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Engineered E. coli Using Formic Acid and CO2 As a C1-Refinery Platform Strain
(Figure: Formic acid and CO2 assimilation pathways consisting of the reconstructed THF cycle and reverse glycine cleavage reaction. This schematic diagram shows the formic acid and CO2 assimilation procedure through the pathway. Plasmids used in this study and the genetic engineering performed in this study are illustrated.) A research group at KAIST has developed an engineered E. coli strain that converts formic acid and CO2 to pyruvate and produces cellular energy from formic acid through reconstructed one-carbon pathways. The strategy described in this study provides a new platform for producing value-added chemicals from one-carbon sources. Formic acid is a carboxylic acid composed of one carbon. Formic acid was produced from CO2 by the chemical method. Recently, the C1 Gas Refinery R&D Center has successfully developed a biological process that produces formic acid from carbon monoxide for the first time. Formic acid is in a liquid state when at room temperature and atmospheric pressure. In addition, it is chemically stable and less toxic, thus, easy to store and transport. Therefore, it can be used as an alternative carbon source in the microbial fermentation process. In order to produce value-added chemicals using formic acid, a metabolic pathway that converts formic acid into cellular molecules composed of multiple carbons is required. However, a metabolic pathway that can efficiently convert formic acid into cellular molecules has not been developed. This acted as an obstacle for the production of value-added chemicals using formic acid A research group of Ph.D. student Junho Bang and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering addressed this issue. This study, entitled “Assimilation of Formic Acid and CO2 by Engineered Escherichia coli Equipped with Reconstructed One-Carbon Assimilation Pathways”, has been published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on September 18. There has been increasing interest in utilizing formic acid as an alternative carbon source for the production of value-added chemicals. This research reports the development of an engineered E. coli strain that can convert formic acid and CO2 to pyruvate and produce cellular energy from formic acid through the reconstructed one-carbon pathways. The metabolic pathway that efficiently converts formic acid and CO2 into pyruvate was constructed by the combined use of the tetrahydrofolate cycle and reverse glycine cleavage reaction. The tetrahydrofolate cycle was reconstructed by utilizing Methylobacterium extorquens formate-THF ligase, methenyl-THF cyclohydrolase, and methylene-THF dehydrogenase. The glycine cleavage reaction was reversed by knocking out the repressor gene (gcvR) and overexpressing the gcvTHP genes that encode enzymes related with the glycine cleavage reaction. Formic acid and CO2 conversion to pyruvate was increased via metabolic engineering of the E. coli strain equipped with the one-carbon assimilation pathway. In addition, in order to reduce glucose consumption and increase formic acid consumption, Candida boidnii formate dehydrogenase was additionally introduced to construct a cellular energy producing pathway from formic acid. This reduces glucose consumption and increases formic acid consumption. The reconstructed one-carbon pathways can supply cellular molecules and cellular energies from the formic acid and CO2. Thus, the engineered E. coli strain equipped with the formic acid and CO2 assimilation pathway and cellular energy producing pathway from formic acid showed cell growth from formic acid and CO2 without glucose. Cell growth was monitored and 13C isotope analysis was performed to confirm E. coli growth from the formic acid and CO2. It was found that the engineered E. coli strain sustained cell growth from the formic acid and CO2 without glucose. Professor Lee said, “To construct the C1-refinery system, a platform strain that can convert one-carbon materials to higher carbon materials needs to be developed. In this report, a one-carbon pathway that can efficiently convert formic acid and CO2 to pyruvate was developed and a cellular energy producing pathway from formic acid was introduced. This resulted in an engineered E. coli strain that can efficiently utilize formic acid as a carbon source while glucose consumption was reduced. The reconstructed one-carbon pathways in this research will be useful for the construction of the C1-refinery system.” This work was supported by the C1 Gas Refinery Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2016M3D3A1A01913250). For further information: Sang Yup Lee, Distinguished Professor of Chemical and Biomolecular Engineering, KAIST (leesy@kaist.ac.kr, Tel: +82-42-350-3930)
2018.09.18
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Transfering Nanowires onto a Flexible Substrate
