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Deep Learning Framework to Enable Material Design in Unseen Domain
Researchers propose a deep neural network-based forward design space exploration using active transfer learning and data augmentation A new study proposed a deep neural network-based forward design approach that enables an efficient search for superior materials far beyond the domain of the initial training set. This approach compensates for the weak predictive power of neural networks on an unseen domain through gradual updates of the neural network with active transfer learning and data augmentation methods. Professor Seungwha Ryu believes that this study will help address a variety of optimization problems that have an astronomical number of possible design configurations. For the grid composite optimization problem, the proposed framework was able to provide excellent designs close to the global optima, even with the addition of a very small dataset corresponding to less than 0.5% of the initial training data-set size. This study was reported in npj Computational Materials last month. “We wanted to mitigate the limitation of the neural network, weak predictive power beyond the training set domain for the material or structure design,” said Professor Ryu from the Department of Mechanical Engineering. Neural network-based generative models have been actively investigated as an inverse design method for finding novel materials in a vast design space. However, the applicability of conventional generative models is limited because they cannot access data outside the range of training sets. Advanced generative models that were devised to overcome this limitation also suffer from weak predictive power for the unseen domain. Professor Ryu’s team, in collaboration with researchers from Professor Grace Gu’s group at UC Berkeley, devised a design method that simultaneously expands the domain using the strong predictive power of a deep neural network and searches for the optimal design by repetitively performing three key steps. First, it searches for few candidates with improved properties located close to the training set via genetic algorithms, by mixing superior designs within the training set. Then, it checks to see if the candidates really have improved properties, and expands the training set by duplicating the validated designs via a data augmentation method. Finally, they can expand the reliable prediction domain by updating the neural network with the new superior designs via transfer learning. Because the expansion proceeds along relatively narrow but correct routes toward the optimal design (depicted in the schematic of Fig. 1), the framework enables an efficient search. As a data-hungry method, a deep neural network model tends to have reliable predictive power only within and near the domain of the training set. When the optimal configuration of materials and structures lies far beyond the initial training set, which frequently is the case, neural network-based design methods suffer from weak predictive power and become inefficient. Researchers expect that the framework will be applicable for a wide range of optimization problems in other science and engineering disciplines with astronomically large design space, because it provides an efficient way of gradually expanding the reliable prediction domain toward the target design while avoiding the risk of being stuck in local minima. Especially, being a less-data-hungry method, design problems in which data generation is time-consuming and expensive will benefit most from this new framework. The research team is currently applying the optimization framework for the design task of metamaterial structures, segmented thermoelectric generators, and optimal sensor distributions. “From these sets of on-going studies, we expect to better recognize the pros and cons, and the potential of the suggested algorithm. Ultimately, we want to devise more efficient machine learning-based design approaches,” explained Professor Ryu.This study was funded by the National Research Foundation of Korea and the KAIST Global Singularity Research Project. -Publication Yongtae Kim, Youngsoo, Charles Yang, Kundo Park, Grace X. Gu, and Seunghwa Ryu, “Deep learning framework for material design space exploration using active transfer learning and data augmentation,” npj Computational Materials (https://doi.org/10.1038/s41524-021-00609-2) -Profile Professor Seunghwa Ryu Mechanics & Materials Modeling Lab Department of Mechanical Engineering KAIST
2021.09.29
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Two Researchers Designated as SUHF Fellows
Professor Taeyun Ku from the Graduate School of Medical Science and Engineering and Professor Hanseul Yang from the Department of Biological Sciences were nominated as 2021 fellows of the Suh Kyungbae Foundation (SUHF). SUHF selected three young promising scientists from 53 researchers who are less than five years into their careers. A panel of judges comprised of scholars from home and abroad made the final selection based on the candidates’ innovativeness and power to influence. Professor You-Bong Hyun from Seoul National University also won the fellowship. Professor Ku’s main topic is opto-connectomics. He will study ways to visualize the complex brain network using innovative technology that transforms neurons into optical elements. Professor Yang will research the possibility of helping patients recover from skin diseases or injuries without scars by studying spiny mouse genes. SUHF was established by Amorepacific Group Chairman Suh Kyungbae in 2016 with 300 billion KRW of his private funds. Under the vision of ‘contributing to humanity by supporting innovative discoveries of bioscience researchers,’ the foundation supports promising Korean scientists who pioneer new fields of research in biological sciences. From 2017 to this year, SUHF has selected 20 promising scientists in the field of biological sciences. Selected scientists are provided with up to KRW 500 million each year for five years. The foundation has provided a total of KRW 48.5 billion in research funds to date.
