Cam Subaru Strategic Program S16A-Wide2 data set, and 1462 quasars with i < 20.2 in the same redshift range from the Sloan Digital Sky Survey data release 7 quasar catalog. Virial black hole (BH) masses of quasars are estimated using the width of the C _IV 1549 Å line and the continuum luminosity at 1350 Å. To obtain the intrinsic broad-line AGN BHMF and ERDF, we correct for the incompleteness in the low-mass and/or low-Eddington-ratio ranges caused by the flux-limited selection. The resulting BHMF is constrained down to $\mathrm{log}{M}_{\mathrm{BH}}/{M}_{\odot }\sim 7.5$ . In comparison with broad-line AGN BHMFs at z ∼ 2 in the literature, we find that the number density of massive SMBHs peaks at higher redshifts, consistent with the downsizing evolutionary scenario. Additionally, the resulting ERDF shows a negative dependence on BH mass, suggesting more massive SMBHs tend to accrete at lower-Eddington ratios at z = 4. With the derived intrinsic broad-line AGN BHMF, we also evaluate the active fraction of broad-line AGNs among the entire SMBH population at z = 4. The resulting active fraction may suggest a positive dependence on BH mass. Finally, we examine the time evolution of broad-line AGN BHMF between z = 4 and 6 through solving the continuity equation. The results suggest that the broad-line AGN BHMFs at z = 4–6 only show evolution in their normalization, but with no significant changes in their shape.

Sub/millimeter galaxies are a key population for the study of galaxy evolution because the majority of star formation at high redshifts occurred in galaxies deeply embedded in dust. To search for this population, we have performed an extensive survey with Atacama Large Millimeter/submillimeter Array (ALMA), called the ALMA Lensing Cluster Survey (ALCS). This survey covers 133 arcmin ^2 area and securely detects 180 sources at z ∼ 0.5–6 with a flux limit of ∼0.2 mJy at 1.2 mm. Here, we report the results of multiwavelength spectral energy distribution analysis of the whole ALCS sample, utilizing the observed-frame UV to millimeter photometry. We find that the majority of the ALCS sources lie on the star-forming main sequence, with a smaller fraction showing intense starburst activities. The ALCS sample contains high infrared-excess sources ( $\mathrm{IRX}=\mathrm{log}({L}_{\mathrm{dust}}/{L}_{\mathrm{UV}})\gt 1$ ), including two extremely dust-obscured galaxies (IRX > 5). We also confirm that the ALCS sample probes a broader range in lower dust mass than conventional submillimeter galaxy samples in the same redshift range. We identify six heavily obscured active galactic nucleus (AGN) candidates that are not detected in the archival Chandra data in addition to the three X-ray AGNs reported by Uematsu et al. (2023). The inferred AGN luminosity density shows a possible excess at z = 2–3 compared with that determined from X-ray surveys below 10 keV.

We study “buried” active galactic nuclei (AGNs) almost fully covered by circumnuclear material in ultra/luminous infrared galaxies (U/LIRGs), which show weak ionized lines from narrow-line regions. Employing an indicator of a [O iv ] 25.89 or [Ne v ] 14.32 μ m line to 12 μ m AGN luminosity ratio, we find 17 buried AGN candidates that are [O iv ]-weak ( L _[O _IV _] / L _12,AGN ≤ −3.0) or [Ne v ]-weak ( L _[Ne V] / L _12,AGN ≤ −3.4) among 30 AGNs in local U/LIRGs. For the [O iv ]-weak AGNs, we estimate their covering fractions of Compton-thick (CT; N _H ≥ 10 ^24 cm ^−2 ) material with an X-ray clumpy torus model to be ${f}_{\mathrm{CT}}^{(\mathrm{spec})}=0.55\pm 0.19$ on average. This value is consistent with the fraction of CT AGNs ( ${f}_{\mathrm{CT}}^{(\mathrm{stat})}=53 \% \pm 12 \% $ ) among the [O iv ]-weak AGNs in U/LIRGs and much larger than that in Swift/Burst Alert Telescope (BAT) AGNs (23% ± 6%). The fraction of [O iv ]-weak AGNs increases from ${27}_{-10}^{+13} \% $ (early) to ${66}_{-12}^{+10} \% $ (late mergers). Similar results are obtained with the [Ne v ] line. The [O iv ]- or [Ne v ]-weak AGNs in late mergers show larger N _H and Eddington ratios ( λ _Edd ) than those of the Swift/BAT AGNs, and the largest N _H is ≳10 ^25 cm ^−2 at $\mathrm{log}{\lambda }_{\mathrm{Edd}}\sim -1$ , close to the effective Eddington limit for CT material. These suggest that (1) the circumnuclear material in buried AGNs is regulated by the radiation force from high- λ _Edd AGNs on the CT obscurers, and (2) their dense material with large ${f}_{\mathrm{CT}}^{(\mathrm{spec})}$ (∼0.5 ± 0.1) in U/LIRGs is a likely cause of a unique structure of buried AGNs, whose amount of material may be maintained through merger-induced supply from their host galaxies.

