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Two More Cross-generation Collaborative Labs Open
< President Sung-Chul Shin (sixth from the left) and Professor Sun Chang Kim (seventh from the left) at the signboard ceremony of KAIST BioDesigneering Laboratory > KAIST opened two more cross-generation collaborative labs last month. KAIST BioDesigneering Laboratory headed by Professor Sun Chang Kim from the Department of Biological Sciences and Nanophotonics Laboratory led by Professor Yong-Hee Lee from the Department of Physics have been selected to receive 500 million KRW funding for five years. A four-member selection committee including the former President of ETH Zürich Professor Emeritus Ralph Eichler and Professor Kwang-Soo Kim of Harvard Medical School conducted a three-month review and evaluation for this selection to be made. With these two new labs onboard, a total of six cross-generation collaborative labs will be operated on campus. The operation of cross-generation collaborative labs has been in trial since March last year, as one of the KAIST’s Vision 2031 research innovation initiatives. This novel approach is to pair up senior and junior faculty members for sustaining research and academic achievements even after the senior researcher retires, so that the spectrum of knowledge and research competitiveness can be extended to future generations. The selected labs will be funded for five years, and the funding will be extended if necessary. KAIST will continue to select new labs every year. One of this year’s selectees Professor Sun Chang Kim will be teamed up with Professor Byung-Kwan Cho from the same department and Professor Jung Kyoon Choi from the Department of Bio and Brain Engineering to collaborate in the fields of synthetic biology, systems biology, and genetic engineering. This group mainly aims at designing and synthesizing optimal genomes that can efficiently manufacture protein drug and biomedical active materials. They will also strive to secure large amounts of high-functioning natural active substances, new adhesive antibacterial peptides, and eco-friendly ecological restoration materials. It is expected that collaboration between these three multigenerational professors will help innovate their bio-convergence technology and further strengthen their international competitiveness in the global bio-market. Another world-renowned scholar Professor Yong-Hee Lee of photonic crystal laser study will be joined by Professor Minkyo Seo from the same department and Professor Hansuek Lee from the Graduate School of Nanoscience and Technology. They will explore the extreme limits of light-material interaction based on optical micro/nano resonators, with the goal of developing future nonlinear optoelectronic and quantum optical devices. The knowledge and technology newly gained from the research are expected to provide an important platform for a diverse range of fields from quantum communications to biophysics. (END)
2019.09.06
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Algorithm Identifies Optimal Pairs for Composing Metal-Organic Frameworks
The integration of metal-organic frameworks (MOFs) and other metal nanoparticles has increasingly led to the creation of new multifunctional materials. Many researchers have integrated MOFs with other classes of materials to produce new structures with synergetic properties. Despite there being over 70,000 collections of synthesized MOFs that can be used as building blocks, the precise nature of the interaction and the bonding at the interface between the two materials still remains unknown. The question is how to sort out the right matching pairs out of 70,000 MOFs. An algorithmic study published in Nature Communications by a KAIST research team presents a clue for finding the perfect pairs. The team, led by Professor Ji-Han Kim from the Department of Chemical and Biomolecular Engineering, developed a joint computational and experimental approach to rationally design MOF@MOFs, a composite of MOFs where an MOF is grown on a different MOF. Professor Kim’s team, in collaboration with UNIST, noted that the metal node of one MOF can coordinately bond with the linker of a different MOF and the precisely matched interface configurations at atomic and molecular levels can enhance the likelihood of synthesizing MOF@MOFs. They screened thousands of MOFs and identified optimal MOF pairs that can seamlessly connect to one another by taking advantage of the fact that the metal node of one MOF can form coordination bonds with the linkers of the second MOF. Six pairs predicted from the computational algorithm successfully grew into single crystals. This computational workflow can readily extend into other classes of materials and can lead to the rapid exploration of the composite MOFs arena for accelerated materials development. Even more, the workflow can enhance the likelihood of synthesizing MOF@MOFs in the form of large single crystals, and thereby demonstrated the utility of rationally designing the MOF@MOFs. This study is the first algorithm for predicting the synthesis of composite MOFs, to the best of their knowledge. Professor Kim said, “The number of predicted pairs can increase even more with the more general 2D lattice matching, and it is worth investigating in the future.” This study was supported by Samsung Research Funding & Incubation Center of Samsung Electronics. (Figure: An example of a rationally synthesized MOF@MOFs (cubic HKUST-1@MOF-5 ))
2019.08.30
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Researchers Describe a Mechanism Inducing Self-Killing of Cancer Cells
