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Simultaneous Analysis of 21 Chemical Reactions... AI to Transform New Drug Development
< Photo 1. (From left) Professor Hyunwoo Kim and students Donghun Kim and Gyeongseon Choi in the Integrated M.S./Ph.D. program of the Department of Chemistry > Thalidomide, a drug once used to alleviate morning sickness in pregnant women, exhibits distinct properties due to its optical isomers* in the body: one isomer has a sedative effect, while the other causes severe side effects like birth defects. As this example illustrates, precise organic synthesis techniques, which selectively synthesize only the desired optical isomer, are crucial in new drug development. Overcoming the traditional methods that struggled with simultaneously analyzing multiple reactants, our research team has developed the world's first technology to precisely analyze 21 types of reactants simultaneously. This breakthrough is expected to make a significant contribution to new drug development utilizing AI and robots. *Optical Isomers: A pair of molecules with the same chemical formula that are mirror images of each other and cannot be superimposed due to their asymmetric structure. This is analogous to a left and right hand, which are similar in form but cannot be perfectly overlaid. KAIST's Professor Hyunwoo Kim's research team in the Department of Chemistry announced on the 16th that they have developed an innovative optical isomer analysis technology suitable for the era of AI-driven autonomous synthesis*. This research is the world's first technology to precisely analyze asymmetric catalytic reactions involving multiple reactants simultaneously using high-resolution fluorine nuclear magnetic resonance spectroscopy (19F NMR). It is expected to make groundbreaking contributions to various fields, including new drug development and catalyst optimization. *AI-driven Autonomous Synthesis: An advanced technology that automates and optimizes chemical substance synthesis processes using artificial intelligence (AI). It is gaining attention as a core element for realizing automated and intelligent research environments in future laboratories. AI predicts and adjusts experimental conditions, interprets results, and designs subsequent experiments independently, minimizing human intervention in repetitive experiments and significantly increasing research efficiency and innovativeness. Currently, while autonomous synthesis systems can automate everything from reaction design to execution, reaction analysis still relies on individual processing using traditional equipment. This leads to slower speeds and bottlenecks, making it unsuitable for high-speed repetitive experiments. Furthermore, multi-substrate simultaneous screening techniques proposed in the 1990s garnered attention as a strategy to maximize reaction analysis efficiency. However, limitations of existing chromatography-based analysis methods restricted the number of applicable substrates. In asymmetric synthesis reactions, which selectively synthesize only the desired optical isomer, simultaneously analyzing more than 10 types of substrates was nearly impossible. < Figure 1. Conventional organic reaction evaluation methods follow a process of deriving optimal reaction conditions using a single substrate, then expanding the substrate scope one by one under those conditions, leaving potential reaction areas unexplored. To overcome this, high-throughput screening is introduced to broadly explore catalyst reactivity for various substrates. When combined with multi-substrate screening, this approach allows for a much broader and more systematic understanding of reaction scope and trends. > To overcome these limitations, the research team developed a 19F NMR-based multi-substrate simultaneous screening technology. This method involves performing asymmetric catalytic reactions with multiple reactants in a single reaction vessel, introducing a fluorine functional group into the products, and then applying their self-developed chiral cobalt reagent to clearly quantify all optical isomers using 19F NMR. Utilizing the excellent resolution and sensitivity of 19F NMR, the research team successfully performed asymmetric synthesis reactions of 21 substrates simultaneously in a single reaction vessel and quantitatively measured the product yield and optical isomer ratio without any separate purification steps. Professor Hyunwoo Kim stated, "While anyone can perform asymmetric synthesis reactions with multiple substrates in one reactor, accurately analyzing all the products has been a challenging problem to solve until now. We expect that achieving world-class multi-substrate screening analysis technology will greatly contribute to enhancing the analytical capabilities of AI-driven autonomous synthesis platforms." < Figure 2. A method for analyzing multi-substrate asymmetric catalytic reactions, where different substrates react simultaneously in a single reactor, using fluorine nuclear magnetic resonance has been implemented. By utilizing the characteristics of fluorine nuclear magnetic resonance, which has a clean background signal and a wide chemical shift range, the reactivity of each substrate can be quantitatively analyzed. It is also shown that the optical activity of all reactants can be simultaneously measured using a cobalt metal complex. > He further added, "This research provides a technology that can rapidly verify the efficiency and selectivity of asymmetric catalytic reactions essential for new drug development, and it is expected to be utilized as a core analytical tool for AI-driven autonomous research." < Figure 3. It can be seen that in a multi-substrate reductive amination reaction using a total of 21 substrates, the yield and optical activity of the reactants according to the catalyst system were simultaneously measured using a fluorine nuclear magnetic resonance-based analysis platform. The yield of each reactant is indicated by color saturation, and the optical activity by numbers. > Donghun Kim (first author, Integrated M.S./Ph.D. program) and Gyeongseon Choi (second author, Integrated M.S./Ph.D. program) from the KAIST Department of Chemistry participated in this research. The study was published online in the Journal of the American Chemical Society on May 27, 2025.※ Paper Title: One-pot Multisubstrate Screening for Asymmetric Catalysis Enabled by 19F NMR-based Simultaneous Chiral Analysis※ DOI: 10.1021/jacs.5c03446 This research was supported by the National Research Foundation of Korea's Mid-Career Researcher Program, the Asymmetric Catalytic Reaction Design Center, and the KAIST KC30 Project. < Figure 4. Conceptual diagram of performing multi-substrate screening reactions and utilizing fluorine nuclear magnetic resonance spectroscopy. >
2025.06.16
View 107
“One Experiment Is All It Takes”: KAIST Team Revolutionizes Drug Interaction Testing, Replacing 60,000 Studies
A groundbreaking new method developed by researchers at KAIST and Chungnam National University could drastically streamline drug interaction testing — replacing dozens of traditional experiments with just one. The research, led by Professor Jae Kyoung Kim of KAIST Department of Mathematical Sciences & IBS Biomedical Mathematics Group and Professor Sang Kyum Kim of Chungnam National University's College of Pharmacy, introduces a novel analysis technique called 50-BOA, published in Nature Communications on June 5, 2025. < Photo 1. (From left) Professor Sang Kyum Kim (Chungnam National University College of Pharmacy, co-corresponding author), Dr. Yun Min Song (IBS Biomedical Mathematics Group, formerly KAIST Department of Mathematical Sciences, co-first author), undergraduate student Hyeong Jun Jang (KAIST, co-first author), Professor Jae Kyoung Kim (KAIST and IBS Biomedical Mathematics Group, co-corresponding author) (Top left in the bubble) Professor Hwi-yeol Yun (Chungnam National University College of Pharmacy, co-author) > For decades, scientists have had to repeat drug inhibition experiments across a wide range of concentrations to estimate inhibition constants — a process seen in over 60,000 scientific publications. But the KAIST-led team discovered that a single, well-chosen inhibitor concentration can yield even more accurate results. < Figure 1. Graphical summary of 50-BOA. 50-BOA improves the accuracy and efficiency of inhibition constant estimation by using only a single inhibitor concentration instead of the traditionally used method of employing multiple inhibitor concentrations. > “This approach challenges long-standing assumptions in experimental pharmacology,” says Prof. Kim. “It shows how mathematics can fundamentally redesign life science experiments.” By mathematically analyzing the sources of error in conventional methods, the team found that over half the data typically collected adds no value or even skews results. Their new method not only cuts experimental effort by over 75%, but also enhances reproducibility and accuracy. To help researchers adopt the method quickly, the team developed a user-friendly tool that takes simple Excel files as input, now freely available on GitHub: ☞ https://github.com/Mathbiomed/50-BOA < Figure 2. The MATLAB and R package of 50-BOA at GitHub > The work holds promise for faster and more reliable drug development, especially in assessing potential interactions in combination therapies. The U.S. FDA already emphasizes accurate enzyme inhibition assessment during early-stage drug evaluation — and this method could soon become a new gold standard.
