Engineering
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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 View 9478 -
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 View 9004 -
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 View 9588 -
KAIST Team Wins International Hacking Competition, "SECCON CTF 2014"
KAIST’s white hacker team, “TOFEL Beginner,” secured the first place in an international hacking competition, SECCON CTF 2014. SECCON is an international hacking competition which has operated for more than 20 years. It uses the Capture the Flag (CTF) method. Last year’s competition was held in Tokyo on December 7, 2014.
The TOFEL Beginner team consisted of two KAIST graduate students and two researchers from a private security company based in Korea: In-Soo Yoon of Computer Science, Eun-Soo Kim of the Graduate School of Information Security (GSIS), and Jong-Ho Lee and Jung-Hoon Lee of Raon Secure.
Of 4,186 competitors, 24 teams made it to the finals. The TOFEL Beginner took the lead with 4,506 points compared with HITCON (3,112 points) of Taiwan and PPP (2,858 points) of the USA.
With this victory, the KAIST team qualified to participate in the most renowned international hacking competition, the DEF CON Hacking Conference in 2015.
Professor Yongdae Kim of the Electrical Engineering Department at KAIST, who advised the TOEFL Beginner team, said, “Our members have achieved an outstanding result. By taking advantage of this opportunity, KAIST will continue to offer the best programs in information security in Korea and hopefully beyond.”
2015.02.24 View 9222 -
Professor Sang Yup Lee Appointed Founding Board Member of Cell Systems
Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST has been appointed a member of the founding editorial board of the newly established journal Cell Systems.
Cell Systems will be a sister journal of Cell, one of the three most prestigious scientific journals along with Nature and Science, that publishes a wide range of papers on biological engineering. The first issue of Cell Systems will be published this July.
Cell Systems plans to publish innovative discoveries, reviews of various research instruments, and research findings on integrated and quantified systems in the field of biology.
Professor Lee is a pioneer in metabolic engineering of microorganism with a focus on biopolymers and metabolites production. He is the editor-in-chief of Biotechnology Journal and serves on the editorial board of numerous international journals. He is also a member of the Global Agenda Council of the World Economic Forum and the Presidential Advisory Committee on Science and Technology in Korea.
Professor Lee said, “Cell Systems will present research findings that discuss whole biological systems methodically.” He continued, “I hope many research findings of Korean scholars will be published in Cell Systems, which will become a representative journal of systems biology and systems biological engineering.”
2015.02.13 View 8581 -
Professor Kwang-Hyun Cho Recognzied by "Scientist of the Month" Award
Professor Kwang-Hyun Cho of KAIST’s Department of Bio and Brain Engineering received the “Scientist of the Month” award in February 2015 from the Ministry of Science, ICT, and Future Planning of the Republic of Korea and the National Research Foundation of Korea. The award was in recognition of Professor Cho’s contribution to the advanced technique of controlling the death of cancer cells based on systems biology, a convergence research in information technology (IT) and biotechnology.
Professor Cho has published around 140 articles in international journals, including 34 papers in renowned science journals such as Nature, Science, and Cell in the past three years. His work also includes systems biology textbooks and many entries in international academic encyclopaedia.
His field, systems biology, is a new biological research paradigm that identifies and controls the fundamental principles of organisms on a systems level.
A well-known tumour suppressor protein, p53, is known to suppress abnormal cell growth and promote apoptosis of can cells, and thus was a focus of research by many scientists, but its effect has been insignificant and brought many side effects. This was due to the complex function of p53 that controls various positive and negative feedbacks. Therefore, there was a limit to understanding the protein with the existing biological approach.
However, Professor Cho found the kinetic change and function of p53 via a systems biology approach. By applying IT technology to complex biological networks, he also identified the response to stress and the survival and death signal transduction pathways of cardiomyocytes and developed new control methods for cancer cells.
Professor Cho said, “This award served as a momentum to turn over a new leaf.” He added, “I hope convergence research such as my field will bring more innovative ideas on the boundaries of academia.”
2015.02.09 View 11476 -
KAIST's Thermoelectric Generator on Glass Fabric Receives the Grand Prize at the Netexplo Forum 2015
The forum announced top ten IT innovations expected to change the world and selected the grand prize on February 4, 2014.
Established in 2007 by Martine Bidegain and Thierry Happe in partnership with the French Senate and the French Ministry for the Digital Economy, the Netexplo Observatory is an independent global organization that studies the impact of digital technology and innovation on society and business.
Every year, the Netexplo Observatory hosts an international conference, the Netexplo Forum, in Paris, France, which surveys digital innovation worldwide. The 8th forum was held in partnership with the United Nations Educational, Scientific and Cultural Organization (UNESCO) on February 4-5, 2015, at the UNESCO House in Paris.
Prior to the conference, the Netexplo Forum 2015 named the top ten most promising digital technologies that will greatly impact the world.
Among them was Professor Byung Jin Cho’s research on a wearable thermoelectric generator (http://www.eurekalert.org/pub_releases/2014-04/tkai-tgo041014.php). The generator was selected as the most innovative technology this year.