Herein, we present the statistical properties of active galactic nuclei (AGNs) for approximately 1 million member galaxies of galaxy groups and clusters with 0.1 < cluster redshift ( z _cl ) < 1.4 selected using the Subaru Hyper Suprime-Cam, the so-called CAMIRA clusters. In this research, we focused on the AGN power fraction ( f _AGN ), which is defined as the proportion of the contribution of AGNs to the total infrared (IR) luminosity, L _IR (AGN)/ L _IR , and examined how f _AGN depends on (i) z _cl and (ii) the distance from the cluster center. We compiled multiwavelength data using the ultraviolet–mid-IR range. Moreover, we performed spectral energy distribution fits to determine f _AGN using the CIGALE code with the SKIRTOR AGN model. We found that (i) the value of f _AGN in the CAMIRA clusters is positively correlated with z _cl , with the correlation slope being steeper than that for field galaxies, and (ii) f _AGN exhibits a high value at the cluster outskirts. These results indicate that the emergence of the AGN population depends on the redshift and environment and that galaxy groups and clusters at high redshifts are important in AGN evolution. Additionally, we demonstrated that cluster–cluster mergers may enhance AGN activity at the outskirts of particularly massive galaxy clusters. Our findings are consistent with a related study on the CAMIRA clusters that was based on the AGN number fraction.

As an inaugural investigation under the X-ray Winds In Nearby-to-distant Galaxies (X-WING) program, we assembled a data set comprising 132 active galactic nuclei (AGNs) spanning redshifts z ∼ 0–4 characterized by blueshifted absorption lines indicative of X-ray winds. Through an exhaustive review of previous research, we compiled the outflow parameters for 583 X-ray winds, encompassing key attributes such as outflow velocities ( V _out ), ionization parameters ( ξ ), and hydrogen column densities. By leveraging the parameters V _out and ξ , we systematically categorized the winds into three distinct groups: ultrafast outflows (UFOs), low-ionization parameter (low-IP) UFOs, and warm absorbers (WAs). Strikingly, a discernible absence of linear correlations in the outflow parameters, coupled with distributions approaching instrumental detection limits, was observed. Another notable finding was the identification of a velocity gap around V _out ∼ 10,000 km s ^−1 . This gap was particularly evident in the winds detected via absorption lines within the ≲2 keV band, indicating disparate origins for low-IP UFOs and WAs. In cases involving Fe xxv /Fe xxvi lines, where the gap might be attributed to potential confusion between emission/absorption lines and the Fe K-edge, the possibility of UFOs and galactic-scale WAs being disconnected is considered. An examination of the outflow and dust sublimation radii revealed a distinction: UFOs appear to consist of dust-free material, whereas WAs likely comprise dusty gas. From 2024, the X-Ray Imaging and Spectroscopy Mission is poised to alleviate observational biases, providing insights into the authenticity of the identified gap, a pivotal question in comprehending AGN feedback from UFOs.

