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Extended discrete material optimization: A generalized framework for multi-material topology optimization of nonlinear material constitutive models
No full textMulti-material topology optimization (MMTO) has been widely studied for designing structures composed of multiple materials to achieve optimal performance. However, conventional MMTOs, typically based on parameter interpolation, are limited to materials governed by the same material constitutive model. In particular, they require the energy density function, evolution laws for inelastic strains, and material parameters to share a common form across all base materials, which fundamentally restricts their applicability to nonlinear materials with distinct behaviors. To overcome this limitation, we propose an extended discrete material optimization (XDMO) framework that generalizes MMTO based on the original concept of DMO. The key idea of XDMO is to interpolate the governing equations and evolution laws (or, conceptually, the potential energy) that define the mechanical response of each base material. This formulation enables the unified treatment of a broad range of nonlinear and irreversible materials, such as those exhibiting plasticity or damage, within a single optimization problem. For generality, the primal, adjoint, and sensitivity equations are derived in an abstract form without assuming specific material models, and the formulation is independent of temporal or spatial discretization schemes. Numerical examples demonstrate the versatility of XDMO in stiffness maximization and plastic dissipation-based design problems. The proposed framework thus represents a significant step toward generalizing MMTO and provides a new pathway for topology optimization involving nonlinear and irreversible material behaviors
IgG4-related disease in the Japanese population: a whole-genome sequencing study
No full textBackground: IgG4-related disease is a rare autoimmune disorder characterised by tissue infiltration of IgG4-positive plasma cells, storiform fibrosis, elevated serum IgG4 concentrations, and increased risk of tumour complications. Previous genetic studies have implicated FCGR2B and HLA loci in susceptibility to IgG4-related disease; however, most relied on microarray-based genotyping and imputation, which have limited resolution in highly polymorphic and structurally complex regions. This study aimed to investigate genetic susceptibility to IgG4-related disease using comprehensive genomic variant analysis, including low-frequency and structural variants not readily captured by microarrays. Methods: We conducted a genome-wide association study using whole-genome sequencing data in a two-set, subtype-stratified case–control design in the Japanese population. Set 1 included samples (cases) from patients with IgG4-related disease from 50 hospitals across Japan participating in the Japanese IgG4-related disease Working Consortium (recruited between Oct 27, 2008, and March 3, 2016) and previously sequenced Japanese population control samples. Set 2 included samples (cases) from patients with IgG4-related disease from eight hospitals of the Consortium (recruited between Aug 12, 2021, and Dec 20, 2023) and previously sequenced healthy individuals residing in the Tokyo metropolitan area (controls). No specific inclusion or exclusion criteria were applied to either cases and controls. We used whole-genome sequencing at depths of 15× or 30× using HiSeqX and NovaSeq platforms (Illumina; San Diego, CA, USA) to enable the inclusion of previously uncaptured single nucleotide polymorphisms and direct analysis of HLA amino acid residues. We investigated complement component 4 copy number variations using short-read sequencing data and established read-depth-based typing methods. People with lived experience of IgG4-related disease were not involved in the study. Findings: This whole-genome sequencing study comprised of 2 sets. Set 1 included 646 patient samples (172 [26·6%] were female, 474 [73·4%] were male, and the mean age was 64·4 years [SD 11·4]) and 2254 population controls (1348 [59·8%] were female and 906 [40·2%] were male). Set 2 included 223 patient samples (78 [35·0%] were female, 145 [65·0%] were male, and the mean age was 63·5 years [10·9]) and 405 population controls (65 [16·0%] were female and 340 [84·0%] were male). All individuals were of Hondo Japanese ancestry. The average IgG4 concentration at diagnosis was 653·1 mg/dL (SD 596·3) in Set 1 and 543·5 mg/dL (603·5) in Set 2. We validated the FCGR2B (p=9·8 × 10⁻¹¹) region as the susceptibility locus for IgG4-related disease. PTCH1 (p=3·8 × 10⁻⁸) and long non-coding RNA LOC102724227 were found to be specific susceptibility loci for Mikulicz's disease. We also confirmed the association between the HLA amino acid residue DRB1-GB-7 (p=1·1 × 10⁻¹⁹) with IgG4-related disease and identified two additional residues, A-GA2-9 (p=4·1 × 10⁻⁶) and DQB1-GB-82 (p=4·7 × 10⁻⁹), that were significantly associated with IgG4-related disease. In the joint-association analysis of complement component 4 copy number variation, C4A showed a protective association with IgG4-related disease (β=–0·127, p=7·9 × 10⁻³), whereas C4B was associated with