(from left: PhD Min-Ho Seo and Professor Jun-Bo Yoon) Boasting excellent physical and chemical properties, nanowires (NWs) are suitable for fabricating flexible electronics; therefore, technology to transfer well-aligned wires plays a crucial role in enhancing performance of the devices. A KAIST research team succeeded in developing NW-transfer technology that is expected to enhance the existing chemical reaction-based NW fabrication technology that has this far showed low performance in applicability and productivity. NWs, one of the most well-known nanomaterials, have the structural advantage of being small and lightweight. Hence, NW-transfer technology has drawn attention because it can fabricate high-performance, flexible nanodevices with high simplicity and throughput. A conventional nanowire-fabrication method generally has an irregularity issue since it mixes chemically synthesized nanowires in a solution and randomly distributes the NWs onto flexible substrates. Hence, numerous nanofabrication processes have emerged, and one of them is master-mold-based, which enables the fabrication of highly ordered NW arrays embedded onto substrates in a simple and cost-effective manner, but its employment is limited to only some materials because of its chemistry-based NW-transfer mechanism, which is complex and time consuming. For the successful transfer, it requires that adequate chemicals controlling the chemical interfacial adhesion between the master mold, NWs, and flexible substrate be present. Here, Professor Jun-Bo Yoon and his team from the School of Electrical Engineering introduced a material-independent mechanical-interlocking-based nanowire-transfer (MINT) method to fabricate ultralong and fully aligned NWs on a large flexible substrate in a highly robust manner. This method involves sequentially forming a nanosacrificial layer and NWs on a nanograting substrate that becomes the master mold for the transfer, then weakening the structure of the nanosacrificial layer through a dry etching process. The nanosacrificial layer very weakly holds the nanowires on the master mold. Therefore, when using a flexible substrate material, the nanowires are very easily transferred from the master mold to the substrate, just like a piece of tape lifting dust off a carpet. This technology uses common physical vapor deposition and does not rely on NW materials, making it easy to fabricate NWs onto the flexible substrates. Using this technology, the team was able to fabricate a variety of metal and metal-oxide NWs, including gold, platinum, and copper – all perfectly aligned on a flexible substrate. They also confirmed that it can be applied to creating stable and applicable devices in everyday life by successfully applying it to flexible heaters and gas sensors. PhD Min-Ho Seo who led this research said, “We have successfully aligned various metals and semiconductor NWs with excellent physical properties onto flexible substrates and applied them to fabricated devices. As a platform-technology, it will contribute to developing high-performing and stable electronic devices.” This research was published in ACS Nano on May 24. Figure 1. Photograph of the fabricated wafer-scale fully aligned and ultralong Au nanowire array on a flexible substrate
2018.09.17
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Mathematical Principle behind AI's 'Black Box'
(from left: Professor Jong Chul Ye, PhD candidates Yoseob Han and Eunju Cha) A KAIST research team identified the geometrical structure of artificial intelligence (AI) and discovered the mathematical principles of highly performing artificial neural networks, which can be applicable in fields such as medical imaging. Deep neural networks are an exemplary method of implementing deep learning, which is at the core of the AI technology, and have shown explosive growth in recent years. This technique has been used in various fields, such as image and speech recognition as well as image processing. Despite its excellent performance and usefulness, the exact working principles of deep neural networks has not been well understood, and they often suffer from unexpected results or errors. Hence, there is an increasing social and technical demand for interpretable deep neural network models. To address these issues, Professor Jong Chul Ye from the Department of Bio & Brain Engineering and his team attempted to find the geometric structure in a higher dimensional space where the structure of the deep neural network can be easily understood. They proposed a general deep learning framework, called deep convolutional framelets, to understand the mathematical principle of a deep neural network in terms of the mathematical tools in Harmonic analysis. As a result, it was found that deep neural networks’ structure appears during the process of decomposition of high dimensionally lifted signal via Hankel matrix, which is a high-dimensional structure formerly studied intensively in the field of signal processing. In the process of decomposing the lifted signal, two bases categorized as local and non-local basis emerge. The researchers found that non-local and local basis functions play a role in pooling and filtering operation in convolutional neural network, respectively. Previously, when implementing AI, deep neural networks were usually constructed through empirical trial and errors. The significance of the research lies in the fact that it provides a mathematical understanding on the neural network structure in high dimensional space, which guides users to design an optimized neural network. They demonstrated improved performance of the deep convolutional framelets’ neural networks in the applications of image denoising, image pixel in painting, and medical image restoration. Professor Ye said, “Unlike conventional neural networks designed through trial-and-error, our theory shows that neural network structure can be optimized to each desired application and are easily predictable in their effects by exploiting the high dimensional geometry. This technology can be applied to a variety of fields requiring interpretation of the architecture, such as medical imaging.” This research, led by PhD candidates Yoseob Han and Eunju Cha, was published in the April 26th issue of the SIAM Journal on Imaging Sciences. Figure 1. The design of deep neural network using mathematical principles Figure 2. The results of image noise cancelling Figure 3. The artificial neural network restoration results in the case where 80% of the pixels are lost
