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Comparing Brain Network Differences between Cognitive Resilience and Vulnerability: A Bayesian ANOVA Multimodal Approach.
No full textStructural and functional characterization of CspR, a 2′-O-methyltransferase acting on wobble position within tRNA
No full textPost-transcriptional modifications of transfer RNA (tRNA) are essential for maintaining decoding fidelity and tRNA stability. Among these, 2′-O-ribosyl methylation is particularly prominent in bacteria. In this study, we provide structural and biochemical evidence identifying CspR from Bacillus subtilis as an ortholog of Escherichia coli TrmL, which specifically methylates the 2′-O-ribose of the wobble position of tRNALeu(CAA), tRNALeu(UAA), and tRNAPhe(GAA), in the presence of 2-methylthio-N6-isopentenyladenosine at position 37 (ms2i6A37). X-ray crystal structures of CspR in complex with tRNALeu(UAA) and in its tRNA-free form reveal substantial conformational rearrangements upon tRNA binding. Notably, the tRNA-bound structure shows specific interactions between the anticodon loop and CspR's dimeric interface, with key residues U33, 5-carboxymethylaminomethyluridine34 (cmnm5U34), and ms2i6A37 adopting flipped-out conformations. Furthermore, the structure uncovers extensive hydrophobic interactions between the isopentenyl group of ms2i6A37 and CspR, explaining the critical requirement of hypermodified A37 for enzymatic activity. © 2025 Elsevier B.V., All rights reserved.TRUEsciescopu
Electromagnetic interference shielding using metal and MXene thin films
No full textThe electronic passivation of small-form-factor devices requires a fundamental change in electromagnetic interference (EMI) shielding, transitioning from bulky metal cans to conformal thin films1, 2, 3–4. However, reducing the thickness induces poor shielding performance associated with the skin depth of shielding materials5,6. To overcome the performance limitations of thin-film shields, absorption during multiple internal reflections should be driven7. For absorption during multiple internal reflections, pores have been intentionally introduced into shielding materials such as metals8, 9, 10, 11–12 and two-dimensional (2D) titanium carbides/nitrides (MXenes)13, 14, 15, 16, 17, 18–19. However, these approaches involve insufficient thinness, non-uniformity and/or processing incompatibility. Here we propose embedding non-porous MXene film into metal thin films to achieve unprecedented shielding performance at a thickness of just 1 μm (about 70 decibels; about 80 decibels at 1.9-μm thickness) without the limitations associated with porous structures. This exceptional performance in simple-stacked metal/MXene/metal structures, which deviates from the typical thickness dependency, arises from the formation of electromagnetic wave confinement walls at the interfaces, driven by the conductivity mismatch between the metal and MXene. The confined electromagnetic waves within the MXene ‘well’ are effectively attenuated through polarization loss, primarily driven by dipoles at the metal–MXene interfaces. Our embedded-MXene-in-metal shields provide conformal EMI protection for portable USB (Universal Serial Bus) 3.0 flash drives and flexible Schottky diodes. Our embedded-MXene-in-metal shields may open new avenues in packaging technologies, enabling EMI-free ubiquitous electronics. © 2025 Elsevier B.V., All rights reserved.FALSEsciescopu
Synthesis and Biological Evaluation of Peripheral 5HT2B Antagonists for Liver Fibrosis
