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Mutations Occurring Only in Brain Responsible for Intractable Epilepsy Identified
KAIST researchers have discovered that brain somatic mutations in MTOR gene induce intractable epilepsy and suggest a precision medicine to treat epileptic seizures. Epilepsy is a brain disorder which afflicts more than 50 million people worldwide. Many epilepsy patients can control their symptoms through medication, but about 30% suffer from intractable epilepsy and are unable to manage the disease with drugs. Intractable epilepsy causes multiple seizures, permanent mental, physical, and developmental disabilities, and even death. Therefore, surgical removal of the affected area from the brain has been practiced as a treatment for patients with medically refractory seizures, but this too fails to provide a complete solution because only 60% of the patients who undergo surgery are rendered free of seizures. A Korean research team led by Professor Jeong Ho Lee of the Graduate School of Medical Science and Engineering at the Korea Advanced Institute of Science and Technology (KAIST) and Professor Dong-Seok Kim of Epilepsy Research Center at Yonsei University College of Medicine has recently identified brain somatic mutations in the gene of mechanistic target of rapamycin (MTOR) as the cause of focal cortical dysplasia type II (FCDII), one of the most important and common inducers to intractable epilepsy, particularly in children. They propose a targeted therapy to lessen epileptic seizures by suppressing the activation of mTOR kinase, a signaling protein in the brain. Their research results were published online in Nature Medicine on March 23, 2015. FCDII contributes to the abnormal developments of the cerebral cortex, ranging from cortical disruption to severe forms of cortical dyslamination, balloon cells, and dysplastic neurons. The research team studied 77 FCDII patients with intractable epilepsy who had received a surgery to remove the affected regions from the brain. The researchers used various deep sequencing technologies to conduct comparative DNA analysis of the samples obtained from the patients’ brain and blood, or saliva. They reported that about 16% of the studied patients had somatic mutations in their brain. Such mutations, however, did not take place in their blood or saliva DNA. Professor Jeong Ho Lee of KAIST said, “This is an important finding. Unlike our previous belief that genetic mutations causing intractable epilepsy exist anywhere in the human body including blood, specific gene mutations incurred only in the brain can lead to intractable epilepsy. From our animal models, we could see how a small fraction of mutations carrying neurons in the brain could affect its entire function.” The research team recapitulated the pathogenesis of intractable epilepsy by inducing the focal cortical expression of mutated mTOR in the mouse brain via electroporation method and observed as the mouse develop epileptic symptoms. They then treated these mice with the drug called “rapamycin” to inhibit the activity of mTOR protein and observed that it suppressed the development of epileptic seizures with cytomegalic neurons. “Our study offers the first evidence that brain-somatic activating mutations in MTOR cause FCDII and identifies mTOR as a treatment target for intractable epilepsy,” said co-author Dr. Dong-Seok Kim, a neurosurgeon at Yonsei Medical Center with the country’s largest surgical experiences in treating patients with this condition. The research paper is titled “Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy.” (Digital Object Identifier #: 10.1038/nm.3824) Picture 1: A schematic image to show how to detect brain specific mutation using next-generation sequencing technology with blood-brain paired sample. Simple comparison of non-overlapping mutations between affected and unaffected tissues is able to detect brain specific mutations. Picture 2: A schematic image to show how to generate focal cortical dysplasia mouse model. This mouse model open the new window of drug screening for seizure patients. Picture 3: Targeted medicine can rescue the focal cortical dysplasia symptoms including cytomegalic neuron & intractable epilepsy.