2025.06.16
View 159
KAIST Turns an Unprecedented Idea into Reality: Quantum Computing with Magnets
What started as an idea under KAIST’s Global Singularity Research Project—"Can we build a quantum computer using magnets?"—has now become a scientific reality. A KAIST-led international research team has successfully demonstrated a core quantum computing technology using magnetic materials (ferromagnets) for the first time in the world. KAIST (represented by President Kwang-Hyung Lee) announced on the 6th of May that a team led by Professor Kab-Jin Kim from the Department of Physics, in collaboration with the Argonne National Laboratory and the University of Illinois Urbana-Champaign (UIUC), has developed a “photon-magnon hybrid chip” and successfully implemented real-time, multi-pulse interference using magnetic materials—marking a global first. < Photo 1. Dr. Moojune Song (left) and Professor Kab-Jin Kim (right) of KAIST Department of Physics > In simple terms, the researchers developed a special chip that synchronizes light and internal magnetic vibrations (magnons), enabling the transmission of phase information between distant magnets. They succeeded in observing and controlling interference between multiple signals in real time. This marks the first experimental evidence that magnets can serve as key components in quantum computing, serving as a pivotal step toward magnet-based quantum platforms. The N and S poles of a magnet stem from the spin of electrons inside atoms. When many atoms align, their collective spin vibrations create a quantum particle known as a “magnon.” Magnons are especially promising because of their nonreciprocal nature—they can carry information in only one direction, which makes them suitable for quantum noise isolation in compact quantum chips. They can also couple with both light and microwaves, enabling the potential for long-distance quantum communication over tens of kilometers. Moreover, using special materials like antiferromagnets could allow quantum computers to operate at terahertz (THz) frequencies, far surpassing today’s hardware limitations, and possibly enabling room-temperature quantum computing without the need for bulky cryogenic equipment. To build such a system, however, one must be able to transmit, measure, and control the phase information of magnons—the starting point and propagation of their waveforms—in real time. This had not been achieved until now. < Figure 1. Superconducting Circuit-Based Magnon-Photon Hybrid System. (a) Schematic diagram of the device. A NbN superconducting resonator circuit fabricated on a silicon substrate is coupled with spherical YIG magnets (250 μm diameter), and magnons are generated and measured in real-time via a vertical antenna. (b) Photograph of the actual device. The distance between the two YIG spheres is 12 mm, a distance at which they cannot influence each other without the superconducting circuit. > Professor Kim’s team used two tiny magnetic spheres made of Yttrium Iron Garnet (YIG) placed 12 mm apart with a superconducting resonator in between—similar to those used in quantum processors by Google and IBM. They input pulses into one magnet and successfully observed lossless transmission of magnon vibrations to the second magnet via the superconducting circuit. They confirmed that from single nanosecond pulses to four microwave pulses, the magnon vibrations maintained their phase information and demonstrated predictable constructive or destructive interference in real time—known as coherent interference. By adjusting the pulse frequencies and their intervals, the researchers could also freely control the interference patterns of magnons, effectively showing for the first time that electrical signals can be used to manipulate magnonic quantum states. This work demonstrated that quantum gate operations using multiple pulses—a fundamental technique in quantum information processing—can be implemented using a hybrid system of magnetic materials and superconducting circuits. This opens the door for the practical use of magnet-based quantum devices. < Figure 2. Experimental Data. (a) Measurement results of magnon-magnon band anticrossing via continuous wave measurement, showing the formation of a strong coupling hybrid system. (b) Magnon pulse exchange oscillation phenomenon between YIG spheres upon single pulse application. It can be seen that magnon information is coherently transmitted at regular time intervals through the superconducting circuit. (c,d) Magnon interference phenomenon upon dual pulse application. The magnon information state can be arbitrarily controlled by adjusting the time interval and carrier frequency between pulses. > Professor Kab-Jin Kim stated, “This project began with a bold, even unconventional idea proposed to the Global Singularity Research Program: ‘What if we could build a quantum computer with magnets?’ The journey has been fascinating, and this study not only opens a new field of quantum spintronics, but also marks a turning point in developing high-efficiency quantum information processing devices.” The research was co-led by postdoctoral researcher Moojune Song (KAIST), Dr. Yi Li and Dr. Valentine Novosad from Argonne National Lab, and Prof. Axel Hoffmann’s team at UIUC. The results were published in Nature Communications on April 17 and npj Spintronics on April 1, 2025. Paper 1: Single-shot magnon interference in a magnon-superconducting-resonator hybrid circuit, Nat. Commun. 16, 3649 (2025) DOI: https://doi.org/10.1038/s41467-025-58482-2 Paper 2: Single-shot electrical detection of short-wavelength magnon pulse transmission in a magnonic ultra-thin-film waveguide, npj Spintronics 3, 12 (2025) DOI: https://doi.org/10.1038/s44306-025-00072-5 The research was supported by KAIST’s Global Singularity Research Initiative, the National Research Foundation of Korea (including the Mid-Career Researcher, Leading Research Center, and Quantum Information Science Human Resource Development programs), and the U.S. Department of Energy.
