GIST Scholar
Not a member yet
30271 research outputs found
Sort by
Development of an AI Model for PROTAC Drug Activity Prediction
No full textRecent advances in molecular biology have accelerated the development of therapeutic strategies targeting disease-associated proteins. Such targeted therapies are actively being explored in both academia and the pharmaceutical industry due to their superior efficacy and reduced side effects compared to conventional treatments. Most targeted therapeutics inhibit protein function by binding to the active site of the target protein. However, they face limitations when the target protein lacks a druggable binding pocket or forms large protein complex, making it difficult to achieve effective inhibition. Consequently, over 80% of human proteins are classified as 'undruggable targets,' highlighting the need for alternative strategies to overcome these limitations. Targeted protein degradation (TPD) has emerged as a promising strategy to address this undruggable target challenge. Unlike traditional pharmaceutical approaches, TPD utilizes the cellular protein degradation mechanism to eliminate the target protein itself. Among various TPD strategies, PROteolysis TArgeting Chimera (PROTAC) which leverages the ubiquitin-proteasome system has gained significant attention. PROTACs can induce protein degradation without strong binding affinity and offer selectivity through the choice of E3 ligase. However, their relatively large molecular weights and complex synthesis procedures pose challenges in terms of time and cost. In this study, we developed an artificial intelligence (AI) model to predict the degradation activity of PROTAC molecules. Public data from PROTAC-DB and PROTACpedia were collected for model training and performance evaluation. The proposed model demonstrated consistent performance improvements in the condition of unseen protein, unseen PROTAC, and even the combined unseen setting. Furthermore, the generalization ability of model was validated using an independent external test set. An ablation study confirmed the proposed model architecture contributes to performance enhancement.MasterⅠ. Introduction 1
1. 1. Undruggable Proteins Problem 1
1. 2. Targeted Protein Degradation 2
1. 3. Proteolysis Targeting Chimera 3
1. 4. Related Studies 4
1. 5. Research Objectives 5
Ⅱ. Materials and Methods 6
2. 1. Dataset 6
2. 2. Model Overview 8
2. 2. 1. Protein Encoder 9
2. 2. 2. Compound Encoder 10
2. 2. 3. PROTAC Activity Predictor 11
2. 3. Implementation Details 12
Ⅲ. Results and Discussion 14
3. 1. Model Performance 14
3. 2. External test 17
3. 2. 1. Histone Acetyltransferase p300 18
3. 2. 2. Estrogen receptor alpha 20
3. 3. Ablation study 22
3. 4. Reliability analysis 24
Ⅳ. Conclusion 26
Summary 27
References 28
Acknowledgement 33
Curriculum Vitae 3
Decoding Laver Discoloration: Insights from Marine Multi-Omics into Chlorosis Mechanisms
No full textDeep learning-based holography for T-linear resistivity
No full textWe employ deep learning within holographic duality to investigate T-linear resistivity, a hallmark of strange metals. Utilizing physics-informed neural networks, we incorporate boundary data for T-linear resistivity and bulk differential equations into a loss function. This approach allows us to derive dilaton potentials in Einstein-Maxwell-dilaton-axion theories, capturing essential features of strange metals, such as T-linear resistivity and linear specific heat scaling. We also explore the impact of the resistivity slope on dilaton potentials. Regardless of slope, dilaton potentials exhibit universal exponential growth at low temperatures, driving T-linear resistivity and matching infrared geometric analyses. At a specific slope, our method rediscovers the Gubser-Rocha model, a well-known holographic model of strange metals. Additionally, the robustness of T-linear resistivity at higher temperatures correlates with the asymptotic Anti-de Sitter behavior of the dilaton coupling to the Maxwell term. Our findings suggest that deep learning could help uncover mechanisms in holographic condensed matter systems and advance our understanding of strange metals.TRUEsciescopu
Roles of Nanoscale Defects of Graphene in Remote Epitaxy of GaN