2018.09.12
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Distinguished Professor Sang Yup Lee Announced as the Eni Award Recipient
(Distinguished Professor Sang Yup Lee) Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering will be awarded the 2018 Eni Advanced Environmental Solutions Prize in recognition of his innovations in the fields of energy and environment. The award ceremony will take place at the Quirinal Palace, the official residence of Italian President Sergio Mattarella, who will also be attending on October 22. Eni, an Italian multinational energy corporation established the Eni Award in 2008 to promote technological and research innovation of efficient and sustainable energy resources. The Advanced Environmental Solutions Prize is one of the three categories of the Eni Award. The other two categories are Energy Transition and Energy Frontiers. The Award for Advanced Environmental Solutions recognizes a researcher or group of scientists that has achieved internationally significant R&D results in the field of environmental protection and recovery. The Eni Award is referred to as the Nobel Award in the fields of energy and environment. Professor Lee, a pioneering leader in systems metabolic engineering was honored with the award for his developing engineered bacteria to produce chemical products, fuels, and non-food biomass materials sustainably and with a low environmental impact. He has leveraged the technology to develop microbial bioprocesses for the sustainable and environmentally friendly production of chemicals, fuels, and materials from non-food renewable biomass. The award committee said that they considered the following elements in assessing Professor Lee’s achievement: the scientific relevance and the research innovation level; the impact on the energy system in terms of sustainability as well as fairer and broader access to energy; and the adequacy between technological and economic aspects. Professor Lee, who already won two other distinguished prizes such as the George Washington Carver Award and the PV Danckwerts Memorial Lecture Award this year, said, “I am so glad that the international academic community as well as global industry leaders came to recognize our work that our students and research team has made for decades.” Dr. Lee’s lab has been producing a lot of chemicals in environmentally friendly ways. Among them, many were biologically produced for the first time and some of these processes have been already commercialized. “We will continue to strive for research outcomes with two objectives: First, to develop bio-based processes suitable for sustainable chemical industry. The other is to contribute to the human healthcare system through development of platform technologies integrating medicine and nutrition,” he added.
2018.09.12
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Center for Industrial Future Strategy Takes Off at KAIST
(Professor Wonjoon Kim from the School of Business and Technology Management) Professors from KAIST and major international universities launched a mega-scale research center focusing on the Fourth Industrial Revolution, named the Center for Industrial Future Strategy (CIFS). This center is funded by the National Research Foundation Korea and will receive 2.25 billion KRW over four years. Directed by Professor Wonjoon Kim from the School of Business and Technology Management, the center is comprised of ten top-tier researchers and four research associates, including Professor Hawoon Jeong (KAIST), Professor Scott Stern (MIT), Professor Aaron Chatterji (Duke University), Dr. Yong Suk Lee (Stanford University) and Professor Hyejin Youn (Northwestern University). The center will conduct research on technical, social, and economic changes derived by a new paradigm of technological innovation. Moreover, they will study policies and strategies in relation to innovation in the corporate and government sectors to achieve economic growth in a sustainable manner. The center will also propose policies and strategies in a variety of economic and industrial settings to establish a sustainable and global innovation ecosystem. To carry out these studies successfully, CIFS will further expand the AIEA-NBER Conference with the Asia Innovation and Entrepreneurship Association (AIEA) and the National Bureau of Economic Research (NBER) in which numerous Nobel Laureates in Economics are affiliated. They will also comprise thematic research teams with co-founding universities to build stronger cooperation with one another. Besides the academic cooperation, the center will also build partnerships with international organizations, including the Asian Development Bank and the Inter-American Development Bank to carry out their missions at multilateral levels. Their research topics include changes to value chains in a new paradigm of technological innovation, labor market changes in the Fourth Industrial Revolution, sharing economies and social interests, big data, artificial intelligence & privacy policy, and innovation & ethical and institutional countermeasures to AI technology. Professor Kim said, “The new paradigm of technological innovation is evolving social, economic, and industrial structures, such as R&D, industry, technology, labor, finance, and institutions. The Center will contribute to proposing policies and strategies so that Korea, as well as the international community, can take appropriate measures to these big changes.”