(Professor Kim (left) and lead author Lee) Researchers have described a new mechanism which induces the self-killing of cancer cells by perturbing ion homeostasis. A research team from the Department of Biochemical Engineering has developed helical polypeptide potassium ionophores that lead to the onset of programmed cell death. The ionophores increase the active oxygen concentration to stress endoplasmic reticulum to the point of cellular death. The electrochemical gradient between extracellular and intracellular conditions plays an important role in cell growth and metabolism. When a cell’s ion homeostasis is disturbed, critical functions accelerating the activation of apoptosis are inhibited in the cell. Although ionophores have been intensively used as an ion homeostasis disturber, the mechanisms of cell death have been unclear and the bio-applicability has been limited. In the study featured at Advanced Science, the team presented an alpha helical peptide-based anticancer agent that is capable of transporting potassium ions with water solubility. The cationic, hydrophilic, and potassium ionic groups were combined at the end of the peptide side chain to provide both ion transport and hydrophilic properties. These peptide-based ionophores reduce the intracellular potassium concentration and at the same time increase the intracellular calcium concentration. Increased intracellular calcium concentrations produce intracellular reactive oxygen species, causing endoplasmic reticulum stress, and ultimately leading to apoptosis. Anticancer effects were evaluated using tumor-bearing mice to confirm the therapeutic effect, even in animal models. It was found that tumor growth was strongly inhibited by endoplasmic stress-mediated apoptosis. Lead author Dr. Dae-Yong Lee said, “A peptide-based ionophore is more effective than conventional chemotherapeutic agents because it induces apoptosis via elevated reactive oxygen species levels. Professor Yeu-Chun Kim said he expects this new mechanism to be widely used as a new chemotherapeutic strategy. This research was funded by the National Research Foundation.
2019.08.28
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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
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Highly Uniform and Low Hysteresis Pressure Sensor to Increase Practical Applicability
< Professor Steve Park (left) and the First Author Mr. Jinwon Oh (right) > Researchers have designed a flexible pressure sensor that is expected to have a much wider applicability. A KAIST research team fabricated a piezoresistive pressure sensor of high uniformity with low hysteresis by chemically grafting a conductive polymer onto a porous elastomer template. The team discovered that the uniformity of pore size and shape is directly related to the uniformity of the sensor. The team noted that by increasing pore size and shape variability, the variability of the sensor characteristics also increases. Researchers led by Professor Steve Park from the Department of Materials Science and Engineering confirmed that compared to other sensors composed of randomly sized and shaped pores, which had a coefficient of variation in relative resistance change of 69.65%, their newly developed sensor exhibited much higher uniformity with a coefficient of variation of 2.43%. This study was reported in Small as the cover article on August 16. Flexible pressure sensors have been actively researched and widely applied in electronic equipment such as touch screens, robots, wearable healthcare devices, electronic skin, and human-machine interfaces. In particular, piezoresistive pressure sensors based on elastomer‐conductive material composites hold significant potential due to their many advantages including a simple and low-cost fabrication process. Various research results have been reported for ways to improve the performance of piezoresistive pressure sensors, most of which have been focused on increasing the sensitivity. Despite its significance, maximizing the sensitivity of composite-based piezoresistive pressure sensors is not necessary for many applications. On the other hand, sensor-to-sensor uniformity and hysteresis are two properties that are of critical importance to realize any application. The importance of sensor-to-sensor uniformity is obvious. If the sensors manufactured under the same conditions have different properties, measurement reliability is compromised, and therefore the sensor cannot be used in a practical setting. In addition, low hysteresis is also essential for improved measurement reliability. Hysteresis is a phenomenon in which the electrical readings differ depending on how fast or slow the sensor is being pressed, whether pressure is being released or applied, and how long and to what degree the sensor has been pressed. When a sensor has high hysteresis, the electrical readings will differ even under the same pressure, making the measurements unreliable. Researchers said they observed a negligible hysteresis degree which was only 2%. This was attributed to the strong chemical bonding between the conductive polymer and the elastomer template, which prevents their relative sliding and displacement, and the porosity of the elastomer that enhances elastic behavior. “This technology brings forth insight into how to address the two critical issues in pressure sensors: uniformity and hysteresis. We expect our technology to play an important role in increasing practical applications and the commercialization of pressure sensors in the near future,” said Professor Park. This work was conducted as part of the