Purpose: To evaluate customizing a knowledge-based planning (KBP) model using dosimetric analysis for volumetric modulated arc therapy for pancreatic cancer. Materials and Methods: The first model (M1) using 56 plans and the second model (M2) using 31 plans were created in the first 7 months of the study. The ratios of volume of both kidneys overlapping the expanded planning target volume to the total volume of both kidneys (Voverlap/Vwhole) were calculated in all cases to customize M1. Regression lines were derived from Voverlap/Vwhole and mean dose to both kidneys. The third model (M3) was created using 30 plans which data put them below the regression line. For validation, KBP was performed with the three models on 21 patients. Results: V18 of the left kidney for M1 plans was 7.3% greater than for clinical plans. Dmean of the left kidney for M2 plans was 2.2% greater than for clinical plans. There was no significant difference between all kidney doses in M3 and clinical plans. Dmean of the left kidney for M2 plans was 2.2% greater than for clinical plans. Dmean to both kidneys did not differ significantly between the three models in validation plans with Voverlap/Vwhole lower than average. In plans with larger than average volumes, the Dmean of validation plans created by M3 was significantly lower for both kidneys by 1.7 and 0.9 Gy than with M1 and M2, respectively. Conclusions: Selecting plans to register in a model by analyzing dosimetry and geometry is an effective means of improving the KBP model.

Since the discovery of mechanically planar chiral rotaxanes and topologically chiral catenanes, their asymmetric synthesis has been a long-standing challenge. Here, the authors report enantioselective preparation of mechanically planar chiral rotaxanes with up to 99.9% ee in 29% yield.

Background/Aim: HyperArc (HA) is an automated planning technique enabling single-isocenter brain stereotactic radiotherapy (SRT); however, dosimetric outcomes may be influenced by the planner's expertise. This study aimed to assess the impact of institutional experience on the plan quality of HA-SRT for both single and multiple brain metastases. Materials and Methods: Twenty patients who underwent HASRT for single metastasis between 2020 and 2021 comprised the earlier group, while those treated between 2022 and 2024 constituted the later group. For multiple metastases, 40 patients who received HA-SRT from 2020-2024 were divided into earlier and later treatment groups. Dosimetric parameters including gross tumor volume (GTV) doses (D98% and Dmean), volumes of the normal brain (Brain-GTV V25Gy and V30Gy), homogeneity index (HI), gradient index (GI), and total monitor unit (MU) were compared. A linear regression model was used to evaluate the effects of planning target volume (PTV) on volumes of normal brain via interaction between PTV volume and treatment era group (earlier vs. later). Results: The later group exhibited significantly higher D98% and Dmean values for both single and multiple metastases, while V25Gy and V30Gy and GI mean values were comparable. Consequently, mean HI and total MU values increased significantly. Both single and multiple metastases showed significant interaction between PTV volume and treatment era group. Conclusion: Enhanced dosimetric outcomes in the later group suggested that accumulated experience contributed to improve GTV and brain dose in HA SRT. Institutional experience is important to improve the plan quality for SRT even with automatic planning such as HA. [ABSTRACT FROM AUTHOR]

Abstract Background Total scalp irradiation presents technical and dosimetric challenges. While reports suggest that HyperArc, a new stereotactic radiosurgery planning technique applied to non-coplanar volumetric-modulated arc therapy (VMAT) technique, is associated with high conformity and rapid dose fall-off, the performance of HyperArc for total scalp irradiation has not been explored. The current study aimed to compare the dosimetric performance of HyperArc plans with those of non-coplanar VMAT plans in angiosarcoma of the scalp. Methods Ten patients with angiosarcoma of the scalp were included in this study. The performance of three different plans administered using TrueBeam Edge were compared: non-coplanar VMAT using flattening filter (FF) beams (VMAT-FF), HyperArc using FF beams (HyperArc-FF), and HyperArc using flattening filter free (FFF) beams (HyperArc-FFF). The dose distribution, dosimetric parameters, and dosimetric accuracy for each of these plans were evaluated. Results The three plans showed no statistically significant differences in target volume coverage, conformity, and homogeneity. The HyperArc-FF and HyperArc-FFF plans provided significantly lower mean brain doses (12.63 ± 3.31 Gy and 12.71 ± 3.40 Gy) than did the VMAT-FF plans (17.11 ± 5.25 Gy). There were almost no differences in sparing the organs at risk between the HyperArc-FF and HyperArc-FFF plans. The HyperArc-FF and HyperArc-FFF plans provided a shorter beam-on time than did the VMAT-FF plan. The 3%/2 mm gamma test pass rates were above 95% for all three plans. Conclusions Our results suggest that the HyperArc plan can be potentially used for radiation therapy of target regions with large and complicated shapes, such as the scalp, and that there are no advantages of using FFF beams.