2018.09.11
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Electron Heating in Weakly Ionized Collisional Plasmas
(from left: Professor Wonho Choe and Research Professor Sanghoo Park) A KAIST research team successfully identified the underlying principles behind electron heating, which is one of the most important phenomena in plasmas. As the electric heating determines wide range of physical and chemical properties of plasmas, this outcome will allow relevant industries to extend and effectively customize a range of plasma characteristics for their specific needs. Plasma, frequently called the fourth state of matter, can be mostly formed by artificially energizing gases in standard temperature (25°C) and pressure (1 atm) range. Among the many types of plasma, atmospheric-pressure plasmas have been gaining a great deal of attention due to their unique features and applicability in various scientific and industrial fields. Because plasma characteristics strongly depends on gas pressure in the sub-atmospheric to atmospheric pressure range, characterizing the plasma at different pressures is a prerequisite for understanding the fundamental principles of plasmas and for their industrial applications. In that sense, information on the spatio-temporal evolution in the electron density and temperature is very important because various physical and chemical reactions within a plasma arise from electrons. Hence, electron heating has been an interesting topic in the field of plasma. Because collisions between free electrons and neutral gases are frequent under atmospheric-pressure conditions, there are physical limits to measuring the electron density and temperature in plasmas using conventional diagnostic tools, thus the principles behind free electron heating could not be experimentally revealed. Moreover, lacking information on a key parameter of electron heating and its controlling methods is troublesome and limit improving the reactivity and applicability of such plasmas. To address these issues, Professor Wonho Choe and his team from the Department of Nuclear and Quantum Engineering employed neutral bremsstrahlung-based electron diagnostics in order to accurately examine the electron density and temperature in target plasmas. In addition, a novel imaging diagnostics for two dimensional distribution of electron information was developed. Using the diagnostic technique they developed, the team measured the nanosecond-resolved electron temperature in weakly ionized collisional plasmas, and they succeeded in revealing the spatiotemporal distribution and the fundamental principle involved in the electron heating process. The team successfully revealed the fundamental principle of the electron heating process under atmospheric to sub-atmospheric pressure (0.25-1atm) conditions through conducting the experiment on the spatiotemporal evolution of electron temperature. Their findings of the underlying research data on free electrons in weakly ionized collisional plasmas will contribute to enhancing the field of plasma science and their commercial applications. Professor Choe said, “The results of this study provide a clear picture of electron heating in weakly ionized plasmas under conditions where collisions between free electrons and neutral particles are frequent. We hope this study will be informative and helpful in utilizing and commercializing atmospheric-pressure plasma sources in the near future.” Articles related to this research, led by Research Professor Sanghoo Park, were published in Scientific Reports on May 14 and July 5. Figure 1. Nanosecond-resolved visualization of the electron heating structure. Spatiotemporal evolution of 514.5-nm continuum radiation,Te, Ar I emission Figure 2. Nanosecond-resolved visualization of electron heating. Spatiotemporal evolution of neutral bremsstrahlung at 514.5 nm
2018.09.10
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KAIST Core Technology Fair Accelerates Commercialization
(President Shin makes opening remarks at the KAIST Core Tech Transfer Day in Seoul.) Technology commercialization is the one of the innovation initiatives KAIST is strongly driving. KAIST showcased six core technologies developed by KAIST research teams during the 2018 KAIST Core Tech Transfer Day on September 10 at Coex in Seoul. More than 300 investors, buyers, and venture capitalists showed up for the fair. This is the second fair organized as one of the strategic innovation initiatives that KAIST is promoting. Developers of key technologies selected in the fields of bio, nano, AI, and semiconductors presented their distinct technological prowess to the attendees. The technologies are highly relevant for the new industrial environment trends in the Fourth Industrial Revolution. The 15-member committee comprised of patent attorneys, venture capitalists, and commercialization specialists selected the six core technologies based on their innovativeness, applicability, and marketability. The Office of University-Industry Cooperation (OUIC) plans to offer buyers various services for developing business models, business strategy analysis, and marketing at home and abroad. The six core technologies featured at the fair include: - Novel technology of a nano patterning platform by Professor Hee Tae Chung from the Department of Chemical and Biomolecular Engineering - Anticancer therapeutic candidate materials strengthening immune function by Professor Byung Sok Choi from the Department of Chemistry - Biofuel mass production using micro-organisms by Distinguished Professor Sang-Yup Lee from the Department of Chemical and Biomolecular Engineering - Compact single-shot hyperspectral camera technology by Min Hyuk Kim from the School of Computing - AI-powered high speed ultra-high definition upscaling technology by Professor Munchurl Kim from the School of Electrical Engineering - A radiation strong MOSFET device by Hee Chul Lee from the School of Electrical Engineering President Sung-Chul Shin stressed in his opening remarks that universities should make contributions to economic development through innovation. “Global leading universities are taking an instrumental role in creating new jobs and economic growth with their own technologies. KAIST, as the leading university in Korea, is accelerating the commercialization of technology produced internally to create a meaningful impact for the economy as well as the job market beyond Korea,” he said. “We are aiming for the global market, not just in Korea. I want KAIST to be a global value creator that can contribute to the betterment of the world through our innovations,” he added.
