13197 research outputs found
Sort by
Development of flexible carbon nanotube ribbons with high thermal conductivity
Full text link奈良先端科学技術大学院大学博士（工学）doctoral thesi
The Effect of Pre-event Psychiatric States to the Event-Related Distress: A Study using the COVID-19 Pandemic Data
Full text link奈良先端科学技術大学院大学博士（理学）doctoral thesi
Structures of Polyhydroxyalkanoate Synthase PhaC from Aeromonas caviae, Producing Biodegradable Plastics
No full textPolyhydroxyalkanoate (PHA) is a biodegradable polyester that can serve as a promising alternative to petrochemical plastics, which present a serious source of pollution. PHA synthase (PhaC) is a key enzyme responsible for producing a wide variety of PHAs in microorganisms. Here, we present crystal structures of full-length PhaC from Aeromonas caviae, a high-performance PhaC employed for industrial use. The structure reveals an N-terminal helical domain that mediates head-to-head dimerization and stabilizes the C-terminal α/β catalytic domain to form a tunnel that connects the catalytic center embedded inside the protein to the protein surface. We showed that this tunnel is a putative egress tunnel for the product PHA chain. Our results establish a fundamental understanding of the PhaC machinery that should lead to improvement of this enzyme in industrial applications.journal articl
Prospects for functional genomics of genes involved in coffee-specialized metabolism through cross-species integrative omics
No full textCoffee (Coffea spp.) is one of the most economically important crop species and serves as a rich source of bioactive specialized (secondary) metabolites with various health-promoting properties. Advances in analytical food chemistry and phytochemistry have elucidated an extensive and structurally diverse specialized metabolism in coffee beans, much of which contributes to both organoleptic attributes and adaptive physiological responses in coffee plants. Recent developments in omics-driven methodologies have provided new insights into both coffee metabolism and breeding strategies, particularly those aimed at enhancing both quality traits and environmental resilience. Comparative genomic analyses across Coffea species and cultivars have facilitated the detection of metabolic polymorphisms, enabling inter- and intra-species assessments of biosynthetic pathway variation and the refinement of biosynthetic frameworks for further functional genomics approaches. Such approaches yield critical information regarding the genetic and biochemical determinants underlying specialized metabolite accumulations, which can be directly applied for targeted metabolic engineering and crop improvement. Moreover, cross-species comparative omics and multi-omics integrative analyses, particularly in relation to phylogenetically relevant taxa such as Solanaceae species, exemplified by the model crop tomato (Solanum lycopersicum), provide valuable translational insights into conserved and divergent metabolic architectures.journal articl
ジェイコンパス : ジッコウ ケイロ ノ ヒカク ト カシカ オ オコナウ コード レビュー ムケ ツール
Full text linkソフトウェア開発においてプログラム理解は重要なタスクの1つである．プログラム理解が重要な場面としてコードレビューが挙げられる．特に変更に対するレビューでは，ソースコードの差分以外にも前後の挙動を理解してプログラムを読み進める必要がある．しかし，プログラムを実行することで得られる動的な情報に着目したレビューの支援技術は少ない．そこで本研究では．didiffffという既存のツールを拡張し，ソースコードの変更前後におけるメソッドの実行の変化を可視化するツールJCompathsを作成した．このツールは，プログラム実行時に変数トークンがとった値の系列(トレース)に着目する．メソッドの実行を1回ずつ順に比較し，その実行経路とともにトレースの差分を表示することで，ソースコードの差分が実行に与えた影響を可視化する．また，JCompathsの有用性を評価するために被験者実験を行った．結果として，タスクの所要時間と点数，およびユーザビリティの総合スコアのいずれにおいても，JCompathsと他のツールとの間で統計的に有意な差は見られなかった．しかしながら，自由記述からは，JCompaths独自の機能が，実験で用いたような繰り返し実行を含むコードに対してはユーザにとって役立つことが確認できた．journal articl
PD-1 is conserved from sharks to humans: new insights into PD-1, PD-L1, PD-L2, and SHP-2 evolution
No full textProgrammed cell death protein 1 (PD-1) is an immune checkpoint molecule until recently believed to exist only in tetrapod species. However, together with a very recent study dedicated to the CD28/CTLA4 molecule family, this study—using database information—identifies the PD-1 gene in both bony and cartilaginous fish, while being the first to present a detailed molecular analysis of the evolution of PD-1 and its ligands. Conserved sequence motifs imply an ancient origin of PD-1’s binding modes to its extracellular ligand PD-L1 and its intracellular ligand Src homology region 2 domain-containing phosphatase-2 (SHP-2), and also of its N116 glycosylation motif—a less well