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Efficiently Producing Fatty Acids and Biofuels from Glucose
Researchers have presented a new strategy for efficiently producing fatty acids and biofuels that can transform glucose and oleaginous microorganisms into microbial diesel fuel, with one-step direct fermentative production. The newly developed strain, created by Distinguished Professor Sang Yup Lee and his team, showed the highest efficiency in producing fatty acids and biodiesels ever reported. It will be expected to serve as a new platform to sustainably produce a wide array of fatty acid-based products from glucose and other carbon substrates. Fossil fuels, which have long been energy resources for our daily lives, are now facing serious challenges: depletion of their reserves and their role in global warming. The production of sustainable bio-based renewable energy has emerged as an essential alternative and many studies to replace fossil fuels are underway. One of the representative examples is biodiesel. Currently, it is mainly being produced through the transesterification of vegetable oils or animal fats. The research team engineered oleaginous microorganisms, Rhodococcus opacus, to produce fatty acids and their derivatives that can be used as biodiesel from glucose, one of the most abundant and cheap sugars derived from non-edible biomass. Professor Lee’s team has already engineered Escherichia coli to produce short-chain hydrocarbons, which can be used as gasoline (published in Nature as the cover paper in 2013). However, the production efficiency of the short-chain hydrocarbons using E. coli (0.58 g/L) fell short of the levels required for commercialization. To overcome these issues, the team employed oil-accumulating Rhodococcus opacus as a host strain in this study. First, the team optimized the cultivation conditions of Rhodococcus opacus to maximize the accumulation of oil (triacylglycerol), which serves as a precursor for the biosynthesis of fatty acids and their derivatives. Then, they systematically analyzed the metabolism of the strain and redesigned it to enable higher levels of fatty acids and two kinds of fatty acid-derived biodiesels (fatty acid ethyl esters and long-chain hydrocarbons) to be produced. They found that the resulting strains produced 50.2, 21.3, and 5.2 g/L of fatty acids, fatty acid ethyl esters, and long-chain hydrocarbons, respectively. These are all the highest concentrations ever reported by microbial fermentations. It is expected that these strains can contribute to the future industrialization of microbial-based biodiesel production. “This technology creates fatty acids and biodiesel with high efficiency by utilizing lignocellulose, one of the most abundant resources on the Earth, without depending on fossil fuels and vegetable or animal oils. This will provide new opportunities for oil and petroleum industries, which have long relied on fossil fuels, to turn to sustainable and eco-friendly biotechnologies,” said Professor Lee. This paper titled “Engineering of an oleaginous bacterium for the production of fatty acids and fuels” was published in Nature Chemical Biology on June 17. This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557). (Figure: Metabolic engineering for the production of free fatty acids (FFAs), fatty acid ethyl esters (FAEEs), and long-chain hydrocarbons (LCHCs) in Rhodococcus opacus PD630. Researchers have presented a new strategy for efficiently producing fatty acids and biofuels that can transform glucose and oleaginous microorganisms into microbial diesel fuel, with one-step direct fermentative production.) # # # Source: Hye Mi Kim, Tong Un Chae, So Young Choi, Won Jun Kim and Sang Yup Lee. Engineering of an oleaginous bacterium for the production of fatty acids and fuels. Nature Chemical Biology ( https://www.nature.com/nchembio/ ) DOI: 10.1038/s41589-019-0295-5 Profile Dr. Sang Yup Lee leesy@kaist.ac.kr Distinguished Professor at the Department of Chemical and Biomolecular Engineering KAIST
2019.06.19
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Novel Via-Hole-Less Multilevel Metal Interconnection Methods
Forming reliable multi-level metal interconnections is a key technology for integrating devices into organic integrated circuits (ICs). The conventional approach, called “via-hole,” locally removes the insulator and utilizes metal interconnects through the holes. Due to the high sensitivity of organic materials to chemical solvents, heat, and photo-radiation used in conventional “via-hole” methods, alternative printing methods or laser drilling methods have been developed. However, finding a reliable and practical metal interconnection for organic ICs is still challenging. The research team of KAIST Professor Sung Gap Im and Postech Professor Kim Jae-Joon reported a new interconnection method that does not require via-hole formation, “via-hole-less