2025.06.12
View 449
KAIST develops technology for selective RNA modification in living cells and animals
· A team led by Professor Won Do Heo from the Department of Biological Sciences, KAIST, has developed a pioneering technology that selectively acetylates specific RNA molecules in living cells and tissues. · The platform uses RNA-targeting CRISPR tools in combination with RNA-modifying enzymes to chemically modify only the intended RNA. · The method opens new possibilities for gene therapy by enabling precise control of disease-related RNA without affecting the rest of the transcriptome. < Photo 1. (From left) Professor Won Do Heo and Jihwan Yu, a Ph.D. Candidate of the Department of Biological Sciences > CRISPR-Cas13, a powerful RNA-targeting technology is gaining increasing attention as a next-generation gene therapy platform due to its precision and reduced side effects. Utilizing this system, researchers at KAIST have now developed the world’s first technology capable of selectively acetylating (chemically modifying) specific RNA molecules among countless transcripts within living cells. This breakthrough enables precise, programmable control of RNA function and is expected to open new avenues in RNA-based therapeutic development. KAIST (President Kwang Hyung Lee) announced that a research team led by Professor Won Do Heo in the Department of Biological Sciences has recently developed a groundbreaking technology capable of selectively acetylating specific RNA molecules within the human body using the CRISPR-Cas13 system—an RNA-targeting platform gaining increasing attention in the fields of gene regulation and RNA-based therapeutics. RNA molecules can undergo chemical modifications—the addition of specific chemical groups—which alter their function and behavior without changing the underlying nucleotide sequence. However, some of these modifications, a critical layer of post-transcriptional gene regulation, remain poorly understood. Among them, N4-acetylcytidine (ac4C) has been particularly enigmatic, with ongoing debate about its existence and function in human messenger RNA (mRNA), the RNA that encodes proteins. To address this gap, the KAIST research team developed a targeted RNA acetylation system, named dCas13-eNAT10. This platform combines a catalytically inactive Cas13 enzyme (dCas13) that guides the system to specific RNA targets, with a hyperactive variant of the NAT10 enzyme (eNAT10), which performs RNA acetylation. This approach enables precise acetylation of only the desired RNA molecules among the vast pool of transcripts within the cell. < Figure 1. Development of hyperactive variant eNAT10 through NAT10 protein engineering. By engineering the NAT10 protein, which performs RNA acetylation in human cells, based on its domain and structure, eNAT10 was developed, showing approximately a 3-fold increase in RNA acetylation activity compared to the wild-type enzyme. > Using this system, the researchers demonstrated that guide RNAs could direct the dCas13-eNAT10 complex to acetylate specific RNA targets, and acetylation significantly increased protein expression from the modified mRNA. Moreover, the study revealed, for the first time, that RNA acetylation plays a role in intracellular RNA localization, facilitating the export of RNA from the nucleus to the cytoplasm—a critical step in gene expression regulation. To validate its therapeutic potential, the team successfully delivered the targeted RNA acetylation system into the livers of live mice using adeno-associated virus (AAV), a commonly used gene therapy vector. This marks the first demonstration of in vivo RNA modification, extending the applicability of RNA chemical modification tools from cell culture models to living organisms. < Figure 2. Acetylation of various RNA in cells using dCas13-eNAT10 fusion protein. Utilizing the CRISPR-Cas13 system, which can precisely target specific RNA through guide RNA, a dCas13-eNAT10 fusion protein was created, demonstrating its ability to specifically acetylate various endogenous RNA at different locations within cells. > Professor Won Do Heo, who previously developed COVID-19 treatment technology using RNA gene scissors and technology to activate RNA gene scissors with light, stated, "Existing RNA chemical modification research faced difficulties in controlling specificity, temporality, and spatiality. However, this new technology allows selective acetylation of desired RNA, opening the door for accurate and detailed research into the functions of RNA acetylation." He added, "The RNA chemical modification technology developed in this study can be widely used as an RNA-based therapeutic agent and a tool for regulating RNA functions in living organisms in the future." < Figure 3. In vivo delivery of targeted RNA acetylation system. The targeted RNA acetylation system was encoded in an AAV vector, commonly used in gene therapy, and delivered intravenously to adult mice, showing that target RNA in liver tissue was specifically acetylated according to the guide RNA. > This research, with Ph.D. candidate Jihwan Yu from the Department of Biological Sciences at KAIST as the first author, was published in the journal Nature Chemical Biology on June 2, 2025. (Title: Programmable RNA acetylation with CRISPR-Cas13, Impact factor: 12.9, DOI: https://doi.org/10.1038/s41589-025-01922-3) This research was supported by the Samsung Future Technology Foundation and the Bio & Medical Technology Development Program of the National Research Foundation of Korea.
