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COVID-19 Update: Precautionary Measures Reschedule Spring Semester to March 16
(Campus-wide preventive measures against the new coronavirus are being enforced.)
In response to the coronavirus outbreak, KAIST has decided to alter the academic calendar, postponing the opening of the spring semester until March 16, two weeks behind the original schedule. This is following the decision of the Deans’ Council to postpone or cancel the major academic ceremonies and events scheduled in February.
According to the decision, the commencement ceremony scheduled on February 21 will be postponed; meanwhile the freshmen orientation and matriculation ceremonies have been cancelled. Additionally, the ceremonies for the KAIST anniversary and faculty retirement ceremony scheduled on February 14 and the faculty workshop on February 27 have been postponed. There have been no confirmed coronavirus cases among the KAIST community as of February 6.
The university is also enhancing campus-wide precautionary safety measures to prevent the spread of the disease. The Facilities Management Office said that they will start disinfecting all dining facilities, cafeterias, libraries, lecture halls, and student halls for two days from Feb. 6. Plastic gloves are provided at cafeteria, which is using buffet spoons and tongs, and cafeteria patrons are being asked to wear the plastic gloves when they place food on their own plate in a preventive measure to avoid possible contact between individuals.
KAIST also launched a 24/7-hour Emergency Response Team and disseminated a response manual to KAIST community members. The Office of Student Life surveyed students, faculty, and staff to report if anyone has traveled to China or been in contact with visitors who made a trip to China within the last two weeks.
The university designated a building in one of the dorm complexes as a quarantine facility and a total of 11 people who visited China have been self-quarantined for two weeks from January 31.
Provost and Executive Vice President Kwang Hyung Lee explained in his letter to KAIST community members on February 4 that the university is exerting all possible measures and efforts against the spreading virus and asked for every member’s cooperation to prevent the further spread of the disease.
“Those who self-quarantined don’t have any symptoms. This is just a precautionary measure. The self-quarantine at our facility is only limited to those who declared that they do not have a legal residence in Korea,” said Provost Lee. The transportation to the facility is specially arranged and meal boxes are delivered to the quarantined room individually. A full-time guard in front of the isolated dorm building will be on duty 24 hours a day.
He explained the university chose the Hwaam Complex as the self-quarantine facility because each building in the complex is set apart from the others and each room has its own bathroom and shower facilities. Provost Lee said that the university will use another dorm complex if any current dorm residents where the quarantine facility has been set up wish to move to other dorm complexes.
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2020.02.06 View 3893 -
Professor Junil Choi Receives Stephen O. Rice Prize
< Professor Junil Choi (second from the left) >
Professor Junil Choi from the School of Electrical Engineering received the Stephen O. Rice Prize at the Global Communications Conference (GLOBECOM) hosted by the Institute of Electrical and Electronics Engineers (IEEE) in Hawaii on December 10, 2019.
The Stephen O. Rice Prize is awarded to only one paper of exceptional merit every year. The IEEE Communications Society evaluates all papers published in the IEEE Transactions on Communications journal within the last three years, and marks each paper by aggregating its scores on originality, the number of citations, impact, and peer evaluation.
Professor Choi won the prize for his research on one-bit analog-to-digital converters (ADCs) for multiuser massive multiple-input and multiple-output (MIMO) antenna systems published in 2016. In his paper, Professor Choi proposed a technology that can drastically reduce the power consumption of the multiuser massive MIMO antenna systems, which are the core technology for 5G and future wireless communication. Professor Choi’s paper has been cited more than 230 times in various academic journals and conference papers since its publication, and multiple follow-up studies are actively ongoing.
In 2015, Professor Choi received the IEEE Signal Processing Society Best Paper Award, an award equals to the Stephen O. Rice Prize. He was also selected as the winner of the 15th Haedong Young Engineering Researcher Award presented by the Korean Institute of Communications and Information Sciences (KICS) on December 6, 2019 for his outstanding academic achievements, including 34 international journal publications and 26 US patent registrations.
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2019.12.23 View 9038 -
Professor Sung Yong Kim Elected as the Chair of PICES MONITOR
< Professor Sung Yong Kim >
Professor Sung Yong Kim from the Department of Mechanical Engineering was elected as the chair of the Technical Committee on Monitoring (MONITOR) of the North Pacific Marine Science Organization (PICES).