metal interconnection,” in Nature Communications on June 3. Metal electrodes in different layers can be isolated from each other by patterned dielectric layers, where they then can be interconnected to others in the open area where the dielectric layer is not present. See the images below. Vapor phase deposition and in-situ patterning of dielectric layer using iCVD (initiated chemical vapor deposition), used in the “via-hole-less” method, ensure a damage-free process for organic semiconductor materials and result in outstanding performance of the organic devices as multilevel metal interconnects are reliably formed. The team successfully demonstrated three-dimensional (3D) stacking of five organic transistors and integrated circuits using the proposed via-hole-less interconnect method. See the image below. Vapor phase deposition and in-situ patterning of dielectric layer using iCVD (initiated chemical vapor deposition), used in the “via-hole-less” method, ensure a damage-free process for organic semiconductor materials and result in outstanding performance of the organic devices as multilevel metal interconnects are reliably formed. The team successfully demonstrated three-dimensional (3D) stacking of five organic transistors and integrated circuits using the proposed via-hole-less interconnect method. See the image below. Professor Kim explained, “Our proposed via-hole-less interconnect method using a selectively patterned dielectric overcomes the limitations of the previous time-consuming, one-by-one via-hole formation process and provides reliable methods for creating metal interconnects in organic ICs. We expect the via-hole-less scheme to bring advances to organic IC technology.”
2019.06.18
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5 Biomarkers for Overcoming Colorectal Cancer Drug Resistance Identified
< Professor Kwang-Hyun Cho's Team > KAIST researchers have identified five biomarkers that will help them address resistance to cancer-targeting therapeutics. This new treatment strategy will bring us one step closer to precision medicine for patients who showed resistance. Colorectal cancer is one of the most common types of cancer worldwide. The number of patients has surpassed 1 million, and its five-year survival rate significantly drops to about 20 percent when metastasized. In Korea, the surge of colorectal cancer has been the highest in the last 10 years due to increasing Westernized dietary patterns and obesity. It is expected that the number and mortality rates of colorectal cancer patients will increase sharply as the nation is rapidly facing an increase in its aging population. Recently, anticancer agents targeting only specific molecules of colon cancer cells have been developed. Unlike conventional anticancer medications, these selectively treat only specific target factors, so they can significantly reduce some of the side-effects of anticancer therapy while enhancing drug efficacy. Cetuximab is the most well-known FDA approved anticancer medication. It is a biomarker that predicts drug reactivity and utilizes the presence of the ‘KRAS’ gene mutation. Cetuximab is prescribed to patients who don’t carry the KRAS gene mutation. However, even in patients without the KRAS gene mutation, the response rate of Cetuximab is only about fifty percent, and there is also resistance to drugs after targeted chemotherapy. Compared with conventional chemotherapy alone, the life expectancy only lasts five months on average. In research featured in the FEBS Journal as the cover paper for the April 7 edition, the KAIST research team led by Professor Kwang-Hyun Cho at the Department of Bio and Brain Engineering presented five additional biomarkers that could increase Cetuximab responsiveness using systems biology approach that combines genomic data analysis, mathematical modeling, and cell experiments. The experimental inhibition of newly discovered biomarkers DUSP4, ETV5, GNB5, NT5E, and PHLDA1 in colorectal cancer cells has been shown to overcome Cetuximab resistance in KRAS-normal genes. The research team confirmed that when suppressing GNB5, one of the new biomarkers, it was shown to overcome resistance to Cetuximab regardless of having a mutation in the KRAS gene. Professor Cho said, “There has not been an example of colorectal cancer treatment involving regulation of the GNB5 gene.” He continued, “Identifying the principle of drug resistance in cancer cells through systems biology and discovering new biomarkers that could be a new molecular target to overcome drug resistance suggest real potential to actualize precision medicine.” This study was supported by the National Research Foundation of Korea (NRF) and funded by the Ministry of Science and ICT (2017R1A2A1A17069642 and 2015M3A9A7067220). Image 1. The cover of FEBS Journal for April 2019
2019.05.27
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'Think Out of the Box,' Team Circos Wins the P4G Innovation Sprint
