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A bstract We discuss deep learning inference for the neutron star equation of state (EoS) using the real observational data of the mass and the radius. We make a quantitative comparison between the conventional polynomial regression and the neural network approach for the EoS parametrization. For our deep learning method to incorporate uncertainties in observation, we augment the training data with noise fluctuations corresponding to observational uncertainties. Deduced EoSs can accommodate a weak first-order phase transition, and we make a histogram for likely first-order regions. We also find that our observational data augmentation has a byproduct to tame the overfitting behavior. To check the performance improved by the data augmentation, we set up a toy model as the simplest inference problem to recover a double-peaked function and monitor the validation loss. We conclude that the data augmentation could be a useful technique to evade the overfitting without tuning the neural network architecture such as inserting the dropout.

A bstract We find a novel confinement mechanism in the two-flavor dense quark matter proposed recently, that consists of the 2SC condensates and the P -wave diquark condensates of d -quarks. This quark matter exhibiting color superconductivity as well as superfluidity is classified into two phases; confined and deconfined phases of vortices. We establish that the criterion of the confinement is color neutrality of Aharonov-Bohm (AB) phases: vortices exhibiting color non-singlet AB phases are confined by the so-called AB defects to form color-singlet bound states. In the deconfined phase, the most stable vortices are non-Abelian Alice strings, which are superfluid vortices with fractional circulation and non-Abelian color magnetic fluxes therein, exhibiting color non-singlet AB phases. On the other hand, in the confined phase, these non-Abelian vortices are confined to either a baryonic or mesonic bound state in which constituent vortices are connected by AB defects. The baryonic bound state consists of three non-Abelian Alice strings with different color magnetic fluxes with the total flux canceled out connected by a domain wall junction, while the mesonic bound state consists of two non-Abelian Alice strings with the same color magnetic fluxes connected by a single domain wall. Interestingly, the latter contains a color magnetic flux in its core, but this can exist because of color neutrality of its AB phase.

Heat shock protein 105 (HSP105) is overexpressed in many cancers, including colorectal cancer (CRC) and esophageal cancer (EC). We carried out a phase I clinical trial of HLA‐A24‐ and HLA‐A2‐restricted HSP105 peptide vaccines in patients with CRC or EC. In this additional study of the trial, we examined the immunological efficacy of the novel vaccine. Thirty patients with advanced CRC or EC underwent HSP105 peptide vaccination. Immunological responses were evaluated by ex vivo and in vitro γ‐interferon enzyme‐linked immunospot assays and their correlation with patients’ prognosis was analyzed. The HSP105 peptide vaccines induced peptide‐specific CTLs in 15 of 30 patients. Among HLA‐A24 patients (n = 15), 7 showed induction of CTLs only ex vivo, whereas among HLA‐A2 patients (n = 15), 4 showed the induction ex vivo and 6 in vitro. Heat shock protein 105‐specific CTL induction correlated with suppression of cancer progression and was revealed as a potential predictive biomarker for progression‐free survival (P = .008; hazard ratio = 3.03; 95% confidence interval, 1.34‐6.85) and overall survival (P = .025; hazard ratio = 2.72; 95% confidence interval, 1.13‐6.52). Production of cytokines by HSP105 peptide‐specific CTLs was observed at the injection sites (skin) and tumor tissues, suggesting that HSP105‐specific CTLs not only accumulated at vaccination sites but also infiltrated tumors. Furthermore, we established 2 HSP105 peptide‐specific CTL clones, which showed HSP105‐specific cytokine secretion and cytotoxicity. Our results suggest that the HSP105 peptide vaccine could induce immunological effects in cancer patients and improve their prognosis. Heat shock protein 105 (HSP105) peptide vaccine could induce peptide‐specific CTLs in vaccinated patients. We also established peptide‐specific CTL clones, which showed HSP105‐specific cytokine secretion and cytotoxicity.

A three-component coupling reaction of structurally simple 6–8 was successfully applied for expeditious synthesis of the 6/5/9-membered tricyclic structure 3 of cladieunicellin D (1) and klysimplexin U (2). Upon treatment with the Et3B/O2 reagent system, α-alkoxyacyl telluride 6, six-membered enone 7, and (Z)-4-hexenal (8) were linked in one pot to provide the densely functionalized 5 via sequential decarbonylative radical generation, radical addition, boron enolate formation, and intermolecular aldol reaction. Subsequent Lewis acid-promoted reductive etherification and SiO2-induced C10-epimerization gave rise to the cis-fused five-membered ether of 4. Finally, cyclization of the nine-membered ring was achieved by the ring-closing metathesis reaction, giving rise to 3. Compound 3 possesses the six stereocenters of 1 and 2, and would thus serve as an advanced intermediate for their total syntheses.

We show that Quarkyonic Matter can mitigate the hyperon puzzle. The key observation is that the hyperon threshold is shifted to a higher density by a factor of constituent strange quark mass. We illustrate this effect by using the ideal dual Quarkyonic (IdylliQ) model with multiple flavors.

Epidermal growth factor receptor (EGFR) is a prototypic cell-surface receptor belonging to the ErbB/HER onocogene family. Overexpression or somatic mutations of EGFR have been reported to play an important role in tumorigenesis in various types of epithelial cancers. Therefore, targeting of EGFR with specific blocking antibodies or inhibitors have been developing for treatment for EGFR-associated tumors. Immune responses to HER2, another molecule of the ErbB/HER onocogene family, have been well studied, but only limited information on the immune responses to EGFR in cancer has been currently available. In this review, we have summarized the available data and discussed potential clinical importance of the anti-EGFR immune responses and EGFR-mediated immune regulation in cancer. Several lines of evidence suggest that cellular and humoral immune responses to EGFR might be useful as a marker and/or target for cancer therapy against EGFR-associated tumors. In addition, recent studies suggest the critical roles of EGFR-mediated signaling in regulation of expression of an immune checkpoint molecule, programmed death-ligand 1 (PD-L1) in tumor cells. Further studies are warranted to clarify the impact of the anti-EGFR immune responses and EGFR-mediated immunomodulation for clinical application for cancer treatment.