Professor Cho of KAIST’s Electrical Engineering Department developed a glass fabric-based thermoelectric generator that is extremely light and flexible and that produces electricity from the heat of the human body. This technology can be applied widely to wearable computers and mobile devices.
The full list of innovations follows below:
Wearable Thermo-Element, South Korea: The human body becomes a source of energy for mobile devices.
W.Afate 3D-printer, Togo: An environmentally friendly fablab that makes a low-cost 3D-printer from recycling electronic components.
Slack, USA: By combining email, Skype, and file-sharing and social networks, internal communication becomes much easier and simpler.
PhotoMath, Croatia: A free app that enables smartphone users to solve mathematical problems simply by scanning the mathematical texts.
Kappo, Chile: Connected cyclists produce and transmit useful data for urban planning to make the city more bike-friendly.
Branching Minds, USA: An improved learning process for students in difficulty through a personalized approach.
Baidu Kuai Sou, China: Smart chopsticks that can check food hazards.
SCio, Israel: A pocket molecular sensor with various applications and data
Rainforest Connection, USA: Fighting deforestation with recycled smartphones
Sense Ebola Followup, Nigeria: A mobile tool to help contain Ebola
For more details on the wearable thermos-element which received the 2015 Netexplo Award, please go to https://www.netexplo.org/en/intelligence/innovation/wearable-thermo-element.
Pictures 1 and 2: A high-performance wearable thermoelectric generator that is extremely flexible and light.
Picture 3: Senator Catherine Morin-Desailly (left) of the French Parliament presents the 2015 Netexplo Award to Professor Byung Jin Cho (right) on February 4, 2015 at the UNESCO House in Paris.
Credit of Loran Dhérines
Picture 4: Professor Byung Jin Cho (left) poses with Dr. Joël de Rosnay (right).
Credit of Loran Dhérines
2015.02.06 View 12870 -
Press Release on Piezoelectric Nanogenerators of ZnO with Aluminium Nitride Stacked Layers by the American Institute of Physics
The
American Institute of Physics (AIP) released a news article entitled “Zinc
Oxide Materials Tapped for Tiny Energy Harvesting Devices” on January 13, 2015.
The
article described the research led by Professor Giwan Yoon of the
Electrical Engineering Department at KAIST. It was published in the January
12, 2015 issue of Applied Physics Letters.
AIP publishes the journal. For the news release, please visit the
link below:
The American
Institute of Physics, January 13, 2015
“Zinc
Oxide Materials Tapped for Tiny Energy Harvesting Devices”
New research helps
pave the way toward highly energy-efficient zinc oxide-based micro energy
harvesting devices with applications in portable communications, healthcare and
environmental monitoring, and more
http://www.aip.org/publishing/journal-highlights/zinc-oxide-materials-tapped-tiny-energy-harvesting-devices
2015.02.04 View 31633 -
News Article: Flexible, High-performance Nonvolatile Memory Developed with SONOS Technology
Professor Yang-Kyu Choi of KAIST’s Department of Electrical Engineering and his team presented a research paper entitled “Flexible High-performance Nonvolatile Memory by Transferring GAA Silicon Nanowire SONOS onto a Plastic Substrate” at the conference of the International Electron Devices Meeting that took place on December 15-17, 2014 in San Francisco.
The Electronic Engineering Journal (http://www.eejournal.com/) recently posted an article on the paper:
Electronic Engineering Journal, February 2, 2015
“A Flat-Earth Memory”
Another Way to Make the Brittle Flexible
http://www.techfocusmedia.net/archives/articles/20150202-flexiblegaa/?printView=true
2015.02.03 View 7110 -
Light Driven Drug-Enzyme Reaction Catalytic Platform Developed
Low Cost Dye Used, Hope for Future Development of High Value Medicinal Products to Treat Cardiovascular Disease and Gastric Ulcers
A KAIST research team from the Departments of Materials Science and Engineering and of Chemical and Biomolecular Engineering, led respectively by Professors Chan Beum Park and Ki Jun Jeong, has developed a new reaction platform to induce drug-enzyme reaction using light.
The research results were published in the journal Angewandte Chemie, International Edition, as the back cover on 12 January 2015.
Applications of this technology may enable production of high value products such as medicine for cardiovascular disease and gastric ulcers, for example Omeprazole, using an inexpensive dye.
Cytochrome P450 is an enzyme involved in oxidative response which has an important role in drug and hormone metabolism in organisms. It is known to be responsible for metabolism of 75% of drugs in humans and is considered a fundamental factor in new drug development.
To activate cytochrome P450, the enzyme must receive an electron by reducing the enzyme. In addition, NADPH (a coenzyme) needs to be present. However, since NADPH is expensive, the use of cytochrome P450 was limited to the laboratory and has not yet been commercialized.
