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Accurate Detection of Low-Level Somatic Mutation in Intractable Epilepsy
KAIST medical scientists have developed an advanced method for perfectly detecting low-level somatic mutation in patients with intractable epilepsy. Their study showed that deep sequencing replicates of major focal epilepsy genes accurately and efficiently identified low-level somatic mutations in intractable epilepsy.
According to the study, their diagnostic method could increase the accuracy up to 100%, unlike the conventional sequencing analysis, which stands at about 30% accuracy. This work was published in Acta Neuropathologica.
Epilepsy is a neurological disorder common in children. Approximately one third of child patients are diagnosed with intractable epilepsy despite adequate anti-epileptic medication treatment.
Somatic mutations in mTOR pathway genes, SLC35A2, and BRAF are the major genetic causes of intractable epilepsies. A clinical trial to target Focal Cortical Dysplasia type II (FCDII), the mTOR inhibitor is underway at Severance Hospital, their collaborator in Seoul, Korea. However, it is difficult to detect such somatic mutations causing intractable epilepsy because their mutational burden is less than 5%, which is similar to the level of sequencing artifacts. In the clinical field, this has remained a standing challenge for the genetic diagnosis of somatic mutations in intractable epilepsy.
Professor Jeong Ho Lee’s team at the Graduate School of Medical Science and Engineering analyzed paired brain and peripheral tissues from 232 intractable epilepsy patients with various brain pathologies at Severance Hospital using deep sequencing and extracted the major focal epilepsy genes.
They narrowed down target genes to eight major focal epilepsy genes, eliminating almost all of the false positive calls using deep targeted sequencing. As a result, the advanced method robustly increased the accuracy and enabled them to detect low-level somatic mutations in unmatched Formalin Fixed Paraffin Embedded (FFPE) brain samples, the most clinically relevant samples.
Professor Lee conducted this study in collaboration with Professor Dong Suk Kim and Hoon-Chul Kang at Severance Hospital of Yonsei University. He said, “This advanced method of genetic analysis will improve overall patient care by providing more comprehensive genetic counseling and informing decisions on alternative treatments.”
Professor Lee has investigated low-level somatic mutations arising in the brain for a decade. He is developing innovative diagnostics and therapeutics for untreatable brain disorders including intractable epilepsy and glioblastoma at a tech-startup called SoVarGen. “All of the technologies we used during the research were transferred to the company. This research gave us very good momentum to reach the next phase of our startup,” he remarked.
The work was supported by grants from the Suh Kyungbae Foundation, a National Research Foundation of Korea grant funded by the Ministry of Science and ICT, the Korean Health Technology R&D Project from the Ministry of Health & Welfare, and the Netherlands Organization for Health Research and Development.
(Figure: Landscape of somatic and germline mutations identified in intractable epilepsy patients. a Signaling pathways for all of the mutated genes identified in this study. Bold: somatic mutation, Regular: germline mutation. b The distribution of variant allelic frequencies (VAFs) of identified somatic mutations. c The detecting rate and types of identified mutations according to histopathology. Yellow: somatic mutations, green: two-hit mutations, grey: germline mutations.)
2019.08.14 View 27790 -
Professor Sang Gyu Kim Receives Yeochon Award for Ecology
Professor Sang-Gyu Kim from the Department of Biological Sciences was selected as the winner of the 12th Yeochon Award for Ecology presented by the Yeochon Association for Ecological Research.
The award was conferred on August 13 in Jeju at the annual conference co-hosted by the Ecological Society of Korea and the Yeochon Association for Ecological Research. Professor Kim received 10 million KRW in prize money.
Professor Kim was recognized for his achievements and contributions in studying herbivorous insects ‘rice weevils’ and their host plant ‘wild tobacco’, especially for having explored the known facts in traditional ecology at the molecular level. His findings are presented in his paper titled ‘Trichobaris weevils distinguish amongst toxic host plants by sensing volatiles that do not affect larval performance’ published in Molecular Ecology in July 2016.
Furthermore, Professor Kim’s research team is continuing their work to identify the ecological functions of plant metabolites as well as interactions between flowers and insect vectors at the molecular level. In doing so, the team edits genes in various plant species using the latest gene editing technology.