known PD-1 feature—important for binding galectins. The PD-1 cytoplasmic tail binds SHP-2 by two motifs, defined as an immunoreceptor tyrosine-based inhibitory motif (ITIM) and immunoreceptor tyrosine-based switch motif (ITSM), but sequence conservation patterns show that these definitions warrant a discussion. As in mammals, PD-1 transcripts in fish could be found co-expressed with markers of regulatory and exhausted T cells, suggesting a similar immune checkpoint function. Agreeing with previous reports, the PD-L1/PD-L2 gene duplication was only found in tetrapod species, while we newly discovered that features that consistently distinguish the two molecules are PD-L2 IgC domain motifs. Among PD-L1 (the name given to the single PD-L ancestral molecule) of many ray-finned fish, conservation of a very long cytoplasmic tail motif supports previous claims that PD-L1 cytoplasmic tails may have a function. Surprisingly, we found a gene similar to SHP-2—that we named SHP-2-like (SHP-2L)—to be conserved from sharks to mammals, although lost or inactivated in higher primates and rodents. SHP-2L is expected to bind PD-1 similar to SHP-2. This comparative analysis of PD-1 and its interacting molecules across jawed vertebrates highlights conserved immune checkpoint features while revealing new insights and lineage-specific adaptations.journal articl
Elucidating Celecoxib's Preventive Effect in Capecitabine-Induced Hand-Foot Syndrome Using Medical Natural Language Processing
No full textPURPOSE Capecitabine, an oral anticancer agent, frequently causes hand-foot syndrome (HFS), affecting patients' quality of life and treatment adherence. However, such symptomatic toxicities are often difficult to detect in structured electronic health record (EHR) data. This study primarily aimed to validate a natural language processing (NLP) approach to identifying capecitabine-induced HFS from unstructured clinical text and demonstrate its application in evaluating medication-associated adverse event trends in real-world settings. METHODS We conducted a retrospective cohort study using EHRs from the University of Tokyo Hospital (2004-2021). HFS cases were identified using the MedNERN-CR-JA NLP model. After propensity score matching, we compared capecitabine users with and without celecoxib and assessed time to HFS onset using Cox proportional hazards models. NLP-based HFS detection was validated through manual annotation of aggregated clinical notes. Negative control and sensitivity analyses ensured robustness. RESULTS Among 44,502 patients with cancer, 669 capecitabine users were analyzed. HFS incidence was significantly higher among capecitabine users (hazard ratio [HR], 1.93 [95% CI, 1.48 to 2.52]; P < .001) compared with nonusers. Celecoxib use showed a suggestive association with a reduced HFS risk (HR, 0.51 [95% CI, 0.24 to 1.07]; P = .073). The NLP model demonstrated high accuracy in identifying HFS, achieving a precision of 0.875, recall of 1.000, and F1 score of 0.933, based on manual annotation of patient-level clinical notes. Outcome trends remained consistent when using manually annotated HFS case labels instead of NLP-detected events, supporting the method's robustness.CONCLUSION These findings demonstrate the effectiveness of NLP in detecting HFS from real-world clinical records. The application to celecoxib-HFS detection illustrates the potential utility of this approach for retrospective safety analysis. Further work is needed to evaluate generalizability across diverse clinical settings.journal articl
Impairment in global protein synthesis uncouples UPR gene induction from HAC1 mRNA splicing in Saccharomyces cerevisiae
No full textUpon dysfunction of the endoplasmic reticulum (ER), also known as ER stress, eukaryotic cells alter their transcriptomes. This cytoprotective response is called the unfolded protein response (UPR), which is mediated by Ire1 and HAC1 in the yeast Saccharomyces cerevisiae. ER stress induces self-association and activation of the ER-resident transmembrane endoribonuclease Ire1, which catalyzes the splicing of HAC1 mRNA. It is widely accepted that HAC1 mRNA is translated into the nuclear transcription factor Hac1, only after being spliced. To investigate the cellular response to ethanol-induced ER stress, here we gradually added ethanol into S. cerevisiae cultures until reaching a final concentration of 16%. Unlike conventional