PICES is an intergovernmental marine science organization that was established in 1992 through a collaboration between six North Pacific nations including South Korea, Russia, the United States, Japan, China, and Canada to exchange and discuss research on the Pacific waters. Its headquarters is located in Canada and the organization consists of seven affiliated maritime science and marine technology committees.
Professor Kim was elected as the chair of the technical committee that focuses on monitoring and will be part of the Science Board as an ex-officio member. His term will last three years from November 2019.
Professor Kim was recognized for his academic excellence, expertise, and leadership among oceanographers both domestically and internationally.
Professor Kim will also participate as an academia civilian committee member of the Maritime and Fisheries Science and Technology Committee under the Korean Ministry of Oceans and Fisheries for two years from December 18, 2019.
He stated, “I will give my full efforts to broaden Korean oceanography research by participating in maritime leadership positions at home and abroad, and help South Korea become a maritime powerhouse.”
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2019.12.22 View 7617 -
New Liquid Metal Wearable Pressure Sensor Created for Health Monitoring Applications
Soft pressure sensors have received significant research attention in a variety of fields, including soft robotics, electronic skin, and wearable electronics. Wearable soft pressure sensors have great potential for the real-time health monitoring and for the early diagnosis of diseases.
A KAIST research team led by Professor Inkyu Park from the Department of Mechanical Engineering developed a highly sensitive wearable pressure sensor for health monitoring applications. This work was reported in Advanced Healthcare Materials on November 21 as a front cover article.
This technology is capable of sensitive, precise, and continuous measurement of physiological and physical signals and shows great potential for health monitoring applications and the early diagnosis of diseases.
A soft pressure sensor is required to have high compliance, high sensitivity, low cost, long-term performance stability, and environmental stability in order to be employed for continuous health monitoring. Conventional solid-state soft pressure sensors using functional materials including carbon nanotubes and graphene have showed great sensing performance. However, these sensors suffer from limited stretchability, signal drifting, and long-term instability due to the distance between the stretchable substrate and the functional materials.
To overcome these issues, liquid-state electronics using liquid metal have been introduced for various wearable applications. Of these materials, Galinstan, a eutectic metal alloy of gallium, indium, and tin, has great mechanical and electrical properties that can be employed in wearable applications. But today’s liquid metal-based pressure sensors have low-pressure sensitivity, limiting their applicability for health monitoring devices.
The research team developed a 3D-printed rigid microbump array-integrated, liquid metal-based soft pressure sensor. With the help of 3D printing, the integration of a rigid microbump array and the master mold for a liquid metal microchannel could be achieved simultaneously, reducing the complexity of the manufacturing process. Through the integration of the rigid microbump and the microchannel, the new pressure sensor has an extremely low detection limit and enhanced pressure sensitivity compared to previously reported liquid metal-based pressure sensors. The proposed sensor also has a negligible signal drift over 10,000 cycles of pressure, bending, and stretching and exhibited excellent stability when subjected to various environmental conditions.
These performance outcomes make it an excellent sensor for various health monitoring devices. First, the research team demonstrated a wearable wristband device that can continuously monitor one’s pulse during exercise and be employed in a noninvasive cuffless BP monitoring system based on PTT calculations. Then, they introduced a wireless wearable heel pressure monitoring system that integrates three 3D-BLiPS with a wireless communication module.
Professor Park said, “It was possible to measure health indicators including pulse and blood pressure continuously as well as pressure of body parts using our proposed soft pressure sensor. We expect it to be used in health care applications, such as the prevention and the monitoring of the pressure-driven diseases such as pressure ulcers in the near future. There will be more opportunities for future research including a whole-body pressure monitoring system related to other physical parameters.”
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT.