The Yeochon Award for Ecology was first established in 2005 with funds donated by a senior ecologist, the late Honorary Professor Joon-Ho Kim of Seoul National University. The award is named after the professor’s pen name “Yeochon” and is intended to encourage promising next-generation ecologists to produce outstanding research achievements in the field of basic ecology.
Professor Kim said, “I will take this award as encouragement to continue taking challenging risks to observe ecological phenomenon from a new perspective. I will continue my research with my students with joy and enthusiasm.”
2019.08.14 View 6054 -
Manipulating Brain Cells by Smartphone
Researchers have developed a soft neural implant that can be wirelessly controlled using a smartphone. It is the first wireless neural device capable of indefinitely delivering multiple drugs and multiple colour lights, which neuroscientists believe can speed up efforts to uncover brain diseases such as Parkinson’s, Alzheimer’s, addiction, depression, and pain.
A team under Professor Jae-Woong Jeong from the School of Electrical Engineering at KAIST and his collaborators have invented a device that can control neural circuits using a tiny brain implant controlled by a smartphone. The device, using Lego-like replaceable drug cartridges and powerful, low-energy Bluetooth, can target specific neurons of interest using drugs and light for prolonged periods. This study was published in Nature Biomedical Engineering.
“This novel device is the fruit of advanced electronics design and powerful micro and nanoscale engineering,” explained Professor Jeong. “We are interested in further developing this technology to make a brain implant for clinical applications.”
This technology significantly overshadows the conventional methods used by neuroscientists, which usually involve rigid metal tubes and optical fibers to deliver drugs and light. Apart from limiting the subject’s movement due to bulky equipment, their relatively rigid structure causes lesions in soft brain tissue over time, therefore making them not suitable for long-term implantation. Although some efforts have been made to partly mitigate adverse tissue response by incorporating soft probes and wireless platforms, the previous solutions were limited by their inability to deliver drugs for long periods of time as well as their bulky and complex control setups.
To achieve chronic wireless drug delivery, scientists had to solve the critical challenge of the exhaustion and evaporation of drugs. To combat this, the researchers invented a neural device with a replaceable drug cartridge, which could allow neuroscientists to study the same brain circuits for several months without worrying about running out of drugs.
These ‘plug-n-play’ drug cartridges were assembled into a brain implant for mice with a soft and ultrathin probe (with the thickness of a human hair), which consisted of microfluidic channels and tiny LEDs (smaller than a grain of salt), for unlimited drug doses and light delivery.
Controlled with an elegant and simple user interface on a smartphone, neuroscientists can easily trigger any specific combination or precise sequencing of light and drug delivery in any implanted target animal without the need to be physically inside the laboratory. Using these wireless neural devices, researchers can also easily setup fully automated animal studies where the behaviour of one animal could affect other animals by triggering light and/or drug delivery.
“The wireless neural device enables chronic chemical and optical neuromodulation that has never been achieved before,” said lead author Raza Qazi, a researcher with KAIST and the University of Colorado Boulder.
This work was supported by grants from the National Research Foundation of Korea, US National Institute of Health, National Institute on Drug Abuse, and Mallinckrodt Professorship.
(A neural implant with replaceable drug cartridges and Bluetooth low-energy can target specific neurons .)
(Micro LED controlling using smartphone application)
2019.08.07 View 31328 -
Chem-E-Car Team to Vie for World Title
Team KAItalyst, composed of KAIST undergraduate students, celebrated victory in the regional qualifying rounds of the 2019 International Chem-E-Car Competition held at KAIST’s Main Campus in Daejeon on July 20. The high finish in the national rankings qualified the team for a trip to the world finals to be held in Orlando, Florida, USA, in November.
The Chem-E-Car Competition involves designing and building a shoebox-sized model car that is powered and controlled by chemical reactions. University students from all over the world have been actively participating in this competition since the competition was introduced by the American Institute of Chemical Engineers (AIChE) in 1999.
KAIST first entered the competition in 2014, won the world finals in 2016, and then received the Most Consistent Award in 2017 and 2018. In recognition of KAIST’s consistently outstanding performance in the competition, AIChE asked KAIST to host this year’s regional competition for the first time in Korea.
Although a number of Korean university student teams have shown great interest in participating in this regional competition, most were not able to successfully implement their technology, and only two teams each from KAIST and Seoul National University (SNU) joined the competition.