2025.06.10
View 393
A 10-Month Journey of Tiny Flaps Completed: A Special Family Returns to KAIST Duck Pond
On the morning of June 9, 2025, gentle activity stirred early around the KAIST campus duck pond. It was the day a special family of ducks—and two goslings—were to be released back into the pond after spending a month in a temporary shelter. One by one, the ducklings cautiously emerged from their box, waddling toward the water's edge and scanning their surroundings, followed closely by their mother. < The landscape manager from the KAIST Facilities Team releases the ducks and goslings. > The mother duck, once a rescued loner who couldn’t integrate with the flock, returned triumphantly as the head of a new family—caring for both ducklings and goslings. Students and faculty looked on quietly, welcoming them back and reflecting on their remarkable 10-month journey. The story began in July 2024, as a student filed a report of spotting two ducklings wandering near the pond without a mother. Based on their soft down, flat beaks, and lack of fear around humans, it was presumed they had been abandoned. Professor Won Do Heo of the Department of Biological Sciences—affectionately known as the “Goose Dad”—and the KAIST Facilities Team quickly stepped in to rescue them. After about a month of care, the ducklings were released back into the pond. < On June 9, the day of the release, KAIST President Kwang-Hyung Lee (left), the former “Goose Dad,” and Professor Won Do Heo (right), the current “Goose Dad,” watched the flock as they freely wobbled about. > At first, the ducklings seemed to adapt, but they started distancing themselves from the established goose flock. One eventually disappeared, and the remaining duckling was found injured by the pond during winter. Although KAIST typically avoids making human interference in the natural ecosystem, an exception was made to save the young duck’s life. It was put under the care of Professor Heo and the Facilities Team to regain its health within a month. In the spring, the healed duck began laying eggs. Professor Heo supported the process by adjusting its diet, avoiding further intervention. On Children’s Day, May 5, the duck’s eggs hatched. The once-isolated duck had become a mother. Ten days later, on May 15, four goslings also hatched from the resident goose flock. With new life flourishing, the pond was more vibrant than ever. < Rescued baby goslings near the pond, alongside the duck family that took them in. The mother duck—once a vulnerable duckling herself—had grown strong enough to care for others in need. > But just days later, the mother goose disappeared, and two goslings—still unable to swim—were found shivering by the pond. Dahyeon Byeon, a student from Seoul National University who came for a visit on that day, reported this upon sighting, prompting another rescue. The vulnerable goslings were brought to the shelter to stay with the duck family. Initially, the interspecies cohabitation was uneasy. But the mother duck did not reject the goslings. Slowly, they began to eat and sleep together, forming a new kind of family. After a month, they were released together into the pond—and to everyone’s surprise, the existing goose flock accepted both the goslings and the duck family. < A peaceful moment for the duck family. The baby goslings naturally followed the mother duck. > It took ten months for this family to return. From abandonment and injury to healing, birth, and unexpected bonds, this was more than a story of survival. It was a journey of transformation. The duck family’s ten-month saga is a quiet miracle—written in small moments of crisis, care, and connection—and a lasting memory on the KAIST campus. < The resident goose flock at KAIST’s pond naturally accepted the returning duck and goslings as part of their group. >
2025.06.10
View 452
KAIST-UIUC researchers develop a treatment platform to disable the ‘biofilm’ shield of superbugs
< (From left) Ph.D. Candidate Joo Hun Lee (co-author), Professor Hyunjoon Kong (co-corresponding author) and Postdoctoral Researcher Yujin Ahn (co-first author) from the Department of Chemical and Biomolecular Engineering of the University of Illinois at Urbana-Champaign and Ju Yeon Chung (co-first author) from the Integrated Master's and Doctoral Program, and Professor Hyun Jung Chung (co-corresponding author) from the Department of Biological Sciences of KAIST > A major cause of hospital-acquired infections, the super bacteria Methicillin-resistant Staphylococcus aureus (MRSA), not only exhibits strong resistance to existing antibiotics but also forms a dense biofilm that blocks the effects of external treatments. To meet this challenge, KAIST researchers, in collaboration with an international team, successfully developed a platform that utilizes microbubbles to deliver gene-targeted nanoparticles capable of break ing down the biofilms, offering an innovative solution for treating infections resistant to conventional antibiotics. KAIST (represented by President Kwang Hyung Lee) announced on May 29 that a research team led by Professor Hyun Jung Chung from the Department of Biological Sciences, in collaboration with Professor Hyunjoon Kong's team at the University of Illinois, has developed a microbubble-based nano-gene delivery platform (BTN MB) that precisely delivers gene suppressors into bacteria to effectively remove biofilms formed by MRSA. The research team first designed short DNA oligonucleotides that simultaneously suppress three major MRSA genes, related to—biofilm formation (icaA), cell division (ftsZ), and antibiotic resistance (mecA)—and engineered nanoparticles (BTN) to effectively deliver them into the bacteria. < Figure 1. Effective biofilm treatment using biofilm-targeting nanoparticles controlled by microbubbler system. Schematic illustration of BTN delivery with microbubbles (MB), enabling effective permeation of ASOs targeting bacterial genes within biofilms infecting skin wounds. Gene silencing of targets involved in biofilm formation, bacterial proliferation, and antibiotic resistance leads to effective biofilm removal and antibacterial efficacy in vivo. > In addition, microbubbles (MB) were used to increase the permeability of the microbial membrane, specifically the biofilm formed by MRSA. By combining these two technologies, the team implemented a dual-strike strategy that fundamentally blocks bacterial growth and prevents resistance acquisition. This treatment system operates in two stages. First, the MBs induce pressure changes within the bacterial biofilm, allowing the BTNs to penetrate. Then, the BTNs slip through the gaps in the biofilm and enter the bacteria, delivering the gene suppressors precisely. This leads to gene regulation within MRSA, simultaneously blocking biofilm regeneration, cell proliferation, and antibiotic resistance expression. In experiments conducted in a porcine skin model and a mouse wound model infected with MRSA biofilm, the BTN MB treatment group showed a significant reduction in biofilm thickness, as well as remarkable decreases in bacterial count and inflammatory responses. < Figure 2. (a) Schematic illustration on the evaluation of treatment efficacy of BTN-MB gene therapy. (b) Reduction in MRSA biofilm mass via simultaneous inhibition of multiple genes. (c, d) Antibacterial efficacy of BTN-MB over time in a porcine skin infection biofilm model. (e) Schematic of the experimental setup to verify antibacterial efficacy in a mouse skin wound infection model. (f) Wound healing effects in mice. (g) Antibacterial effects at the wound site. (h) Histological analysis results. > These results are difficult to achieve with conventional antibiotic monotherapy and demonstrate the potential for treating a wide range of resistant bacterial infections. Professor Hyun Jung Chung of KAIST, who led the research, stated, “This study presents a new therapeutic solution that combines nanotechnology, gene suppression, and physical delivery strategies to address superbug infections that existing antibiotics cannot resolve. We will continue our research with the aim of expanding its application to systemic infections and various other infectious diseases.” < (From left) Ju Yeon Chung from the Integrated Master's and Doctoral Program, and Professor Hyun Jung Chung from the Department of Biological Sciences > The study was co-first authored by Ju Yeon Chung, a graduate student in the Department of Biological Sciences at KAIST, and Dr. Yujin Ahn from the University of Illinois. The study was published online on May 19 in the journal, Advanced Functional Materials. ※ Paper Title: Microbubble-Controlled Delivery of Biofilm-Targeting Nanoparticles to Treat MRSA Infection ※ DOI: https://doi.org/10.1002/adfm.202508291 This study was supported by the National Research Foundation and the Ministry of Health and Welfare, Republic of Korea; and the National Science Foundation and National Institutes of Health, USA.