<The winning team of the P4G Innovation Sprint poses with the Crown Prince of Denmark (sixth from the left in the first row) and President Shin (fifth from the left in the first row) during the awarding ceremony.> Team Circos from KAIST and Denmark made a new sustainable business model for Hempel, a global coating supplier group in Denmark, and won the first prize at the P4G (the Partnership for Green Growth and Global Goals) Innovation Sprint held at KAIST’s Seoul campus on May 22. The six-member team was awarded one million KRW in prize money by the Crown Prince of Denmark. Two of winning team members have the privilege of traveling to visit Hempel in Denmark. The winning team thought outside the box, inspired by box wine which reduced the sales price from traditional bottled wine. Six teams made up of members from different academic disciplines spent two nights and three days brainstorming ways to resolve the challenges of corporations such as Velux and Hempel from Denmark and SK from Korea. The P4G Innovation Sprint is one of the events co-hosted by KAIST and Technological University of Denmark in celebration of the 60th anniversary of diplomatic relations establishment between Denmark and Korea and the 8th anniversary of the Green Growth Alliance between the two countries. The Crown Prince Couple also made a royal visit to Korea in honor of the 60th anniversary celebration and Green Growth Alliance between the two countries. This Innovation Sprint aimed to develop young academics’ perspectives, skills, and talents for the next generation to better research the Sustainable Development Goals set by UN. Three teams made their final five-minute pitches before the Crown Prince and President Sung-Chul Shin and responded to questions from the four-member jury. The Crown Prince of Denmark and President Shin both agreed that the collaborative and convergent ideas will address global problems. The Crown Prince stressed in his congratulatory remarks the importance of partnership in this polarizing world to achieve sustainable improvements saying, “Partnerships are only possible to sustain through collaboration and hard work while staying curious, creative, and critical. " He also shared the special relationship with KAIST. His father-in-law Professor John Donaldson used to be a visiting professor of applied mathmatics at KAIST back in 2003. President Shin added, “Collaboration across boundaries is most critical for responding to these issues. In that sense, this P4G Innovation Sprint is a shining example for demonstrating the collaborative efforts between teammates from diverse disciplines. When we work together and build convergent ideas, we will be more innovative and go further.” <Winning team member Nicolai Thorball from DTU pitches at the final in the presence of the Crown Prince of Denmark and KAIST President Shin.> “The canned packaging in the paint industry results in 40 times more carbon emission in the course of production. However, when using aluminum packaging which is recyclable, the waste amount will be cut dramatically,” pitched Nicolai Thorball from DTU on exchange at Seoul National University. Nicolai, whose major is environmental engineering, is one of two Danish students including Thomsen Xandra Flyvbjerg from the University of Southern Denmark. Flyvbjergy, majoring in business, is now on exchange at Sungkynkwan University. “I am very glad to have the chance to understand the concept of the circular economy and green growth at the sprint. It was also very challenging to make ideation from so many ideas brainstormed,” said Dong-Eun Lee, a KAIST undergraduate from the Department of Biological Sciences. He said that he learned a lot from his two other teammates who are from the Program of Green Business & Policy at KAIST College of Business, Jae-Hee Park and Kyung-Hyun Kim. Juho Park majoring in mechanical engineering at KAIST was one of the team. Circos’ solution for a sustainable model received acclaim from the jury members. DTU Senior Vice President Marianne Thellerson, one of jurors, claimed their model has very high market feasibility, saying, “Their idea could be commercialized right now into the market.” Professor Hee-Kyung Park from KAIST who helped participants’ ideation as one of four mentors said, “The winning team perfectly met all the components of the evaluation criteria, Solution, Acceleration, and Pitch.” At this sprint, 10 students from Denmark and 29 KAIST students were divided into 6 teams and given the challenges of three companies. The Danish window facility company Velux presented its future glass window system and the paint company Hempel their circular economic new business model. SK challenged the students to help it become a global clean energy solution company. The event was based on a hacker blueprint that found the optimal solution to the topics proposed.