Each team collaborated to fabricate a chemically powered model car that could carry a payload, and travel any distance between 15 and 30 meters. The weight of the payload and the travelling distance were randomly set an hour before the competition started, to require the participating teams adapt and perform calculations in a short period of time. The goal was to stop travelling exactly at the randomly chosen distance. The car closest to the finish line at the end of the race earned the highest amount of points. Precise control over chemical reactions was key to landing directly on the mark.
Team KAItalyst, consisting of six KAIST undergraduate students majoring in chemical and biomolecular engineering and mechanical engineering, beat their SNU rivals by stopping their car 1.5 meters closer to the goal at the end of the 22.5 meter-long race. Team KAItalyst loaded vanadium redox flow batteries onto their car to stabilize its output, and further increased the accuracy and velocity of chemical reactions through iodine clock reactions. 200 USD was awarded to Team KAItalyst, and 100 USD in prize money went to the SNU team.
KAItalyst team leader Jee-Hyun Hong said, “This was the first time for us to develop and drive our own chemically-powered model car, and we learned a lot from the challenges we faced,” Hong continued, “We will step up our efforts to perform better in the upcoming international competition.” The world finals will be held during the AIChE Fall Meeting in Orlando, Florida in November. Students from over 50 universities worldwide including the Georgia Institute of Technology and Carnegie Mellon University will compete against each other. The first, second, and third prizes at the finals will be 2,000, 1,000, and 500 USD respectively.
Professor Dong-Yeun Koh of the KAIST Chemical and Biomolecular Engineering Department who advised Team KAItalyst remarked, “I hope this year’s regional competition that KAIST held for the first time as a Korean university will be a possible starting point for more Korean universities to participate and compete in the future.”
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2019.08.05 View 6084 -
Synthesizing Single-Crystalline Hexagonal Graphene Quantum Dots
(Figure: Uniformly ordered single-crystalline graphene quantum dots of various sizes synthesized through solution chemistry.)
A KAIST team has designed a novel strategy for synthesizing single-crystalline graphene quantum dots, which emit stable blue light. The research team confirmed that a display made of their synthesized graphene quantum dots successfully emitted blue light with stable electric pressure, reportedly resolving the long-standing challenges of blue light emission in manufactured displays. The study, led by Professor O Ok Park in the Department of Chemical and Biological Engineering, was featured online in Nano Letters on July 5.
Graphene has gained increased attention as a next-generation material for its heat and electrical conductivity as well as its transparency. However, single and multi-layered graphene have characteristics of a conductor so that it is difficult to apply into semiconductor. Only when downsized to the nanoscale, semiconductor’s distinct feature of bandgap will be exhibited to emit the light in the graphene. This illuminating featuring of dot is referred to as a graphene quantum dot.
Conventionally, single-crystalline graphene has been fabricated by chemical vapor deposition (CVD) on copper or nickel thin films, or by peeling graphite physically and chemically. However, graphene made via chemical vapor deposition is mainly used for large-surface transparent electrodes. Meanwhile, graphene made by chemical and physical peeling carries uneven size defects.
The research team explained that their graphene quantum dots exhibited a very stable single-phase reaction when they mixed amine and acetic acid with an aqueous solution of glucose. Then, they synthesized single-crystalline graphene quantum dots from the self-assembly of the reaction intermediate. In the course of fabrication, the team developed a new separation method at a low-temperature precipitation, which led to successfully creating a homogeneous nucleation of graphene quantum dots via a single-phase reaction.
Professor Park and his colleagues have developed solution phase synthesis technology that allows for the creation of the desired crystal size for single nanocrystals down to 100 nano meters. It is reportedly the first synthesis of the homogeneous nucleation of graphene through a single-phase reaction.
Professor Park said, "This solution method will significantly contribute to the grafting of graphene in various fields. The application of this new graphene will expand the scope of its applications such as for flexible displays and varistors.”
This research was a joint project with a team from Korea University under Professor Sang Hyuk Im from the Department of Chemical and Biological Engineering, and was supported by the National Research Foundation of Korea, the Nano-Material Technology Development Program from the Electronics and Telecommunications Research Institute (ETRI), KAIST EEWS, and the BK21+ project from the Korean government.