2025.05.29
View 528
KAIST Develops Virtual Staining Technology for 3D Histopathology
Moving beyond traditional methods of observing thinly sliced and stained cancer tissues, a collaborative international research team led by KAIST has successfully developed a groundbreaking technology. This innovation uses advanced optical techniques combined with an artificial intelligence-based deep learning algorithm to create realistic, virtually stained 3D images of cancer tissue without the need for serial sectioning nor staining. This breakthrough is anticipated to pave the way for next-generation non-invasive pathological diagnosis. < Photo 1. (From left) Juyeon Park (Ph.D. Candidate, Department of Physics), Professor YongKeun Park (Department of Physics) (Top left) Professor Su-Jin Shin (Gangnam Severance Hospital), Professor Tae Hyun Hwang (Vanderbilt University School of Medicine) > KAIST (President Kwang Hyung Lee) announced on the 26th that a research team led by Professor YongKeun Park of the Department of Physics, in collaboration with Professor Su-Jin Shin's team at Yonsei University Gangnam Severance Hospital, Professor Tae Hyun Hwang's team at Mayo Clinic, and Tomocube's AI research team, has developed an innovative technology capable of vividly displaying the 3D structure of cancer tissues without separate staining. For over 200 years, conventional pathology has relied on observing cancer tissues under a microscope, a method that only shows specific cross-sections of the 3D cancer tissue. This has limited the ability to understand the three-dimensional connections and spatial arrangements between cells. To overcome this, the research team utilized holotomography (HT), an advanced optical technology, to measure the 3D refractive index information of tissues. They then integrated an AI-based deep learning algorithm to successfully generate virtual H&E* images.* H&E (Hematoxylin & Eosin): The most widely used staining method for observing pathological tissues. Hematoxylin stains cell nuclei blue, and eosin stains cytoplasm pink. The research team quantitatively demonstrated that the images generated by this technology are highly similar to actual stained tissue images. Furthermore, the technology exhibited consistent performance across various organs and tissues, proving its versatility and reliability as a next-generation pathological analysis tool. < Figure 1. Comparison of conventional 3D tissue pathology procedure and the 3D virtual H&E staining technology proposed in this study. The traditional method requires preparing and staining dozens of tissue slides, while the proposed technology can reduce the number of slides by up to 10 times and quickly generate H&E images without the staining process. > Moreover, by validating the feasibility of this technology through joint research with hospitals and research institutions in Korea and the United States, utilizing Tomocube's holotomography equipment, the team demonstrated its potential for full-scale adoption in real-world pathological research settings. Professor YongKeun Park stated, "This research marks a major advancement by transitioning pathological analysis from conventional 2D methods to comprehensive 3D imaging. It will greatly enhance biomedical research and clinical diagnostics, particularly in understanding cancer tumor boundaries and the intricate spatial arrangements of cells within tumor microenvironments." < Figure 2. Results of AI-based 3D virtual H&E staining and quantitative analysis of pathological tissue. The virtually stained images enabled 3D reconstruction of key pathological features such as cell nuclei and glandular lumens. Based on this, various quantitative indicators, including cell nuclear distribution, volume, and surface area, could be extracted. > This research, with Juyeon Park, a student of the Integrated Master’s and Ph.D. Program at KAIST, as the first author, was published online in the prestigious journal Nature Communications on May 22. (Paper title: Revealing 3D microanatomical structures of unlabeled thick cancer tissues using holotomography and virtual H&E staining. [https://doi.org/10.1038/s41467-025-59820-0] This study was supported by the Leader Researcher Program of the National Research Foundation of Korea, the Global Industry Technology Cooperation Center Project of the Korea Institute for Advancement of Technology, and the Korea Health Industry Development Institute.
2025.05.26
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KAIST and Mainz Researchers Unveil 3D Magnon Control, Charting a New Course for Neuromorphic and Quantum Technologies
< Professor Se Kwon Kim of the Department of Physics (left), Dr. Zarzuela of the University of Mainz, Germany (right) > What if the magnon Hall effect, which processes information using magnons (spin waves) capable of current-free information transfer with magnets, could overcome its current limitation of being possible only on a 2D plane? If magnons could be utilized in 3D space, they would enable flexible design, including 3D circuits, and be applicable in various fields such as next-generation neuromorphic (brain-mimicking) computing structures, similar to human brain information processing. KAIST and an international joint research team have, for the first time in the world, predicted a 3D magnon Hall effect, demonstrating that magnons can move freely and complexly in 3D space, transcending the conventional concept of magnons. KAIST (President Kwang Hyung Lee) announced on May 22nd that Professor Se Kwon Kim of the Department of Physics, in collaboration with Dr. Ricardo Zarzuela of the University of Mainz, Germany, has revealed that the interaction between magnons (spin waves) and solitons (spin vortices) within complex magnetic structures (topologically textured frustrated magnets) is not simple, but complex in a way that enables novel functionalities. Magnons (spin waves), which can transmit information like electron movement, are garnering attention as a next-generation information processing technology that transmits information without using current, thus generating no heat. Until now, magnon research has focused on simple magnets where spins are neatly aligned in one direction, and the mathematics describing this was a relatively simple 'Abelian gauge theory.' The research team demonstrated, for the first time in the world, that in complex spin structures like frustrated magnets, magnons interact and become entangled in complex ways from various directions. They applied an advanced mathematical framework, 'non-Abelian gauge theory,' to describe this movement, which is a groundbreaking achievement. This research presents the possibility of future applications in low-power logic devices using magnons and topology-based quantum information processing technologies, indicating a potential paradigm shift in future information technology. In conventional linear magnetic materials, the value representing the magnetic state (order parameter) is given as a vector. In magnonics research based on this, it has been interpreted that a U(1) Abelian gauge field is induced when magnons move in soliton structures like skyrmions. This means that the interaction between solitons and magnons has a structure similar to quantum electrodynamics (QED), which has successfully explained various experimental results such as the magnon Hall effect in 2D magnets. < Figure. Schematic diagram of non-Abelian magnon quantum chromodynamics describing the dynamics of three types of magnons discovered for the first time in this study.> However, through this research, the team theoretically revealed that in frustrated magnets, the order parameter must be expressed not as a simple vector but as a quaternion. As a result, the gauge field experienced by magnons resembles an SU(3) non-Abelian gauge field, rather than a simple U(1) Abelian gauge field. This implies that within frustrated magnets, there are not one or two types of magnons seen in conventional magnets, but three distinct types of magnons, each interacting and intricately entangled with solitons. This structure is highly significant as it resembles quantum chromodynamics (QCD) that describes the strong interaction between quarks mediated by gluons rather than quantum electrodynamics (QED) that describes electromagnetic forces. Professor Se Kwon Kim stated, "This research presents a powerful theoretical framework to explain the dynamics of magnons occurring within the complex order of frustrated magnets," adding, "By pioneering non-Abelian magnonics, it will be a conceptual turning point that can influence quantum magnetism research as a whole." The research results, with Dr. Ricardo Zarzuela of the University of Mainz, Germany, as the first author, were published in the world-renowned physics journal Physical Review Letters on May 6th.※ Paper title: "Non-Abelian Gauge Theory for Magnons in Topologically Textured Frustrated Magnets," Phys. Rev. Lett. 134, 186701 (2025)DOI: https://doi.org/10.1103/PhysRevLett.134.186701 This research was supported by the Brain Pool Plus program of the National Research Foundation of Korea.