2021.09.15
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MCM Utilized at Residential Treatment Center in Gyeonggi
The Mobile Clinic Module (MCM) developed by the KAIST Action for Respiratory Epidemics was installed at special residential treatment center in Gyeonggi Province on September 13. The MCM is an isolate negative pressure unit fitted with high-quality medical equipment, developed by Professor Taek-Jin Nam of the Department of Industrial Design under the KAIST New Deal R&D Initiative. This is also a part of the Korean Disease Control Package Development Project from last July. In January, a ward with four beds for critical care was installed at the Korea Institute for Radiological & Medical Sciences in Seoul for a trial operation, and two mild cases were treated there. It was also implemented as an isolated negative pressure unit in the Daejeon Konyang University Hospital emergency room in June, and has treated 138 cases since. The special residential treatment center installed in the Gyeonggi Provincial Academy gymnasium, which consists of 28 beds in 14 rooms (double occupancy) and a multipurpose room (for X-rays and treatment), is to remain open through October 10. Unlike existing treatment centers that have quarantined COVID-19 patients for two weeks, the Gyeonggi MCM will act as a self-treatment-associated short-term treatment center. While in self-treatment, patients showing symptoms requiring special attention will be moved to the MCM, followed by short-term hospitalization of 1-3 days for observation before further measures are taken. Patients can be treated using the MCM’s own treatment capacities, including in-person and oxygen treatment, X-rays, and IVs. There are individual bathrooms in each room, and the pressure, ventilation, and the automatic opening and closing of the entrance can be centrally monitored and controlled. Patients showing symptoms during treatment will be moved to a specially designated hospital for critical care, and will return to the self-treatment center if no further abnormalities are reported. The Gyeonggi Provincial Medical Center’s Ansung Hospital will take charge of operating the special treatment center. Each day, one or two doctors, three nurses, two nursing assistants, one administrative staff member, two or three disinfection specialists, and a medical imaging engineer will work in three shifts. There will also be about 20 additional specially designated staff members including KAIST researchers, firefighters, and police officers. The MCM was internationally recognized as an excellent medical facility not only for its functionality, economic feasibility, and utility, but also for its unique design and aesthetics. It received two Best of Best awards at the Red Dot Award in product design and Communication Design in user interface. By running this special treatment center, KAIST will conduct research on how to build an optimized model for efficient negative pressure medical units. This research is expected to lead to advances in waste water treatment systems, mobile bathrooms optimized for infectious cases, and MCM user interfaces for electronic devices, etc. Professor Taek-Jin Nam, the general director of the project and design, said “if there is a gymnasium available, we can convert it into a special treatment center fitted with a waste water treatment system, and pressure equipment in two weeks even without additional infrastructure.” The head of the KAIST New Deal R&D Initiative Choongsik Bae said, “our MCM research started in July of last year, and in just over a year, it has become a successful and innovative case that has undergone trials and become commercialized in a short period of time.” He added, “In response to COVID-19, KAIST is conducting research and empirical studies, not just in relation to the MCM, but in other areas of disease control as well.” Based on the excellent disease control technologies developed by KAIST research teams, the KAIST Action for Respiratory Epidemics is conducting technology transfers and industrialization, and is developing a Korean disease control package model
2021.09.15
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Professor Il-Doo Kim Receives the Science Minister’s Award
Professor Il-Doo Kim from the Department of Materials Science and Engineering received the Science and ICT Minister’s Award in recognition of his commercialization and technology transfer achievements during the Day of IP celebration. Professor Kim, who has made over 222 patents application and registration home and abroad, has advanced toxic gas detection and breath gas sensor technology by arraying nanosensor fibers. His technological advances in micro-electro-mechanical systems (MEMS) helped to advance the commercialization of the MEMS-related sensor and improve its overall competitiveness. He founded the Il-Doo Kim Research Center in 2019 and focuses on the commercialization of nanofiber manufacturing through electrospinning and highly efficient nanofiber filters. For instance, he succeeded in manufacturing a nano-filter recyclable mask that maintains excellent filtering efficiency even after hand washing through the development of proprietary technology that aligns nanofibers with a diameter of 100~500 nanometers in orthogonal or unidirectional directions. Professor Kim also serves as an associate editor at ACS Nano. He said, “The importance of IP goes without saying. I look forward to the registration and application of more KAIST patents leading to commercialization, paving the way for national technological competitiveness.”