2019.08.02 View 32141 -
'Flying Drones for Rescue'
(Video Credit: ⓒNASA JPL)
< Team USRG and Professor Shim (second from the right) >
Having recently won the AI R&D Grand Challenge Competition in Korea, Team USRG (Unmanned System Research Group) led by Professor Hyunchul Shim from the School of Electrical Engineering is all geared up to take on their next challenges: the ‘Defense Advanced Research Projects Agency Subterranean Challenge (DARPA SubT Challenge)’ and ‘Lockheed Martin’s AlphaPilot Challenge’ next month.
Team USRG won the obstacle course race in the ‘2019 AI R&D Grand Challenge Competition’ on July 12. They managed to successfully dominate the challenging category of ‘control intelligence.’ Having to complete the obstacle course race solely using AI systems without any connection to the internet made it difficult for most of the eight participating teams to pass the third section of the race, and only Team USRG passed the long pipeline course during their attempt in the main event. They also demonstrated, after the main event, that their drone can navigate all of the checkpoints including landing on the “H” mark using deep learning.
Their drone flew through polls and pipes, and escaped from windows and mazes against strong winds, amid cheers and groans from the crowd gathered at the Korea Exhibition Center (KINTEX) in Goyang, Korea. The team was awarded three million KRW in prize money, and received a research grant worth six hundred million KRW from the Ministry of Science and ICT (MSIT).
“Being ranked first in the race for which we were never given a chance for a test flight means a lot to our team. Considering that we had no information on the exact size of the course in advance, this is a startling result,” said Professor Shim. “We will carry out further research with this funding, and compete once again with the improved AI and drone technology in the 2020 competition,” he added.
The AI R&D Grand Challenge Competition, which was first started in 2017, has been designed to promote AI research and development and expand its application to addressing high-risk technical challenges with significant socio-economic impact.
This year’s competition presented participants with a task where they had to develop AI software technology for drones to navigate themselves autonomously during complex disaster relief operations such as aid delivery.
Each team participated in one of the four tracks of the competition, and their drones were evaluated based on the criteria for each track. The divisions were broken up into intelligent context-awareness, intelligent character recognition, auditory intelligence, and control intelligence.
Team USRG’s technological prowess has been already well acclaimed among international peer groups. Teamed up with NASA JPL, Caltech, and MIT, they will compete in the subterranean mission during the ‘DARPA SubT Challenge’.
Team CoSTAR, as its name stands for, is working together to build ‘Collaborative SubTerranean Autonomous Resilient Robots.’ Professor Shim emphasized the role KAIST plays in Team CoSTAR as a leader in drone technology.
“I think when our drone technology will be added to our peers’ AI and robotics, Team CoSTAR will bring out unsurpassable synergy in completing the subterrestrial and planetary applications. I would like to follow the footprint of Hubo, the winning champion of the 2015 DARPA Robotics Challenge and even extend it to subterranean exploration,” he said.
These next generation autonomous subsurface explorers are now all optimizing the physical AI robot systems developed by Team CoSTAR. They will test their systems in more realistic field environments August 15 through 22 in Pittsburgh, USA. They have already received funding from DARPA for participating.
Team CoSTAR will compete in three consecutive yearly events starting this year, and the last event, planned for 2021, will put the team to the final test with courses that incorporate diverse challenges from all three events. Two million USD will be awarded to the winner after the final event, with additional prizes of up to 200,000 USD for self-funded teams.
Team USRG also ranked third in the recent Hyundai Motor Company’s ‘Autonomous Vehicle Competition’ and another challenge is on the horizon: Lockheed Martin’s ‘AlphaPilot Challenge’. In this event, the teams will be flying their drones through a series of racing gates, trying to beat the best human pilot. The challenge is hosted by Lockheed Martin, the world’s largest military contractor and the maker of the famed F-22 and F-35 stealth fighters, with the goal of stimulating the development of autonomous drones. Team USRG was selected from out of more than 400 teams from around the world and is preparing for a series of races this fall, beginning from the end of August.
Professor Shim said, “It is not easy to perform in a series of competitions in just a few months, but my students are smart, hardworking, and highly motivated. These events indeed demand a lot, but they really challenge the researchers to come up with technologies that work in the real world. This is the way robotics really should be.”
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2019.07.26 View 11356 -
Flexible User Interface Distribution for Ubiquitous Multi-Device Interaction
< Research Group of Professor Insik Shin (center) >
KAIST researchers have developed mobile software platform technology that allows a mobile application (app) to be executed simultaneously and more dynamically on multiple smart devices. Its high flexibility and broad applicability can help accelerate a shift from the current single-device paradigm to a multiple one, which enables users to utilize mobile apps in ways previously unthinkable.
