13197 research outputs found
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Designing Hybrid In Silico/In-Cell Controllers that Handle Process-Model Mismatches in Microbial Bioprocesses
Get PDF奈良先端科学技術大学院大学博士（工学）doctoral thesi
AFM observation of protein translocation mediated by one unit of SecYEG-SecA complex
No full textProtein translocation across cellular membranes is an essential and nano-scale dynamic process. In the bacterial cytoplasmic membrane, the core proteins in this process are a membrane protein complex, SecYEG, corresponding to the eukaryotic Sec61 complex, and a cytoplasmic protein, SecA ATPase. Despite more than three decades of extensive research on Sec proteins, from genetic experiments to cutting-edge single-molecule analyses, no study has visually demonstrated protein translocation. Here, we visualize the translocation, via one unit of a SecYEG-SecA-embedded nanodisc, of an unfolded substrate protein by high-speed atomic force microscopy (HS-AFM). Additionally, the uniform unidirectional distribution of nanodiscs on a mica substrate enables the HS-AFM image data analysis, revealing dynamic structural changes in the polypeptide-crosslinking domain of SecA between wide-open and closed states depending on nucleotides. The nanodisc-AFM approach will allow us to execute detailed analyses of Sec proteins as well as visualize nano-scale events of other membrane proteins.journal articl
Implantable imaging and photostimulation devices for biomedical applications
No full textUnlike traditional methods that implant passive optical components like fibers and rod lenses, optoelectronic semiconductor-based devices directly implant active optoelectronic semiconductors into the brain. This approach offers several advantages—the devices are compact and lightweight, enabling measurement and control without hindering the movement of small animals like mice. Additionally, it allows for simultaneous implantation of multiple devices, and integration with other functions. However, potential temperature increment and biocompatibility due to the active nature of these devices are major drawbacks. This paper reviews novel optoelectronic semiconductor-based devices for measuring and controlling brain nerve function. The advantages of brain-implantable optoelectronic semiconductor devices for fluorescence imaging and photostimulation are highlighted. We address potential limitations and propose future improvements, demonstrating their significant potential to advance neuroscience and pharmacology.journal articl
Natural language processing of electronic medical records identifies cardioprotective agents for anthracycline induced cardiotoxicity
No full textIn this retrospective observational study, we aimed to investigate the potential of natural language processing (NLP) for drug repositioning by analyzing the preventive effects of cardioprotective drugs against anthracycline-induced cardiotoxicity (AIC) using electronic medical records. We evaluated the effects of angiotensin II receptor blockers/angiotensin-converting enzyme inhibitors (ARB/ACEIs), beta-blockers (BBs), statins, and calcium channel blockers (CCBs) on AIC using signals extracted from clinical texts via NLP. The study included 2935 patients prescribed anthracyclines at a single hospital, with concomitant prescriptions of ARB/ACEIs, BBs, statins, and CCBs. Upon propensity score matching, groups with and without these medications were compared, and expressions suggestive of cardiotoxicity, extracted via NLP, were considered as the outcome. The hazard ratios for ARB/ACEIs, BBs, statins, and CCBs were 0.58 [95% CI: 0.38–0.88], 0.71 [95% CI: 0.35–1.44], 0.60 [95% CI 0.38–0.95], and 0.63 [95% CI: 0.45–0.88], respectively. ARB/ACEIs, statins, and CCBs significantly suppressed AIC, whereas BBs did not demonstrate statistical significance, possibly due to limited statistical power. NLP-extracted signals from clinical texts reflected the known effects of these medications, demonstrating the feasibility of NLP-based drug repositioning. Further investigation is needed to determine if similar results can be replicated using electronic medical records from other institutions.journal articl
Beyond case-control study in neuroimaging for psychiatric disorders: Harmonizing and utilizing the brain images from multiple sites
No full textRecent magnetic resonance imaging (MRI) research has advanced our understanding of brain pathophysiology in psychiatric disorders. This progress necessitates re-evaluation of the diagnostic system for psychiatric disorders based on MRI-based biomarkers, with implications for precise clinical diagnosis and optimal therapeutics. To achieve this goal, large-scale multi-site studies are essential to develop a standardized MRI database, with the analysis of several thousands of images and the incorporation of new data. A critical challenge in these studies is to minimize sampling and measurement biases in MRI studies to accurately capture the diversity of disease-derived biomarkers. Various techniques have been employed to consolidate datasets from multiple sites in case-control studies. Traveling subject harmonization stands out as a powerful tool that can differentiate measurement bias from sample variety and sampling bias. A non-linear statistical model for a normative trajectory across the lifespan also strengthens the database to mitigate sampling bias from known factors such as age and sex. These approaches can enhance the alterations between psychiatric disorders and integrate new data and follow-up scans into existing life-course trajectory, enhancing the reliability of machine learning classification and subtyping. Although this approach has been developed using T1-weighted structural image features, future research may extend this framework to other modalities and measures. The required sample size and methodological establishment are needed for future investigations, leading to novel insights into the brain pathophysiology of psychiatric disorders and the development of optimal therapeutics for bedside clinical applications. Sharing big data and their findings also need to be considered.journal articl
Federated Financial Security: Towards Robust & Resilient Detection of Dynamic Cyberthreats
Get PDF奈良先端科学技術大学院大学博士（工学）doctoral thesi
Structural basis of substrate recognition by SecDF driving protein translocation across the membrane
Get PDF奈良先端科学技術大学院大学博士（バイオサイエンス）doctoral thesi