2025.05.22
View 1533
Life Springs at KAIST: A Tale of Two Special Campus Families
A Gift of Life on Teachers' Day: Baby Geese Born at KAIST Pond On Teachers' Day, a meaningful miracle of life arrived at the KAIST campus. A pair of geese gave birth to two goslings by the duck pond. < On Teachers' Day, a pair of geese and their goslings leisurely swim in the pond. > The baby goslings, covered in yellow down, began exploring the pond's edge, scurrying about, while their aunt geese steadfastly stood by. Their curious glances, watchful gazes, playful hops on waterside rocks, and the procession of babies swimming behind their parents in the water melted the hearts of onlookers. < As night falls on the duck pond, the goose family gathers among the reeds. > This special new life, born on Teachers' Day, seems to symbolize the day's meaning of "care" and "growth." This wondrous scene of life brought warm comfort and joy to KAIST members, adding the inspiration of nature to a campus that is a space for research and learning. < Under the protection of the adult geese, the goslings take their first steps, exploring the pond's grassy areas and rocks. > This adorable family is already roaming the area leisurely, like the pond's owners. With the joy of life added to the spring-filled pond, warm smiles are spreading across the KAIST campus. < The geese look around, surveying their surroundings, while caring for their goslings. > The pond has now become a small but special haven for students and staff. This goose family, arriving on Teachers' Day, quietly reminds us of the meaning of care and learning conveyed by nature. < The goose family shows care and growth, and warm moments together are anticipated. > --- On Children's Day 2025, a Duck Becomes a Mother In July 2024, a special guest arrived at the KAIST campus. With soft yellow down, waddling gait, and a flat beak, it was undeniably a baby duck. However, for some reason, its mother was nowhere to be seen. Given that it wasn't afraid of people and followed them well, it was clear that someone had abandoned the duck. Fortunately, the baby duck was safely rescued thanks to prompt reporting by students. < Two ducks found on a corner of campus, immediately after their rescue in summer 2024. > The ducks, newly integrated into KAIST, seemed to adapt relatively peacefully to campus life. As new additions, they couldn't blend in with the existing goose flock that had settled on campus, but the geese didn't ostracize them either. Perhaps because they were awkward neighbors, there was hope that the ducks would soon join the existing goose flock. < Following their rescue based on a student's report in summer 2024, the ducks adapted to campus life under the protection of the campus facility team and Professor Won Do Heo. > Professor Won Do Heo of the Department of Biological Sciences, widely known as "Goose Dad," stepped forward to protect them along with the KAIST facility team. Professor Heo is well-known for consistently observing and protecting the campus geese and ducks, which are practically symbols of KAIST. Thanks to the care of the staff and Professor Heo, the two ducks were safely released back onto campus approximately one month after their rescue. < A moment on campus: Before winter, the ducks lived separately from the goose flock, maintaining a certain distance. While there were no conflicts, they rarely socialized. > However, as winter passed, sad news arrived. One duck went missing, and the remaining one was found injured by the pond. While the policy of the facility team and Professor Heo was to minimize intervention to allow campus animals to maintain their natural state, saving the injured duck was the top priority. After being isolated again for a month of recovery, the duck fully recovered and was able to greet spring under the sun. < The mother duck left alone in winter: One went missing, and the remaining one was found injured. After indoor isolation and recovery, she was released back onto campus in the spring. > As spring, the ducks' breeding season, began, Professor Heo decided to offer a little more help. When signs of egg-laying appeared, he consistently provided "special meals for pregnant mothers" throughout March. On the morning of May 5th, Children's Day, 28 days after the mother duck began incubating her eggs with the care and attention of KAIST members, new life finally hatched. It was a precious outcome achieved solely by the duck that had survived abandonment and injury, with no special protection other than food. The duck, having overcome hardship and injury to stand alone, has now formed a new family. Although there is still some distance from the existing goose flock, it is expected that they will naturally find their place in the campus ecosystem, as KAIST's geese are not aggressive or exclusive. The KAIST goose flock already has experience protecting and raising five ducklings. < A new beginning by the pond on Children's Day: On the morning of May 5th, the 28th day of incubation, four ducklings hatched by the pond. This was a natural hatching, achieved without protective equipment. > A single duck brought a special spring to the KAIST campus on Children's Day. The outcome achieved by that small life, leading to the birth of a new family, also symbolizes the harmonious coexistence of people and animals on the KAIST campus. The careful intervention of KAIST members, providing only the necessary assistance from rescue to hatching, makes us reconsider what "desirable coexistence between animals and people" truly means.