2015.03.25
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KAIST Develops a Credit-Card-Thick Flexible Lithium Ion Battery
Since the battery can be charged wirelessly, useful applications are expected including medical patches and smart cards. Professor Jang Wook Choi at KAIST’s Graduate School of Energy, Environment, Water, and Sustainability (EEWS) and Dr. Jae Yong Song at the Korea Research Institute of Standards and Science jointly led research to invent a flexible lithium ion battery that is thinner than a credit card and can be charged wirelessly. Their research findings were published online in Nano Letters on March 6, 2015. Lithium ion batteries are widely used today in various electronics including mobile devices and electronic cars. Researchers said that their work could help accelerate the development of flexible and wearable electronics. Conventional lithium ion batteries are manufactured based on a layering technology, stacking up anodes, separating films, and cathodes like a sandwich, which makes it difficult to reduce their thickness. In addition, friction arises between layers, making the batteries impossible to bend. The coating films of electrodes easily come off, which contributes to the batteries’ poor performance. The research team abandoned the existing production technology. Instead, they removed the separating films, layered the cathodes and anodes collinearly on a plane, and created a partition between electrodes to eliminate potential problems, such as short circuits and voltage dips, commonly present in lithium ion batteries. After more than five thousand consecutive flexing experiments, the research team confirmed the possibility of a more flexible electrode structure while maintaining the battery performance comparable to the level of current lithium ion batteries. Flexible batteries can be applied to integrated smart cards, cosmetic and medical patches, and skin adhesive sensors that can control a computer with voice commands or gesture as seen in the movie “Iron Man.” Moreover, the team has successfully developed wireless-charging technology using electromagnetic induction and solar batteries. They are currently developing a mass production process to combine this planar battery technology and printing, to ultimately create a new paradigm to print semiconductors and batteries using 3D printers. Professor Choi said, “This new technology will contribute to diversifying patch functions as it is applicable to power various adhesive medical patches.” Picture 1: Medical patch (left) and flexible secondary battery (right) Picture 2: Diagram of flexible battery Picture 3: Smart card embedding flexible battery
2015.03.24
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KAIST and Hancom Sign for Development of Mobile Healthcare
KAIST signed a memorandum of understanding with Hancom, Inc., an office suite developer in Korea, to foster mobile healthcare software programs. President Steve Kang and Chairman Sang-Chul Kim of Hancom held a signing ceremony on March 13, 2015 at the KAIST campus. Based on the agreement, KAIST and Hancom will exchange research personnel to build Dr. M, a smart healthcare platform developed by the university, collaborate in research and development, and cooperate in the transfer of research developments from the university to the software industry including Hancom. KAIST and Hancom also signed a memorandum of understanding on the development of software in April 2014. The Hancom-KAIST Research Center opened on campus last October.
2015.03.20
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Qualcomm Innovation Award Recognizes 20 KAIST Students
The award provides research fellowships, worth of USD 100,000, to 20 KAIST graduate students With an audience of 100 people present, KAIST held a ceremony for the Qualcomm Innovation Award 2015 at the Information Technology Convergence building on campus on March 12, 2015. The Qualcomm Innovation Award, established in 2010, is a fellowship that supports innovative science and engineering master’s and doctoral students at KAIST. Qualcomm donated USD 100,000 to KAIST, stipulating that it be used to foster a creative research environment for graduate students. To select the recipients, KAIST formed an award committee chaired by Professor Soo-Young Lee of the Department of Electrical Engineering and accepted research proposals until late January. The award committee first selected 37 proposals from 75 papers submitted and then chose the final 20 research proposals on March 12, 2015 after presentation evaluations. The presentations had to show promise of innovation and creativity; prospective influence on wireless communications and mobile industry; and the prospect of being implemented. Each recipient received a USD 4,500 research fellowship along with an opportunity to present their research findings at a workshop where Qualcomm engineers and other distinguished individuals of the industry will attend. Previously, Qualcomm has donated research fellowships to KAIST graduate students in 2011 and 2013.
2015.03.19
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Emeritus Professors' Social Service for Embracing Multicultural Families
Korea has become a melting pot over recent years, with many families embracing diverse nationalities, cultures, and ethnicities. A group of KAIST emeritus professors volunteered to help these multicultural families, which are often formed through international marriages, better cope with life in Korea by creating a continuing education program called “Multicultural Mother School.” The school admitted a total of ten non-Korean mothers for its first class and held an entrance ceremony for the students on March 14, 2015, at the IFC Hope Church in Daejeon. Classes began since March 16, 2015, offering the first lecture to students remotely via the Internet. Professor Emeritus Byung-Kyu Choi, who organized the volunteering program and is the director of the Multicultural Mother School, said, “About 5% of newborns in Korea currently come from multicultural families. It is important that we should support them to assimilate well into the Korean society. Since 60% of multicultural children have yet to enter the public school system, particularly at the elementary schools level, offering their mothers opportunities to learn more about Korea will serve a greater good.”