an increased risk (β=0·151, p=1·9 × 10⁻²). A low level of linkage disequilibrium (r²<0·15) was observed between the C4A and C4B alleles and the identified HLA amino acid residues in the main island Japanese population. Interpretation: C4 copy number variation, in addition to HLA and FCGR2B, was found to be a distinct genetic factor associated with IgG4-related disease susceptibility, illustrating the complex polygenic nature of the disease. Furthermore, the identification of PTCH1 and the long non-coding RNA LOC102724227 as Mikulicz's disease-specific susceptibility loci suggests that genetic heterogeneity might underlie the clinical diversity of IgG4-related disease, particularly with respect to the affected organs. Funding: The Japanese Ministry of Health, Labour, and Welfare, the Japanese Agency of Medical Research and Development, the Kyoto University Grant for Top Global University Japan Project, and the Kyoto University Division of Graduate Studies SPRING Program
Chlorine and potassium enrichment in the Cassiopeia A supernova remnant
No full textWhere the elements come from. 京都大学プレスリリース. 2025-12-05.巨大な星の活動で作られた生命必須元素 --超新星残骸観測で掴んだ塩素・カリウムの大量生成の証拠-- . 京都大学プレスリリース. 2025-12-09.The elements in the Universe are synthesized primarily in stars and supernovae, where nuclear fusion favours the production of even-Z elements. In contrast, odd-Z elements are less abundant and their yields are highly dependent on detailed stellar physics, making theoretical predictions of their cosmic abundance uncertain. In particular, the origin of odd-Z elements such as phosphorus (P), chlorine (Cl) and potassium (K), which are important for planet formation and life, is poorly understood. While the abundances of these elements in Milky Way stars are close to solar values, supernova explosion models systematically underestimate their production by up to an order of magnitude, indicating that key mechanisms for odd-Z nucleosynthesis are currently missing from theoretical models. Here we report the observation of P, Cl and K in the Cassiopeia A supernova remnant using high-resolution X-ray spectroscopy with X-Ray Imaging and Spectroscopy Mission data, with the detection of K at above the 6σ level being the most significant finding. Supernova explosion models of normal massive stars cannot explain the element abundance pattern, especially the high abundances of Cl and K, while models that include stellar rotation, binary interactions or shell mergers agree closely with the observations. Our observations suggest that such stellar activity plays an important role in supplying these elements to the Universe
Damage Identification Based on Bridge Displacement Response Considering Autocorrelation of the Dynamic Component
No full textBridges demand efficient and reliable methods of structural health monitoring, as visual inspection is time-consuming and resource-intensive. To address this challenge, this study proposes a damage identification method for bridges based on Bayesian inference, using displacement responses induced by traffic loads. Unlike conventional influence line (IL)–based methods, the proposed method directly employs displacement responses, thereby avoiding explicit IL calculation. The bridge span is divided into multiple regions, and correction factors for bending stiffness are estimated to identify both the location and the severity of damage. In this framework, the dynamic component-treated as the residual between measured and predicted displacement responses-is explicitly modeled through a covariance matrix incorporating its time-domain correlation. To assess its effectiveness, the proposed method is compared against conventional IL-based methods-using both unfiltered and low-pass filtered ILs-in both numerical simulations and experimental applications. Numerical simulations using a simply supported beam model were carried out for three damage scenarios, which were designed based on the actual damage conditions introduced in the model bridge. The results indicated that filtering reduced variability in the estimated values but led to decreased identification accuracy near the bridge ends. In contrast, explicitly modeling the dynamic component with a covariance matrix improves the accuracy of identifying stiffness reductions near the bridge ends, thereby enhancing overall identification performance. In experimental validation, the proposed method accurately identified damaged locations, demonstrating its practical applicability. Furthermore, the estimated correction factors exhibited a clear correlation with actual damage severity, indicating the potential for quantitative damage assessment. These findings demonstrate the effectiveness of the proposed method and its potential to enhance bridge maintenance strategies
Expletive Constructions and Agreement in Labeling Theory
No full textIn this paper, I explain how agreement occurs in English expletive constructions, in accord with recent work in the Minimalist Program. I develop a proposal that relies on feature unification and probe-goal agreement, as well as the notion that internal merge of arguments generally applies freely. I take the position that there can be unification of identical unvalued features associated with a probe and an expletive goal. An expletive must end up in a phrase that is labeled by a shared person feature. In addition, the notion that internal merge is generally free accounts for the possibility of thematization/extraction, in which an object that is associated with an expletive appears in a preverbal position in a passivized construction