2021.09.15
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The Dynamic Tracking of Tissue-Specific Secretory Proteins
Researchers develop a versatile and powerful tool for studying the spatiotemporal dynamics of secretory proteins, a valuable class of biomarkers and therapeutic targets Researchers have presented a method for profiling tissue-specific secretory proteins in live mice. This method is expected to be applicable to various tissues or disease models for investigating biomarkers or therapeutic targets involved in disease progression. This research was reported in Nature Communications on September 1. Secretory proteins released into the blood play essential roles in physiological systems. They are core mediators of interorgan communication, while serving as biomarkers and therapeutic targets. Previous studies have analyzed conditioned media from culture models to identify cell type-specific secretory proteins, but these models often fail to fully recapitulate the intricacies of multi-organ systems and thus do not sufficiently reflect biological realities. These limitations provided compelling motivation for the research team led by Jae Myoung Suh and his collaborators to develop techniques that could identify and resolve characteristics of tissue-specific secretory proteins along time and space dimensions. For addressing this gap in the current methodology, the research team utilized proximity-labeling enzymes such as TurboID to label secretory proteins in endoplasmic reticulum lumen using biotin. Thereafter, the biotin-labeled secretory proteins were readily enriched through streptavidin affinity purification and could be identified through mass spectrometry. To demonstrate its functionality in live mice, research team delivered TurboID to mouse livers via an adenovirus. After administering the biotin, only liver-derived secretory proteins were successfully detected in the plasma of the mice. Interestingly, the pattern of biotin-labeled proteins secreted from the liver was clearly distinctive from those of hepatocyte cell lines. First author Kwang-eun Kim from the Graduate School of Medical Science and Engineering explained, “The proteins secreted by the liver were significantly different from the results of cell culture models. This data shows the limitations of cell culture models for secretory protein study, and this technique can overcome those limitations. It can be further used to discover biomarkers and therapeutic targets that can more fully reflect the physiological state.” This work research was supported by the National Research Foundation of Korea, the KAIST Key Research Institutes Project (Interdisciplinary Research Group), and the Institute for Basic Science in Korea. -PublicationKwang-eun Kim, Isaac Park et al., “Dynamic tracking and identification of tissue-specific secretory proteins in the circulation of live mice,” Nature Communications on Sept.1, 2021(https://doi.org/10.1038/s41467-021-25546-y) -ProfileProfessor Jae Myoung Suh Integrated Lab of Metabolism, Obesity and Diabetes Researchhttps://imodkaist.wixsite.com/home Graduate School of Medical Science and Engineering College of Life Science and BioengineeringKAIST
2021.09.14
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How Stingrays Became the Most Efficient Swimmers in Nature
Study shows the hydrodynamic benefits of protruding eyes and mouth in a self-propelled flexible stingray With their compressed bodies and flexible pectoral fins, stingrays have evolved to become one of nature’s most efficient swimmers. Scientists have long wondered about the role played by their protruding eyes and mouths, which one might expect to be hydrodynamic disadvantages. Professor Hyung Jin Sung and his colleagues have discovered how such features on simulated stingrays affect a range of forces involved in propulsion, such as pressure and vorticity. Despite what one might expect, their research team found these protruding features actually help streamline the stingrays. ‘The influence of the 3D protruding eyes and mouth on a self-propelled flexible stingray and its underlying hydrodynamic mechanism are not yet fully understood,” said Professor Sung. “In the present study, the hydrodynamic benefit of protruding eyes and mouth was explored for the first time, revealing their hydrodynamic role.” To illustrate the complex interplay between hydrodynamic forces, the researchers set to work creating a computer model of a self-propelled flexible plate. They clamped the front end of the model and then forced it to mimic the up-and-down harmonic oscillations stingrays use to propel themselves. To re-create the effect of the eyes and mouth on the surrounding water, the team simulated multiple rigid plates on the model. They compared this model to one without eyes and a mouth using a technique called the penalty immersed boundary method. “Managing random