2019.05.23
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Engineered Microbial Production of Grape Flavoring
(Image 1: Engineered bacteria that produce grape flavoring.) Researchers report a microbial method for producing an artificial grape flavor. Methyl anthranilate (MANT) is a common grape flavoring and odorant compound currently produced through a petroleum-based process that uses large volumes of toxic acid catalysts. Professor Sang-Yup Lee’s team at the Department of Chemical and Biomolecular Engineering demonstrated production of MANT, a naturally occurring compound, via engineered bacteria. The authors engineered strains of Escherichia coli and Corynebacetrium glutamicum to produce MANT through a plant-based engineered metabolic pathway. The authors tuned the bacterial metabolic pathway by optimizing the levels of AAMT1, the key enzyme in the process. To maximize production of MANT, the authors tested six strategies, including increasing the supply of a precursor compound and enhancing the availability of a co-substrate. The most productive strategy proved to be a two-phase extractive culture, in which MANT was extracted into a solvent. This strategy produced MANT on the scale of 4.47 to 5.74 grams per liter, a significant amount, considering that engineered microbes produce most natural products at a scale of milligrams or micrograms per liter. According to the authors, the results suggest that MANT and other related molecules produced through industrial processes can be produced at scale by engineered microbes in a manner that would allow them to be marketed as natural one, instead of artificial one. This study, featured at the Proceeding of the National Academy of Sciences of the USA on May 13, was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT. (Image 2. Overview of the strategies applied for the microbial production of grape flavoring.)
2019.05.15
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Education Innovation Day Reaffirms Rewarding of Excellence
Professors Tae-Eog Lee and Il-Chul Moon from the Department of Industrial & Systems Engineering received the Linkgenesis Best Teacher Award and the Soo-Young Lee Teaching Innovation Award on May 10. They were each awarded with 10 million KRW in prize money during the Education Innovation Day ceremony held at the Chung Kun-mo conference hall. The award was endowed by KAIST Alumni Scholarship Chairman Hyung-Kyu Lim and KAIST Foundation Chairman Soo-Young Lee to support the innovation initiative and acknowledge faculty members who made significant contributions to educational innovation and benefited the general public though their innovations. “KAIST’s vision for excellence and commitment to innovation is a game changer. Educational innovation is one of five pillars of Vision 2031, and it is our priority to foster critical and creative thinking students,” said President Sung-Chul Shin at the ceremony. All the awardees made presentation on their innovative projects and shared their ideas on better pedagogical methodology for next generation. Professor Lee, dean of the KAIST Academy and the head of the Center for Excellence in Learning & Teaching was recognized for his contribution to enhancing educational quality through innovative learning and teaching methodology development. He has set up an Education 3.0 Initiative, an online education platform for flipped learning at KAIST. Professor Moon also upgraded the online education platform to the 4.0 version and extended KAIST’s massive online courses through KOOC framework. This open platform offers more than 62 courses, with more than 170 thousand users registered since 2014. Professor Song-Hong Park from the Department of Bio and Brain Engineering and Professor Jae-Woo Lee from the Department of Chemical and Biomolecular Engineering also won the Excellence Award.
2019.05.10
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KAIST Identifies the Cause of Sepsis-induced Lung Injury
(Professor Pilhan Kim from the Graduate School of Medical Science and Engineering) A KAIST research team succeeded in visualizing pulmonary microcirculation and circulating cells in vivo with a custom-built 3D intravital lung microscopic imaging system. They found a type of leukocyte called neutrophils aggregate inside the capillaries during sepsis-induced acute lung injury (ALI), leading to disturbances and dead space in blood microcirculation. According to the researchers, this phenomenon is responsible for tissue hypoxia causing lung damage in the sepsis model, and mitigating neutrophils improves microcirculation as well as hypoxia. The lungs are responsible for exchanging oxygen with carbon dioxide gases during the breathing process, providing an essential function for sustaining life. This gas exchange occurs in the alveoli, each surrounded by many capillaries containing the circulating red blood cells. Researchers have been making efforts to observe microcirculation in alveoli, but it has been technically challenging to capture high-resolution images of capillaries and red blood cells inside the lungs that are in constant breathing motion. Professor Pilhan Kim from the Graduate School of Medical Science and Engineering and his team developed an ultra-fast laser scanning confocal microscope and an imaging chamber that could minimize the movement of a lung while preserving its respiratory state. They used this