< Figure 1. The front cover image of Advanced Healthcare Materials, Volume 8, Issue 22. >
< Figure 2. Highly sensitive liquid metal-based soft pressure sensor integrated with 3D-printed microbump array. >
< Figure 3. High pressure sensitivity and reliable sensing performances of the proposed sensor and wireless heel pressure monitoring application. >
-ProfileProfessor Inkyu ParkMicro/Nano Transducers Laboratoryhttp://mintlab1.kaist.ac.kr/
Department of Mechanical EngineeringKAIST
2019.12.20 View 11941 -
Two Professors Receive Awards from the Korea Robotics Society
< Professor Jee-Hwan Ryu and Professor Ayoung Kim >
The Korea Robotics Society (KROS) conferred awards onto two KAIST professors from the Department of Civil and Environmental Engineering in recognition of their achievements and contributions to the development of the robotics industry in 2019. Professor Jee-Hwan Ryu has been actively engaged in researching the field of teleoperation, and this led him to win the KROS Robotics Innovation (KRI) Award. The KRI Award was newly established in 2019 by the KROS, in order to encourage researchers who have made innovative achievements in robotics. Professor Ryu shared the honor of being the first winner of this award with Professor Jaeheung Park of Seoul National University. Professor Ayoung Kim, from the same department, received the Young Investigator Award presented to emerging robitics researchers under 40 years of age. (END)
2019.12.19 View 7820 -
Korea Policy Center for the Fourth Industrial Revolution Opens
The World Economic Forum’s Center for the Fourth Industrial Revolution opened its Korean affiliate center at KAIST on December 10. The Korea Policy Center for the 4th Industrial Revolution (KPC4IR) will develop policy norms and frameworks for accelerating the benefits of emerging technologies.
Many dignitaries including KAIST President Sung-Chul Shin, National Assemblyman Sang-Min Lee, Daejeon City Mayor Her Tae-Jeong, and Managing Director of the WEF Center for the Fourth Industrial Revolution Murat Sonmez attended the opening ceremony.
The center will play a vital role in helping to shape the development of national Fourth Industrial Revolution strategies and public-private initiatives. The Center will actively engage with the government on policy design and piloting activities.
The Center is the result of KAIST’s close partnership with the WEF and its Center for the Fourth Industrial Revolution in San Francisco. KAIST signed an MOU with the WEF in 2017 for this collaboration. Dr. Klaus Schwab expressed his high hopes many times regarding Korea’s potential in responding to the Fourth Industrial Revolution. In addition, he said that KAIST and the City of Daejeon would play a significant role in helping the Fourth Industrial Revolution move forward.
During a meeting with President Moon Jae-In last June, Dr. Schwab expressed his strong desire to collaborate with Korea, and the Korean government designated KAIST as an affiliate center of the WEF.
The KPC4IR had already begun conducting policy research in the areas of block chain and precision medicine even before making a partnership with the WEF. The director of the Center, Distinguished Professor Sang Yup Lee, said, “We have focused on the development of technology but rarely talk about governance. Technology should come with policy. We will conduct policy development on how to ensure inclusive growth capitalizing on emerging technologies. We will also make policy guidelines for technological applications after considering all the ethical perspectives.
President Shin also said in his opening remarks, “Korea has been a fast follower over the past decades in making economic development and innovations. I believe that the Fourth Industrial Revolution gives us the best opportunity to play the role of ‘first mover.’ I look forward to the KPC4IR serving as a ‘Think and Do’ tank, not limiting itself to the role of ‘think tank.’ We will continue to work closely with the WEF in the fields of AI, blockchain, and precision medicine.
2019.12.10 View 7305 -
Gallium-Based Solvating Agent Efficiently Analyzes Optically Active Alcohols
A KAIST research team has developed a gallium-based metal complex enabling the rapid chiral analysis of alcohols. A team working under Professor Hyunwoo Kim reported the efficient new alcohol analysis method using nuclear magnetic resonance (NMR) spectroscopy in iScience.
Enantiopure chiral alcohols are ubiquitous in nature and widely utilized as pharmaceuticals. This importance of chirality in synthetic and medicinal chemistry has advanced the search for rapid and facile methods to determine the enantiomeric purities of compounds. To date, chiral analysis has been performed using high-performance liquid chromatography (HPLC) with chiral columns.
Along with the HPLC technique, chiral analysis using NMR spectroscopy has gained tremendous attention as an alternative to traditionally employed chromatographic methods due to its simplicity and rapid detection for real-time measurement. However, this method carries drawbacks such as line-broadening, narrow substrate scope, and poor resolution. Thus, compared with popular methods of chromatographic analysis, NMR spectroscopy is infrequently used for chiral analysis.