KAIST‐funded Global Singularity Research Program for 2019, and also supported by the KUSTAR‐KAIST Institute. Figure 1. Image of a porous elastomer template with uniform pore size and shape (left), Graph showing high uniformity in the sensors’ performance (right). Figure 2. Hysteresis loops of the sensor at different pressure levels (left), and after a different number of cycles (right). Figure 3. The cover page of Small Journal, Volume 15, Issue 33. Publication: Jinwon Oh, Jin‐Oh Kim, Yunjoo Kim, Han Byul Choi, Jun Chang Yang, Serin Lee, Mikhail Pyatykh, Jung Kim, Joo Yong Sim, and Steve Park. 2019. Highly Uniform and Low Hysteresis Piezoresistive Pressure Sensors Based on Chemical Grafting of Polypyrrole on Elastomer Template with Uniform Pore Size. Small. Wiley-VCH Verlag GmbH & Co. KgaA, Weinheim, Germany, Volume No. 15, Issue No. 33, Full Paper No. 201901744, 8 pages. https://doi.org/10.1002/smll.201901744 Profile: Prof. Steve Park, MS, PhD stevepark@kaist.ac.kr http://steveparklab.kaist.ac.kr/ Assistant Professor Organic and Nano Electronics Laboratory Department of Materials Science and Engineering Korea Advanced Institute of Science and Technology (KAIST) http://kaist.ac.kr Daejeon 34141, Korea Profile: Mr. Jinwon Oh, MS jwoh1701@gmail.com http://steveparklab.kaist.ac.kr/ Researcher Organic and Nano Electronics Laboratory Department of Materials Science and Engineering Korea Advanced Institute of Science and Technology (KAIST) http://kaist.ac.kr Daejeon 34141, Korea Profile: Prof. Jung Kim, MS, PhD jungkim@kaist.ac.kr http://medev.kaist.ac.kr/ Professor Biorobotics Laboratory Department of Mechanical Engineering Korea Advanced Institute of Science and Technology (KAIST) http://kaist.ac.kr Daejeon 34141, Korea Profile: Joo Yong Sim, PhD jsim@etri.re.kr Researcher Bio-Medical IT Convergence Research Department Electronics and Telecommunications Research Institute (ETRI) https://www.etri.re.krDaejeon 34129, Korea (END)
2019.08.19
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Accurate Detection of Low-Level Somatic Mutation in Intractable Epilepsy
KAIST medical scientists have developed an advanced method for perfectly detecting low-level somatic mutation in patients with intractable epilepsy. Their study showed that deep sequencing replicates of major focal epilepsy genes accurately and efficiently identified low-level somatic mutations in intractable epilepsy. According to the study, their diagnostic method could increase the accuracy up to 100%, unlike the conventional sequencing analysis, which stands at about 30% accuracy. This work was published in Acta Neuropathologica. Epilepsy is a neurological disorder common in children. Approximately one third of child patients are diagnosed with intractable epilepsy despite adequate anti-epileptic medication treatment. Somatic mutations in mTOR pathway genes, SLC35A2, and BRAF are the major genetic causes of intractable epilepsies. A clinical trial to target Focal Cortical Dysplasia type II (FCDII), the mTOR inhibitor is underway at Severance Hospital, their collaborator in Seoul, Korea. However, it is difficult to detect such somatic mutations causing intractable epilepsy because their mutational burden is less than 5%, which is similar to the level of sequencing artifacts. In the clinical field, this has remained a standing challenge for the genetic diagnosis of somatic mutations in intractable epilepsy. Professor Jeong Ho Lee’s team at the Graduate School of Medical Science and Engineering analyzed paired brain and peripheral tissues from 232 intractable epilepsy patients with various brain pathologies at Severance Hospital using deep sequencing and extracted the major focal epilepsy genes. They narrowed down target genes to eight major focal epilepsy genes, eliminating almost all of the false positive calls using deep targeted sequencing. As a result, the advanced method robustly increased the accuracy and enabled them to detect low-level somatic mutations in unmatched Formalin Fixed Paraffin Embedded (FFPE) brain samples, the most clinically relevant samples. Professor Lee conducted this study in collaboration with Professor Dong Suk Kim and Hoon-Chul Kang at Severance Hospital of Yonsei University. He said, “This advanced method of genetic analysis will improve overall patient care by providing more comprehensive genetic counseling and informing decisions on alternative treatments.” Professor Lee has investigated low-level somatic mutations arising in the brain for a decade. He is developing innovative diagnostics and therapeutics for untreatable brain disorders including intractable epilepsy and glioblastoma at a tech-startup called SoVarGen. “All of the technologies we used during the research were transferred to the company. This research gave us very good momentum to reach the next phase of our startup,” he remarked. The work was supported by grants from the Suh Kyungbae Foundation, a National Research Foundation of Korea grant funded by the Ministry of Science and ICT, the Korean Health Technology R&D Project from the Ministry of Health & Welfare, and the Netherlands Organization for Health Research and Development. (Figure: Landscape of somatic and germline mutations identified in intractable epilepsy patients. a Signaling pathways for all of the mutated genes identified in this study. Bold: somatic mutation, Regular: germline mutation. b The distribution of variant allelic frequencies (VAFs) of identified somatic mutations. c The detecting rate and types of identified mutations according to histopathology. Yellow: somatic mutations, green: two-hit mutations, grey: germline mutations.)