fish swimming and isolating the desired purpose of the measurements from numerous factors was difficult,” Sung said. “To overcome these limitations, the penalty immersed boundary method was adopted to find the hydrodynamic benefits of the protruding eyes and mouth.” The team discovered that the eyes and mouth generated a vortex of flow in the forward-backward , which increased negative pressure at the simulated animal’s front, and a side-to-side vortex that increased the pressure difference above and below the stingray. The result was increased thrust and accelerated cruising. Further analysis showed that the eyes and mouth increased overall propulsion efficiency by more than 20.5% and 10.6%, respectively. Researchers hope their work, driven by curiosity, further stokes interest in exploring fluid phenomena in nature. They are hoping to find ways to adapt this for next-generation water vehicle designs based more closely on marine animals. This study was supported by the National Research Foundation of Korea and the State Scholar Fund from the China Scholarship Council. -ProfileProfessor Hyung Jin SungDepartment of Mechanical EngineeringKAIST -PublicationHyung Jin Sung, Qian Mao, Ziazhen Zhao, Yingzheng Liu, “Hydrodynamic benefits of protruding eyes and mouth in a self-propelled flexible stingray,” Aug.31, 2021, Physics of Fluids (https://doi.org/10.1063/5.0061287) -News release from the American Institute of Physics, Aug.31, 2021
2021.09.06
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Genomic Data Reveals New Insights into Human Embryonic Development
KAIST researchers have used whole-genome sequencing to track the development from a single fertilized-egg to a human body Genomic scientists at KAIST have revealed new insights into the process of human embryonic development using large-scale, whole-genome sequencing of cells and tissues from adult humans. The study, published in Nature on Aug.25, is the first to analyse somatic mutations in normal tissue across multiple organs within and between humans. An adult human body comprises trillions of cells of more than 200 types. How a human develops from a single fertilized egg to a fully grown adult is a fundamental question in biomedical science. Due to the ethical challenges of performing studies on human embryos, however, the details of this process remain largely unknown. To overcome these issues, the research team took a different approach. They analysed genetic mutations in cells taken from adult human post-mortem tissue. Specifically, they identified mutations that occur spontaneously in early developmental cell divisions. These mutations, also called genomic scars, act like unique genetic fingerprints that can be used to trace the embryonic development process. The study, which looked at 334 single-cell colonies and 379 tissue samples from seven recently deceased human body donors, is the largest single-cell, whole-genome analysis carried out to date. The researchers examined the genomic scars of each individual in order to reconstruct their early embryonic cellular dynamics. The result revealed several key characteristics of the human embryonic development process. Firstly, mutation rates are higher in the first cell division, but then decrease to approximately one mutation per cell during later cell division. Secondly, early cells contributed unequally to the development of the embryo in all informative donors, for example, at the two-cell stage, one of the cells always left more progeny cells than the other. The ratio of this was different from person to person, implying that the process varies between individuals and is not fully deterministic. The researchers were also able to deduce the timing of when cells begin to differentiate into individual organ-specific cells. They found that within three days of fertilization, embryonic cells began to be distributed asymmetrically into tissues for the left and right sides of the body, followed by differentiation into three germ layers, and then differentiation into specific tissues and organs. “It is an impressive scientific achievement that, within 20 years of the completion of human genome project, genomic technology has advanced to the extent that we are now able to accurately identify mutations in a single-cell genome,” said Professor Young Seok Ju from the Graduate School of Medical Science and Engineering at KAIST. “This technology will enable us to track human embryogenesis at even higher resolutions in the future.” The techniques used in this study could be used to improve our understanding of rare diseases caused by abnormalities in embryonic development, and to design new precision diagnostics and treatments for patients. The research was completed in collaboration with Kyungpook National University Hospital, the Korea Institute of Science and Technology Information, Catholic University of Korea School of Medicine, Genome Insights Inc, and Immune Square Inc. This work was supported by the Suh Kyungbae Foundation, the Ministry of Health and Welfare of Korea, the National Research Foundastion of Korea. -PublicationSeongyeol Park, Nanda Mali, Ryul Kim et al. ‘Clonal dynamics in early human embryogenesis inferred from somatic mutation’ Nature Online ahead of print, Aug. 25, 2021 (https://doi.org/10.1038/s41586-021-03786-8) -ProfileProfessor Young Seok JuLab of Cancer Genomics (https://www.julab.kaist.ac.kr/)Graduate School of Medical Science and EngineeringKAIST