In principle, a chiral solvating agent is additionally required for the NMR measurement of chiral alcohols to obtain two distinct signals. However, NMR analysis of chiral alcohols has been challenging due to weak binding interactions with chiral solvating agents. To overcome the intrinsic difficulty of relatively weak molecular interactions that are common for alcohols, many researchers have used multifunctional alcohols to enhance interactions with solvating agents.
Instead, the KAIST team successfully varied the physical properties of metal complexes to induce stronger interactions with alcohols rather than the strategy of using multifunctional analytes, in the hopes of developing a universal chiral solvating agent for alcohols. Compared to the current method of chiral analysis used in the pharmaceutical industry, alcohols that do not possess chromophores can also be directly analyzed with the gallium complexes.
Professor Kim said that this method could be a complementary chiral analysis technique at the industry level in the near future. He added that since the developed gallium complex can determine enantiomeric excess within minutes, it can be further utilized to monitor asymmetric synthesis. This feature will benefit a large number of researchers in the organic chemistry community, as well as the pharmaceutical industry.
(Figure: Schematic view of the in-situ direct 1H NMR chiral analysis.)
-Profile:
Professor Hyunwoo Kim
Department of Chemistry
KAIST
http://mdos.kaist.ac.kr
hwk34@kaist.ac.kr
For more on this article,
please go to https://doi.org/10.1016/j.isci2019.07051
2019.11.14 View 10082 -
A Mathematical Model Reveals Long-Distance Cell Communication Mechanism
How can tens of thousands of people in a large football stadium all clap together with the same beat even though they can only hear the people near them clapping?
A combination of a partial differential equation and a synthetic circuit in microbes answers this question. An interdisciplinary collaborative team of Professor Jae Kyoung Kim at KAIST, Professor Krešimir Josić at the University of Houston, and Professor Matt Bennett at Rice University has identified how a large community can communicate with each other almost simultaneously even with very short distance signaling. The research was reported at Nature Chemical Biology.
Cells often communicate using signaling molecules, which can travel only a short distance. Nevertheless, the cells can also communicate over large distances to spur collective action. The team revealed a cell communication mechanism that quickly forms a network of local interactions to spur collective action, even in large communities.
The research team used an engineered transcriptional circuit of combined positive and negative feedback loops in E. coli, which can periodically release two types of signaling molecules: activator and repressor. As the signaling molecules travel over a short distance, cells can only talk to their nearest neighbors. However, cell communities synchronize oscillatory gene expression in spatially extended systems as long as the transcriptional circuit contains a positive feedback loop for the activator.
Professor Kim said that analyzing and understanding such high-dimensional dynamics was extremely difficult. He explained, “That’s why we used high-dimensional partial differential equation to describe the system based on the interactions among various types of molecules.” Surprisingly, the mathematical model accurately simulates the synthesis of the signaling molecules in the cell and their spatial diffusion throughout the chamber and their effect on neighboring cells.
The team simplified the high-dimensional system into a one-dimensional orbit, noting that the system repeats periodically. This allowed them to discover that cells can make one voice when they lowered their own voice and listened to the others. “It turns out the positive feedback loop reduces the distance between moving points and finally makes them move all together. That’s why you clap louder when you hear applause from nearby neighbors and everyone eventually claps together at almost the same time,” said Professor Kim.
Professor Kim added, “Math is a powerful as it simplifies complex thing so that we can find an essential underlying property. This finding would not have been possible without the simplification of complex systems using mathematics."
The National Institutes of Health, the National Science Foundation, the Robert A. Welch Foundation, the Hamill Foundation, the National Research Foundation of Korea, and the T.J. Park Science Fellowship of POSCO supported the research.
(Figure: Complex molecular interactions among microbial consortia is simplified as interactions among points on a limit cycle (right).)
2019.10.15 View 24110 -
School of Transdisciplinary Studies Aims to Attract New Talents
KAIST opened the School of Transdisciplinary Studies to foster ‘convergent talents’ who can create new knowledge through a transdisciplinary approach. The new department will officially start classes in the spring semester of 2020 while recruiting its first cohorts during the fall semester among current freshmen.