2015.03.14
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KAIST Develops Ultrathin Polymer Insulators Key to Low-Power Soft Electronics
Using an initiated chemical vapor deposition technique, the research team created an ultrathin polymeric insulating layer essential in realizing transistors with flexibility and low power consumption. This advance is expected to accelerate the commercialization of wearable and soft electronics. A group of researchers at the Korea Advanced Institute of Science and Technology (KAIST) developed a high-performance ultrathin polymeric insulator for field-effect transistors (FETs). The researchers used vaporized monomers to form polymeric films grown conformally on various surfaces including plastics to produce a versatile insulator that meets a wide range of requirements for next-generation electronic devices. Their research results were published online in Nature Materials on March 9th, 2015. FETs are an essential component for any modern electronic device used in our daily life from cell phones and computers, to flat-panel displays. Along with three electrodes (gate, source, and drain), FETs consist of an insulating layer and a semiconductor channel layer. The insulator in FETs plays an important role in controlling the conductance of the semiconductor channel and thus current flow within the translators. For reliable and low-power operation of FETs, electrically robust, ultrathin insulators are essential. Conventionally, such insulators are made of inorganic materials (e.g., oxides and nitrides) built on a hard surface such as silicon or glass due to their excellent insulating performance and reliability. However, these insulators were difficult to implement into soft electronics due to their rigidity and high process temperature. In recent years, many researchers have studied polymers as promising insulating materials that are compatible with soft unconventional substrates and emerging semiconductor materials. The traditional technique employed in developing a polymer insulator, however, had the limitations of low surface coverage at ultra-low thickness, hindering FETs adopting polymeric insulators from operating at low voltage. A KAIST research team led by Professor Sung Gap Im of the Chemical and Biomolecular Engineering Department and Professor Seunghyup Yoo and Professor Byung Jin Cho of the Electrical Engineering Department developed an insulating layer of organic polymers, “pV3D3,” that can be greatly scaled down, without losing its ideal insulating properties, to a thickness of less than 10 nanometers (nm) using the all-dry vapor-phase technique called the “initiated chemical vapor deposition (iCVD).” The iCVD process allows gaseous monomers and initiators to react with each other in a low vacuum condition, and as a result, conformal polymeric films with excellent insulating properties are deposited on a substrate. Unlike the traditional technique, the surface-growing character of iCVD can overcome the problems associated with surface tension and produce highly uniform and pure ultrathin polymeric films over a large area with virtually no surface or substrate limitations. Furthermore, most iCVD polymers are created at room temperature, which lessens the strain exerted upon and damage done to the substrates. With the pV3D3 insulator, the research team built low-power, high-performance FETs based on various semiconductor materials such as organics, graphene, and oxides, demonstrating the pV3D3 insulator’s wide range of material compatibility. They also manufactured a stick-on, removable electronic component using conventional packaging tape as a substrate. In collaboration with Professor Yong-Young Noh from Dongguk University in Korea, the team successfully developed a transistor array on a large-scale flexible substrate with the pV3D3 insulator. Professor Im said, “The down-scalability and wide range of compatibility observed with iCVD-grown pV3D3 are unprecedented for polymeric insulators. Our iCVD pV3D3 polymeric films showed an insulating performance comparable to that of inorganic insulating layers, even when their thickness were scaled down to sub-10 nm. We expect our development will greatly benefit flexible or soft electronics, which will play a key role in the success of emerging electronic devices such as wearable computers.” The title of the research paper is “Synthesis of ultrathin polymer insulating layers by initiated chemical vapor deposition for low-power soft electronics” (Digital Object Identifier (DOI) number is 10.1038/nmat4237). Picture 1: A schematic image to show how the initiated chemical vapor deposition (iCVD) technique produces pV3D3 polymeric films: (i) introduction of vaporized monomers and initiators, (ii) activation of initiators to thermally dissociate into radicals, (iii) adsorption of monomers and initiator radicals onto a substrate, and (iv) transformation of free-radical polymerization into pV3D3 thin films. Picture 2: This is a transistor array fabricated on a large scale, highly flexible substrate with pV3D3 polymeric films. Picture 3: This photograph shows an electronic component fabricated on a conventional packaging tape, which is attachable or detachable, with pV3D3 polymeric films embedded.