technology to successfully capture red blood cell circulation inside the capillaries of animal models with sepsis. During the process, they found that hypoxia was induced by the increase of dead space inside the lungs of a sepsis model, a space where red blood cells do not circulate. This phenomenon is due to the neutrophils aggregating and trapping inside the capillaries and the arterioles. It was also shown that trapped neutrophils damage the lung tissue in the sepsis model by inhibiting microcirculation as well as releasing reactive oxygen species. Further studies showed that the aggregated neutrophils inside pulmonary vessels exhibit a higher expression of the Mac-1 receptor (CD11b/CD18), which is a receptor involved in intercellular adhesion, compared to the neutrophils that normally circulate. Additionally, they confirmed that Mac-1 inhibitors can improve inhibited microcirculation, ameliorate hypoxia, while reducing pulmonary edema in the sepsis model. Their high-resolution 3D intravital microscope technology allows the real-time imaging of living cells inside the lungs. This work is expected to be used in research on various lung diseases, including sepsis. The research team’s pulmonary circulation imaging and precise analytical techniques will be used as the base technology for developing new diagnostic technologies, evaluating new therapeutic agents for various diseases related to microcirculation. Professor Kim said, “In the ALI model, the inhibition of pulmonary microcirculation occurs due to neutrophils. By controlling this effect and improving microcirculation, it is possible to eliminate hypoxia and pulmonary edema – a new, effective strategy for treating patients with sepsis.” Their 3D intravital microscope technology was commercialized through IVIM Technology, Inc., which is a faculty startup at KAIST. They released an all-in-one intravital microscope model called ‘IVM-CM’ and ‘IVM-C’. This next-generation imaging equipment for basic biomedical research on the complex pathophysiology of various human diseases will play a crucial role in the future global bio-health market. This research, led by Dr. Inwon Park from the Department of Emergency Medicine at Seoul National University Bundang Hospital and formally the Graduate School of Medical Science and Engineering at KAIST, was published in the European Respiratory Journal (2019, 53:1800736) on March 28, 2019. Figure 1. Custom-built high-speed real-time intravital microscope platform Figure 2. Illustrative schematic and photo of a 3D intravital lung microscopic imaging system Figure 3. Aggregation of neutrophils and consequent flow disturbance in pulmonary arteriole in sepsis-induced lung injury
2019.05.07
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Nanomaterials Mimicking Natural Enzymes with Superior Catalytic Activity and Selectivity for Detecting Acetylcholine
(Professor Jinwoo Lee from the Department of Chemical and Biomolecular Engineering) A KAIST research team doped nitrogen and boron into graphene to selectively increase peroxidase-like activity and succeeded in synthesizing a peroxidase-mimicking nanozyme with a low cost and superior catalytic activity. These nanomaterials can be applied for early diagnosis of Alzheimer’s disease. Enzymes are the main catalysts in our body and are widely used in bioassays. In particular, peroxidase, which oxidizes transparent colorimetric substrates to become a colored product in the presence of hydrogen peroxide, is the most common enzyme that is used in colorimetric bioassays. However, natural enzymes consisting of proteins are unstable against temperature and pH, hard to synthesize, and costly. Nanozymes, on the other hand, do not consist of proteins, meaning the disadvantages of enzymes can be overcome with their robustness and high productivity. In contrast, most nanonzymes do not have selectivity; for example, peroxidase-mimicking nanozymes demonstrate oxidase-like activity that oxidizes colorimetric substrates in the absence of hydrogen peroxide, which keeps them away from precisely detecting the target materials, such as hydrogen peroxide. Professor Jinwoo Lee from the Department of Chemical and Biomolecular Engineering and his team were able to synthesize a peroxidase-mimicking nanozyme with superior catalytic activity and selectivity toward hydrogen peroxide. Co-doping of nitrogen and boron into graphene, which has negligible peroxidase-like activity, selectively increased the peroxidase-like activity without oxidase-like activity to accurately mimic the nature peroxidase and has become a powerful candidate to replace the peroxidase. The experimental results were also verified with computational chemistry. The nitrogen and boron co-doped graphene was also applied to the colorimetric detection of acetylcholine, which is an important neurotransmitter and successfully detected the acetylcholine even better than the nature peroxidase. Professor Lee said, “We began to study nanozymes due to their potential for replacing existing enzymes. Through this study, we have secured core technologies to synthesize nanozymes that have high enzyme activity along with selectivity. We believe that they can be applied to effectively detect acetylcholine for quickly diagnosing Alzheimer’s disease. This research, led by PhD Min Su Kim, was published in ACS Nano (10.1021/acsnano.8b09519) on March 25, 2019. Figure 1. Comparison of the catalytic activities of various nanozymes and horseradish peroxidase (HRP) toward TMB and H₂O₂ Figure 2. Schematic illustration of NB-rGO Reactions in Bioassays