2025.05.21
View 1328
Decoding Fear: KAIST Identifies An Affective Brain Circuit Crucial for Fear Memory Formation by Non-nociceptive Threat Stimulus
Fear memories can form in the brain following exposure to threatening situations such as natural disasters, accidents, or violence. When these memories become excessive or distorted, they can lead to severe mental health disorders, including post-traumatic stress disorder (PTSD), anxiety disorders, and depression. However, the mechanisms underlying fear memory formation triggered by affective pain rather than direct physical pain have remained largely unexplored – until now. A KAIST research team has identified, for the first time, a brain circuit specifically responsible for forming fear memories in the absence of physical pain, marking a significant advance in understanding how psychological distress is processed and drives fear memory formation in the brain. This discovery opens the door to the development of targeted treatments for trauma-related conditions by addressing the underlying neural pathways. < Photo 1. (from left) Professor Jin-Hee Han, Dr. Junho Han and Ph.D. Candidate Boin Suh of the Department of Biological Sciences > KAIST (President Kwang-Hyung Lee) announced on May 15th that the research team led by Professor Jin-Hee Han in the Department of Biological Sciences has identified the pIC-PBN circuit*, a key neural pathway involved in forming fear memories triggered by psychological threats in the absence of sensory pain. This groundbreaking work was conducted through experiments with mice.*pIC–PBN circuit: A newly identified descending neural pathway from the posterior insular cortex (pIC) to the parabrachial nucleus (PBN), specialized for transmitting psychological threat information. Traditionally, the lateral parabrachial nucleus (PBN) has been recognized as a critical part of the ascending pain pathway, receiving pain signals from the spinal cord. However, this study reveals a previously unknown role for the PBN in processing fear induced by non-painful psychological stimuli, fundamentally changing our understanding of its function in the brain. This work is considered the first experimental evidence that 'emotional distress' and 'physical pain' are processed through different neural circuits to form fear memories, making it a significant contribution to the field of neuroscience. It clearly demonstrates the existence of a dedicated pathway (pIC-PBN) for transmitting emotional distress. The study's first author, Dr. Junho Han, shared the personal motivation behind this research: “Our dog, Lego, is afraid of motorcycles. He never actually crashed into one, but ever since having a traumatizing event of having a motorbike almost run into him, just hearing the sound now triggers a fearful response. Humans react similarly – even if you didn’t have a personal experience of being involved in an accident, a near-miss or exposure to alarming media can create lasting fear memories, which may eventually lead to PTSD.” He continued, “Until now, fear memory research has mainly relied on experimental models involving physical pain. However, much of real-world human fears arise from psychological threats, rather than from direct physical harm. Despite this, little was known about the brain circuits responsible for processing these psychological threats that can drive fear memory formation.” To investigate this, the research team developed a novel fear conditioning model that utilizes visual threat stimuli instead of electrical shocks. In this model, mice were exposed to a rapidly expanding visual disk on a ceiling screen, simulating the threat of an approaching predator. This approach allowed the team to demonstrate that fear memories can form in response to a non-nociceptive, psychological threat alone, without the need for physical pain. < Figure 1. Artificial activation of the posterior insular cortex (pIC) to lateral parabrachial nucleus (PBN) neural circuit induces anxiety-like behaviors and fear memory formation in mice. > Using advanced chemogenetic and optogenetic techniques, the team precisely controlled neuronal activity, revealing that the lateral parabrachial nucleus (PBN) is essential to form fear memories in response to visual threats. They further traced the origin of these signals to the posterior insular cortex (pIC), a region known to process negative emotions and pain, confirming a direct connection between the two areas. The study also showed that inhibiting the pIC–PBN circuit significantly reduced fear memory formation in response to visual threats, without affecting innate fear responses or physical pain-based learning. Conversely, artificially activating this circuit alone was sufficient to drive fear memory formation, confirming its role as a key pathway for processing psychological threat information. < Figure 2. Schematic diagram of brain neural circuits transmitting emotional & physical pain threat signals. Visual threat stimuli do not involve physical pain but can create an anxious state and form fear memory through the affective pain signaling pathway. > Professor Jin-Hee Han commented, “This study lays an important foundation for understanding how emotional distress-based mental disorders, such as PTSD, panic disorder, and anxiety disorder, develop, and opens new possibilities for targeted treatment approaches.” The findings, authored by Dr. Junho Han (first author), Ph.D. candidate Boin Suh (second author), and Dr. Jin-Hee Han (corresponding author) of the Department of Biological Sciences, were published online in the international journal Science Advances on May 9, 2025.※ Paper Title: A top-down insular cortex circuit crucial for non-nociceptive fear learning. Science Advances (https://doi.org/10.1101/2024.10.14.618356)※ Author Information: Junho Han (first author), Boin Suh (second author), and Jin-Hee Han (corresponding author) This research was supported by grants from the National Research Foundation of Korea (NRF-2022M3E5E8081183 and NRF-2017M3C7A1031322).
2025.05.15
View 1769
KAIST's Pioneering VR Precision Technology & Choreography Tool Receive Spotlights at CHI 2025
Accurate pointing in virtual spaces is essential for seamless interaction. If pointing is not precise, selecting the desired object becomes challenging, breaking user immersion and reducing overall experience quality. KAIST researchers have developed a technology that offers a vivid, lifelike experience in virtual space, alongside a new tool that assists choreographers throughout the creative process. KAIST (President Kwang-Hyung Lee) announced on May 13th that a research team led by Professor Sang Ho Yoon of the Graduate School of Culture Technology, in collaboration with Professor Yang Zhang of the University of California, Los Angeles (UCLA), has developed the ‘T2IRay’ technology and the ‘ChoreoCraft’ platform, which enables choreographers to work more freely and creatively in virtual reality. These technologies received two Honorable Mention awards, recognizing the top 5% of papers, at CHI 2025*, the best international conference in the field of human-computer interaction, hosted by the Association for Computing Machinery (ACM) from April 25 to May 1. < (From left) PhD candidates Jina Kim and Kyungeun Jung along with Master's candidate, Hyunyoung Han and Professor Sang Ho Yoon of KAIST Graduate School of Culture Technology and Professor Yang Zhang (top) of UCLA > T2IRay: Enabling Virtual Input with Precision T2IRay introduces a novel input method that allows for precise object pointing in virtual environments by expanding traditional thumb-to-index gestures. This approach overcomes previous limitations, such as interruptions or reduced accuracy due to changes in hand position or orientation. The technology uses a local coordinate system based on finger relationships, ensuring continuous input even as hand positions shift. It accurately captures subtle