2015.03.10
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System Approach Using Metabolite Structural Similarity Toward TOM Suggested
A Korean research team at KAIST suggests that a system approach using metabolite structural similarity helps to elucidate the mechanisms of action of traditional oriental medicine. Traditional oriental medicine (TOM) has been practiced in Asian countries for centuries, and is gaining increasing popularity around the world. Despite its efficacy in various symptoms, TOM has been practiced without precise knowledge of its mechanisms of action. Use of TOM largely comes from empirical knowledge practiced over a long period of time. The fact that some of the compounds found in TOM have led to successful modern drugs such as artemisinin for malaria and taxol (Paclitaxel) for cancer has spurred modernization of TOM. A research team led by Sang-Yup Lee at KAIST has focused on structural similarities between compounds in TOM and human metabolites to help explain TOM’s mechanisms of action. This systems approach using structural similarities assumes that compounds which are structurally similar to metabolites could affect relevant metabolic pathways and reactions by biosynthesizing structurally similar metabolites. Structural similarity analysis has helped to identify mechanisms of action of TOM. This is described in a recent study entitled “A systems approach to traditional oriental medicine,” published online in Nature Biotechnology on March 6, 2015. In this study, the research team conducted structural comparisons of all the structurally known compounds in TOM and human metabolites on a large-scale. As a control, structures of all available approved drugs were also compared against human metabolites. This structural analysis provides two important results. First, the identification of metabolites structurally similar to TOM compounds helped to narrow down the candidate target pathways and reactions for the effects from TOM compounds. Second, it suggested that a greater fraction of all the structurally known TOM compounds appeared to be more similar to human metabolites than the approved drugs. This second finding indicates that TOM has a great potential to interact with diverse metabolic pathways with strong efficacy. This finding, in fact, shows that TOM compounds might be advantageous for the multitargeting required to cure complex diseases. “Once we have narrowed down candidate target pathways and reactions using this structural similarity approach, additional in silico tools will be necessary to characterize the mechanisms of action of many TOM compounds at a molecular level,” said Hyun Uk Kim, a research professor at KAIST. TOM’s multicomponent, multitarget approach wherein multiple components show synergistic effects to treat symptoms is highly distinctive. The researchers investigated previously observed effects recorded since 2000 of a set of TOM compounds with known mechanisms of action. TOM compounds’ synergistic combinations largely consist of a major compound providing the intended efficacy to the target site and supporting compounds which maximize the efficacy of the major compound. In fact, such combination designs appear to mirror the Kun-Shin-Choa-Sa design principle of TOM. That principle, Kun-Shin-Choa-Sa (君臣佐使 or Jun-Chen-Zuo-Shi in Chinese) literally means “king-minister-assistant-ambassador.” In ancient East Asian medicine, treating human diseases and taking good care of the human body are analogous to the politics of governing a nation. Just as good governance requires that a king be supported by ministers, assistants and/or ambassadors, treating diseases or good care of the body required the combined use of herbal medicines designed based on the concept of Kun-Shin-Choa-Sa. Here, the Kun (king or the major component) indicates the major medicine (or herb) conveying the major drug efficacy, and is supported by three different types of medicines: the Shin (minister or the complementary component) for enhancing and/or complementing the efficacy of the Kun, Choa (assistant or the neutralizing component) for reducing any side effects caused by the Kun and reducing the minor symptoms accompanying major symptom, and Sa (ambassador or the delivery/retaining component) which facilitated the delivery of the Kun to the target site, and retaining the Kun for prolonged availability in the cells. The synergistic combinations of TOM compounds reported in the literature showed four different types of synergisms: complementary action (similar to Kun-Shin), neutralizing action (similar to Kun-Choa), facilitating action or pharmacokinetic potentiation (both similar to Kun-Choa or Kun-Sa). Additional structural analyses for these compounds with synergism show that they appeared to affect metabolism of amino acids, co-factors and vitamins as major targets. Professor Sang Yup Lee remarks, “This study lays a foundation for the integration of traditional oriental medicine with modern drug discovery and development. The systems approach taken in this analysis will be used to elucidate mechanisms of action of unknown TOM compounds which will then be subjected to rigorous validation through clinical and in silico experiments.” Sources: Kim, H.U. et al. “A systems approach to traditional oriental medicine.” Nature Biotechnology. 33: 264-268 (2015). This work was supported by the Bio-Synergy Research Project (2012M3A9C4048759) of the Ministry of Science, ICT and Future Planning through the National Research Foundation. This work was also supported by the Novo Nordisk Foundation. The picture below presents the structural similarity analysis of comparing compounds in traditional oriental medicine and those in all available approved drugs against the structures of human metabolites.