Introduction: Several studies have reported the relation between the imaging dose and secondary cancer risk and have emphasized the need to minimize the additional imaging dose as low as reasonably achievable. The iterative cone-beam computed tomography (iCBCT) algorithm can improve the image quality by utilizing scatter correction and statistical reconstruction. We investigate the use of a novel iCBCT reconstruction algorithm to reduce the patient dose while maintaining low-contrast detectability and registration accuracy. Methods: Catphan and anthropomorphic phantoms were analyzed. All CBCT images were acquired with varying dose levels and reconstructed with a Feldkamp–Davis–Kress algorithm-based CBCT (FDK-CBCT) and iCBCT. The low-contrast detectability was subjectively assessed using a 9-point scale by 4 reviewers and objectively assessed using structure similarity index (SSIM). The soft tissue-based registration error was analyzed for each dose level and reconstruction technique. Results: The results of subjective low-contrast detectability found that the iCBCT acquired at two-thirds of a dose was superior to the FDK-CBCT acquired at a full dose (6.4 vs 5.4). Relative to FDK-CBCT acquired at full dose, SSIM was higher for iCBCT acquired at one-sixth dose in head and head and neck region while equivalent with iCBCT acquired at two-thirds dose in pelvis region. The soft tissue-based registration was 2.2 and 0.6 mm for FDK-CBCT and iCBCT, respectively. Conclusion: Use of iCBCT reconstruction algorithm can generally reduce the patient dose by approximately two-thirds compared to conventional reconstruction methods while maintaining low-contrast detectability and accuracy of registration.

We report the multiwavelength properties of millimeter galaxies hosting X-ray detected active galactic nuclei (AGNs) from the ALMA Lensing Cluster Survey (ALCS). ALCS is an extensive survey of well-studied lensing clusters with ALMA, covering an area of 133 arcmin ^2 over 33 clusters with a 1.2 mm flux-density limit of ∼60 μ Jy (1 σ ). Utilizing the archival data of Chandra, we identify three AGNs at z = 1.06, 2.09, and 2.84 among the 180 millimeter sources securely detected in the ALCS (of which 155 are inside the coverage of Chandra). The X-ray spectral analysis shows that two AGNs are not significantly absorbed ( $\mathrm{log}{N}_{{\rm{H}}}/{\mathrm{cm}}^{-2}\lt 23$ ), while the other shows signs of moderate absorption ( $\mathrm{log}{N}_{{\rm{H}}}/{\mathrm{cm}}^{-2}\sim 23.5$ ). We also perform spectral energy distribution modeling of X-ray to millimeter photometry. We find that our X-ray AGN sample shows both high mass-accretion rates (intrinsic 0.5–8 keV X-ray luminosities of ∼10 ^44–45 erg s ^−1 ) and star formation rates (≳100 M _⊙ yr ^−1 ). This demonstrates that a wide-area survey with ALMA and Chandra can selectively detect intense growth of both galaxies and supermassive black holes in the high-redshift universe.

We conduct hard X-ray to radio multiwavelength spectral energy distribution (SED) decomposition for 57 local luminous and ultraluminous infrared galaxies observed with the Nuclear Spectroscopic Telescope Array and/or Swift/Burst Alert Telescope in the GOALS sample. We modify the latest SED-fitting code X-CIGALE by implementing the infrared (IR) CLUMPY model, allowing us to conduct the multiwavelength study with the X-ray torus model XCLUMPY self-consistently. Adopting the torus parameters obtained by the X-ray fitting, we estimate the properties of the host galaxies, active galactic nucleus (AGN) tori, and polar dust. The star formation rates (SFRs) become larger with merger stage and most of them are above the main sequence. The SFRs are correlated with radio luminosity, indicating starburst emission is dominant in the radio band. Although polar-dust extinction is much smaller than torus extinction, the UV-to-IR (mainly IR) polar dust luminosities are ∼2 times larger than the torus ones. The polar-dust temperature decreases while the physical size, estimated by the temperature and dust sublimation radius, increases with AGN luminosity from a few tens of parsec (early mergers) to kiloparsec scales (late mergers), where the polar dust likely comes from expanding (i.e., evolving) dusty outflows. A comparison between the SFRs and intrinsic AGN luminosities suggests that starbursts occur first and AGNs arise later, and overall their growth rates follow the simultaneous coevolution local galaxy–SMBH mass relation. We confirm the coexistence of intense starbursts, AGNs, and large-scale outflows in late mergers, supporting a standard AGN feedback scenario.

