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Clusters and their progenitors (protoclusters) at z ∼ 2 − 4, the peak epoch of star formation, are ideal laboratories to study the formation process of both the clusters themselves and their member galaxies. However, a complete census of their member galaxies has been challenging due to observational difficulties. Here we present new JWST/NIRCam observations targeting the distant cluster CLJ1001 at z = 2.51 from the COSMOS-Web program, which, in combination with previous narrowband imaging targeting H α emitters and deep millimeter surveys of CO emitters, provide a complete view of massive galaxy assembly in CLJ1001. In particular, JWST reveals a population of massive, extremely red cluster members in the long-wavelength bands that were invisible in previous Hubble Space Telescope (HST)/F160W imaging (HST-dark members). Based on this highly complete spectroscopic sample of member galaxies, we show that the spatial distribution of galaxies in CLJ1001 exhibits a strong central concentration, with the central galaxy density already resembling that of low- z clusters. Moreover, we reveal a “top-heavy” stellar mass function for the star-forming galaxies (SFGs), with an overabundance of massive SFGs piled up in the cluster core. These features strongly suggest that CLJ1001 is caught in a rapid transition, with many of its massive SFGs likely soon becoming quiescent. In the context of cluster formation, these findings suggest that the earliest clusters form from the inside out and top to bottom, with the massive galaxies in the core assembling first, followed by the less massive ones in the outskirts.

This study examines the impact of cluster environments on galaxy properties using data from the Hyper Suprime-Cam Subaru Strategic Program and an optically selected CAMIRA cluster sample. Specifically, the study analyzes the fractions of quiescent and green valley galaxies with stellar masses above 10 ^8.6 M _⊙ at z ∼ 0.2 and 10 ^9.8 M _⊙ at z ∼ 1.1, investigating their trends in radius and density. The results indicate that a slow quenching mechanism is at work, as evidenced by a radially independent specific star formation rate reduction of 0.1 dex for star-forming galaxies in a cluster environment. The study also finds that slow quenching dominates fast quenching only for low-mass galaxies (

The LIGO/Virgo detected a gravitational wave (GW) event, named GW200224_222234 (also known as S200224ca) and classified as a binary-black hole coalescence, on 2020 February 24. Given its relatively small localization skymap (71 deg ^2 for a 90% credible region; revised to 50 deg ^2 in GWTC-3), we performed target-of-opportunity observations using the Subaru/Hyper Suprime-Cam (HSC) in the r 2 and z bands. Observations were conducted on 2020 February 25 and 28 and March 23, with the first epoch beginning 12.3 hr after the GW detection. The survey covered the highest-probability sky area of 56.6 deg ^2 , corresponding to a 91% probability. This was the first deep follow-up ( m _r ≳ 24, m _z ≳ 23) for a binary-black hole merger covering >90% of the localization. By performing image subtraction and candidate screening including light-curve fitting with transient templates and examples, we found 22 off-nucleus transients that were not ruled out as the counterparts of GW200224_222234 with our Subaru/HSC data alone. We also performed GTC/OSIRIS spectroscopy of the probable host galaxies for five candidates; two are likely to be located within the 3D skymap, whereas the others are not. In conclusion, 19 transients remain as possible optical counterparts of GW200224_222234; but we could not identify a unique promising counterpart. If there are no counterparts in the remaining candidates, the upper limits of the optical luminosity are $\nu {L}_{\nu }\lt {5.2}_{-1.9}^{+2.4}\times {10}^{41}$ erg s ^−1 and $\nu {L}_{\nu }\lt {1.8}_{-0.6}^{+0.8}\times {10}^{42}$ erg s ^−1 in the r 2 and z bands, respectively, at ∼12 hr after GW detection. We also discuss improvements in the strategies of optical follow-ups for future GW events.

Kajiura and Yoshizawa et al. identify three new prenyltransferases in the tree Eucommia ulmoides that synthesize exceptionally high molecular weight trans-1,4-polyisoprene (TPI). Through crystal structure and mutational analyses, they identify key residues required for TPI synthesis and reveal its functional importance in seed development.

Abstract The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nerve-dependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration. The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nervedependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration.

PURPOSE: We investigated the effect of systemic fasudil hydrochloride and an inhibitor of nuclear translocation of myocardin-related transcription factor-A (MRTF-A) on capsular contraction in a puncture-injured lens in mice. MATERIALS AND METHODS: Lens injury of an anterior capsular break was achieved in male adult C57Bl/6 mice under general and topical anesthesia at 1 h after systemic fasudil hydrochloride (intraperitoneal, 10 mg/kg body weight) or vehicle administration. The mice were allowed to heal after instillation of ofloxacin ointment, for 5 and 10 days with daily administration of fasudil hydrochloride or vehicle. In another series of experiment, we examined the effect of systemic administration of an MRTF-A inhibitor (CCG-203971, 100 mg/kg twice a day) on fibrogenic reaction and tissue contraction in an injured lens on day 5 or 10. The eye was processed for histology and immunohistochemistry for SM22, proliferating cell nuclear antigen (PCNA), or MRTF-A. In hematoxylin and eosin -stained samples, the distance between each edge of the break of the anterior capsule was measured and statistically analyzed. RESULTS: A cluster of lens cell accumulation was formed adjacent to the edge of the capsular break on day 5. It contained cells labeled for SM22 and PCNA. The size of the cell cluster was larger in fasudil group of mice than in control mice on day 5. Systemic fasudil or CCG-203971 suppressed an excess contraction of the capsular break at certain time points. CONCLUSION: Systemic administration of fasudil hydrochloride could be a treatment strategy of postoperative capsular contraction following cataract-intraocular lens surgery.