ER stressors, such as tunicamycin and dithiothreitol (DTT), the ethanol exposure did not elicit the Ire1- and HAC1-dependent UPR gene induction, even though Ire1 was activated and HAC1-mRNA was efficiently spliced. Under the ethanol stress condition, global protein synthesis was nearly abolished, and the Hac1 protein level remained low, despite the presence of spliced HAC1 mRNA. Furthermore, treatment with the translation inhibitor cycloheximide abolished DTT-induced UPR gene induction. As the UPR signaling pathway requires translation of the spliced HAC1 mRNA, integrity of the translation machinery is deduced to be essential for UPR gene induction. In summary, we demonstrated that impairment of the translation machinery can actually block UPR gene induction under certain stress conditions. We also propose that this represents an advantageous regulatory system that prevents unnecessary gene induction.journal articl
Functional framework of the kinetochore and spindle assembly checkpoint in Arabidopsis
No full textThe kinetochore, critical for accurate chromosome segregation and genome stability in eukaryotes, comprises the Constitutive Centromere Associated Network (CCAN) and the KMN network. In animals, the CCAN associates with centromeric nucleosomes throughout the cell cycle, while the KMN network assembles at kinetochores during M phase, binding spindle microtubules and serving as a platform for the spindle assembly checkpoint (SAC) complex. Despite conserved functions, kinetochore components vary across organisms. In this study, we investigated the subcellular localization and interaction maps of core kinetochore components in Arabidopsis (Arabidopsis thaliana). Of the four conserved CCAN components, we found that only Centromere protein C (CENP-C) localizes to kinetochores, while all KMN components consistently localize to the kinetochore throughout the cell cycle. Immunoprecipitation assays revealed interactions between core kinetochore proteins and regulators involved in DNA replication, histone modification, and chromatin remodeling, suggesting that the kinetochore may also function outside of M phase. Examining interactions between kinetochore and SAC components allowed us to elucidate plant-specific SAC localization mechanisms, providing a functional framework for understanding plant kinetochores and offering insights into SAC regulation in plants.journal articl
KeyMPs: One-Shot Vision-Language Guided Motion Generation by Sequencing DMPs for Occlusion-Rich Tasks
No full textDynamic Movement Primitives (DMPs) provide a flexible framework wherein smooth robotic motions are encoded into modular parameters. However, they face challenges in integrating multimodal inputs commonly used in robotics like vision and language into their framework. To fully maximize DMPs’ potential, enabling them to handle multimodal inputs is essential. In addition, we also aim to extend DMPs’ capability to handle object-focused tasks requiring one-shot complex motion generation, as observation occlusion could easily happen mid-execution in such tasks (e.g., knife occlusion in cake icing, hand occlusion in dough kneading, etc.). A promising approach is to leverage Vision-Language Models (VLMs), which process multimodal data and can grasp high-level concepts. However, they typically lack enough knowledge and capabilities to directly infer low-level motion details and instead only serve as a bridge between high-level instructions and low-level control. To address this limitation, we propose Keyword Labeled Primitive Selection and Keypoint Pairs Generation Guided Movement Primitives (KeyMPs), a framework that combines VLMs with sequencing of DMPs. KeyMPs use VLMs’ high-level reasoning capability to select a reference primitive through keyword labeled primitive selection and VLMs’ spatial awareness to generate spatial scaling parameters used for sequencing DMPs by generalizing the overall motion through keypoint pairs generation, which together enable one-shot vision-language guided motion generation that aligns with the intent expressed in the multimodal input. We validate our approach through experiments on two occlusion-rich tasks: object cutting, conducted in both simulated and real-world environments, and cake icing, performed in simulation. These evaluations demonstrate superior performance over other DMP-based methods that integrate VLM support.journal articl