No full textLiver fibrosis is characterized by an excessive accumulation of extracellular matrix components, leading to the distortion of liver architecture and function. Recent studies have shown that antagonizing 5-hydroxytryptamine receptor 2B (5HT2B) stimulates the apoptosis of activated hepatic stellate cells and inhibits their proliferation while concurrently regressing hepatocyte proliferation. In this study, we present compound 19c, which demonstrates promising efficacy both in vitro and in vivo. 19c showed robust in vitro activity with an IC50 value of 1.09 nM and limited blood-brain barrier penetration. Furthermore, 19c did not significantly inhibit hERG and cytochrome P450 enzymes. 19c markedly reduced fibrotic deposition, with a decrease in fibrosis stage and area in the CCl4-induced liver fibrosis mouse model. Additionally, treatment with 19c led to downregulation of key fibrosis-related genes, including alpha-SMA, Timp1, Col1a1, and Col3a1. Taken together, these results suggest that 19c has the potential to be a novel antifibrotic agent.FALSEsciescopu
Rapid axially scanned and de-scanned line-scan confocal microscopy with a tunable acoustic gradient index of refraction lens for high-speed volumetric in vivo imaging
No full textSignificance: Rapid acquisition of high-resolution volumetric images has been critical to effectively monitor dynamic biological processes in vivo, yet it faces tradeoffs between image resolution, penetration depth, and imaging speed. These limitations hinder the ability to study rapid neurophysiological events such as cerebrovascular dynamics and cellular activity, highlighting the need for advanced high-speed 3D imaging system. Aim: To address these challenges in volumetric imaging performances, we aimed to develop a high-speed volumetric imaging system capable of resolving fast biological dynamics with minimal compromise in spatial resolution or imaging depth. Approach: We devised a rapid axially scanned and de-scanned (RASAD) scheme by integrating a TAG lens (tunable acoustic gradient index of refraction lens) into a line-scan confocal microscope. The TAG lens enabled axial (depth) scanning frequency at 70 kHz, allowing 3D projection imaging at rates up to 200 Hz with a detection depth of 135 mu m while minimally sacrificing the image quality (i.e., a lateral resolution of similar to 2.6 mu m). Results: We validated its performance through in vitro imaging of spontaneously contracting cardiomyocyte aggregates, capturing real-time calcium transients and synchronized contractions, and through in vivo imaging of the mouse cortical tissue, where volumetric acquisition over a 450x450x100 mu m(3) region enabled quantification of blood flow velocities up to 3.64 mm/s across various vessel types. Conclusions: The RASAD system enables high-speed, high-resolution 3D imaging of dynamic biological processes, providing a valuable tool for advancing studies of neurophysiological mechanisms and biomedical applications.TRUEsciescopu
Chiral hybrid Structures under molecular assembly-based nanoconfinement tags for optoelectronics
No full textWe precisely controlled nanoparticle arrangements within self-assembled structures through stereoselective molecular assembly. Our strategy leverages the interaction between chiral molecules and circular polarization to achieve unique optical responses. Using specific stereochemical properties, we achieved controlled self-assembly enabling template- directed synthesisof inorganic nanoparticles. The confined environment allowsprecise control over the nanoparticles' size and morphology, enhancing plasmonic properties. The hybrid nanocomposites exhibit distinctive optical characteristics through synergistic interaction between chiral structures and inorganic nanoparticles. Our research explores these hybrid systems for security applications, particularly in physically unclonable functions, integrating artificial intelligence with TEM imaging for enhanced structural identification
Discovery of novel anti-cancer microbiome and immune checkpoint protein for improving immunotherapy efficacy