2019.04.30
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Research Day Highlights Most Outstanding Research Achievements
Professor Byung Jin Cho from the School of Electrical Engineering was selected as the Grand Research Prize Winner in recognition of his innovative research achievement in the fields of nano electric and flexible energy devices during the 2019 KAIST Research Day ceremony held on April 23 at the Chung Kunmo Conference Hall. The ten most outstanding research achievements from the past year were also awarded in the three areas of Research, Innovation, Convergence Researches. Professor Cho is an internationally recognized researcher in the field of future nano and energy device technology. Professor Cho’s team has continued to research on advanced CMOS (complementary metal-oxide semiconductors). CMOS has become his key research topic over the past three decades. In 2014, he developed a glass fabric-based thermoelectric generator, which is extremely light and flexible and produces electricity from the heat of the human body. It is so flexible that the allowable bending radius of the generator is as low as 20 mm. There are no changes in performance even if the generator bends upward and downward for up to 120 cycles. His wearable thermoelectric generator was selected as one of the top ten most promising digital technologies by the Netexplo Forum in 2015. He now is working on high-performance and ultra-flexible CMOS IC for biomedical applications, expanding his scope to thermal haptic technology in VR using graphene-CMOS hybrid integrated circuits; to self-powered wireless sensor nodes and self-powered ECG system using wearable thermoelectric generators . In his special lecture at the ceremony, Professor Cho stressed the importance of collaboration in making scientific research and presented how he moved to future devices after focusing on scaling the devices. “When I started the research on semiconductors, I focused on how to scale the device down as much as possible. For decades, we have conducted a number of procedures to produce tiny but efficient materials. Now we have shifted to develop flexible thermoelements and wearable devices,” said Professor Cho. “We all thought the scaling down is the only way to create value-added technological breakthroughs. Now, the devices have been scaled down to 7nm and will go down to 5 nm soon. Over the past few years, I think we have gone through all the possible technological breakthroughs for reducing the size to 5nm. The semiconductor devices are made of more 1 billion transistors and go through 1,000 technological processes. So, there won’t be any possible way for a single genius to make a huge breakthrough. Without collaboration with others, it is nearly impossible to make any new technological breakthroughs.” Professor Cho has published more than 240 papers in renowned academic journals and presented more than 300 papers at academic conferences. He has also registered approximately 50 patents in the field of semiconductor device technology. The top ten research highlights of 2018 as follows: - Rydberg-Atom Quantum Simulator Development by Professor Jaewook Ahn and Heung-Sun Sim from the Department of Physics - From C-H to C-C Bonds at Room Temperature by Professor Mu-Hyun Baik from the Department of Chemistry - The Role of Rodlike Counterions on the Interactions of DNAs by Professor Yong Woon Kim of the Graduate School of Nanoscience and Technology - The Medal Preoptic Area Induces Hunting-Like Behaviors to Target Objects and Prey by Professor Daesoo Kim from the Department of Biological Sciences - Identification of the Origin of Brain Tumors and New Therapeutic Strategy by Professor Jeong Ho Lee from the Graduate School of Medical Science and Engineering - The Linear Frequency Conversion of Light at a Spatiotemporal Boundary by Professor Bumki Min from the Department of Mechanical Engineering - An Industrial Grade Flexible Transparent Force Touch Sensor by Professor Jun-Bo Yoon from the School of Electrical Engineering - The Detection and Clustering of Mixed-Type Defect Patterns in Wafer Bin Maps by Professor Heeyoung Kim from the Department of Industrial and Systems Engineering - The Development of a Reconfigurable Spin-Based Logic Device by Professor Byong-Guk Park from the Department of Materials Science and Engineering - The Development of a Miniaturized X-Ray Tube Based on Carbon Nanotube and Electronic Brachytherapy Device by Professor Sung Oh Cho from the Department of Nuclear and Quantum Engineering Professor YongKeun Park from the Department of Physics and Professor In-Chel Park from the School of Electrical Engineering received the Research Award. For the Innovation Award, Professor Munchurl Kim from the School of Electrical Engineering was the recipient and the Convergence Research Awards was conferred to Professor Sung-Yool Choi from the School of Electrical Engineering, Professor Sung Gap Im from the Department of Chemical and Biomolecular Engineering, and Professor SangHee Park from the Department of Materials Science and Engineering during the ceremony. For more on KAIST’s Top Research Achievements and Highlight of 2018, please refer to the attached below. click.
