Tokyo Ohka Kogyo (Japan)

Abstract Emerging classes of wearable microfluidic sensors of eccrine sweat enable non‐invasive and real‐time monitoring of health status in applications that range from sports to worker safety, environmental exposures, and medical care. Opportunities for improving the performance of these systems include those in colorimetric detection of biochemical species with high accuracy across a wide dynamic range, in efficient collection of sweat and local measurements of sweat loss across a broad spectrum of sweat rates, and in an expanded set of biomarker targets. This paper introduces concepts in 3D microfluidic structures, surface chemistry, interface design, and colorimetric chemical reagents that address these opportunities. Demonstrations involve accurate quantification of sweat rate and total loss over a wide range, as well as precise colorimetric sensing of chloride, xanthine, and creatinine, as biomarkers associated with electrolyte balance, purine metabolism, and kidney function, respectively. Benchtop evaluations confirm high sensitivity and reproducibility, while on‐body trials illustrate reliable biomarker tracking in response to dietary intake and physiological activity. These ideas and chemistries expand the possibilities in sweat‐based diagnostic strategies, in strategies that have the potential to align with established, high‐volume manufacturing practices for commercial production.

Resist stochastics ultimately limit patterning, a result of interplay of resist composition, exposure, bake and development. Metrologies like OCD and CD-SEM only measure uniformity after development, offering limited process control. Each step modifies molecular bonds, leaving IR (5-20 μm) fingerprints in activated chemical structures. When combining IR & AFM, nearfield effects resolve alterations at the nm scale. We show how IR-AFM offers chemical selectivity and lateral resolution to resolve modifications in latent DSA and EUVL images, even before PEB and development. Metrology data from these images facilitate improved process control.

Block copolymers (BCPs) have garnered significant attention due to their ability to spontaneously assemble into well-ordered, periodic nanostructures, making them promising candidates for next-generation lithography. In this study, polystyrene-block-{poly[2-hydroxy-3-(2,2,2-trifluoroethylsulfanyl)-propyl methacrylate]-random-poly(n-butyl methacrylate)-random-poly(methyl methacrylate)} (PS-b-PGFBM), a derivative of the well-established PS-b-PMMA system, was synthesized. By introducing a fluorinated poly(glycidyl methacrylate) segment, PS-b-PGFBM achieves a higher level of chemical incompatibility between styrene and methacrylate blocks compared to PS-b-PMMA. Furthermore, poly(n-butyl methacrylate) (PnBMA), which has a low glass transition temperature (Tg, ~25 °C), was incorporated to lower the overall Tg of the BCP, thereby facilitating self-assembly at reduced annealing temperatures. Notably, thin films of PS-b-PGFBM, spin-coated onto neutral layer-modified silicon substrates, formed perpendicular lamellae with a domain spacing of 15.6 nm after thermal annealing at 160 °C, 40 °C lower than the annealing temperature required for similar BCPs without PnBMA.

ObjectivesAppropriate categorization based on magnetic resonance imaging (MRI) findings is important for managing intraductal papillary mucinous neoplasms (IPMNs). In this study, a large language model (LLM) that classifies IPMNs based on MRI findings was developed, and its performance was compared with that of less experienced human readers.MethodsThe medical image management and processing systems of our hospital were searched to identify MRI reports of branch-duct IPMNs (BD-IPMNs). They were assigned to the training, validation, and testing datasets in chronological order. The model was trained on the training dataset, and the best-performing model on the validation dataset was evaluated on the test dataset. Furthermore, two radiology residents (Readers 1 and 2) and an intern (Reader 3) manually sorted the reports in the test dataset. The accuracy, sensitivity, and time required for categorizing were compared between the model and readers.ResultsThe accuracy of the fine-tuned LLM for the test dataset was 0.966, which was comparable to that of Readers 1 and 2 (0.931–0.972) and significantly better than that of Reader 3 (0.907). The fine-tuned LLM had an area under the receiver operating characteristic curve of 0.982 for the classification of cyst diameter ≥ 10 mm, which was significantly superior to that of Reader 3 (0.944). Furthermore, the fine-tuned LLM (25 s) completed the test dataset faster than the readers (1,887–2,646 s).ConclusionThe fine-tuned LLM classified BD-IPMNs based on MRI findings with comparable performance to that of radiology residents and significantly reduced the time required.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00261-025-05062-z.