2019.08.14
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Professor Sang Gyu Kim Receives Yeochon Award for Ecology
Professor Sang-Gyu Kim from the Department of Biological Sciences was selected as the winner of the 12th Yeochon Award for Ecology presented by the Yeochon Association for Ecological Research. The award was conferred on August 13 in Jeju at the annual conference co-hosted by the Ecological Society of Korea and the Yeochon Association for Ecological Research. Professor Kim received 10 million KRW in prize money. Professor Kim was recognized for his achievements and contributions in studying herbivorous insects ‘rice weevils’ and their host plant ‘wild tobacco’, especially for having explored the known facts in traditional ecology at the molecular level. His findings are presented in his paper titled ‘Trichobaris weevils distinguish amongst toxic host plants by sensing volatiles that do not affect larval performance’ published in Molecular Ecology in July 2016. Furthermore, Professor Kim’s research team is continuing their work to identify the ecological functions of plant metabolites as well as interactions between flowers and insect vectors at the molecular level. In doing so, the team edits genes in various plant species using the latest gene editing technology. The Yeochon Award for Ecology was first established in 2005 with funds donated by a senior ecologist, the late Honorary Professor Joon-Ho Kim of Seoul National University. The award is named after the professor’s pen name “Yeochon” and is intended to encourage promising next-generation ecologists to produce outstanding research achievements in the field of basic ecology. Professor Kim said, “I will take this award as encouragement to continue taking challenging risks to observe ecological phenomenon from a new perspective. I will continue my research with my students with joy and enthusiasm.”
2019.08.14
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Manipulating Brain Cells by Smartphone
Researchers have developed a soft neural implant that can be wirelessly controlled using a smartphone. It is the first wireless neural device capable of indefinitely delivering multiple drugs and multiple colour lights, which neuroscientists believe can speed up efforts to uncover brain diseases such as Parkinson’s, Alzheimer’s, addiction, depression, and pain. A team under Professor Jae-Woong Jeong from the School of Electrical Engineering at KAIST and his collaborators have invented a device that can control neural circuits using a tiny brain implant controlled by a smartphone. The device, using Lego-like replaceable drug cartridges and powerful, low-energy Bluetooth, can target specific neurons of interest using drugs and light for prolonged periods. This study was published in Nature Biomedical Engineering. “This novel device is the fruit of advanced electronics design and powerful micro and nanoscale engineering,” explained Professor Jeong. “We are interested in further developing this technology to make a brain implant for clinical applications.” This technology significantly overshadows the conventional methods used by neuroscientists, which usually involve rigid metal tubes and optical fibers to deliver drugs and light. Apart from limiting the subject’s movement due to bulky equipment, their relatively rigid structure causes lesions in soft brain tissue over time, therefore making them not suitable for long-term implantation. Although some efforts have been made to partly mitigate adverse tissue response by incorporating soft probes and wireless platforms, the previous solutions were limited by their inability to deliver drugs for long periods of time as well as their bulky and complex control setups. To achieve chronic wireless drug delivery, scientists had to solve the critical challenge of the exhaustion and evaporation of drugs. To combat this, the researchers invented a neural device with a replaceable drug cartridge, which could allow neuroscientists to study the same brain circuits for several months without worrying about running out of drugs. These ‘plug-n-play’ drug cartridges were assembled into a brain implant for mice with a soft and ultrathin probe (with the thickness of a human hair), which