President Sung-Chul Shin, the Head of the School of Transdisciplinary Studies Jong Duk Kim, and other prominent members of KAIST’s administration celebrated the opening of the new department during a ceremony on September 18. Students who will declare their major this semester and many parents showed strong interests in this new department while attending the ceremony. They all toured the new facilities together and attended the special lecture sessions.
The School of Transdisciplinary Studies is designed to empower students to create new solutions to emerging complex technologies and rapidly evolving global issues. This is one of the education innovation initiatives under Vision 2031, the plan President Sung-Chul Shin has launched to nurture creative young convergent leaders, and the first single transdisciplinary department that will be introduced in a Korean university.
The new faculty aims to educate students who will have a deeper understanding of the humanities, scientific creativity, the ability to conceive new ideas, complex problem-solving skills, and global leadership. The curriculum boasts a strong foundation of basic science and humanities over six required courses in physics, chemistry, molecular biology, applied mathematics modeling, data structure, and economics. Then, students will explore their academic depth by choosing one of eight emerging fields. The eight concentration majors encompass data and AI, smart cities and media, healthcare, culture and media, management and startups, materials and matter, energy and environment, and machinery and precision. In their third and fourth years, students can customize their study course based on their career path and academic interest after consultation with a faculty mentor and an internship. Upon graduation, they will earn a bachelor’s degree in convergent science or a bachelor of convergent engineering degree. They may also elect to receive a bachelor’s degree in science or engineering.
“This faculty offers deep knowledge in basic science and humanities to help students explore their specialties more creatively. Specialties built upon strong theory and creative applicability will be the key to solving the global challenges in an era of volatility, uncertainty, complexity, and ambiguity,” said Professor Kim, the head of the school, at the ceremony.
President Shin also stressed the importance of convergence education during his special lecture, saying, “We will continue to strive to foster new talents who will create new convergent knowledge in emerging technologies such as IoT, big data, 5G, and AI. By fostering such young convergent talents, we will take the lead in national development and work for the prosperity of humanity.”
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2019.09.19 View 4992 -
Artificial Muscles Bloom, Dance, and Wave
Wearing a flower brooch that blooms before your eyes sounds like magic. KAIST researchers have made it real with robotic muscles.
Researchers have developed an ultrathin, artificial muscle for soft robotics. The advancement, recently reported in the journal Science Robotics, was demonstrated with a robotic blooming flower brooch, dancing robotic butterflies and fluttering tree leaves on a kinetic art piece.
The robotic equivalent of a muscle that can move is called an actuator. The actuator expands, contracts or rotates like muscle fibers using a stimulus such as electricity. Engineers around the world are striving to develop more dynamic actuators that respond quickly, can bend without breaking, and are very durable. Soft, robotic muscles could have a wide variety of applications, from wearable electronics to advanced prosthetics.
The team from KAIST’s Creative Research Initiative Center for Functionally Antagonistic Nano-Engineering developed a very thin, responsive, flexible and durable artificial muscle. The actuator looks like a skinny strip of paper about an inch long. They used a particular type of material called MXene, which is class of compounds that have layers only a few atoms thick.
Their chosen MXene material (T3C2Tx) is made of thin layers of titanium and carbon compounds. It was not flexible by itself; sheets of material would flake off the actuator when bent in a loop. That changed when the MXene was “ionically cross-linked” — connected through an ionic bond — to a synthetic polymer. The combination of materials made the actuator flexible, while still maintaining strength and conductivity, which is critical for movements driven by electricity.
Their particular combination performed better than others reported. Their actuator responded very quickly to low voltage, and lasted for more than five hours moving continuously.
To prove the tiny robotic muscle works, the team incorporated the actuator into wearable art: an origami-inspired brooch mimics how a narcissus flower unfolds its petals when a small amount of electricity is applied. They also designed robotic butterflies that move their wings up and down, and made the leaves of a tree sculpture flutter.
“Wearable robotics and kinetic art demonstrate how robotic muscles can have fun and beautiful applications,” said Il-Kwon Oh, lead paper author and professor of mechanical engineering. “It also shows the enormous potential for small, artificial muscles for a variety of uses, such as haptic feedback systems and active biomedical devices.”
The team next plans to investigate more practical applications of MXene-based soft actuators and other engineering applications of MXene 2D nanomaterials.
2019.08.22 View 23737 -
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 37636 -
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 33570