Recent trends in mobile and IoT technologies in this era of 5G high-speed wireless communication have been hallmarked by the emergence of new display hardware and smart devices such as dual screens, foldable screens, smart watches, smart TVs, and smart cars. However, the current mobile app ecosystem is still confined to the conventional single-device paradigm in which users can employ only one screen on one device at a time. Due to this limitation, the real potential of multi-device environments has not been fully explored.
A KAIST research team led by Professor Insik Shin from the School of Computing, in collaboration with Professor Steve Ko’s group from the State University of New York at Buffalo, has developed mobile software platform technology named FLUID that can flexibly distribute the user interfaces (UIs) of an app to a number of other devices in real time without needing any modifications. The proposed technology provides single-device virtualization, and ensures that the interactions between the distributed UI elements across multiple devices remain intact.
This flexible multimodal interaction can be realized in diverse ubiquitous user experiences (UX), such as using live video steaming and chatting apps including YouTube, LiveMe, and AfreecaTV. FLUID can ensure that the video is not obscured by the chat window by distributing and displaying them separately on different devices respectively, which lets users enjoy the chat function while watching the video at the same time.
In addition, the UI for the destination input on a navigation app can be migrated into the passenger’s device with the help of FLUID, so that the destination can be easily and safely entered by the passenger while the driver is at the wheel.
FLUID can also support 5G multi-view apps – the latest service that allows sports or games to be viewed from various angles on a single device. With FLUID, the user can watch the event simultaneously from different viewpoints on multiple devices without switching between viewpoints on a single screen.
PhD candidate Sangeun Oh, who is the first author, and his team implemented the prototype of FLUID on the leading open-source mobile operating system, Android, and confirmed that it can successfully deliver the new UX to 20 existing legacy apps.
“This new technology can be applied to next-generation products from South Korean companies such as LG’s dual screen phone and Samsung’s foldable phone and is expected to embolden their competitiveness by giving them a head-start in the global market.” said Professor Shin.
This study will be presented at the 25th Annual International Conference on Mobile Computing and Networking (ACM MobiCom 2019) October 21 through 25 in Los Cabos, Mexico. The research was supported by the National Science Foundation (NSF) (CNS-1350883 (CAREER) and CNS-1618531).
Figure 1. Live video streaming and chatting app scenario
Figure 2. Navigation app scenario
Figure 3. 5G multi-view app scenario
Publication: Sangeun Oh, Ahyeon Kim, Sunjae Lee, Kilho Lee, Dae R. Jeong, Steven Y. Ko, and Insik Shin. 2019. FLUID: Flexible User Interface Distribution for Ubiquitous Multi-device Interaction. To be published in Proceedings of the 25th Annual International Conference on Mobile Computing and Networking (ACM MobiCom 2019). ACM, New York, NY, USA. Article Number and DOI Name TBD.
Video Material:
https://youtu.be/lGO4GwH4enA
Profile: Prof. Insik Shin, MS, PhD
ishin@kaist.ac.kr
https://cps.kaist.ac.kr/~ishin
Professor
Cyber-Physical Systems (CPS) Lab
School of Computing
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
Profile: Sangeun Oh, PhD Candidate
ohsang1213@kaist.ac.kr
https://cps.kaist.ac.kr/
PhD Candidate
Cyber-Physical Systems (CPS) Lab
School of Computing
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
Profile: Prof. Steve Ko, PhD
stevko@buffalo.edu
https://nsr.cse.buffalo.edu/?page_id=272
Associate Professor
Networked Systems Research Group
Department of Computer Science and Engineering
State University of New York at Buffalo
http://www.buffalo.edu/ Buffalo 14260, USA
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2019.07.20 View 38640 -
Deciphering Brain Somatic Mutations Associated with Alzheimer's Disease
Researchers have found a potential link between non-inherited somatic mutations in the brain and the progression of Alzheimer’s disease
Researchers have identified somatic mutations in the brain that could contribute to the development of Alzheimer’s disease (AD). Their findings were published in the journal Nature Communications last week.