2021.08.31
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Aline and Blow-yancy Win the Red Dot Design Awards: Brand & Communications Design 2021
‘Aline’ and ‘Blow-yancy’ developed by Professor Sang Su Lee’s team at the Department of Industrial Design won the Red Dot Design Awards in Brand & Communications Design. Aline is a mobile investment portfolio application used in the NH Investment & Securities Co. Blow-yancy is a suva diving VR device for neutral buoyancy training.Professor Lee sought ‘sustainability’ while developing Aline to meet the growing awareness of ESG (environmental, social, and governance) investing. ESG investing relies on independent ratings that help consumers assess a company’s behavior and policies when it comes to its social impact. Aline’s personal value index with six main criteria translates values into sustainable finance. By gathering data from the initial survey and regular value updates, the index is weighted according to the user’s values. Based on the index, the investment portfolio will be adjusted, and consumption against the values will be tracked. Blow-yancy is a diving VR device for neutral buoyancy training. Blow-yancy’s VR mask helps divers feel like they are wearing an actual diving mask. Users can breathe through a regulator with a built-in breathing sensor. It allows training like actual diving without going into the water, therefore enabling safer diving. “We got an idea that about 74% of scuba divers come into contact with corals underwater at least once and that can cause an emergency situation. Divers who cannot maintain neutral buoyance will experience a tough time avoiding them,” said Professor Lee. The hardware consists of a nose covering VR mask, a regulator with a built-in breath sensor, and a controller for virtual BCD control. Blow-yancy’s five virtual missions were organized according to the diving process required by PADI, a professional diving education institute. Professor Lee’s team already received eight recognitions at the iF Design Award in April. Professor Lee said, “We will continue to develop the best UX design items that will improve our global recognition.”
2021.08.26
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A Mechanism Underlying Most Common Cause of Epileptic Seizures Revealed
An interdisciplinary study shows that neurons carrying somatic mutations in MTOR can lead to focal epileptogenesis via non-cell-autonomous hyperexcitability of nearby nonmutated neurons During fetal development, cells should migrate to the outer edge of the brain to form critical connections for information transfer and regulation in the body. When even a few cells fail to move to the correct location, the neurons become disorganized and this results in focal cortical dysplasia. This condition is the most common cause of seizures that cannot be controlled with medication in children and the second most common cause in adults. Now, an interdisciplinary team studying neurogenetics, neural networks, and neurophysiology at KAIST has revealed how dysfunctions in even a small percentage of cells can cause disorder across the entire brain. They published their results on June 28 in Annals of Neurology. The work builds on a previous finding, also by a KAIST scientists, who found that focal cortical dysplasia was caused by mutations in the cells involved in mTOR, a pathway that regulates signaling between neurons in the brain. “Only 1 to 2% of neurons carrying mutations in the mTOR signaling pathway that regulates cell signaling in the brain have been found to include seizures in animal models of focal cortical dysplasia,” said Professor Jong-Woo Sohn from the Department of Biological Sciences. “The main challenge of this study was to explain how nearby non-mutated neurons are hyperexcitable.” Initially, the researchers hypothesized that the mutated cells affected the number of excitatory and inhibitory synapses in all neurons, mutated or not. These neural gates can trigger or halt activity, respectively, in other neurons. Seizures are a result of extreme activity, called hyperexcitability. If the mutated cells upend the balance and result in more excitatory cells, the researchers thought, it made sense that the cells would be more susceptible to hyperexcitability and, as a result, seizures. “Contrary to our