Cumulative fracture behavior of short fiber type C/SiC

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Total Synthesis of Zephycarinatines via Photocatalytic Reductive Radical ipso‐Cyclization

We report herein a nonbiomimetic strategy for the total synthesis of the plicamine‐type alkaloids zephycarinatines C and D. The key feature of the synthesis is a stereoselective reductive radical ipso‐cyclization using visible‐light‐mediated photoredox catalysis. This cyclization enabled the construction of a 6, 6‐spirocyclic core structure through the addition of a carbon‐centered radical onto the aromatic ring. Biological evaluation of zephycarinatines and their derivatives revealed that the synthetic derivative with a keto group displays moderate inhibitory activity against LPS‐induced NO production. This approach could offer future opportunities to expand the chemical diversity of plicamine‐type alkaloids as well as providing useful intermediates for their syntheses

An Iterative Reconstruction Algorithm for Faraday Tomography

Faraday tomography offers crucial information on the magnetized astronomical objects, such as quasars, galaxies, or galaxy clusters, by observing its magnetoionic media. The observed linear polarization spectrum is inverse Fourier transformed to obtain the Faraday dispersion function (FDF), providing us a tomographic distribution of the magnetoionic media along the line of sight. However, this transform gives a poor reconstruction of the FDF because of the instrument's limited wavelength coverage. The current Faraday tomography techniques' inability to reliably solve the above inverse problem has noticeably plagued cosmic magnetism studies. We propose a new algorithm inspired by the well-studied area of signal restoration, called the Constraining and Restoring iterative Algorithm for Faraday Tomography (CRAFT). This iterative model-independent algorithm is computationally inexpensive and only requires weak physically-motivated assumptions to produce high fidelity FDF reconstructions. We demonstrate an application for a realistic synthetic model FDF of the Milky Way, where CRAFT shows greater potential over other popular model-independent techniques. The dependence of observational frequency coverage on the various techniques' reconstruction performance is also demonstrated for a simpler FDF. CRAFT exhibits improvements even over model-dependent techniques (i.e., QU-fitting) by capturing complex multi-scale features of the FDF amplitude and polarization angle variations within a source. The proposed approach will be of utmost importance for future cosmic magnetism studies, especially with broadband polarization data from the Square Kilometre Array and its precursors. We make the CRAFT code publicly available.Comment: Accepted for publication in MNRAS. 13 pages and 12 figure

Modalities of Subtitling and Foreign Language Learning

本論文は、（１）映像と英語音声＋日本語字幕、（２）映像と英語音声＋英語字幕、（３）映像と日本語音声＋英語字幕の三つの異なる音声と字幕のコンビネーションが、言語獲得の前提となる内容理解にどのように影響するかを実証的に考察したものである。被験者は、日本人中級英語学習者156名で、英語聴解力テストにより3つの等質なグループに分けられた。このそれぞれのグループに、上記の3条件で題材を提示し、その内容理解を調べた。題材にはアメリカ映画の一部を利用した。その結果、（２）→（１）→（３）の順に内容理解が高いことがわかった。この結果を被験者のアンケートなどから得られた結果と総合すると、中級学習者にとっては、多様な情報源（映像、音声、文字）を利用することが困難であり、特に情報が外国語で提示された場合には、外国語字幕→外国語音声の順で困難さが増すことがわかった。本論文では、この結果に基づき、効果的な音声と字幕のコンビネーションの在り方、今後の研究の方向性などについても言及していく

Viral entry and translation in brain endothelia provoke influenza-associated encephalopathy