No full textThe rapid advancements in cancer immunotherapy, particularly immune checkpoint inhibitors (ICIs), have significantly transformed cancer treatment. However, their efficacy remains limited to a subset of patients due to immune evasion mechanisms and resistance. This dissertation explores two novel approaches to overcoming these challenges. First, we investigate the potential of Melanoma Cell Adhesion Molecule (MCAM) as a new immune checkpoint protein (ICP) involved in immune evasion. Through transcriptomic analysis, we identified elevated MCAM expression in non-responders to PD-1 blockade therapy. Using purified MCAM protein and MCAM- knockdown cells, produced via genome-editing based on CRISPR-Cas9, we performed T cell activity assays and employed various preclinical mouse models to determine that MCAM plays a multifaceted role in inhibiting T cell activity: (1) MCAM directly suppresses T cell proliferation and cytotoxicity by delivering inhibitory signals to T cells, leading to immune suppression within the tumor microenvironment; (2) it limits T cell infiltration into tumors, creating an immunosuppressive barrier that hinders effective immune surveillance and attack; and (3) MCAM acts independently of the PD-1/PD-L1 axis, impairing the efficacy of anti-PD-1 therapy even in patients with high PD-L1 expression, while showing synergistic effects when combined with anti-PD-1 treatment. These results suggest that MCAM is a promising target for improving ICI efficacy. Second, we investigate the role of gut microbiota in enhancing anti-tumor immunity through Lactococcus lactis subsp. lactis GEN001 (L. lac_G01), a strain isolated from healthy Korean individuals. Through multi-omics analyses and preclinical models, we identified multiple mechanisms by which L. lac_G01 exerts its anti-cancer effects: (1) L. lac_G01 treatment led to an increase in both CD8+ T cells and NK cells, but through blockade experiments, we confirmed that the anti-tumor effects were primarily mediated by CD8+ T cells, indicating that CD8+ T cells play a key role in L. lac_G01's mechanism; (2) the immune activation driven by L. lac_G01 is mediated by IL-7 and IL-15, leading to a stronger immune response against tumors; (3) metabolomics analysis identified 1-monopalmitin, an effective metabolite produced by L. lac_G01, which promotes T cell proliferation and differentiation into effector cells, further contributing to the anti-tumor effect; and (4) L. lac_G01 inhibits Monoacylglycerol lipase (MAGL), leading to reduced lipid metabolism in cancer cells, thereby limiting tumor growth. These results demonstrate the therapeutic potential of L. lac_G01 and its metabolites in modulating immune responses and metabolic pathways to enhance anti-tumor efficacy and reshape the tumor microenvironment. Together, these findings offer new strategies to overcome the limitations of current immunotherapies, providing a dual approach targeting both immune checkpoints and the microbiome to enhance cancer treatment outcomes.DoctorAbstract i
Contents ii
List of Figures v
List of Tables vii
I. Introduction 1
1. Early Immunotherapies 1
2. Immune Checkpoint Inhibitions (ICIs) 2
3. Future Directions in Next-Generation Immunotherapies 3
4. Overview of This Study 4
II. Part 1. Targeting MCAM as a New Immunotherapy Strategy for Enhanced T-Cell Immunity and
Overcoming Anti-PD-1 Resistance 5
1. Introduction 5
2. Materials and Methods 8
2.1. Ethical approval and consent information 8
2.2. Data availability for 37-patient gastric cancer cohort 8
2.3. Clinical analysis of tumor gene expression and immune profiling in anti-PD-1 therapy response 8
2.4. Mammalian cell culture 9
2.5. MCAM knockdown by CRIPSR-Cas9 system 9
2.6. Mice experiments 11
2.7. T cell isolation 12
2.8. T cell proliferation assay 12
2.9. T cell Cytotoxicity assay 13
2.10. IFN-γ, TNF-α treatment 13
2.11. Immune cell profiling 14
2.12. Protein structure imaging 15
iii
2.13. Quantitative PCR (RT-PCR) 16