2015.03.09
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Interactions Features KAIST's Human-Computer Interaction Lab
Interactions, a bi-monthly magazine published by the Association for Computing Machinery (ACM), the largest educational and scientific computing society in the world, featured an article introducing Human-Computer Interaction (HCI) Lab at KAIST in the March/April 2015 issue (http://interactions.acm.org/archive/toc/march-april-2015). Established in 2002, the HCI Lab (http://hcil.kaist.ac.kr/) is run by Professor Geehyuk Lee of the Computer Science Department at KAIST. The lab conducts various research projects to improve the design and operation of physical user interfaces and develops new interaction techniques for new types of computers. For the article, see the link below: ACM Interactions, March and April 2015 Day in the Lab: Human-Computer Interaction Lab @ KAIST http://interactions.acm.org/archive/view/march-april-2015/human-computer-interaction-lab-kaist
2015.03.02
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The Real Time Observation of the Birth of a Molecule
From right to left: Dr. Kyung-Hwan Kim, Professor Hyotcherl Lhee, and Jong-Gu Kim, a Ph.D. candidate Professor Hyotcherl Lhee of the Department of Chemistry at KAIST and Japanese research teams jointly published their research results showing that they have succeeded in the direct observation of how atoms form a molecule in the online issue of Nature on February 19, 2015. The researchers used water in which gold atoms ([Au(CN) 2- ]) are dissolved and fired X-ray pulses over the specimen in femtosecond timescales to study chemical reactions taking place among the gold atoms. They were able to examine in real time the instant process of how gold atoms bond together to become a molecule, to a trimer or tetramer state. This direct viewing of the formation of a gold trimer complex ([Au(CN) 2- ] 3 ) will provide an opportunity to understand complex chemical and biological systems. For details, please see the following press release that was distributed by the High Energy Accelerator Research Organization, KEK, in Japan: Direct Observation of Bond Formations February 18, 2015 A collaboration between researchers from KEK, the Institute for Basic Science (IBS), the Korea Advanced Institute of Science and Technology (KAIST), RIKEN, and the Japan Synchrotron Radiation Research Institute (JASRI) used the SACLA X-ray free electron laser (XFEL) facility for a real time visualization of the birth of a molecular that occurs via photoinduced formation of a chemical bonds. This achievement was published in the online version of the scientific journal “Nature” (published on 19 February 2015). Direct “observation” of the bond making, through a chemical reaction, has been longstanding dream for chemists. However, the distance between atoms is very small, at about 100 picometer, and the bonding is completed very quickly, taking less than one picosecond (ps). Hence, previously, one could only imagine the bond formation between atoms while looking at the chemical reaction progressing in the test-tube. In this study, the research group focused on the process of photoinduced bond formation between gold (Au) ions dissolved in water. In the ground state (S 0 state in Fig. 1) Au ions that are weakly bound to each other by an electron affinity and aligned in a bent geometry. Upon a photoexcitation, the S 0 state rapidly converts into an excited (S 1 state in Fig. 1) state where Au-Au covalent bonds are formed among Au ions aligned in a linear geometry. Subsequently, the S 1 state transforms to a triplet state (T 1 state in Fig. 1) in 1.6 ps while accompanying further contraction of Au-Au bonds by 0.1 Å. Later, the T 1 state of the trimer converts to a tetramer (tetramer state in Fig. 1) on nanosecond time scale. Finally, the Au ions returned to their original loosely interacting bent structure. In this research, the direct observation of a very fast chemical reaction, induced by the photo-excitation, was succeeded (Fig. 2, 3). Therefore, this method is expected to be a fundamental technology for understanding the light energy conversion reaction. The research group is actively working to apply this method to the development of viable renewable energy resources, such as a photocatalysts for artificial photosynthesis using sunlight. This research was supported by the X-ray Free Electron Laser Priority Strategy Program of the MEXT, PRESTO of the JST, and the the Innovative Areas "Artificial Photosynthesis (AnApple)" grant from the Japan Society