The research team used photosensitizer eosin Y instead of NADPH to develop “Whole Cell Photo-Biocatalysis” in bacteria E. coli. By exposing inexpensive eosin Y to light, cytochrome P450 reaction was catalyzed to produce the expensive metabolic material.
Professor Park said, “This research enabled industrial application of cytochrome P450 enzyme, which was previous limited.” He continued, “This technology will help greatly in producing high value medical products using cytochrome P450 enzyme.”
The research was funded by the National Research Foundation of Korea and KAIST's High Risk High Return Project (HRHRP).
Figure 1: Mimetic Diagram of Electron Transfer from Light to Cytochrome P450 Enzyme via Eosin Y, EY
Figure 2: The back cover of Angewandte Chemie published on 12 January 2015, showing the research results
2015.01.26 View 9597 -
KAIST Develops a Method to Transfer Graphene by Stamping
Professor Sung-Yool Choi’s research team from KAIST's Department of Electrical Engineering has developed a technique that can produce a single-layer graphene from a metal etching. Through this, transferring a graphene layer onto a circuit board can be done as easily as stamping a seal on paper.
The research findings were published in the January 14th issue of Small as the lead article.
This technology will allow different types of wafer transfer methods such as transfer onto a surface of a device or a curved surface, and large surface transfer onto a 4 inch wafer. It will be applied in the field of wearable smart gadgets through commercialization of graphene electronic devices.
The traditional method used to transfer graphene onto a circuit board is a wet transfer. However, it has some drawbacks as the graphene layer can be damaged or contaminated during the transfer process from residue from the metal etching. This may affect the electrical properties of the transferred graphene.
After a graphene growth substrate formed on a catalytic metal substrate is pretreated in an aqueous poly vinyl alcohol (PVA) solution, a PVA film forms on the pretreated substrate. The substrate and the graphene layers bond strongly. The graphene is lifted from the growth substrate by means of an elastomeric stamp.
The delaminated graphene layer is isolated state from the elastomeric stamp and thus can be freely transferred onto a circuit board. As the catalytic metal substrate can be reused and does not contain harmful chemical substances, such transfer method is very eco-friendly.
Professor Choi said, “As the new graphene transfer method has a wide range of applications and allows a large surface transfer, it will contribute to the commercialization of graphene electronic devices.” He added that “because this technique has a high degree of freedom in transfer process, it has a variety of usages for graphene and 2 dimensional nano-devices.”
This research was sponsored by the Ministry of Science, ICT and Future Planning, the Republic of Korea.
Figure 1. Cover photo of the journal Small which illustrates the research findings
Figure 2. Above view of Graphene layer transferred through the new method
Figure 3. Large surface transfer of Graphene
2015.01.23 View 10248 -
KAIST Announces the Recipients of Distinguished Alumni Awards
The KAIST Alumni Association (KAA) announced four “Proud KAIST Alumni” awards recipients for the year 2014: Sung-Wook Park, the Chief Executive Officer and President of SK Hynix; Seung Ho Shin, the President of Kangwon National University; Kew-Ho Lee, the President of the Korea Research Institute of Chemical Technology; and Mun-Kee Choi, the former Minister of Science, ICT and Future Planning of the Republic of Korea. The award ceremony took place during the 2015 KAA’s New Year's ceremony on January 17, 2015 at the Palace Hotel in Seoul.
Sung-Wook Park (M.S. ’82 and Ph.D. ’88, Department of Materials Science and Engineering), the Chief Executive Officer and President of SK Hynix, has worked as an expert in the field of memory semi-conductors for the past 30 years. He developed innovative technology and improved production efficiency, enabling the Korean semi-conductor industry to become a global leader.
Seung Ho Shin (M.S. ’79 and Ph.D. ’87, Department of Physics), the President of Kangwon National University (KNU), worked in the field of optical information processing, producing excellent research achievements and teaching the next generation of scientists. As the president of KNU, he has set an exemplary leadership in higher education.
Kew-Ho Lee (M.S. ’75, Department of Chemistry), the President of the Korea Research Institute of Chemical Technology, pioneered the field of separation film production which contributed greatly to Korean technological developments. He led several domestic and international societies to facilitate dynamic exchanges between industry and academia and with the international community.
Mun-Kee Choi (M.S. ’76, Department of Industrial and Systems Engineering), the former Minister of Science, ICT and Future Planning, the Republic of Korea, is a great contributor to the information and communications technology in Korea, working as a leader in the field of broadband integrated service digital network. He is also an educator for gifted students in science and technology, and a manager of the Electronics and Telecommunications Research Institute.
The Alumni Association established the “Proud KAIST Alumni Awards” in 1992 to recognize its alumni’s outstanding contributions to Korea and KAIST.
Pictured from left to right, Sung-Wook Park (the Chief Executive Officer and President of SK Hynix), Seung Ho Shin (the President of Kangwon National University), Kew-Ho Lee (the President of the Korea Research Institute of Chemical Technology), and Mun-Kee Choi (the former Minister of Science, ICT and Future Planning)
2015.01.19 View 12740