Objectives: Raman spectroscopy yields precise information, not only regarding the secondary structure of proteins but also regarding the discrimination between normal and malignant tissues. There is, however, no standard measurement method. We evaluated the use of a miniaturized, handheld, all-in-one Raman spectrometer with a 1064-nm laser excitation source for the diagnosis of colorectal cancer. The ultimate goal is real-time, in vivo diagnosis. Methods: Tissue samples were obtained from 20 patients who underwent surgery for colorectal cancer. The samples were irradiated with the portable Progeny™ Raman spectrometer, with which the Raman spectra were also obtained. We searched for characteristic Raman shifts and examined whether these shifts could distinguish the cancer tissues. To improve accuracy, we divided the spectra into 100 cm−1 bands and applied principal component analysis (PCA) to each range. We evaluated the contribution of each range for cancer discrimination. Results: Intensities at 1261 and 1427 cm−1 differed significantly between the normal tissues and cancer tissues, but these did not efficiently discriminate the cancer tissues. However, we were able to identify the characteristic spectral range in fingerprint regions; accuracy was 85.1%. Conclusions: Use of the all-in-one type Raman spectrometer can efficiently discriminate colorectal cancer, not on the basis of the intensities at 1261 and 1427 cm−1 but rather on the basis of PCA. Thus, Raman spectroscopy performed using a handheld device has potential to become a clinically powerful tool for producing high-quality data, obtaining highly reproducible measurements, and thus accurately diagnosing colorectal cancer.

It has been reported that cavitation bubbles (air–liquid interface) by femtosecond laser and ultrasonic irradiations are effective for metastable phase crystallization in polymorph control. It has also been noted that cavitation bubbles are generated by mechanical shock when dropping a vial. Here we describe the crystallization of acetaminophen by drop impact. In the condition where spontaneous nucleation did not occur, the drop impact produced the metastable form (form II) and trihydrate. This supports the potency of the air–liquid interface in metastable phase formation. Furthermore, crystallization by drop impact is a completely new phenomenon, and new developments are expected in the future.

BackgroundClimate change, as a defining issue of the current time, is causing severe heat-related illness in the context of extremely hot weather conditions. In Japan, the remarkable temperature increase in summer caused by an urban heat island and climate change has become a threat to public health in recent years.MethodsThis study aimed to determine the potential risk factors for heatstroke by analysing data extracted from the records of emergency transport to the hospital due to heatstroke in Fukuoka City, Japan. In this regard, a negative binomial regression model was used to account for overdispersion in the data. Age-structure analyses of heatstroke patients were also embodied to identify the sub-population of Fukuoka City with the highest susceptibility.ResultsThe daily maximum temperature and wet-bulb globe temperature (WBGT), along with differences in both the mean temperature and time-weighted temperature from those of the consecutive past days were detected as significant risk factors for heatstroke. Results indicated that there was a positive association between the resulting risk factors and the probability of heatstroke occurrence. The elderly of Fukuoka City aged 70 years or older were found to be the most vulnerable to heatstroke. Most of the aforementioned risk factors also encountered significant and positive associations with the risk of heatstroke occurrence for the group with highest susceptibility.ConclusionThese results can provide insights for health professionals and stakeholders in designing their strategies to reduce heatstroke patients and to secure the emergency transport systems in summer.

Various modes of transportation are available when people travel within cities, and trips can be classified into two types depending on whether some type of vehicle is used. Compared to vehicular travel, trips conducted only by walking have the advantages of lower environmental impact and less space required for road networks. By assuming that the proportion of walking-only trips decreases exponentially with the distance traveled, we explore the problem of finding a city shape with a fixed land area that maximizes the number of walking-only trips based on Manhattan distance. For many-to-one travel with the city center as the destination, we show that the optimal city shape is a diamond. For many-to-many travel, a method is presented that expresses the number of walking-only trips as a double integral, originally formulated as a four-dimensional integral. Using this, an optimization problem is formulated whose variables are the vertex coordinates of a polygon, and approximate solutions for the optimal city shape under several different settings are obtained numerically. For many-to-many travel, it is shown that a large number of walking-only trips occur when the city shape is close to being circular, although the exact shape varies with the distance deterrence coefficient.