2019.04.25
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KAIST Unveils the Hidden Control Architecture of Brain Networks
(Professor Kwang-Hyun Cho and his team) A KAIST research team identified the intrinsic control architecture of brain networks. The control properties will contribute to providing a fundamental basis for the exogenous control of brain networks and, therefore, has broad implications in cognitive and clinical neuroscience. Although efficiency and robustness are often regarded as having a trade-off relationship, the human brain usually exhibits both attributes when it performs complex cognitive functions. Such optimality must be rooted in a specific coordinated control of interconnected brain regions, but the understanding of the intrinsic control architecture of brain networks is lacking. Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering and his team investigated the intrinsic control architecture of brain networks. They employed an interdisciplinary approach that spans connectomics, neuroscience, control engineering, network science, and systems biology to examine the structural brain networks of various species and compared them with the control architecture of other biological networks, as well as man-made ones, such as social, infrastructural and technological networks. In particular, the team reconstructed the structural brain networks of 100 healthy human adults by performing brain parcellation and tractography with structural and diffusion imaging data obtained from the Human Connectome Project database of the US National Institutes of Health. The team developed a framework for analyzing the control architecture of brain networks based on the minimum dominating set (MDSet), which refers to a minimal subset of nodes (MD-nodes) that control the remaining nodes with a one-step direct interaction. MD-nodes play a crucial role in various complex networks including biomolecular networks, but they have not been investigated in brain networks. By exploring and comparing the structural principles underlying the composition of MDSets of various complex networks, the team delineated their distinct control architectures. Interestingly, the team found that the proportion of MDSets in brain networks is remarkably small compared to those of other complex networks. This finding implies that brain networks may have been optimized for minimizing the cost required for controlling networks. Furthermore, the team found that the MDSets of brain networks are not solely determined by the degree of nodes, but rather strategically placed to form a particular control architecture. Consequently, the team revealed the hidden control architecture of brain networks, namely, the distributed and overlapping control architecture that is distinct from other complex networks. The team found that such a particular control architecture brings about robustness against targeted attacks (i.e., preferential attacks on high-degree nodes) which might be a fundamental basis of robust brain functions against preferential damage of high-degree nodes (i.e., brain regions). Moreover, the team found that the particular control architecture of brain networks also enables high efficiency in switching from one network state, defined by a set of node activities, to another – a capability that is crucial for traversing diverse cognitive states. Professor Cho said, “This study is the first attempt to make a quantitative comparison between brain networks and other real-world complex networks. Understanding of intrinsic control architecture underlying brain networks may enable the development of optimal interventions for therapeutic purposes or cognitive enhancement.” This research, led by Byeongwook Lee, Uiryong Kang and Hongjun Chang, was published in iScience (10.1016/j.isci.2019.02.017) on March 29, 2019. Figure 1. Schematic of identification of control architecture of brain networks. Figure 2. Identified control architectures of brain networks and other real-world complex networks.