thumb movements within this coordinate system, integrating natural head movements to allow fluid, intuitive control across a wide range. < Figure 1. T2IRay framework utilizing the delicate movements of the thumb and index fingers for AR/VR pointing > Professor Sang Ho Yoon explained, “T2IRay can significantly enhance the user experience in AR/VR by enabling smooth, stable control even when the user’s hands are in motion.” This study, led by first author Jina Kim, was supported by the Excellent New Researcher Support Project of the National Research Foundation of Korea under the Ministry of Science and ICT, as well as the University ICT Research Center (ITRC) Support Project of the Institute of Information and Communications Technology Planning and Evaluation (IITP). ▴ Paper title: T2IRay: Design of Thumb-to-Index Based Indirect Pointing for Continuous and Robust AR/VR Input▴ Paper link: https://doi.org/10.1145/3706598.3713442 ▴ T2IRay demo video: https://youtu.be/ElJlcJbkJPY ChoreoCraft: Creativity Support through VR for Choreographers In addition, Professor Yoon’s team developed ‘ChoreoCraft,’ a virtual reality tool designed to support choreographers by addressing the unique challenges they face, such as memorizing complex movements, overcoming creative blocks, and managing subjective feedback. ChoreoCraft reduces reliance on memory by allowing choreographers to save and refine movements directly within a VR space, using a motion-capture avatar for real-time interaction. It also enhances creativity by suggesting movements that naturally fit with prior choreography and musical elements. Furthermore, the system provides quantitative feedback by analyzing kinematic factors like motion stability and engagement, helping choreographers make data-driven creative decisions. < Figure 2. ChoreoCraft's approaches to encourage creative process > Professor Yoon noted, “ChoreoCraft is a tool designed to address the core challenges faced by choreographers, enhancing both creativity and efficiency. In user tests with professional choreographers, it received high marks for its ability to spark creative ideas and provide valuable quantitative feedback.” This research was conducted in collaboration with doctoral candidate Kyungeun Jung and master’s candidate Hyunyoung Han, alongside the Electronics and Telecommunications Research Institute (ETRI) and One Million Co., Ltd. (CEO Hye-rang Kim), with support from the Cultural and Arts Immersive Service Development Project by the Ministry of Culture, Sports and Tourism. ▴ Paper title: ChoreoCraft: In-situ Crafting of Choreography in Virtual Reality through Creativity Support Tools▴ Paper link: https://doi.org/10.1145/3706598.3714220 ▴ ChoreoCraft demo video: https://youtu.be/Ms1fwiSBjjw *CHI (Conference on Human Factors in Computing Systems): The premier international conference on human-computer interaction, organized by the ACM, was held this year from April 25 to May 1, 2025.
2025.05.13
View 2014
Editing Parkinson's Disease – KAIST Makes World's First Discovery of an Inflammatory RNA Editing Enzyme through Co-work with UCL Researchers
< Professor Minee Choi of the Department of Brain and Cognitive Sciences (top left). Professor Sonia Gandhi (top right) and Professor Klenerman of the University College London (bottom right) > Parkinson's disease (PD) is a neurodegenerative disorder in which the α-synuclein protein abnormally aggregates within brain cells, causing neuronal damage. Through international collaboration, researchers at KAIST have revealed that RNA editing plays a crucial role in regulating neuroinflammation, a key pathology of Parkinson's disease. KAIST (represented by President Kwang-Hyung Lee) announced on the 27th of April that a research team led by Professor Minee L. Choi from the Department of Brain and Cognitive Sciences, in collaboration with University College London (UCL) and the Francis Crick Institute, discovered that the RNA editing enzyme ADAR1 plays an important role in controlling immune responses in astrocytes, glial cells that trigger protective reactions in the brain, and demonstrated that this mechanism is critically involved in the progression of Parkinson’s disease. Professor Choi's research team created a co-culture model composed of astrocytes and neurons derived from stem cells originating from Parkinson's disease patients, in order to study the inflammatory responses of brain immune cells. They then treated the model with α-synuclein aggregates, which are known to cause Parkinson’s disease, and analyzed how the immune cells' inflammatory responses changed. < Figure 1. Schematic diagram of the inflammatory RNA editing model in Parkinson's disease > As a result, it was found that early pathological forms of α-synuclein, known as oligomers, activated the Toll-like receptor pathway, which acts as a danger sensor in astrocytes, as well as the interferon response pathway, an immune signaling network that combats viruses and pathogens. During this process, the RNA editing enzyme ADAR1 was expressed and transformed into an isoform with an altered protein structure and function. Notably, the RNA editing activity of ADAR1, which normally functions to regulate immune responses during viral infections by converting adenosine (A) to inosine (I) through a process known as A-to-I RNA editing, was found to be abnormally focused on genes that cause inflammation rather than operating under normal conditions. This phenomenon was observed not only in the patient-derived neuron models but also in postmortem brain tissues from actual Parkinson’s disease patients. < Figure 2. Experimental design and inflammatory response induction in astrocytes following treatment with α-synuclein oligomers (abnormally folded protein fragments) > This directly proves that the dysregulation of RNA editing induces chronic inflammatory responses in astrocytes, ultimately leading to neuronal toxicity and pathological progression. This study is significant in that it newly identified the regulation of RNA editing within astrocytes as a key mechanism behind neuroinflammatory responses. In particular, it suggests that ADAR1 could serve as a novel genetic target for the treatment of Parkinson’s disease. It is also noteworthy that the study reflected actual pathological characteristics of patients by utilizing patient-specific induced pluripotent stem cell-based precision models for brain diseases. Professor Minee L. Choi stated, “This study demonstrates that the regulator of inflammation caused by protein aggregation operates at the new layer of RNA editing, offering a completely different therapeutic strategy from existing approaches to Parkinson's disease treatment." She further emphasized, “RNA editing technology could become an important turning point in the development of therapeutics for neuroinflammation.” < Figure 3. When treated with α-synuclein oligomers, the causative agent of Parkinson's disease, A-to-I RNA editing is induced to change genetic information by ADAR in patient-derived stem cell-differentiated glial cells, confirming that α-synuclein is likely to be associated with the progression of Parkinson's disease through RNA editing > This study was published in Science Advances on April 11, with Professor Choi listed as a co-first author. Paper Title: Astrocytic RNA editing regulates the host immune response to alpha-synuclein, Science Advances Vol.11, Issue 15. (DOI:10.1126/sciadv.adp8504) Lead Authors: Karishma D’Sa (UCL, Co-First Author), Minee L. Choi (KAIST, Co-First Author), Mina Ryten (UCL, Corresponding Author), Sonia Gandhi (Francis Crick Institute, University of Cambridge, Corresponding Author) This research was supported by the Brain Research Program and the Excellent Young Researcher Program of the National Research Foundation of Korea, as well as KAIST’s Daekyo Cognitive Enhancement Program.
2025.05.02
View 2796
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