2018.09.10
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There Won't Be a Singularity: Professor Jerry Kaplan
(Professor Jerry Kaplan gave a lecture titled, Artificial Intelligence: Think Again at KAIST) “People are so concerned about super intelligence, but the singularity will not happen,” said Professor Jerry Kaplan at Stanford University, an AI guru and Silicon Valley entrepreneur during a lecture at KAIST. He visited KAIST to give a lecture on Artificial Intelligence: Think Again on September 6. Professor Kaplan said that some people argue that Korea’s AI research is behind the US and China but he doesn’t agree with that. “Korea is the most digitally connected one and has the world’s best engineers in the field. Korean companies are building products the consumers really like at reasonable prices. Those are attracting global consumers,” he added. Instead of investing loads of money on AI research, he suggested three tasks for Korea taking a better position in the field of AI: Collecting and saving lots of data; training engineers, not the research talents in AI; and investing in AI infrastructure and relieving regulations by the government. Referring to AI hype, Professor Kaplan argued that machines are intelligent, but they do not think in the way humans can, and assured the audience that the singularity some futurists predict will not be coming. He said, “Machine learning is a tool extracting useful information, but it does not mean they are so smart that they are taking over the world.” (Professor Jerry Kaplan gave a lecture titled, Artificial Intelligence: Think Again at KAIST) But what has made us believing AI myths? He first began pointing out how AI has been mythicized by three major drivers. Those are the entertainment industry, the popular media, and the AI community all wanting to attract more public attention and prestige. The abovementioned drivers are falsely making robots more human and are adding human characteristics. Instead of being captivated by those AI myths and thinking about how to save the world from robots, he strongly argued, “We need to develop standards for the unintended side effects from AI.” To provide machines socially and ethically mingling with the human world, he believed principles should be set as follows: Define the Safe Operating Envelope (SOE), “safe modes” when out of bounds, study human behavior programmatically, certification and licensing standards, limitations on machine “agency,” and basic computational ethics such as when it is okay to break the law. Professor Kaplan gave a positive view of AI for humans. “The future will be bright, thanks to AI. They do difficult work and help us and that will drive wealth and quality of life. The rich might get richer, but the benefits will spread throughout the people. It is time to think of innovative ways for using AI for building better world,” he concluded.