expectations, the synaptic input balance was not changed in either the mutated or non-mutated neurons,” said Professor Jeong Ho Lee from the Graduate School of Medical Science and Engineering. “We turned our attention to a protein overproduced by mutated neurons.” The protein is adenosine kinase, which lowers the concentration of adenosine. This naturally occurring compound is an anticonvulsant and works to relax vessels. In mice engineered to have focal cortical dysplasia, the researchers injected adenosine to replace the levels lowered by the protein. It worked and the neurons became less excitable. “We demonstrated that augmentation of adenosine signaling could attenuate the excitability of non-mutated neurons,” said Professor Se-Bum Paik from the Department of Bio and Brain Engineering. The effect on the non-mutated neurons was the surprising part, according to Paik. “The seizure-triggering hyperexcitability originated not in the mutation-carrying neurons, but instead in the nearby non-mutated neurons,” he said. The mutated neurons excreted more adenosine kinase, reducing the adenosine levels in the local environment of all the cells. With less adenosine, the non-mutated neurons became hyperexcitable, leading to seizures. “While we need further investigate into the relationship between the concentration of adenosine and the increased excitation of nearby neurons, our results support the medical use of drugs to activate adenosine signaling as a possible treatment pathway for focal cortical dysplasia,” Professor Lee said. The Suh Kyungbae Foundation, the Korea Health Technology Research and Development Project, the Ministry of Health & Welfare, and the National Research Foundation in Korea funded this work. -Publication:Koh, H.Y., Jang, J., Ju, S.H., Kim, R., Cho, G.-B., Kim, D.S., Sohn, J.-W., Paik, S.-B. and Lee, J.H. (2021), ‘Non–Cell Autonomous Epileptogenesis in Focal Cortical Dysplasia’ Annals of Neurology, 90: 285 299. (https://doi.org/10.1002/ana.26149) -ProfileProfessor Jeong Ho Lee Translational Neurogenetics Labhttps://tnl.kaist.ac.kr/ Graduate School of Medical Science and Engineering KAIST Professor Se-Bum Paik Visual System and Neural Network Laboratory http://vs.kaist.ac.kr/ Department of Bio and Brain EngineeringKAIST Professor Jong-Woo Sohn Laboratory for Neurophysiology, https://sites.google.com/site/sohnlab2014/home Department of Biological SciencesKAIST Dr. Hyun Yong Koh Translational Neurogenetics LabGraduate School of Medical Science and EngineeringKAIST Dr. Jaeson Jang Ph.D.Visual System and Neural Network LaboratoryDepartment of Bio and Brain Engineering KAIST Sang Hyeon Ju M.D.Laboratory for NeurophysiologyDepartment of Biological SciencesKAIST
2021.08.26
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Brain-Inspired Highly Scalable Neuromorphic Hardware Presented
Neurons and synapses based on single transistor can dramatically reduce the hardware cost and accelerate the commercialization of neuromorphic hardware KAIST researchers fabricated a brain-inspired highly scalable neuromorphic hardware by co-integrating single transistor neurons and synapses. Using standard silicon complementary metal-oxide-semiconductor (CMOS) technology, the neuromorphic hardware is expected to reduce chip cost and simplify fabrication procedures. The research team led by Yang-Kyu Choi and Sung-Yool Choi produced a neurons and synapses based on single transistor for highly scalable neuromorphic hardware and showed the ability to recognize text and face images. This research was featured in Science Advances on August 4. Neuromorphic hardware has attracted a great deal of attention because of its artificial intelligence functions, but consuming ultra-low power of less than 20 watts by mimicking the human brain. To make neuromorphic hardware work, a neuron that generates a spike when integrating a certain signal, and a synapse remembering the connection between two neurons are necessary, just like the biological brain. However, since neurons and synapses constructed on digital or analog circuits occupy a large space, there is a limit in terms of hardware efficiency and costs. Since the human brain consists of about 1011 neurons and 1014 synapses, it is necessary to improve the hardware cost in order to apply it to mobile and IoT devices. To solve the problem, the research team mimicked the behavior of biological neurons and synapses with a single transistor, and co-integrated them onto an 8-inch wafer. The manufactured neuromorphic transistors have the same structure as the transistors for memory and logic that are currently mass-produced. In addition, the neuromorphic transistors proved for the first time that they can be implemented with a ‘Janus structure’ that functions as both neuron and synapse, just like coins have heads and tails. Professor Yang-Kyu Choi said that this work can dramatically reduce the hardware cost by replacing the neurons and synapses that were based on complex digital and analog circuits with a single transistor. "We have demonstrated that neurons and synapses can be implemented using a single transistor," said Joon-Kyu Han, the first author. "By co-integrating single transistor neurons and synapses on the same wafer using a standard CMOS process, the hardware cost of the neuromorphic hardware has been improved, which will accelerate the commercialization of neuromorphic hardware,” Han added.This research was supported by the National Research Foundation (NRF) and IC Design Education Center (IDEC). -PublicationJoon-Kyu Han, Sung-Yool Choi, Yang-Kyu Choi, et al.