We present a catalog of the millimeter-wave (mm-wave) continuum properties of 98 nearby ( z < 0.05) active galactic nuclei (AGNs) selected from the 70 month Swift/BAT hard-X-ray catalog that have precisely determined X-ray spectral properties and subarcsecond-resolution Atacama Large Millimeter/submillimeter Array Band 6 (211–275 GHz) observations as of 2021 April. Due to the hard-X-ray (>10 keV) selection, the sample is nearly unbiased for obscured systems at least up to Compton-thick-level obscuration, and provides the largest number of AGNs with high-physical-resolution mm-wave data (≲100–200 pc). Our catalog reports emission peak coordinates, spectral indices, and peak fluxes and luminosities at 1.3 mm (230 GHz). Additionally, high-resolution mm-wave images are provided. Using the images and creating radial surface brightness profiles of mm-wave emission, we identify emission extending from the central sources and isolated blob-like emission. Flags indicating the presence of these emission features are tabulated. Among 90 AGNs with significant detections of nuclear emission, 37 AGNs (≈41%) appear to have both or one of extended or blob-like components. We, in particular, investigate AGNs that show well-resolved mm-wave components and find that these seem to have a variety of origins (i.e., a jet, radio lobes, a secondary AGN, stellar clusters, a narrow-line region, galaxy disk, active star formation regions, or AGN-driven outflows), and some components have currently unclear origins.

Purpose: This study aimed to investigate the influence of cleaned-up knowledge-based treatment planning (KBP) models on the plan quality for volumetric-modulated arc therapy (VMAT) of prostate cancer. Materials and Methods: Thirty prostate cancer VMAT plans were enrolled and evaluated according to four KBP modeling methods as follows: (1) model not cleaned – trained by fifty other clinical plans (KBPORIG); (2) cases cleaned by removing plans that did not meet all clinical goals of the dosimetric parameters, derived from dose–volume histogram (DVH) (KBPC-DVH); (3) cases cleaned outside the range of ±1 standard deviation through the principal component analysis regression plots (KBPC-REG); and (4) cases cleaned using both methods (2) and (3) (KBPC-ALL). Rectal and bladder structures in the training models numbered 34 and 48 for KBPC-DVH, 37 and 33 for KBPC-REG, and 26 and 33 for KBPC-ALL, respectively. The dosimetric parameters for each model with one-time auto-optimization were compared. Results: All KBP models improved target dose coverage and conformity and provided comparable sparing of organs at risks (rectal and bladder walls). There were no significant differences in plan quality among the KBP models. Nevertheless, only the KBPC-ALLmodel generated no cases of >1% V78 Gy(prescribed dose) to the rectal wall, whereas the KBPORIG, KBPC-DVH, and KBPC-REG modelsincluded two, four, and three cases, respectively, which were difficult to overcome with KBP because the planning target volume (PTV) and rectum regions overlapped. Conclusions: The cleaned-up KBP model based on DVH and regression plots improved plan quality in the PTV–rectum overlap region.

Background/Aim: Intensity-modulated radiation therapy can deliver a highly conformal dose to a target while minimizing the dose to the organs at risk (OARs). Delineating the contours of OARs is time-consuming, and various automatic contouring software programs have been employed to reduce the delineation time. However, some software operations are manual, and further reduction in time is possible. This study aimed to automate running atlas-based auto-segmentation (ABAS) and software operations using a scripting function, thereby reducing work time. Materials and Methods: Dice coefficient and Hausdorff distance were used to determine geometric accuracy. The manual delineation, automatic delineation, and modification times were measured. While modifying the contours, the degree of subjective correction was rated on a four-point scale. Results: The model exhibited generally good geometric accuracy. However, some OARs, such as the chiasm, optic nerve, retina, lens, and brain require improvement. The average contour delineation time was reduced from 57 to 29 min (p<0.05). The subjective revision degree results indicated that all OARs required minor modifications; only the submandibular gland, thyroid, and esophagus were rated as modified from scratch. Conclusion: The ABAS model and scripted automation in head and neck cancer reduced the work time and software operations. The time can be further reduced by improving contour accuracy. [ABSTRACT FROM AUTHOR]