When harmful bacteria are detected in the final product at a food manufacturing plant, it is necessary to identify and eliminate the source of contamination so that it does not occur again. In the current study, the source of contamination was tracked using core genome multilocus sequence typing (cgMLST) analysis in cases where Escherichia coli was detected in the final product at a food manufacturing plant. cgMLST analysis was performed on 40 strains of E . coli collected from the environment [floor (26 strains), drainage ditch (5 strains), container (4 strains), post-heating production line (1 strain)] and products [final product (3 strains) and intermediate product (1 strain)]. In total, 40 E . coli isolates were classified into 17 genogroups by cgMLST analysis. The 4 E . coli strains isolated from the intermediate and final products were classified into two genogroups (I and II). Certain isolates collected from the environment also belonged to those genogroups, it was possible to estimate the transmission of E . coli in the manufacturing plant. Thus, the dynamics of E . coli in the food manufacturing location were clarified by using cgMLST analysis. In conclusion, our results indicate that cgMLST analysis can be effectively used for hygiene management at food manufacturing locations.

The gut-liver-muscle axis is associated with the development of sarcopenia in liver cirrhosis. The present study aimed to illustrate the combined effects of rifaximin and L-carnitine on skeletal muscle atrophy in cirrhotic rats with steatohepatitis. For this purpose, a total of 344 Fischer rats were fed a choline-deficient L-amino acid-defined (CDAA) diet with the daily oral administration of rifaximin (100 mg/kg) and/or L-carnitine (200 mg/kg), and measurements of psoas muscle mass index and forelimb grip strength were performed. After feeding for 12 weeks, blood samples, and liver, ileum and gastrocnemius muscle tissues were harvested. The effects of L-carnitine on rat myocytes were assessed using in vitro assays. Treatment with rifaximin attenuated hyperammonemia and liver fibrosis in the CDAA-fed rats. Moreover, it improved intestinal permeability with the restoration of tight junction proteins and suppressed the lipopolysaccharide (LPS)-mediated hepatic macrophage activation and pro-inflammatory response. In addition, rifaximin prevented skeletal muscle mass atrophy and weakness by decreasing intramuscular myostatin and pro-inflammatory cytokine levels. Moreover, rifaximin synergistically enhanced the L-carnitine-mediated improvement of skeletal muscle wasting by promoting the production of insulin-like growth factor-1 and mitochondrial biogenesis, resulting in the inhibition of the ubiquitin-proteasome system (UPS). The in vitro assays revealed that L-carnitine directly attenuated the impairment of mitochondrial biogenesis, thereby inhibiting the UPS in rat myocytes that were stimulated with LPS or tumor necrosis factor-α. On the whole, the present study demonstrates that the combination of rifaximin with L-carnitine may provide a clinical benefit for liver cirrhosis-related sarcopenia.

The liver’s susceptibility to oxidative stress after a combination of forced swim test (FST) and low-dose-rate γ-irradiation has been observed. Therefore, this study aims to clarify the effects of low-dose (0.1 and 0.5 Gy)/high-dose-rate (1.2 Gy/min) irradiation on combined oxidative stressors—liver damage associated with FST and alcohol administration. In addition, the effects of similar irradiation on FST-induced immobility, which induces psychomotor retardation, and antioxidative effects on the brain, lungs, liver and kidneys were investigated, and the results were compared with those of a similar previous study that utilized low-dose-rate irradiation. Low-dose/high-dose-rate (especially 0.5 Gy) irradiation temporarily worsened liver antioxidant function and hepatic function with FST- and alcohol administration-related oxidative damage; however, the damages improved soon after. In addition, the increase in total glutathione content in the liver contributed to the early improvement of hepatic functions. However, pre-irradiation did not suppress immobility during the FST. The results also suggested that the effects of low-dose/high-dose-rate irradiation on the antioxidant functions of each organ after the FST were different from those of low-dose/low-dose-rate irradiation. Overall, this study provides further insights into the effects of low-dose irradiation on exposure to a combination of different oxidative stressors. It will also contribute to the elucidation of dose rate effects on oxidative stress in the low-dose irradiation range.

Ceramides have several well-known biological properties, including anti-pigmentation and anti-melanogenesis, which make them applicable for use in skincare products in cosmetics. However, the efficacy of ceramides is still limited. Dermal or transdermal drug delivery systems can enhance the anti-pigmentation properties of ceramides, although there is currently no systemic evaluation method for the efficacy of these systems. Here we prepared several types of lecithin-based emulsion of maize-derived glucosylceramide, determining PC70-ceramide (phosphatidylcholine-base) to be the safest and most effective anti-pigmentation agent using zebrafish larvae. We also demonstrated the efficacy of PC70 as a drug delivery system by showing that PC70-Nile Red (red fluorescence) promoted Nile Red accumulation in the larval bodies. In addition, PC70-ceramide suppressed melanin in mouse B16 melanoma cells compared to ceramide alone. In conclusion, we developed a lecithin-based dermal delivery method for ceramide using zebrafish larvae with implications for human clinical use.