2018.09.10
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NEREC Summer Program Keeps Fellows Thinking, Engaged in Nuclear Nonproliferation
Nuclear technology is more than just technology. It is the fruit of the most advanced science and technology. It also requires high standards of policymaking and global cooperation for benefiting the technology. As part of the fifth annual Nuclear Nonproliferation Education and Research Center (NEREC) Summer Fellows Program at KAIST, 24 students from 15 countries participated in six-week intensive education and training program. NEREC is the only university-based center dedicated to nuclear nonproliferation education and research established in 2014. The program, which provides multidisciplinary lectures and seminars on nuclear technology and policy as well as international relations, was designed to nurture global nuclear technology experts well equipped in three areas: in-depth knowledge of technology, applicability gained from sound policy building, and negotiating for international cooperation. It now has grown into the most popular summer program at KAIST. During the program from July 6 to August 18, participants were able to engage in enriching and stimulating learning experiences in tandem with policies and technology for the utilization and provision of peaceful and safe nuclear technology. Participating fellows also had to conduct a group research project on a given topic. This year, they explored nuclear nonproliferation issues in relation to nuclear exports and brainstormed some recommendations for current policy. They presented their outcomes at the 2018 NEREC Conference on Nuclear Nonproliferation. After intensive lecture sessions and group research work, the fellows went off to key policy think-tanks, nuclear research institutes, and research power facilities in Korea, Japan, and China. “NEREC emphasizes nuclear nonproliferation issues related to civilian nuclear power and the associated nuclear fuel cycle development from the point of technology users. I am very glad that the number of participants are increasing year by year,” said the Director of NEREC Man-Sung Yim, a professor in the Department of Nuclear and Quantum Engineering. Participants’ majors vary from nuclear engineering to international relations to economics. The fellows divided into two groups of graduate and undergraduate courses. They expressed their deep satisfactory in the multidisciplinary lectures by scholars from KAIST, Seoul National University, and Korea National Defense University. Many participants reported that they learned a lot, not only about policy and international relations but on the research they are conducting and what the key issues will be in dealing for producing meaningful research work. Moad Aldbissi from the KTH Royal Institute of Technology is one of the students who shared the same view. He said, “Coming from a technical background in nuclear engineering, I managed to learn a lot about nuclear policy and international relations. The importance of integrating the technical and political fields became even clearer.” Most students concurred that they recognized how important it was to make international collaboration in this powerful field for each country through this program. “As an engineering student, I just approached this program like an empty glass in policy areas. While working with colleagues during the program, I came to understand how important it is to make cooperation in these fields for the better result of national development and international relations,” said Thanataon Pornphatdetaudom from the Tokyo Institute of Technology. To Director Yim, this program is becoming well positioned to educate nuclear policy experts in a number of countries of strategic importance. He believes the continuous supply of these experts will contribute to promoting global nuclear nonproliferation and the peaceful use of nuclear energy while the use of nuclear technology continues.
2018.09.04
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Adding Smart to Science Museum
KAIST and the National Science Museum (NSM) created an Exhibition Research Center for Smart Science to launch exhibitions that integrate emerging technologies in the Fourth Industrial Revolution, including augmented reality (AR), virtual reality (VR), Internet of Things (IoTs), and artificial intelligence (AI). There has been a great demand for a novel technology for better, user-oriented exhibition services. The NSM continuously faces the problem of not having enough professional guides. Additionally, there have been constant complaints about its current mobile application for exhibitions not being very effective. To tackle these problems, the new center was founded, involving 11 institutes and universities. Sponsored by the National Research Foundation, it will oversee 15 projects in three areas: exhibition-based technology, exhibition operational technology, and exhibition content. The group first aims to provide a location-based exhibition guide system service, which allows it to incorporate various technological services, such as AR/VR to visitors. An indoor locating system named KAILOS, which was developed by KAIST, will be applied to this service. They will also launch a mobile application service that provides audio-based exhibition guides. To further cater to visitors’ needs, the group plans to apply a user-centered ecosystem, a living lab concept to create pleasant environment for visitors. “Every year, hundred thousands of young people visit the National Science Museum. I believe that the exhibition guide system has to be innovative, using cutting-edge IT technology in order to help them cherish their dreams and inspirations through science,” Jeong Heoi Bae, President of Exhibition and Research Bureau of NSM, emphasized. Professor Dong Soo Han from the School of Computing, who took the position of research head of the group, said, “We will systematically develop exhibition technology and contents for the science museum to create a platform for smart science museums. It will be the first time to provide an exhibition guide system that integrates AR/VR with an indoor location system.” The center will first apply the new system to the NSM and then expand it to 167 science museums and other regional museums.