The version of record of this article, first published in Acta Neuropathologica, is available online at Publisher’s website: https://doi.org/10.1007/s00401-024-02723-z.Influenza-associated encephalopathy (IAE) is extremely acute in onset, with high lethality and morbidity within a few days, while the direct pathogenesis by influenza virus in this acute phase in the brain is largely unknown. Here we show that influenza virus enters into the cerebral endothelium and thereby induces IAE. Three-weeks-old young mice were inoculated with influenza A virus (IAV). Physical and neurological scores were recorded and temporal-spatial analyses of histopathology and viral studies were performed up to 72 h post inoculation. Histopathological examinations were also performed using IAE human autopsy brains. Viral infection, proliferation and pathogenesis were analyzed in cell lines of endothelium and astrocyte. The effects of anti-influenza viral drugs were tested in the cell lines and animal models. Upon intravenous inoculation of IAV in mice, the mice developed encephalopathy with brain edema and pathological lesions represented by micro bleeding and injured astrocytic process (clasmatodendrosis) within 72 h. Histologically, massive deposits of viral nucleoprotein were observed as early as 24 h post infection in the brain endothelial cells of mouse models and the IAE patients. IAV inoculated endothelial cell lines showed deposition of viral proteins and provoked cell death, while IAV scarcely amplified. Inhibition of viral transcription and translation suppressed the endothelial cell death and the lethality of mouse models. These data suggest that the onset of encephalopathy should be induced by cerebral endothelial infection with IAV. Thus, IAV entry into the endothelium, and transcription and/or translation of viral RNA, but not viral proliferation, should be the key pathogenesis of IAE

Toward the Establishment of Country -by-Country SILL (Strategy Inventory for Language Learning) Norms

This papre attmpts to establish the country-by-county SILL (Strategy Inventory for language Learning) norms advocated by Oxford and Burry-Stock(1995). First, a brief description of the SILL, a self-report quetionnaire, is provided, and empirical studies indicating its drawbacks are summarized. Then we report an analysis that shows the underlying factor structure of the SILL when administered to 200 college students studying English as a Foreign Language in Japan. In this analysis, the universality of the SILL is challenged, and also, a sugggestion is made that not only county-by-coungry SILL norms but also proficiency level-by-level norms should be establised. After the factor analysis, relationships are sought, using a multiple regression procedure, between the factors found and EFL proficiency measered by the TOEFL. The rsults provide theoretical implications for further improvement of the SILL (especially concerning the validity issue) as well as for the development of sound strategy training programs in the EFL environment

AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells

A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated lung cancer. However, some patients show intrinsic resistance and an insufficient response to osimertinib. This study showed that osimertinib stimulated AXL by inhibiting a negative feedback loop. Activated AXL was associated with EGFR and HER3 in maintaining cell survival and inducing the emergence of cells tolerant to osimertinib. AXL inhibition reduced the viability of EGFR-mutated lung cancer cells overexpressing AXL that were exposed to osimertinib. The addition of an AXL inhibitor during either the initial or tolerant phases reduced tumor size and delayed tumor re-growth compared to osimertinib alone. AXL was highly expressed in clinical specimens of EGFR-mutated lung cancers and its high expression was associated with a low response rate to EGFR-TKI. These results indicated pivotal roles for AXL and its inhibition in the intrinsic resistance to osimertinib and the emergence of osimertinib-tolerant cells

Intensive endoscopic resection for downstaging of polyp burden in patients with familial adenomatous polyposis (J-FAPP Study III) : a multicenter prospective interventional study

Background Total colectomy is the standard treatment for familial adenomatous polyposis (FAP). Recently, an increasing number of young patients with FAP have requested the postponement of surgery or have refused to undergo surgery. We aimed to evaluate the effectiveness of intensive endoscopic removal for downstaging of polyp burden (IDP) in FAP. Method A single-arm intervention study was conducted at 22 facilities. Participants were patients with FAP, aged ≥ 16 years, who had not undergone colectomy or who had undergone colectomy but had ≥ 10 cm of large intestine remaining. For IDP, colorectal polyps of ≥ 10 mm were removed, followed by polyps of ≥ 5 mm. The primary end point was the presence/absence of colectomy during a 5-year intervention period. Results 222 patients were eligible, of whom 166 had not undergone colectomy, 46 had undergone subtotal colectomy with ileorectal anastomosis, and 10 had undergone partial resection of the large intestine. During the intervention period, five patients (2.3 %, 95 % confidence interval [CI] 0.74 %–5.18 %) underwent colectomy, and three patients died. Completion of the 5-year intervention period without colectomy was confirmed in 150 /166 patients who had not undergone colectomy (90.4 %, 95 %CI 84.8 %–94.4 %) and in 47 /56 patients who had previously undergone colectomy (83.9 %, 95 %CI 71.7 %–92.4 %). Conclusion IDP in patients with mild-to-moderate FAP could have the potential to be a useful means of preventing colorectal cancer without implementing colectomy. However, if the IDP protocol was proposed during a much longer term, it may not preclude the possibility that a large proportion of colectomies may still need to be performed