No full textRemote epitaxy through graphene enables the fabrication of freestanding membranes, facilitating the "peel-and-stack" process for semiconductor hetero-integration. While previous studies have emphasized graphene thickness, substrate bonding ionicity, and damage-free transfer of graphene for implementing remote epitaxy, the impact of nanoscale microscopic defects in graphene remains unexplored. Metal-organic chemical vapor deposition (MOCVD) of GaN requires high temperatures and a radical reaction environment, which can damage graphene. This study investigates the effects of chemical doping and nanoscale defects in graphene on remote epitaxy during MOCVD growth of GaN crystallites on graphene-coated Al2O3 for understanding the early growth stage and the resulting crystal quality. Three distinct modes are identified: remote epitaxy, anchored remote epitaxy, and epitaxial lateral overgrowth (ELOG). Pristine graphene enables pure remote epitaxy of well-aligned, strain-relaxed GaN crystallites. N-doped graphene promotes chemically anchored nucleation, causing slightly misaligned crystallites due to altered remote atomic interaction, newly termed "anchored remote epitaxy". Graphene pinholes induce direct GaN-Al2O3 covalent bonding for ELOG, resulting in significant compressive strain in GaN. How graphene's chemical and physical defects affect epitaxial crystallite quality (i.e., alignment, strain relaxation, density) is further explored based on bonding mechanisms, providing insights into remote epitaxy for next-generation semiconductor fabrication.FALSEsciescopu
MV2: A Large-Scale 360-Degree Multi-View Maritime Vision Dataset for Object Detection and Segmentation
No full textLow-dose rapamycin microdepots promote hair regrowth via autophagy modulation
No full textPurpose: Current therapies for hair loss, including orally administered finasteride, baricitinib, and topically applied minoxidil, are effective but have limitations related to poor patient compliance or low absorption, leading to inconsistent outcomes. This study developed injectable microdepots containing poly(lactic-co-glycolic acid) and rapamycin (RAPMD) to address these issues. Methods: RAPMD was fabricated using an emulsification solvent-evaporation method. The microdepots were comprehensively characterized, including their size, loading capacity, loading efficiency, and release profile. The in vitro and in vivo efficacy of RAPMD were evaluated through gene analysis and further assays. Results: RAPMD exhibited a spherical shape with an average size of 6 μm and a loading efficiency of approximately 71%. The in vitro release study revealed a sustained release of rapamycin, with about 70% released over 35 days, remarkably promoting hair regrowth. Importantly, in vivo results demonstrated that low-dose RAPMD effectively induced the transition of hair follicles into the anagen phase in mice models via modulating autophagy and Wnt/β-catenin pathway. Conclusion: These findings highlight that local injection of PLGA microdepots, with their sustained drug release profile is an effective strategy for promoting hair regrowth in patients experiencing hair loss. © The Author(s) 2025.TRUEsciescopuskc
Arsenic and Heavy Metals in Soils and Plants near Sulfide Mines: Implications for Phytoremediation and Phytomanagement
No full textThe accumulation of heavy metals (i.e., As, Cu, Ni, Pb, and Zn) in soils and native plant species near copper, nickel, and pyrite mines in Vietnam was assessed. The highest soil As, Cu, Ni, Pb, and Zn concentrations recorded in mine soils were 42.3, 1570, 9870, 128, and 462 mg/kg, and those in agricultural soils were 11.4, 453, 94.9, 34.4, and 147 mg/kg, respectively. Pollution index (PI) values indicated heavy pollution (PI = 3.99–13.0) for mine soils, and unpolluted to severely polluted (PI = 0.65–2.84) for agricultural soils. Soil enrichment factors had a wide range, from minimal to extreme enrichment of heavy metals (EF = 0.03–91.4). Arsenic minerals may be the main source of high As concentrations in sulfide mines. The As, Cu, Ni, Pb, and Zn concentrations of 20 native plant species near three mines were in the ranges of 0.05–1150, 3.17–123, 0.47–291, 0.08–6.34, and 6.87–168 mg/kg (dry