2019.04.23
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On-chip Drug Screening for Identifying Antibiotic Interactions in Eight Hours
(from left: Seunggyu Kimand Professor Jessie Sungyun Jeon) A KAIST research team developed a microfluidic-based drug screening chip that identifies synergistic interactions between two antibiotics in eight hours. This chip can be a cell-based drug screening platform for exploring critical pharmacological patterns of antibiotic interactions, along with potential applications in screening other cell-type agents and guidance for clinical therapies. Antibiotic susceptibility testing, which determines types and doses of antibiotics that can effectively inhibit bacterial growth, has become more critical in recent years with the emergence of antibiotic-resistant pathogenic bacteria strains. To overcome the antibiotic-resistant bacteria, combinatory therapy using two or more kinds of antibiotics has been gaining considerable attention. However, the major problem is that this therapy is not always effective; occasionally, unfavorable antibiotic pairs may worsen results, leading to suppressed antimicrobial effects. Therefore, combinatory testing is a crucial preliminary process to find suitable antibiotic pairs and their concentration range against unknown pathogens, but the conventional testing methods are inconvenient for concentration dilution and sample preparation, and they take more than 24 hours to produce the results. To reduce time and enhance the efficiency of combinatory testing, Professor Jessie Sungyun Jeon from the Department of Mechanical Engineering, in collaboration with Professor Hyun Jung Chung from the Department of Biological Sciences, developed a high-throughput drug screening chip that generates 121 pairwise concentrations between two antibiotics. The team utilized a microfluidic chip with a sample volume of a few tens of microliters. This chip enabled 121 pairwise concentrations of two antibiotics to be automatically formed in only 35 minutes. They loaded a mixture of bacterial samples and agarose into the microchannel and injected reagents with or without antibiotics into the surrounding microchannel. The diffusion of antibiotic molecules from the channel with antibiotics to the one without antibiotics resulted in the formation of two orthogonal concentration gradients of the two antibiotics on the bacteria-trapping agarose gel. The team observed the inhibition of bacterial growth by the antibiotic orthogonal gradients over six hours with a microscope, and confirmed different patterns of antibiotic pairs, classifying the interaction types into either synergy or antagonism. Professor Jeon said, “The feasibility of microfluidic-based drug screening chips is promising, and we expect our microfluidic chip to be commercialized and utilized in near future.” This study, led by Seunggyu Kim, was published in Lab on a Chip (10.1039/c8lc01406j) on March 21, 2019. Figure 1. Back cover image for the “Lab on a Chip”. Figure 2. Examples of testing results using the microfluidic chips developed in this research.
2019.04.18
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A Hole in One for Holographic Display
(Professor YongKeun Park) Researchers have designed an ultrathin display that can project dynamic, multi-coloured, 3D holographic images, according to a study published in Nature Communications. The system’s critical component is a thin film of titanium filled with tiny holes that precisely correspond with each pixel in a liquid crystal display (LCD) panel. This film acts as a ‘photon sieve’ – each pinhole diffracts light emerging from them widely, resulting in a high-definition 3D image observable from a wide angle. The entire system is very small: they used a 1.8-inch off-the-shelf LCD panel with a resolution of 1024 x 768. The titanium film, attached to the back of the panel, is a mere 300 nanometres thick. “Our approach suggests that holographic displays could be projected from thin devices, like a cell phone,” says Professor YongKeun Park, a physicist at KAIST who led the research. The team demonstrated their approach by producing a hologram of a moving, tri-coloured cube. Specifically, the images are made by pointing differently coloured laser beams made of parallel light rays at the small LCD panel. The photon sieve has a hole for each pixel in the LCD panel. The holes are precisely positioned to correspond to the pixel’s active area. The pinholes diffract the light emerging from them, producing 3D images. Previous studies from Professor Park’s group have used optical diffusors for the same purpose, but the size of the device was bulky and difficult to be operated, and it took a long period of time to calibrate. In the present work, on the other hand, the group tailored their photon sieve to demonstrate a simple, compact and scalable method for 3D holographic display. This technique can be readily applied to existing LCD displays. Applications for holograms have been limited by cumbersome techniques, high computation requirements, and poor image quality. Improving current techniques could lead to a wide variety of applications, including 3D cinema viewing without the need for glasses, watching holographic videos on television and smart phone screens. Figure 1. The actual 3D holographic display, and an electron microscope image of the non-periodic pinholes. Figure 2. Three-dimensional dynamic color hologram operating at 60 Hz
2019.04.18
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