Tracheal stenosis caused by malignancy is a life-threatening complication. Herein, we performed tumor ablation and airway stenting using a hybrid stent on a patient with upper tracheal stenosis caused by endobronchial metastasis of ovarian cancer. To date, only 9 cases of endobronchial metastasis of ovarian cancer have been reported. This is the first reported case of endobronchial metastasis in the upper part of the trachea, which had a favorable outcome after tumor ablation as a sequential treatment and use of a hybrid stent. In addition, 10 cases of endobronchial metastasis of ovarian cancer, including ours and other case reports, were reviewed.

The growth of acetaminophen polymorphic crystals and the solution-mediated phase transition from trihydrate to form II in agarose gel were investigated. The form II crystals grown in gels, presumably because of the agarose content, dissolved less rapidly at high temperatures and were more stable than in water. The trihydrate crystals in the gel were also expected to be stabilized by containing agarose, but in fact the fine morphology resulted in reduced stability. The solution-mediated phase transition from trihydrate to form II via form II seeding took longer in the gel because the gel slowed down the dissolution of the trihydrate by hindering the dispersion of the form II seeds and delayed the growth of form II by reducing the diffusion rate of the molecules dissolved from the trihydrate. Delays in solution-mediated phase transition and changes in stability for crystals grown in gels indicate the effectiveness of gels in controlling polymorphisms in pharmaceutical compounds.

A 70-year-old woman diagnosed with advanced, non-resectable programmed cell death ligand 1-positive-non-small-cell lung carcinoma was treated with pembrolizumab as first-line therapy. Soon after therapy initiation, she presented with severe dyspnea, and chest computed tomography revealed a soft tissue mass in the lower trachea of the right main bronchus. During bronchoscopy, she became severely hypoxic, and we performed endoscopic tumor ablation and Dumon Y-stent placement. We considered this severe deterioration caused by pseudoprogression, and suggest that it is necessary to perform bronchoscopy and to prepare for the bronchial intervention when treating patients with immune checkpoint inhibitors. Keywords: Tracheal stent, Dumon Y-stent, Immune checkpoint inhibitors, Pembrolizumab, Non-small-cell lung cancer

The flow interception location model (FILM) focuses on vehicular traffic in a road network and locates a fixed number of facilities so as to maximize the total flow that can be serviced at facilities along preplanned routes, such as a daily commute to work. This paper develops a version of FILM, the railway flow interception location model (R-FILM), that explicitly focuses on railway passenger flows. For railway users, accessing a facility placed at an origin, destination, or transfer station (ODT station) is easier than visiting a facility at other stations included in the travel path. Accessing a facility at a non-ODT station involves the additional cost of disembarking the train to obtain a service and then boarding another train after consuming the service. R-FILM introduces this railway-specific structure to FILM by introducing two different coverages according to the types of station intercepted for each flow. Concretely, a given flow is called strongly covered when at least one facility is located at an ODT station. Similarly, a given flow is called weakly covered when no facility is located at an ODT station, but at least one facility is located among stations included in the travel path. We present an integer programming formulation of the proposed R-FILM. Using it, we conduct a large-scale case study of the Tokyo metropolitan railway network, which includes about 1500 railway stations. Input flow is constructed using census data for commuter traffic, with about 100,000 distinct flow paths. Optimal solutions of both models for single- and multi-facility problems are analyzed. In R-FILM solutions, large terminal stations tend to be selected more often than with FILM. Keywords: Discrete location problem, Flow interception location model, Integer programming, Railway passenger flow, Tokyo metropolitan railway network

This paper proposes a mathematical optimization model for designing safe walking routes for children from school to homes. We focus on the existing bi-objective model, the safe walking route design problem, which minimizes both the total walking risk and the total route distances for all children from school to home. The original problem assumes that the combined routes for all children forms a directed out-tree rooted at the school. However, making this assumption excludes solutions such as those involving cycles. This paper explores how to relax the assumption that the graph is an out-tree by using a layered network constructed from the original network. Using the layered network formulation, we obtain some solutions that have better objective values than those obtained by the original formulation when we strongly emphasize reducing the risk objective. The results also show that the new formulation produces the same out-tree solution when minimization of the risk objective and the distance objective are suitably balanced.

This paper extends the maximum flow-covering location and service start time problem (MFCLSTP) by additionally imposing a minimum stay at a facility before the service can be used. The original formulation determines the locations of facilities and the start times of fixed-duration services so as to maximally cover flows of commuters who access services on the way home from work. In MFCLSTP, commuters must stay at a facility from the start of the service until the end of the service in order to consume it. Examples of such services include movies, lectures, and baseball games. There are, however, many on-demand services, which can be consumed by commuters who access the providing facility for a fixed continuous duration of a hours during any of c (≥ a) open hours of the facility. To deal with this situation, we extend the definition of coverage in the original model and provide an integer programming formulation of the proposed problem. The model is applied to the Tokyo metropolitan railway network, using census data of commuter traffic for railway users in this area. Exact optimal solutions are obtained by using a mathematical optimization solver with both the original and extended problems, and the characteristics of the solutions are compared. The results show that the optimal solutions for the extended problem allow a much larger flow than the optimal solutions for the original problem do, even when a is very close to c. The locations selected for the optimal solutions of the proposed problem are seen to be much more spatially dispersed than those chosen for the original problem.