weight, DW), respectively. Based on the recorded hyperaccumulation levels (1150 mg/kg, DW), bioaccumulation factors (BAF = 2.4–90.0), biomass, and rapid growth, Pteris vittata L. is considered a promising plant for phytoextraction of As in soils. Bidens pilosa L. has potential for phytostabilization of sulfide-bearing soils, given its low concentrations of heavy metals in plant shoots, BAF values of <1, high biomass, and wide distribution. Integrated phytoremediation and phytomanagement are applicable to metal-contaminated soils. Phytomining, energy crops, and vegetation cover should be investigated for the phytomanagement of metal-contaminated soils in mining areas. Graphical Abstract: (Figure presented.) © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.FALSEsciescopu
Understanding the Effect of Acid-Base Equilibria in Ligand Exchange on the Overall Quality of Inorganic Perovskite Nanocrystals and Light-Emitting Devices
No full textPhotoluminescence quantum yield (PLQY) losses in inorganic perovskite nanocrystals (PeNCs) due to ligand desorption hamper high external quantum efficiencies (EQE) in corresponding perovskite light-emitting devices (PeLEDs). Their low PLQYs derive mainly from ligand desorption during device fabrication. Post-synthesis treatments contribute to inefficiently adsorbed ligands due to their unfavorable chemical environments. Here the acid/base dynamics of treatments are investigated by applying a chemoselective and aprotic-driven ligand exchange strategy that favors neutral environments, in lieu of traditional acid-mediated strategies. Mild ligand-extracting reagents (LERs) are utilized to gently extract native anchoring ligands with their cations, while their anions temporarily passivate the PeNC's surface, ensuring steady colloidal stability. By applying tri-ethyloxonium tetrafluoroborate (TET) as the LER, PeNCs films displayed PLQYs as high as 92.8%. When paired with the widely-employed di-dodecyldimethylammonium bromide (DDAB) ligand, PeLED devices based on TET-treated PeNCs exhibited a maximum EQE of 22.94% for emissions at λ = 512nm. The work highlights the versatility of ligand exchange processes by assessing their overall governing factors. © 2025 Wiley-VCH GmbH.FALSEsciescopu
Adaptive Walker: User Intention and Terrain Aware Intelligent Walker with High-Resolution Tactile and IMU Sensor
No full textIn this paper, we present an adaptive walker system designed to address limitations in current intelligent walker technologies. While recent advancements have been made in this field, existing systems often struggle to seamlessly interpret user intent for speed control and lack adaptability across diverse scenarios and terrain. Our proposed solution incorporates high-resolution tactile sensors, deep learning algorithms, IMU sensors, and linear motors to dynamically adjust to the user's intentions and terrain changes. The system is capable of predicting the user's desired speed with an error margin of only 20.99%, relying solely on tactile input from hand and arm contact points. Additionally, it maintains the walker's horizontal stability with an error of less than 1 degree by adjusting leg lengths in response to variations in ground angle. This adaptive walker enhances user safety and comfort, particularly for individuals with reduced strength or cognitive abilities, and offers reliable assistance on uneven terrain such as uphill and downhill paths. © 2025 Elsevier B.V., All rights reserved
Part Ⅰ: Stereospecific syn-Dibromination and Regiodivergent syn-Bromochlorination of Alkenes via Vicinal Double Electrophilic Activation Strategy Part II: Selectivity Enhancement in syn-Dibromination of Alkenes through Mechanochemistry