Advancement in Cell and Gene Therapy Research: a 35-Year Bibliometric Perspective
No full text細胞・遺伝子治療の35年の研究動向を分析 --モダリティの成熟度や国際連携効果を可視化--. 京都大学プレスリリース. 2026-02-09.Cell and gene therapy across 35 years. 京都大学プレスリリース. 2026-02-13.Background: Cell and gene therapies (CGT) have been increasingly translated into clinical practice over the past three decades; however, their development has been uneven across modalities and regions. Methods: Through a bibliometric analysis indexed in PubMed from 1989 to 2023, supplemented by citation and affiliation data from OpenAlex, we examined modality-specific progression under different regional and collaborative configurations and how transitions from basic to clinical research have emerged. Results: Hematopoietic stem cell therapies have shown sustained growth in both clinical and high-impact publications, reflecting a mature field that remains scientifically relevant. In contrast, mesenchymal stem cell therapies experienced a rise in high-impact papers in the mid-2000s, but clinical publications stagnated, indicating a gap between academic interest and clinical applications. In gene therapy, the number of in vivo approaches increased in the 1990s. However, this was followed by a plateau in high-impact publications and a decline in clinical output, whereas ex vivo strategies have sharply increased since the mid-2010s, marking a transition toward tangible clinical translation. To further evaluate the global research landscape, we analyzed research activity and co-authorship patterns across countries and institutions in CGT. Our findings reveal distinct patterns of international collaboration. The United States and, more recently, China accounted for a large and growing share of CGT publications and high-impact papers, whereas Europe maintained steady contributions, and Japan's presence stagnated. Higher-impact output is generally associated with broader cross-border co-authorship, especially collaborations linking the United States and Europe, whereas collaborations involving China and Japan remain comparatively narrow. Conclusions: These results provide a data-driven foundation for guiding research policies and strategic cooperation in this evolving field
Paraclostridium bifermentans JCM 1386ᵗにおける共役脂肪酸代謝に関与する酵素群の機能解析
No full text京都大学新制・課程博士博士(農学)甲第26409号農博第2699号京都大学大学院農学研究科博士後期課程応用生命科学専攻(主査)教授 小川 順, 教授 栗原 達夫, 教授 由里本 博也学位規則第4条第1項該当Doctor of Agricultural ScienceKyoto UniversityDGA
Efficacy of 10% lidocaine gel for injection site pain associated with treprostinil in the treatment of pulmonary hypertension: a report of four cases
No full text: Treprostinil, a prostacyclin analogue, is an effective treatment for pulmonary arterial hypertension (PAH). However, continuous subcutaneous infusion is often complicated by severe injection site pain, which can limit continuation of therapy. : We report four PAH patients who developed severe injection site pain during subcutaneous treprostinil therapy in the lower abdomen. A hospital-compounded 10% lidocaine gel was applied around the infusion site. Pain was markedly reduced in all cases, with visual analog scale scores improving from 75 to 100/100 to 0-20/100. In two patients, tramadol could be reduced or discontinued, and all patients were able to continue treprostinil therapy without pain-related limitation or treatment interruption. No systemic adverse effects were observed, although one patient experienced mild local skin irritation. : Topical 10% lidocaine gel provided rapid and effective relief of injection site pain associated with subcutaneous treprostinil, facilitating continuation of therapy without pain-related interruption in patients with PAH
Toward the Rational Design of Ion-Conducting Ionic Liquid-Incorporated Metal-Organic Framework Hybrids
No full textSolid-state ionics have been the subject of intense research because of their possible applications as solid electrolytes for all-solid-state electrochemical devices. Ionic liquid-introduced metal-organic frameworks (IL@MOFs) are an emerging class of hybrid solids with superior ionic conductivity, in which the migration of component ions of ILs in the pores is responsible for ionic conduction. In this review, we present an overview of the development of ion-conducting IL@MOF hybrids from the perspective of synthetic methodologies to incorporate ILs into MOFs and the ion-conducting behavior controlled by the IL filling level, ion species of ILs, and MOF structures such as pore size and pore surface state. Finally, we devote attention to the Li⁺-ion conduction, especially the Li⁺-ion transport number, of the pore-encapsulated Li⁺-containing ILs directed toward applications in all-solid-state lithium-ion batteries
REPPUコードレベル8の開発 --トポロジーを取り込んだ複合系磁気圏物理学の創出-- (スーパーコンピュータ共同研究制度 (大規模計算支援枠) 研究報告)
No full textREPPUコードレベル8の開発によって、より詳細な磁気圏トポロジーが再現可能になった。トポロジーは、観測では知ることが出来ない。REPPUによって、これまでのリコネクションだけに依存した磁気圏変動から、トポロジー変化を取り込んだ磁気圏変動に進化することができる