Background: Hepatitis B virus (HBV) is a major cause of morbidity and mortality globally, and chronic infections are associated with cirrhosis and hepatocellular carcinoma. Issues with conventional treatments and vaccines mean there is a need for new therapeutic vaccines, which must elicit a strong and sustainable immune response. Here, we evaluated the immunogenicity of dual-antigen vaccines containing hybrid surface (hy-LHBs) and core (HBc) antigens, combined with a carboxyl-vinyl polymer (CVP) as a mucoadhesive excipient, following intranasal administration in mice. Methods: Mice were intranasally administered a mixed vaccine (10 µg of hy-LHBs and 2.5 or 10 µg of HBc) with or without a CVP excipient, and they were assessed for their immune response (levels of IgGs or IgA antibodies in an ELISA, IFN-γ level in splenocytes in an ELISpot assay, and cytokine/chemokine levels in a BioPlex assay). A protein stability assay was also conducted for vaccine formulations with and without excipients. Results: Significantly enhanced IgG production was noted targeting hy-LHBs and (less markedly) HBc at 10 µg/antigen, but only a non-significant elevation was noted with the vaccine containing 2.5 µg HBc. The BioPlex assay showed a significant increase in IL-2 (#00-07, 0B), IL-12(p40)(#00), eotaxin (#00), MIP1α (#00, #00-07, 0B), and MCP-1 (#00-07, 0B) in mice that received treatment compared to those of untreated mice. The endpoint titers of IgG1 and IgG2a were measured, which were higher with CVP excipients than without. From the IgG2a/IgG1 ratio, a higher IgG1 response was induced by CVPs to hy-LHBs and a higher IgG2a response was induced to HBc. Th2-dominant phenotype to hy-LHBs was induced with CVP#00 in an ELISpot assay. The highest anti-hy-LHBs antibody titer was noted with the conventional CVP#00 excipient. Consistent with these results, a higher amount of neutralizing antibodies of HBV was induced with CVP#00 treatment and followed by #00-03 and #14-00. Conclusions: We consider that the addition of CVP excipients to vaccine formulation enhances immunogenicity and HBV antigen stability for intranasal vaccines. This effect was seen for both humoral and cell-mediated immune responses, indicating the potential of CVPs as excipients in intranasal HBV vaccines.

We show a facile way to obtain perpendicular lamellae using a block copolymer (BCP) with two hydroxy groups between polystyrene and poly(methyl methacrylate). The BCP works as both neutral layers and thin films with microphase-separated structures.

本研究は，浅海域などの多方向流場に建設されている円柱構造物に対して，周辺の局所洗掘を抑制する「網状平板工法」の定量的な有効性を実験的に検討したものである．円柱構造物の表面に90°間隔で取り付けられた4枚の鉛直網状平板は，円柱構造物の上流側の馬蹄形渦，および，下流側のカルマン渦列の両方の大規模渦に対して，「破壊」あるいは「弱体化」といった顕著な効果を示した．また，3方向の接近流に対して，円柱構造物周辺の局所洗掘体積を測定したところ，40％以上の抑制効果が明らかになり，網状平板工法の有効性が確認された．

Abstract A comprehensive understanding of the intricate lignin biosynthesis in grasses could contribute to enhancing our ability to utilize grass biomass. CINNAMATE 4-HYDROXYLASE (C4H), in conjunction with PHENYLALANINE AMMONIA-LYASE (PAL), initiates the entry of phenylalanine into the cinnamate/monolignol pathway, leading to the production of diverse phenylpropanoids, including lignin monomers. Despite extensive research on C4H in eudicots, genetic studies of C4H in grasses remain considerably limited. Notably, the role of C4H in the presence of PHENYLALANINE/TYROSINE AMMONIA-LYASE (PTAL), a grass-specific ammonia-lyase that can bypass the conserved PAL-C4H pathway by recruiting tyrosine into the cinnamate/monolignol pathway, remains unclear. To address this gap, a set of genome-edited rice mutants harboring knockout mutations in riceC4Hgenes were generated and subjected to the analysis of growth phenotype and cell wall chemotype, alongside isotopic feeding and chemical inhibitor assays to test the contributions of the PAL-C4H and PTAL pathways. The phenotype and chemotype characterizations ofC4H-knockout rice mutants demonstrated that class I (OsC4H1/CYP73A38) and class II (OsC4H2a/CYP73A39 and OsC4H2b/CYP73A40) C4Hs cooperatively contribute to lignin biosynthesis in rice. Nevertheless, the impacts ofC4H-deficiency on plant development and lignin formation in rice appeared to be less prominent compared to those reported in eudicots. The13C-labeled phenylalanine and tyrosine feeding experiments demonstrated that even with the phenylalanine-derived PAL-C4H pathway completely blocked, theC4H-knockout rice can still produce significant levels of lignin and maintain sound cell walls by utilizing the tyrosine-derived PTAL pathway. Overall, this study demonstrates the essential but dispensable role of C4H in grass cell wall lignification.

緑化壁面に利用されるヤブコウジ，オタフクナンテン，プミラ，テイカカズラ，ヤブラン，へデラ，ローズマリーを対象に，植物の炭素固定量を簡易に推定する方法について検討した。植物を植栽し，成長に伴う植物の地際から先端までの長さ，葉面積，乾燥重量の変化を測定した。いずれの植物でも植物の地際から先端までの長さと乾燥重量，および葉面積と乾燥重量の間には有意な正の相関関係が見られた。植物体の炭素濃度はどの植物も概ね400～450 g kg-1であった。これらから，植物の長さからおよその炭素固定量を推定可能であった。

Abstract We have developed the Rh‐catalyzed enantioselective [2+2+2] cycloaddition of homopropargyl enamides (tosylamide‐tethered 1,6‐enynes) with alkynes to construct tetrahydroindole skeletons found in natural alkaloids and pharmaceuticals. This cycloaddition proceeds at room temperature in high yields and regio‐ and enantioselectivity with a broad substrate scope. The preparative scale reaction followed by substituent conversion on the nitrogen atom and the diastereoselective [4+2] cycloaddition with singlet O2 affords hexahydroindole‐diols bearing three stereogenic centers and variable substituents on the nitrogen. Mechanistic studies have revealed that the substituents of the enynes change the ratio of intramolecular and intermolecular rhodacycle formation when using terminal alkynes, varying the ee values of the cycloadducts.