Integrin LFA1 is a cell adhesion receptor expressed exclusively in leukocytes, and plays crucial roles in lymphocyte trafficking, antigen recognition, and effector functions. Since the discovery that the adhesiveness of LFA1 can be dynamically changed upon stimulation, one challenge has been understanding how integrins are regulated by inside-out signaling coupled with macromolecular conformational changes, as well as ligand bindings that transduce signals from the extracellular domain to the cytoplasm in outside-in signaling. The small GTPase Rap1 and integrin adaptor proteins talin1 and kindlin-3 have been recognized as critical molecules for integrin activation. However, their cooperative regulation of integrin adhesiveness in lymphocytes requires further research. Recent advances in single-molecule imaging techniques have revealed dynamic molecular processes in real-time and provided insight into integrin activation in cellular environments. This review summarizes integrin regulation and discusses new findings regarding the bidirectionality of LFA1 activation and signaling processes in lymphocytes.

To assess the objective and subjective image quality, and respiratory motion of hepatocellular carcinoma with portal vein tumor thrombosis (PVTT) using the contrast-enhanced four-dimensional dual-energy computed tomography (CE-4D-DECT). For twelve patients, the virtual monochromatic image (VMI) derived from the CE-4D-DECT with the highest contrast to noise ratio (CNR) was determined as the optimal VMI (O-VMI). To assess the objective and subjective image quality, the CNR and five-point score of the O-VMI were compared to those of the standard VMI at 77 keV (S-VMI). The respiratory motion of the PVTT and diaphragm was measured based on the exhale and inhale phase images. The VMI at 60 keV yielded the highest CNR (4.8 ± 1.4) which was significantly higher (p = 0.02) than that in the S-VMI (3.8 ± 1.2). The overall image quality (4.0 ± 0.6 vs 3.1 ± 0.5) and tumor conspicuity (3.8 ± 0.8 vs 2.8 ± 0.6) of the O-VMI determined by three radiation oncologists was significantly higher (p < 0.01) than that of the S-VMI. The diaphragm motion in the L-R (3.3 ± 2.5 vs 1.2 ± 1.1 mm), A-P (6.7 ± 4.0 vs 1.6 ± 1.3mm) and 3D (8.8 ± 3.5 vs 13.1 ± 4.9 mm) directions were significantly larger (p < 0.05) compared to the tumor motion. The improvement of objective and subjective image quality was achieved in the O-VMI. Because the respiratory motion of the diaphragm was larger than that of the PVTT, we need to be pay attention for localizing target in radiotherapy.

The STE20-like serine/threonine kinases MST1 and MST2 (MST1/2) are mammalian homologs of Hippo in flies. MST1/2 regulate organ size by suppressing the transcription factor YAP, which promotes proliferation. MST1 is predominantly expressed in immune cells, where it plays distinct roles. Here, we review the functions of MST1/2 in immune cells, uncovered by a series of recent studies, and discuss the connection between MST1/2 function and immune responses. MST1/2 regulate lymphocyte development, trafficking, survival, and antigen recognition by naive T cells. MST1/2 also regulate the function of regulatory T cells and effector T cell differentiation, thus acting to balance immune activation and tolerance. Interestingly, MST1/2 elicit these functions not by the “canonical” Hippo pathway, but by the non-canonical Hippo pathway or alternative pathways. In these pathways, MST1/2 regulates cellular processes relating to immune response, such as chemotaxis, cell adhesion, immunological synapse, gene transcriptions. Recent advances in our understanding of the molecular mechanisms of these processes have revealed important roles of MST1/2 in regulating cytoskeleton remodeling, integrin activation, and vesicular transport in lymphocytes. We discuss the significance of the MST1/2 signaling in lymphocytes in the regulation of organelle dynamics.