2.14. Quantification and Statistical Analysis 16
3. Results and discussion 17
3.1. The Potential of MCAM as a Therapeutic Target in Cancer 17
3.2. Tumor growth inhibition by MCAM knockdown 19
3.3. The Potential of MCAM as an Immune Checkpoint Protein for Modulating Anti-Tumor Immunity
21
3.4. Mechanism 1: MCAM-Mediated Suppression of T Cell Activity 23
3.5. Mechanism 2: MCAM-Mediated Promotion of T Cell Infiltration into the Tumor Microenvironment
25
3.6. Mechanism 3: MCAM as an Immune Regulator Distinct from the PD-1/PD-L1 Pathway, Leading to
Synergistic Effects with Anti-PD-1 Blockade 28
4. Discussion 33
5. Conclusion 35
III. Part 2. Enhancing Efficacy of PD-1 blockade by Lactococcus lactis subsp. lactis GEN001 and Its Key
Metabolite, 1-Monopalmitin 36
1. Introduction 36
2. Materials and Methods 40
2.1. Bacteria isolation from healthy donors 40
2.2. Bacteria culture and preparation of bacterial supernatant 41
2.3. Mammalian cell culture 41
2.4. Mice experiments 41
2.5. Transcriptome analysis 44
2.6. Metabolome analysis 44
2.7. Co-culture of immune cells with bacteria 47
2.8. Immune cell isolation 48
2.9. T cell proliferation assay 48
2.10. DC-T differentiation assay 48
2.11. ELISA 49
2.12. Immune cell profiling 49
iv
2.13. MAGL inhibition assay 50
2.14. Quantitative PCR 51
2.15. Quantification and Statistical Analysis 51
3. Results 52
3.1. IFN-γ Secretion from CD4+ T cells Induced by L. lac_G01 52
3.2. Safety Evaluation and Pharmacokinetics of L. lac_G01 for Therapeutic Use 54
3.3. Immune System Activation by L. lac_G01, Leading to Enhanced Immunotherapy Response 55
3.4. Mechanism 1: CD8+TEff-Dependent Anti-Tumor Effects of L. lac_G01 59
3.5. Mechanism 2: IL-7 and IL-15 Roles in L. lac_G01-Induced Enhancement of Anti-Tumor Immunity
60
3.6. Mechanism 3-1: 1-Monopalmitin, a Key Metabolite of L. lac_G01. 63
3.7. Mechanism 3-2: 1-Monopalmitin's Effects in Modulating Immune Responses and Enhancing Anti-
Tumor Efficacy 65
3.8. Mechanism 4: Modulation of Lipid Metabolism via MAGL Inhibition 68
4. Discussion 70
5. Conclusion 72
IV. Summary and Further works 73
1. Summarization of Two Novel Approaches to Enhance Cancer Immunotherapy 73
1.1. The role of MCAM as an immune checkpoint protein 73
1.2. The potential of L. lac_G01in boosting antitumor immunity 73
2. Future Works 74
2.1. Molecular Mechanism of MCAM’s immune modulation 74
2.2. Molecular Mechanism of L. lac_G01’s immune boosting effects 74
V. References 75
VI. Acknowledgements 85
VII. Curriculum Vitae 86
Optimal Operation Strategy of Virtual Power Plant Using Electric Vehicle Agent-Based Model Considering Operational Profitability
No full textGrowing EV adoption is reshaping how Distributed Energy Resources (DERs) interact with the grid, playing a pivotal role in global decarbonization efforts and the transition towards a sustainable energy future. This study built a Virtual Power Plant (VPP) operation framework centered on EV behavioral dynamics, connecting individual driving and charging behaviors with the physical and economic layers of energy management. The EV behavioral dynamic model quantifies the stochastic travel, parking, and charging behaviors of individual EVs through an Agent-Based Trip and Charging Chain (AB-TCC) simulation, producing a Behavioral Flexibility Trace (BFT) that represents time-resolved EV availability and flexibility. The Forecasting Model employs a Bi-directional Long Short-Term Memory (Bi-LSTM) network trained on historical meteorological data to predict short-term renewable generation and represent physical variability. The two-stage optimization model integrates behavioral and physical information with market price signals to coordinate day-ahead scheduling and real-time operation, minimizing procurement costs and mitigating imbalance penalties. Simulation results indicate that the proposed framework yielded an approximately 15% increase in revenue over 7 days through EV-based flexibility utilization. These findings demonstrate that the proposed approach effectively leverages EV flexibility to manage renewable generation variability, thereby enhancing both the profitability and operational reliability of VPPs in local distribution systems. This facilitates greater penetration of intermittent renewable energy sources, accelerating the transition to a low-carbon energy system.TRUEsciessciscopu