Decades worth of research has identified inherited mutations that lead to early-onset familial AD. Inherited mutations, however, are behind at most half the cases of late onset sporadic AD, in which there is no family history of the disease. But the genetic factors causing the other half of these sporadic cases have been unclear.
Professor Jeong Ho Lee at the Graduate School of Medical Science and Engineering and colleagues analysed the DNA present in post-mortem hippocampal formations and in blood samples from people aged 70 to 96 with AD and age-matched controls. They specifically looked for non-inherited somatic mutations in their brains using high-depth whole exome sequencing.
The team developed a bioinformatics pipeline that enabled them to detect low-level brain somatic single nucleotide variations (SNVs) – mutations that involve the substitution of a single nucleotide with another nucleotide. Brain somatic SNVs have been reported on and accumulate throughout our lives and can sometimes be associated with a range of neurological diseases.
The number of somatic SNVs did not differ between individuals with AD and non-demented controls. Interestingly, somatic SNVs in AD brains arise about 4.8 times more slowly than in blood. When the team performed gene-set enrichment tests, 26.9 percent of the AD brain samples had pathogenic brain somatic SNVs known to be linked to hyperphosphorylation of tau proteins, which is one of major hallmarks of AD.
Then, they pinpointed a pathogenic SNV in the PIN1 gene, a cis/trans isomerase that balances phosphorylation in tau proteins, found in one AD patient’s brain. They found the mutation was 4.9 time more abundant in AT8-positive – a marker for hyper-phosphorylated tau proteins– neurons in the entorhinal cortex than the bulk hippocampal tissue. Furthermore, in a series of functional assays, they observed the mutation causing a loss of function in PIN1 and such haploinsufficiency increased the phosphorylation and aggregation of tau proteins.
“Our study provides new insights into the molecular genetic factors behind Alzheimer’s disease and other neurodegenerative diseases potentially linked to somatic mutations in the brain,” said Professor Lee.
The team is planning to expand their study to a larger cohort in order to establish stronger links between these brain somatic mutations and the pathogenesis of Alzheimer’s disease.
(Figure 1. Bioinformatic pipeline for detecting low-level brain somatic mutations in AD and non-AD.)
(Figure 2. Pathogenic brain somatic mutations associated with tau phosphorylation are significantly enriched in AD brains.)
(Figure 3. A pathogenic brain somatic mutation in PIN1 (c. 477 C>T) is a loss-of-function and related functional assays show its haploinsufficiency increases phosphorylation and aggregation of tau.)
2019.07.19 View 35050 -
President Shin Shares Innovation Strategy at Moscow
President Sung-Chul Shin shared the recipe for success for rapid national development through university education during the Island 10-22 Conference held at the Skolov Institute of Science and Technology in Moscow on July 16.
President Shin stressed how urgent it is for higher education to rapidly embrace the new global economic environment brought about by the Fourth Industrial Revolution in his keynote address entitled ‘Roles and Responsibilities of Universities for Rapid National Development’.
The Island 10-22 Conference is a summit co-organized by the National University of Science and Technology MISIS and University of the National Technological Initiative 2035 and supported by the Ministry of Science and Higher Education of the Russian Federation. More than 30 world-renowned experts, presidents of leading technological universities including President Peretz Lavie from the Israel Institute of Technology Technion, President Scott Pulsipher from Western Governors University and specialists in big data participated in the conference as speakers and discussed a diverse spectrum of ideas for making innovations and digital transformations in universities. More than 1,600 participants joined the conference.
During his keynote speech, President Shin explained how Korea has achieved such rapid economic growth over the past half century. He cited the Korean government’s vision and innovation policies as factors leading to Korea’s phenomenal success. KAIST, one of the results of the Korean government’s innovation policy, led the nation to advanced technological breakthroughs in industries such as semiconductors. Such visionary policies and investments in science, technology, and education eventually made the Korea of today possible.
President Shin said that KAIST distinguished itself through its new vision of C3 that fosters intellectual creativity, caring for others, and a challenging mind . Under Vision 2031, a blueprint for becoming a leading global university, President Shin said the KAIST continues to strive for innovations in convergent education,research and entreprenurship.
2019.07.18 View 6038 -
High-Performance Sodium Ion Batteries Using Copper Sulfide
(Prof.Yuk and his two PhD candidates Parks)
Researchers presented a new strategy for extending sodium ion batteries’ cyclability using copper sulfide as the electrode material. This strategy has led to high-performance conversion reactions and is expected to advance the commercialization of sodium ion batteries as they emerge as an alternative to lithium ion batteries.