Summary: Extracellular signal-regulated kinase (ERK) plays critical roles in T cell development in the thymus. Nevertheless, the dynamics of ERK activity and the role of ERK in regulating thymocyte motility remain largely unknown due to technical limitations. To visualize ERK activity in thymocytes, we here developed knockin reporter mice expressing a Förster/fluorescence resonance energy transfer (FRET)-based biosensor for ERK from the ROSA26 locus. Live imaging of thymocytes isolated from the reporter mice revealed that ERK regulates thymocyte motility in a subtype-specific manner. Negative correlation between ERK activity and motility was observed in CD4/CD8 double-positive thymocytes and CD8 single-positive thymocytes, but not in CD4 single-positive thymocytes. Interestingly, however, the temporal deviations of ERK activity from the average correlate with the motility of CD4 single-positive thymocytes. Thus, live-cell FRET imaging will open a window to understanding the dynamic nature and the diverse functions of ERK signaling in T cell biology. : Biological Sciences; Components of the Immune System; Molecular Biology Subject Areas: Biological Sciences, Components of the Immune System, Molecular Biology

Abstract Background Although 0.8 mg/kg is considered a lethal dose of colchicine, fatal cases of patients who followed a critical disease course after an intake below this lethal dose have been reported. Case presentation An 18-year-old Japanese woman who had taken an overdose of prescription colchicine (15 mg; 0.2 mg/kg) was brought to our emergency out-patient department. Although her colchicine intake was below 0.8 mg/kg (considered the lethal dose), she reached a critical state and underwent three phases characterizing colchicine poisoning (gastrointestinal symptoms, multiple organ failure, and recovery). Her condition was critical, with a Sequential Organ Failure Assessment score of a maximum of 14. Conclusions Patients might reach a critical stage after colchicine ingestion at a non-lethal dose. Thus, it might be necessary to review which dose of colchicine should be considered lethal.

Abstract Background The aim of this study was to evaluate the performance of a commercial knowledge-based planning system, in volumetric modulated arc therapy for prostate cancer at multiple radiation therapy departments. Methods In each institute, > 20 cases were assessed. For the knowledge-based planning, the estimated dose (ED) based on geometric and dosimetric information of plans was generated in the model. Lower and upper limits of estimated dose were saved as dose volume histograms for each organ at risk. To verify whether the models performed correctly, KBP was compared with manual optimization planning in two cases. The relationships between the EDs in the models and the ratio of the OAR volumes overlapping volume with PTV to the whole organ volume (Voverlap/Vwhole) were investigated. Results There were no significant dosimetric differences in OARs and PTV between manual optimization planning and knowledge-based planning. In knowledge-based planning, the difference in the volume ratio of receiving 90% and 50% of the prescribed dose (V90 and V50) between institutes were more than 5.0% and 10.0%, respectively. The calculated doses with knowledge-based planning were between the upper and lower limits of ED or slightly under the lower limit of ED. The relationships between the lower limit of ED and Voverlap/Vwhole were different among the models. In the V90 and V50 for the rectum, the maximum differences between the lower limit of ED among institutes were 8.2% and 53.5% when Voverlap/Vwhole for the rectum was 10%. In the V90 and V50 for the bladder, the maximum differences of the lower limit of ED among institutes were 15.1% and 33.1% when Voverlap/Vwhole for the bladder was 10%. Conclusion Organs’ upper and lower limits of ED in the models correlated closely with the Voverlap/Vwhole. It is important to determine whether the models in KBP match a different institute’s plan design before the models can be shared.

We determine the low-redshift X-ray luminosity function, active black hole mass function (BHMF), and Eddington ratio distribution function (ERDF) for both unobscured (Type 1) and obscured (Type 2) active galactic nuclei (AGNs), using the unprecedented spectroscopic completeness of the BAT AGN Spectroscopic Survey (BASS) data release 2. In addition to a straightforward 1/ V _max approach, we also compute the intrinsic distributions, accounting for sample truncation by employing a forward-modeling approach to recover the observed BHMF and ERDF. As previous BHMFs and ERDFs have been robustly determined only for samples of bright, broad-line (Type 1) AGNs and/or quasars, ours are the first directly observationally constrained BHMF and ERDF of Type 2 AGNs. We find that after accounting for all observational biases, the intrinsic ERDF of Type 2 AGNs is significantly more skewed toward lower Eddington ratios than the intrinsic ERDF of Type 1 AGNs. This result supports the radiation-regulated unification scenario, in which radiation pressure dictates the geometry of the dusty obscuring structure around an AGN. Calculating the ERDFs in two separate mass bins, we verify that the derived shape is consistent, validating the assumption that the ERDF (shape) is mass-independent. We report the local AGN duty cycle as a function of mass and Eddington ratio, by comparing the BASS active BHMF with the local mass function for all supermassive black holes. We also present the $\mathrm{log}N-\mathrm{log}S$ of the Swift/BAT 70 month sources.