consisted of microfluidic channels and tiny LEDs (smaller than a grain of salt), for unlimited drug doses and light delivery. Controlled with an elegant and simple user interface on a smartphone, neuroscientists can easily trigger any specific combination or precise sequencing of light and drug delivery in any implanted target animal without the need to be physically inside the laboratory. Using these wireless neural devices, researchers can also easily setup fully automated animal studies where the behaviour of one animal could affect other animals by triggering light and/or drug delivery. “The wireless neural device enables chronic chemical and optical neuromodulation that has never been achieved before,” said lead author Raza Qazi, a researcher with KAIST and the University of Colorado Boulder. This work was supported by grants from the National Research Foundation of Korea, US National Institute of Health, National Institute on Drug Abuse, and Mallinckrodt Professorship. (A neural implant with replaceable drug cartridges and Bluetooth low-energy can target specific neurons .) (Micro LED controlling using smartphone application)
2019.08.07
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Synthesizing Single-Crystalline Hexagonal Graphene Quantum Dots
(Figure: Uniformly ordered single-crystalline graphene quantum dots of various sizes synthesized through solution chemistry.) A KAIST team has designed a novel strategy for synthesizing single-crystalline graphene quantum dots, which emit stable blue light. The research team confirmed that a display made of their synthesized graphene quantum dots successfully emitted blue light with stable electric pressure, reportedly resolving the long-standing challenges of blue light emission in manufactured displays. The study, led by Professor O Ok Park in the Department of Chemical and Biological Engineering, was featured online in Nano Letters on July 5. Graphene has gained increased attention as a next-generation material for its heat and electrical conductivity as well as its transparency. However, single and multi-layered graphene have characteristics of a conductor so that it is difficult to apply into semiconductor. Only when downsized to the nanoscale, semiconductor’s distinct feature of bandgap will be exhibited to emit the light in the graphene. This illuminating featuring of dot is referred to as a graphene quantum dot. Conventionally, single-crystalline graphene has been fabricated by chemical vapor deposition (CVD) on copper or nickel thin films, or by peeling graphite physically and chemically. However, graphene made via chemical vapor deposition is mainly used for large-surface transparent electrodes. Meanwhile, graphene made by chemical and physical peeling carries uneven size defects. The research team explained that their graphene quantum dots exhibited a very stable single-phase reaction when they mixed amine and acetic acid with an aqueous solution of glucose. Then, they synthesized single-crystalline graphene quantum dots from the self-assembly of the reaction intermediate. In the course of fabrication, the team developed a new separation method at a low-temperature precipitation, which led to successfully creating a homogeneous nucleation of graphene quantum dots via a single-phase reaction. Professor Park and his colleagues have developed solution phase synthesis technology that allows for the creation of the desired crystal size for single nanocrystals down to 100 nano meters. It is reportedly the first synthesis of the homogeneous nucleation of graphene through a single-phase reaction. Professor Park said, "This solution method will significantly contribute to the grafting of graphene in various fields. The application of this new graphene will expand the scope of its applications such as for flexible displays and varistors.” This research was a joint project with a team from Korea University under Professor Sang Hyuk Im from the Department of Chemical and Biological Engineering, and was supported by the National Research Foundation of Korea, the Nano-Material Technology Development Program from the Electronics and Telecommunications Research Institute (ETRI), KAIST EEWS, and the BK21+ project from the Korean government.