Professor Jong Min Yuk’s team confirmed the stable sodium storage mechanism using copper sulfide, a superior electrode material that is pulverization-tolerant and induces capacity recovery. Their findings suggest that when employing copper sulfide, sodium ion batteries will have a lifetime of more than five years with one charge per a day. Even better, copper sulfide, composed of abundant natural materials such as copper and sulfur, has better cost competitiveness than lithium ion batteries, which use lithium and cobalt.
Intercalation-type materials such as graphite, which serve as commercialized anode materials in lithium ion batteries, have not been viable for high-capacity sodium storage due to their insufficient interlayer spacing. Thus, conversion and alloying reactions type materials have been explored to meet higher capacity in the anode part. However, those materials generally bring up large volume expansions and abrupt crystallographic changes, which lead to severe capacity degradation.
The team confirmed that semi-coherent phase interfaces and grain boundaries in conversion reactions played key roles in enabling pulverization-tolerant conversion reactions and capacity recovery, respectively.
Most of conversion and alloying reactions type battery materials usually experience severe capacity degradations due to having completely different crystal structures and large volume expansion before and after the reactions. However, copper sulfides underwent a gradual crystallographic change to make the semi-coherent interfaces, which eventually prevented the pulverization of particles. Based on this unique mechanism, the team confirmed that copper sulfide exhibits a high capacity and high cycling stability regardless of its size and morphology.
Professor Yuk said, “Sodium ion batteries employing copper sulfide can advance sodium ion batteries, which could contribute to the development of low-cost energy storage systems and address the micro-dust issue”
This study was posted in Advanced Science on April 26 online and selected as the inside back cover for June issue.
(Figure: Schematic model demonstrating grain boundaries and phase interfaces formations.)
2019.07.15 View 27505 -
Mathematical Modeling Makes a Breakthrough for a New CRSD Medication
PhD Candidate Dae Wook Kim (Left) and Professor Jae Kyoung Kim (Right)
- Systems approach reveals photosensitivity and PER2 level as determinants of clock-modulator efficacy -
Mathematicians’ new modeling has identified major sources of interspecies and inter-individual variations in the clinical efficacy of a clock-modulating drug: photosensitivity and PER2 level. This enabled precision medicine for circadian disruption.
A KAIST mathematics research team led by Professor Jae Kyoung Kim, in collaboration with Pfizer, applied a combination of mathematical modeling and simulation tools for circadian rhythms sleep disorders (CRSDs) to analyze the animal data generated by Pfizer. This study was reported in Molecular Systems Biology as the cover article on July 8.
Pharmaceutical companies have conducted extensive studies on animals to determine the candidacy of this new medication. However, the results of animal testing do not always translate to the same effects in human trials. Furthermore, even between humans, efficacy differs across individuals depending on an individual’s genetic and environmental factors, which require different treatment strategies.
To overcome these obstacles, KAIST mathematicians and their collaborators developed adaptive chronotherapeutics to identify precise dosing regimens that could restore normal circadian phase under different conditions.
A circadian rhythm is a 24-hour cycle in the physiological processes of living creatures, including humans. A biological clock in the hypothalamic suprachiasmatic nucleus in the human brain sets the time for various human behaviors such as sleep.
A disruption of the endogenous timekeeping system caused by changes in one’s life pattern leads to advanced or delayed sleep-wake cycle phase and a desynchronization between sleep-wake rhythms, resulting in CRSDs. To restore the normal timing of sleep, timing of the circadian clock could be adjusted pharmacologically.
Pfizer identified PF-670462, which can adjust the timing of circadian clock by inhibiting the core clock kinase of the circadian clock (CK1d/e). However, the efficacy of PF-670462 significantly differs between nocturnal mice and diurnal monkeys, whose sleeping times are opposite.
The research team discovered the source of such interspecies variations in drug response by performing thousands of virtual experiments using a mathematical model, which describes biochemical interactions among clock molecules and PF-670462. The result suggests that the effect of PF-670462 is reduced by light exposure in diurnal primates more than in nocturnal mice. This indicates that the strong counteracting effect of light must be considered in order to effectively regulate the circadian clock of diurnal humans using PF-670462.