We present the second catalog and data release of optical spectral line measurements and active galactic nucleus (AGN) demographics of the BAT AGN Spectroscopic Survey, which focuses on the Swift-BAT hard X-ray detected AGNs. We use spectra from dedicated campaigns and publicly available archives to investigate spectral properties of most of the AGNs listed in the 70 month Swift-BAT all-sky catalog; specifically, 743 of the 746 unbeamed and unlensed AGNs (99.6%). We find a good correspondence between the optical emission line widths and the hydrogen column density distributions using the X-ray spectra, with a clear dichotomy of AGN types for N _H = 10 ^22 cm ^−2 . Based on optical emission-line diagnostics, we show that 48%–75% of BAT AGNs are classified as Seyfert, depending on the choice of emission lines used in the diagnostics. The fraction of objects with upper limits on line emission varies from 6% to 20%. Roughly 4% of the BAT AGNs have lines too weak to be placed on the most commonly used diagnostic diagram, [O iii ] λ 5007/H β versus [N ii ] λ 6584/H α , despite the high signal-to-noise ratio of their spectra. This value increases to 35% in the [O iii ] λ 5007/[O ii ] λ 3727 diagram, owing to difficulties in line detection. Compared to optically selected narrow-line AGNs in the Sloan Digital Sky Survey, the BAT narrow-line AGNs have a higher rate of reddening/extinction, with H α /H β > 5 (∼36%), indicating that hard X-ray selection more effectively detects obscured AGNs from the underlying AGN population. Finally, we present a subpopulation of AGNs that feature complex broad lines (34%, 250/743) or double-peaked narrow emission lines (2%, 17/743).

Abstract Purpose The HyperArc VMAT (HA-VMAT) planning approach was newly developed to fulfill the demands of dose delivery for brain metastases stereotactic radiosurgery. We compared the dosimetric parameters of the HA-VMAT plan with those of the conventional VMAT (C-VMAT). Material and methods For 23 patients (1–4 brain metastases), C-VMAT and HA-VMAT plans with a prescription dose of 20–24 Gy were retrospectively generated, and dosimetric parameters for PTV (homogeneity index, HI; conformity index, CI; gradient index, GI) and brain tissue (V2Gy-V16Gy) were evaluated. Subsequently, the physical characteristics (modulation complexity score for VMAT, MCSV; Monitor unit, MU) of both treatment approaches were compared. Results HA-VMAT provided higher HI (1.41 ± 0.07 vs. 1.24 ± 0.07, p

Purpose: The aim of this study is to compare the interfractional setup reproducibility of two types of patient immobilization devices for prostate cancer receiving image-guided radiation therapy (IGRT). Materials and Methods: The MOLDCARE (MC) involves hydraulic fixation, whereas the BlueBAG (BB) and Vac-Lock (VL) involve vacuum fixation. For 72 patients, each immobilization device was individually customized during computed tomography (CT) simulation. Before the treatment, bony registration was performed using orthogonal kV images and digitally reconstructed radiographs. The shift of the treatment couch was recorded as a benchmark in the first session. In subsequent sessions, the shifts from the benchmark were measured and analyzed. Soft-tissue registration was performed weekly by cone-beam CT and CT images, and the shifts were measured and analyzed. Results: In the superior-inferior and left-right directions, there were nearly no changes in the overall mean among the immobilization devices. In the anterior-posterior (AP) direction, the overall mean for the MC, BB, and VL were 0.34 ± 1.33, −0.47 ± 1.27, and −1.82 ± 1.65 mm, respectively. The mean shifts along the AP direction were approximately 1 mm more in patients immobilized on the BB and 2.5 mm more in those on the VL, compared to those on the MC, after the twentieth treatment. No significant changes were observed among the patients immobilized on those devices, respectively, in soft-tissue registration. Conclusion: It can be concluded that the settling of the vacuum fixation was caused by air leakage in the latter-half treatment, and the immobilization device type has no effect on the treatment-position reproducibility in IGRT.