2018.09.04
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Potential Drug to Cure Ciliopathies
(from left: Professor Joon Kim and PhD candidate Yong Joon Kim) Ciliopathies are rare disorders involving functional and structural abnormalities of cilia. Although they are rare, they may reach 1 in 1,000 births. Unfortunately, there are no small-molecule drugs for treating ciliary defects. A KAIST research team conducted successful research that introduces a potential treatment that will be a foundation for developing drugs to treat the disease as well as a platform for developing small-molecule drugs for similar genetic disorders. It was found that mutations in genes required for the formation or function of primary cilia cause ciliopathies and they result in cerebellar disorders, kidney dysfunction, and retinal degeneration. Primary cilia are cell organelles playing a crucial role in the human body. They participate in intercellular signal transduction during embryonic development and allow retinal photoreceptor cells to function. Currently, there are no approved drugs available for treating most ciliopathies. In fact, this is the case for most of the rare genetic disorders involving functional abnormalities through genetic mutation, and gene therapy is usually the only treatment available. To tackle this issue, a team led by Professor Joon Kim from the Graduate School of Medical Science and Engineering and Ho Jeong Kwon from Yonsei University constructed a cell that mimics a gene-mutated CEP290, one of the main causes of ciliopathies, through genome editing. They then used cell-based compound library screening to obtain a natural small-molecule compound capable of relieving defects in ciliogenesis, the production of cilia. The CEP290 protein forms a complex with a ciliopathy protein called NPHP5 to support the function of the ciliary transition zone. In cases where the CEP290 protein is not formed due to a genetic mutation, NPHP5 will not function normally. Here, the compound was confirmed to partially restore the function of the complex by normalizing the function of NPHP5. The team also identified that the compound is capable of retarding retinal degeneration by injecting the compound into animal models. As a result, they discovered a lead compound for developing medication to treat ciliopathy patients involving retinal degeneration. Hence, the findings imply that chemical compounds that target other proteins interacting with the disease protein can mitigate shortages of a disease protein in recessive genetic disorders. PhD candidate Yong Joon Kim stated, “This study shows how genetic disorders caused by genetic mutation can be treated with small-molecule drugs.” Professor Kim said, “Since the efficacy of the candidate drug has been verified through animal testing, a follow-up study will also be conducted to demonstrate the effect on humans.” This research was published in the Journal of Clinical Investigation on July 23. Figure 1. Identification of compounds that rescue ciliogenesis defects caused by CEP290 knockout Figure 2. Eupatilin injection ameliorates M-opsin trafficking and electrophysiological response of cone photoreceptors in rd16 mice
2018.08.30
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Rh Ensemble Catalyst for Effective Automobile Exhaust Treatment
(from left: Professor Hyunjoo Lee and PhD candidate Hojin Jeong) A KAIST research team has developed a fully dispersed Rh ensemble catalyst (ENS) that shows better performance than commercial diesel oxidation catalyst (DOC). This newly developed ENSs could improve low-temperature automobile exhaust treatment. Precious metals have been used for various heterogeneous reactions, but it is crucial to maximize efficiency of catalysts due to their high cost. Single-atom catalysts (SACs) have received much attention because it is possible for all of the metal atoms to be used for reactions, yet they do not show catalytic activity for reactions that require ensemble sites. Meanwhile, hydrocarbons, such as propylene (C3H6) and propane (C3H8) are typical automobile exhaust gas pollutants and must be converted to carbon dioxide (CO2) and water (H2O) before they are released as exhaust. Since the hydrocarbon oxidation reaction proceeds only during carbon-carbon (C-C) or carbon-hydrogen (C-H) bond cleavage, it is essential to secure the metal ensemble site for the catalytic reaction. Therefore, precious metal catalysts with high dispersion and ensemble sites are greatly needed. To solve this issue, Professor Hyunjoo Lee from the Department of Chemical and Biomolecular Engineering and Professor Jeong Woo Han from POSTECH developed an Rh ensemble catalyst with 100% dispersion, and applied it to automobile after-treatment. Having a 100% dispersion means that every metal atom is used for the reaction since it is exposed on the surface. SACs also have 100% dispersion, but the difference is that ENSs have the unique advantage of having an ensemble site with two or more atoms. As a result of the experiment, the ENSs showed excellent catalytic performance in CO, NO, propylene, and propane oxidation at low temperatures. This complements the disadvantage of nanoparticle catalyst (NPs) that perform catalysis poorly at low temperatures due to low metal dispersion, or SACs without hydrocarbon oxidation. In particular, the ENSs have superior low-temperature activity even better than commercial DOC, hence they are expected to be applied to automobile exhaust treatment. Professor Lee said, “I believe that the ENSs have given academic contribution for proposing a new concept of metal catalysts, differentiating from conventional SACs and NPs. At the same time, they are of great value in the industry of exhaust treatment catalysts.” This research, led by PhD candidate Hojin Jeong, was published in the Journal of the American Chemical Society on July 5. Figure 1. Concept of Rh ensemble catalyst for automobile exhaust treatment Figure 2. Structure and performance comparison of single-atom catalyst and ensemble catalyst Figure 3. Energy-dispersive X-ray spectroscopy (EDS) mapping images for SAC, ENS, and NP, respectively (green, Eh; red, Ce)
2018.08.29
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