“Cointegration of single-transistor neurons and synapses by nanoscale CMOS fabrication for highly scalable neuromorphic hardware,” Science Advances (DOI: 10.1126/sciadv.abg8836) -ProfileProfessor Yang-Kyu ChoiNano-Oriented Bio-Electronics Labhttps://sites.google.com/view/nobelab/ School of Electrical EngineeringKAIST Professor Sung-Yool ChoiMolecular and Nano Device Laboratoryhttps://www.mndl.kaist.ac.kr/ School of Electrical EngineeringKAIST
2021.08.05
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A Study Reveals What Triggers Lung Damage during COVID-19
A longitudinal study of macrophages from SARS-CoV-2 infected lungs offers new insights into dynamic immunological changes A KAIST immunology research team found that a specific subtype of macrophages that originated from blood monocytes plays a key role in the hyper-inflammatory response in SARS-CoV-2 infected lungs, by performing single-cell RNA sequencing of bronchoalveolar lavage fluid cells. This study provides new insights for understanding dynamic changes in immune responses to COVID-19. In the early phase of COVID-19, SARS-CoV-2 infected lung tissue and the immediate defense system is activated. This early and fast response is called ‘innate immunity,’ provided by immune cells residing in lungs. Macrophages are major cell types of the innate immune system of the lungs, and newly differentiated macrophages originating from the bloodstream also contribute to early defenses against viruses. Professor Su-Hyung Park and his collaborators investigated the quantitative and qualitative evaluation of immune responses in the lungs of SARS-CoV-2 infected ferrets. To overcome the limitations of research using patient-originated specimens, the researchers used a ferret infection model to obtain SARS-CoV-2 infected lungs sequentially with a defined time interval. The researchers analyzed the 10 subtypes of macrophages during the five-day course of SARS-CoV-2 infection, and found that infiltrating macrophages originating from activated monocytes in the blood were key players for viral clearance as well as damaged lung tissue. Moreover, they found that the differentiation process of these inflammatory macrophages resembled the immune responses in the lung tissue of severe COVID-19 patients. Currently, the research team is conducting a follow-up study to identify the dynamic changes in immune responses during the use of immunosuppressive agents to control hyper-inflammatory response called ‘cytokine storm’ in patients with COVID-19. Dr. Jeong Seok Lee, the chief medical officer at Genome Insight Inc., explained, “Our analysis will enhance the understanding of the early features of COVID-19 immunity and provide a scientific background for the more precise use of immunosuppressive agents targeting specific macrophage subtypes.” “This study is the first longitudinal study using sequentially obtained immune cells originating from SARS-CoV-2 infected lungs. The research describes the innate immune response to COVID-19 using single cell transcriptome data and enhances our understanding of the two phases of inflammatory responses,” Professor Park said. This work was supported by the Ministry of Health and Welfare and KAIST, and was published in Nature Communications on July 28. -PublicationSu-Hyung Park, Jeong Seok Lee, Su-Hyung Park et al. “Single-cell transcriptome of bronchoalverolar lavage fluid reveals sequential change of macrophages during SARS-CoV-2 infection in ferrets” Nature Communications (https://doi.org/10.1038/s41467-021-24807-0) -ProfileProfessor Su-Hyung ParkLaboratory of Translational Immunology and Vaccinologyhttps://ltiv.kaist.ac.kr/ Graduate School of Medical Science and EngineeringKAIST
2021.08.04
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3D Visualization and Quantification of Bioplastic PHA in a Living Bacterial Cell