No full textPart I: Whereas the conventional anti-dihalogenation of alkenes remains a valuable synthetic method with highly predictable stereospecificity, the restricted reaction mechanism makes it challenging to alter the diastereochemical course into the complementary syn-dihalogenation process. Only a few notable achievements were made recently by inverting one of the stereocenters after anti-addition using a carefully designed reagent system. Here, a conceptually distinctive strategy was developed for the simultaneous double electrophilic activation of the two alkene carbons from the same side. The subsequent iterative displacements of the vicinal leaving groups by nucleophilic halides enabled the syn-dihalogenation. For this purpose, thianthrenium dication was employed, and the syn-dibromination and the regiodivergent syn-bromochlorination were successfully archived.|Part II: Previously, highly stereosepecific syn-dihalogenations and syn-interhalogenation of alkenes were reported by our group. While these methods represented important advances in synthetic methodology, the syn-dibromination still suffered from eroded selectivity compared to syn-dichlorination. To address this limitation, various strategies were investigated. Among them, notable selectivity enhancement was detected under solvent-free conditions. Motivated by this result, mechanochemsistry was employed as a suitable method for conducting the solid phase reaction at high concentration under neat conditions. A series of alkene–thianthrenium salts were evaluated through mechanochemical methods, ultimately achieving improved selectivity in the dibromination process.Doctor1. Introduction 2
1.1. Difficulty in syn-dihalogenation of alkenes 2
1.2. Previous syn-dihalogenation approaches via double inversion strategy 3
1.3. Our new approach of syn-dihalogenation via vicinal double electrophilic activation of alkenes 4
2. Results and Discussion 6
2.1. syn-Dichlorination and syn-dibromination of alkene 6
2.1.1. Reaction condition optimization for syn-dichlorination 6
2.1.2. syn-Dichlorination of alkenes 7
2.1.3. syn-Dibromination of alkenes 9
2.2. syn-Bromochlorination of alkenes 10
2.2.1. Reaction condition optimization 10
2.2.2. Substration scope 13
2.2.3. Mechanistic analysis on the site-selectivity 15
2.3. Attempt to employ fluorine in syn-dihalogenation of alkenes 17
3. Conclusion 18
4. Experimental 19
4.1. General experimental 19
4.2. Experimental procedures 20
4.2.1. Preparation of substrates 20
4.2.2. Preparation of thianthrene-S-oxide (19) 35
4.2.3. General procedure I: syn-dihalogenation of alkenes 36
4.2.4. General procedure II: syn-bromochlorination of alkenes 42
5. References 49
Part II: Selectivity Enhancement in syn-Dibromination of Alkenes through Mechanochemistry
1. Introduction 56
1.1. Stereospecific syn-dibromination of alkene 56
1.2. Reaction condition optimization: temperature, intermediate, and concentration 56
1.3. Mechanochemistry 57
2. Results and Discussion 59
2.1. Preliminary study without solvent 59
2.2. Reaction condition optimization of through ball milling 59
2.3. Examination of substrate scope 63
3. Conclusion 64
4. Experimental 65
4.1. General experimental 65
4.2. Literature preparation 66
4.3. Experimental procedures 66
4.2.1. Preparation of alkene substate 67
4.2.3. General Procedure I: Preparation of alkene-TT2+ salt (2) 67
4.2.4. General Procedure II: syn-Bromochlorination through mechanochemsitry 69
5. References 71
Apendix Part I: Mechanistic investigation on the remote stereocontrol in the chiral Lewis base-catalyzed,
SiCl4-promoted kinetic resolution of chlorinated cis-vinyl epoxides
1. Introduction 74
2. Results and Discussion 76
2.1. Kinetic resolution of α-chloro cis-vinyl epoxide with two β-alkyl substituents 76
2.2. Computatoinal analysis 78
2.2.1. Computational method 78
2.2.2. Transition state calculation for kinetic resolution of chlorinated cis-vinyl epoxides 78
3. Conclusion 82
4. Experimental 83
4.1. General experimental 83
4.2. Experimental procedures 84
4.2.1. Preparation of alkene substate 84
5. References 87
Apendix Part II: Study on syn-Dihalogenation of Alkenes via Pericyclic Mechanism
1. Introduction 95
2. Results and Discussion 97
2.1. [4+2] cycladdition with azine and cis-1,2-dichloroethylene 97
2.2. [4+2] cycloaddition with azine and trisubstituted monochloroalkene 98
2.3. [4+2] cycloaddition with pyrone 99
2.4. Intramolecular [4+2] cycloaddition with trifluoroalkene 100
3. Conclusion 101
4. Experimental 102
4. Preparation of substrate 18 for intramolecular [4+2] cycloaddition 102
4.2. Experimental procedures 102
4.2.1. Preparation of diphenyl tetrazine 1c 102
4.2.2. Preparation of substrate 18 for intramolecular [4+2] cycloaddition 103
5. References 105
Curriculum vitae 106
Acknowledgement 10