for the Promotion of Science (JSPS). Publication: Nature , 518 (19 February 2015) Title: Direct observation of bond formation in solution with femtosecond X-ray scattering Authors: K. H. Kim 1 , J. G. Kim 1 , S. Nozawa 1 , T. Sato 1 , K. Y. Oang, T. W. Kim, H. Ki, J. Jo, S. Park, C. Song, T. Sato, K. Ogawa, T. Togashi, K. Tono, M. Yabashi, T. Ishikawa, J. Kim, R. Ryoo, J. Kim, H. Ihee, S. Adachi. ※ 1: These authors contributed equally to the work. DOI: 10.1038/nature14163 Figure 1. Structure of a gold cyano trimer complex (Au(CN) 2 - ) 3 . Figure 2. Observed changes in the molecular structure of the gold complex Figure 3. Schematic view of the research of photo-chemical reactions by the molecular movie
2015.02.27
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KAIST Develops Subminiature, Power-Efficient Air Pollution Sensing Probe
Professor Inkyu Park and his research team from the Department of Mechanical Engineering at KAIST have developed a subminiature, power-efficient air-pollution sensing probe that can be applied to mobile devices. Their research findings were published online in the January 30th issue of Scientific Reports. As air pollution has increased, people have taken greater interest in health care. The developed technology could allow people to measure independently the air pollution level of their surrounding environments. Previous instruments used to measure air pollution levels were bulky and consumed a lot of power. They also often produced inaccurate results when measuring air pollution in which different toxic gases were mixed. These problems could not be resolved with existing semiconductor manufacturing process. Using local temperature field control technology, Professor Park’s team succeeded in integrating multiple heterogeneous nanomaterials and fitting them onto a small, low-power electronic chip. This microheating sensor can heat microscale regions through local hydrothermal synthesis. Because it requires a miniscale amount of nanomaterials to manufacture, the sensor is most suitable for mobile devices. Professor Park said, “Our research will contribute to the development of convergence technology in such field as air pollution sensing probes, biosensors, electronic devices, and displays.” The team's research was supported by the Ministry of Education and the Ministry of Science, ICT and Future Planning, Republic of Korea. Figure 1 – The Concept of Multiple Nanomaterial Device and Numerical Simulation Results of Precursor Solutions Figure 2 - Multiple Nanomaterial Manufactured in a Microscale Region
2015.02.27
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Dr. Dong-Hee Chung Honored with OYRA by Korean Physicists in America
Dr. Dong-Hee Chung, a KAIST alumnus (class of 2002) who is currently a professor of the Physics Department at the Pennsylvania State University (Penn State), received the 2015 Outstanding Young Researcher Award (OYRA) by the Association of Korean Physicists in America (AKPA). The award ceremony was held on March 3, 2015 at AKPA’s annual conference. According to AKPA, Dr. Chung was recognized for his research achievements in the fields of the early universe, dark energy, and galaxy formation. Dr. Chung finished both his undergraduate and graduate degrees at KAIST and received his doctorate in 2004 from the University of Texas at Austin. He was appointed a professor at Penn State in 2014.
2015.02.27
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Ethiopian Minister of Education Visits KAIST
An Ethiopian delegation headed by the Minister of Education visited the KAIST campus on February 26, 2015. The delegation consisted of Mr. Demitu Hambisa, Minister of Education, Mr. Dibaba Abdetta, Ethiopian Ambassador to Korea, Dr. Jang-Kyu Lee, President of Adama Science and Technology University (ASTU), and Mr. Nurelegne Tefera, President of Addis Ababa Science and Technology University (AASTU). Minister Hambisa explained the purpose of his visit, “We would like to learn about what KAIST has achieved over the years for Korea and its people and increase exchanges and cooperation between our universities and KAIST.” KAIST and the two Ethiopian universities, ASTU and AASTU, signed memoranda of understanding for cooperative programs in science and engineering education. Established in 1993, ASTU appointed Dr. Jang-Kyu Lee, a former professor from Seoul National University, Korea, to become its president since 2011. President Lee is the first Korean ever to have served the institution.
2015.02.26
View 7488
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