Impedance Control of Robot Manipulators Without Relying on External Force Information Minji Kim School of Mechanical and Robotics Engineering Gwangju Institute of Science and Technology
No full text최근협동로봇시장은로봇기술의급속한발전과다양한산업분야에서의수요증가 에힘입어매우빠른속도로성장하고있다.이러한성장의중심에는로봇이외부환경과 물리적으로 상호작용할 때 관성, 감쇠, 강성을 제어하여 안정성과 작업 성능을 동시에 확보하는 임피던스 제어 기술이 자리 잡고 있다. 특히 협동 로봇처럼 인간과 직접적으로 접촉하거나 좁은 공간에서 다양한 작업을 수행해야 하는 시스템에서는 임피던스 제어 가 필수적인 요소로 인식된다. 기존 임피던스 제어 방식은 질량 ·감쇠 ·강성 파라미터를 직접 설계하고, 외부 힘 정보와 자코비안 역행렬을 고려하여 제어 입력을 구성함으로써 다양한 작업 환경에 대응해 왔다. 그러나 이러한 고차원 파라미터 설계는 복잡도가 높 고, 외부 힘 센서 노이즈나 특이점 근접 구간에서의 민감도가 증가하여 제어 안정성이 저하될 가능성이 있었다. 이에 본 연구에서는 임피던스 제어 파라미터의 복잡한 설계 과정을 간소화하면서 도, 제어 법칙에서 외부 힘 항을 직접 제거하여 센서 의존도를 줄이고 특이점 근처에서 발생할 수 있는 불안정성을 최소화할 수 있는 새로운 임피던스 제어 방법을 제안한다. 이는 향후 임피던스 제어 파라미터 선정에 관한 명확한 기준을 제시하고, 외력의 크기가 큰 경우나 특이점과 같은 까다로운 조건에도 안정적으로 대응할 수 있는 제어 전략을 제공한다는 점에서 의의가 있다. |The market for collaborative robots has been expanding at a rapid pace, driven by the rapid advancement of robotic technologies and growing demands across vari- ous industries. At the heart of this growth is impedance control, which enables robots to adjust inertia, damping, and stiffness in real time to achieve both stability and task performance when interacting physically with their surrounding environment. In particular, impedance control has become a critical requirement for systems such as collaborative robots, where direct human-robot contact or operation within confined spaces is common. Conventional impedance control approaches typically involve de- signing mass, damping, and stiffness parameters, taking into account external force information and the inverse of the Jacobian to generate control inputs for diverse work environments. However, this high-dimensional parameter design process tends to be ex- tremely complex, and problems such as sensor noise from external force measurements or increased sensitivity near kinematic singularities can undermine control stability. This paper presents a novel impedance control method that simplifies the complex parameter design process and eliminates the external force term directly from the control law. The proposed approach reduces sensor reliance and mitigates potential instabilities near singular configurations. As a result, it provides systematic guidelines for impedance parameter selection and ensures robust performance under large external forces and singularity conditions, thereby improving overall stability in challenging environments.MasterAbstract (English) i
Abstract (Korean) ii
List of Contents iii
List of Tables v
List of Figures vi
1 Introduction 1
1.1 Overview of Impedance Control 1
1.2 Research Trends 2
1.3 Research Contributions 4
1.4 Organization of the Thesis 5
2 Preliminaries 6
2.1 Fundamentals of Robot Control 6
2.2 Impedance Control 7
3 Proposed Method 11
3.1 Analysis of the Proposed Impedance Control Law 11
3.2 System Stability Analysis of the Proposed Method 15
4 Simulation Results and Analysis 21
4.1 Simulation Environment and Setup 21
4.2 Impedance Parameter Settings 22
4.3 Simulation Results 24
– iii –
4.3.1 Performance Comparison: Conventional Method vs. Proposed
Method 24
4.3.2 Performance Comparison: Simplified Method vs. Proposed Method 40
4.4 Comprehensive Analysis and Discussion 45
5 Conclusion and Future Work 48
5.1 Conclusion 48
5.2 Future Work 49
References 50
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