3D holographic microscopy leads to in-depth analysis of bacterial cells accumulating the bacterial bioplastic, polyhydroxyalkanoate (PHA) A research team at KAIST has observed how bioplastic granule is being accumulated in living bacteria cells through 3D holographic microscopy. Their 3D imaging and quantitative analysis of the bioplastic ‘polyhydroxyalkanoate’ (PHA) via optical diffraction tomography provides insights into biosynthesizing sustainable substitutes for petroleum-based plastics. The bio-degradable polyester polyhydroxyalkanoate (PHA) is being touted as an eco-friendly bioplastic to replace existing synthetic plastics. While carrying similar properties to general-purpose plastics such as polyethylene and polypropylene, PHA can be used in various industrial applications such as container packaging and disposable products. PHA is synthesized by numerous bacteria as an energy and carbon storage material under unbalanced growth conditions in the presence of excess carbon sources. PHA exists in the form of insoluble granules in the cytoplasm. Previous studies on investigating in vivo PHA granules have been performed by using fluorescence microscopy, transmission electron microscopy (TEM), and electron cryotomography. These techniques have generally relied on the statistical analysis of multiple 2D snapshots of fixed cells or the short-time monitoring of the cells. For the TEM analysis, cells need to be fixed and sectioned, and thus the investigation of living cells was not possible. Fluorescence-based techniques require fluorescence labeling or dye staining. Thus, indirect imaging with the use of reporter proteins cannot show the native state of PHAs or cells, and invasive exogenous dyes can affect the physiology and viability of the cells. Therefore, it was difficult to fully understand the formation of PHA granules in cells due to the technical limitations, and thus several mechanism models based on the observations have been only proposed. The team of metabolic engineering researchers led by Distinguished Professor Sang Yup Lee and Physics Professor YongKeun Park, who established the startup Tomocube with his 3D holographic microscopy, reported the results of 3D quantitative label-free analysis of PHA granules in individual live bacterial cells by measuring the refractive index distributions using optical diffraction tomography. The formation and growth of PHA granules in the cells of Cupriavidus necator, the most-studied native PHA (specifically, poly(3-hydroxybutyrate), also known as PHB) producer, and recombinant Escherichia coli harboring C. necator PHB biosynthesis pathway were comparatively examined. From the reconstructed 3D refractive index distribution of the cells, the team succeeded in the 3D visualization and quantitative analysis of cells and intracellular PHA granules at a single-cell level. In particular, the team newly presented the concept of “in vivo PHA granule density.” Through the statistical analysis of hundreds of single cells accumulating PHA granules, the distinctive differences of density and localization of PHA granules in the two micro-organisms were found. Furthermore, the team identified the key protein that plays a major role in making the difference that enabled the characteristics of PHA granules in the recombinant E. coli to become similar to those of C. necator. The research team also presented 3D time-lapse movies showing the actual processes of PHA granule formation combined with cell growth and division. Movies showing the living cells synthesizing and accumulating PHA granules in their native state had never been reported before. Professor Lee said, “This study provides insights into the morphological and physical characteristics of in vivo PHA as well as the unique mechanisms of PHA granule formation that undergo the phase transition from soluble monomers into the insoluble polymer, followed by granule formation. Through this study, a deeper understanding of PHA granule formation within the bacterial cells is now possible, which has great significance in that a convergence study of biology and physics was achieved. This study will help develop various bioplastics production processes in the future.” This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (Grants NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) and the Bio & Medical Technology Development Program (Grant No. 2021M3A9I4022740) from the Ministry of Science and ICT (MSIT) through the National Research Foundation (NRF) of Korea to S.Y.L. This work was also supported by the KAIST Cross-Generation Collaborative Laboratory project. -PublicationSo Young Choi, Jeonghun Oh, JaeHwang Jung, YongKeun Park, and Sang Yup Lee. Three-dimensional label-free visualization and quantification of polyhydroxyalkanoates in individualbacterial cell in its native state. PNAS(https://doi.org./10.1073/pnas.2103956118) -ProfileDistinguished Professor Sang Yup LeeMetabolic Engineering and Synthetic Biologyhttp://mbel.kaist.ac.kr/ Department of Chemical and Biomolecular Engineering KAIST Endowed Chair Professor YongKeun ParkBiomedical Optics Laboratoryhttps://bmokaist.wordpress.com/ Department of PhysicsKAIST
2021.07.28
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