Furthermore, the team also found the source of inter-patients variations in drug efficacy using virtual patients whose circadian clocks were disrupted due to various mutations. The degree of perturbation in the endogenous level of the core clock molecule PER2 affects the efficacy.
This explains why the clinical outcomes of clock-modulating drugs are highly variable and certain subtypes are unresponsive to treatment. Furthermore, this points out the limitations of current treatment strategies tailored to only the patient’s sleep and wake time but not to the molecular cause of sleep disorders.
PhD candidate Dae Wook Kim, who is the first author, said that this motivates the team to develop an adaptive chronotherapy, which identifies a personalized optimal dosing time of day by tracking the sleep-wake up time of patients via a wearable device and allows for a precision medicine approach for CRSDs.
Professor Jae Kyoung Kim said, "As a mathematician, I am excited to help enable the advancement of a new drug candidate, which can improve the lives of so many patients. I hope this result promotes more collaborations in this translational research.”
This research was supported by a Pfizer grant to KAIST (G01160179), the Human Frontiers Science Program Organization (RGY0063/2017), and a National Research Foundation (NRF) of Korea Grant (NRF-2016 RICIB 3008468 and NRF-2017-Fostering Core Leaders of the Future Basic Science Program/ Global Ph.D. Fellowship Program).
Figure 1. Interspecies and Inter-patients Variations in PF-670462 Efficacy
Figure 2. Journal Cover Page
Publication:
Dae Wook Kim, Cheng Chang, Xian Chen, Angela C Doran, Francois Gaudreault, Travis Wager, George J DeMarco, and Jae Kyoung Kim. 2019. Systems approach reveals photosensitivity and PER2 level as determinants of clock-modulator efficacy. Molecular Systems Biology. EMBO Press, Heidelberg, Germany, Vol. 15, Issue No. 7, Article, 16 pages. https://doi.org/10.15252/msb.20198838
Profile: Prof. Jae Kyoung Kim, PhD
jaekkim@kaist.ac.kr
http://mathsci.kaist.ac.kr/~jaekkim
Associate Professor
Department of Mathematical Sciences
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
Profile: Dae Wook Kim, PhD Candidate
0308kdo@kaist.ac.kr
http://mathsci.kaist.ac.kr/~jaekkim
PhD Candidate
Department of Mathematical Sciences
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
Profile: Dr. Cheng Chang, PhD
cheng.chang@pfizer.com
Associate Director of Clinical Pharmacology
Clinical Pharmacology, Global Product Development
Pfizer
https://www.pfizer.com/ Groton 06340, USA
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2019.07.09 View 34485 -
Two Alumni Win the Korea Best Scientist and Technologist Awards
Vice Chairman Ki-Nam Kim (Left) and Distinguished Professor Sukbok Chang (Right)
<ⓒ Photo by MSIT and KOFST>
Distinguished KAIST Professor Sukbok Chang from the Department of Chemistry and Vice Chairman Ki-Nam Kim of Samsung Electronics were selected as the winners of the “2019 Korea Best Scientist and Technologist Awards” by the Ministry of Science and ICT (MSIT) and the Korean Federation of Science and Technology Societies (KOFST). The awards, which were first handed out in 2003, are the highest honor bestowed to the two most outstanding scientists in Korea every year, and this year’s awardees are of greater significance as they are both KAIST alumni.
Professor Chang was recognized for his pioneering achievements and lifetime contributions to the development of carbon-hydrogen activation strategies, especially for carbon-carbon, carbon-nitrogen, and carbon-oxygen formations. His research group has also been actively involved in the development of highly selective catalytic systems allowing the controlled defunctionalization of bio-derived platform substrates under mild conditions, and opening a new avenue for the utilization of biomass-derived platform chemicals. The results of his study have been introduced worldwide through many prestigious journals including Science, Nature Chemistry, and Nature Catalysis, making him one of the world's top 1% researchers by the number of references made to his papers by his peers over four consecutive years from 2015 to 2018.
Vice Chairman Kim, who received his M.E. degree from KAIST’s School of Electrical Engineering in 1983, has been credited with playing a leading role in the development of system semiconductors.
The awards were conferred on July 4 at the opening ceremony of the 2019 Korea Science and Technology Annual Meeting.
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2019.07.09 View 10866