2019.08.02
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'Flying Drones for Rescue'
(Video Credit: ⓒNASA JPL) < Team USRG and Professor Shim (second from the right) > Having recently won the AI R&D Grand Challenge Competition in Korea, Team USRG (Unmanned System Research Group) led by Professor Hyunchul Shim from the School of Electrical Engineering is all geared up to take on their next challenges: the ‘Defense Advanced Research Projects Agency Subterranean Challenge (DARPA SubT Challenge)’ and ‘Lockheed Martin’s AlphaPilot Challenge’ next month. Team USRG won the obstacle course race in the ‘2019 AI R&D Grand Challenge Competition’ on July 12. They managed to successfully dominate the challenging category of ‘control intelligence.’ Having to complete the obstacle course race solely using AI systems without any connection to the internet made it difficult for most of the eight participating teams to pass the third section of the race, and only Team USRG passed the long pipeline course during their attempt in the main event. They also demonstrated, after the main event, that their drone can navigate all of the checkpoints including landing on the “H” mark using deep learning. Their drone flew through polls and pipes, and escaped from windows and mazes against strong winds, amid cheers and groans from the crowd gathered at the Korea Exhibition Center (KINTEX) in Goyang, Korea. The team was awarded three million KRW in prize money, and received a research grant worth six hundred million KRW from the Ministry of Science and ICT (MSIT). “Being ranked first in the race for which we were never given a chance for a test flight means a lot to our team. Considering that we had no information on the exact size of the course in advance, this is a startling result,” said Professor Shim. “We will carry out further research with this funding, and compete once again with the improved AI and drone technology in the 2020 competition,” he added. The AI R&D Grand Challenge Competition, which was first started in 2017, has been designed to promote AI research and development and expand its application to addressing high-risk technical challenges with significant socio-economic impact. This year’s competition presented participants with a task where they had to develop AI software technology for drones to navigate themselves autonomously during complex disaster relief operations such as aid delivery. Each team participated in one of the four tracks of the competition, and their drones were evaluated based on the criteria for each track. The divisions were broken up into intelligent context-awareness, intelligent character recognition, auditory intelligence, and control intelligence. Team USRG’s technological prowess has been already well acclaimed among international peer groups. Teamed up with NASA JPL, Caltech, and MIT, they will compete in the subterranean mission during the ‘DARPA SubT Challenge’. Team CoSTAR, as its name stands for, is working together to build ‘Collaborative SubTerranean Autonomous Resilient Robots.’ Professor Shim emphasized the role KAIST plays in Team CoSTAR as a leader in drone technology. “I think when our drone technology will be added to our peers’ AI and robotics, Team CoSTAR will bring out unsurpassable synergy in completing the subterrestrial and planetary applications. I would like to follow the footprint of Hubo, the winning champion of the 2015 DARPA Robotics Challenge and even extend it to subterranean exploration,” he said. These next generation autonomous subsurface explorers are now all optimizing the physical AI robot systems developed by Team CoSTAR. They will test their systems in more realistic field environments August 15 through 22 in Pittsburgh, USA. They have already received funding from DARPA for participating. Team CoSTAR will compete in three consecutive yearly events starting this year, and the last event, planned for 2021, will put the team to the final test with courses that incorporate diverse challenges from all three events. Two million USD will be awarded to the winner after the final event, with additional prizes of up to 200,000 USD for self-funded teams. Team USRG also ranked third in the recent Hyundai Motor Company’s ‘Autonomous Vehicle Competition’ and another challenge is on the horizon: Lockheed Martin’s ‘AlphaPilot Challenge’. In this event, the teams will be flying their drones through a series of racing gates, trying to beat the best human pilot. The challenge is hosted by Lockheed Martin, the world’s largest military contractor and the maker of the famed F-22 and F-35 stealth fighters, with the goal of stimulating the development of autonomous drones. Team USRG was selected from out of more than 400 teams from around the world and is preparing for a series of races this fall, beginning from the end of August. Professor Shim said, “It is not easy to perform in a series of competitions in just a few months, but my students are smart, hardworking, and highly motivated. These events indeed demand a lot, but they really challenge the researchers to come up with technologies that work in the real world. This is the way robotics really should be.” (END)
2019.07.26
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Newly Identified Meningeal Lymphatic Vessels Answers the Key Questions on Brain Clearance
(Figure: Schematic images of location and features of meningeal lymphatic vessels and their changes associated with ageing.) Just see what happens when your neighborhood’s waste disposal system is out of service. Not only do the piles of trash stink but they can indeed hinder the area’s normal functioning. That is also the case when the brain’s waste management is on the blink. The buildup of toxic proteins in the brain causes a massive damage to the nerves, leading to cognitive dysfunction and increased probability of developing neurodegenerative disorders such as Alzheimer's disease. Though the brain drains its waste via the cerebrospinal fluid (CSF), little has been understood about an accurate route for the brain’s cleansing mechanism. Medical scientists led by Professor Gou Young Koh at the Graduate School of Medical Science and Engineering have reported the basal side of the skull as the major route, so called “hotspot” for CSF drainage. They found that basal meningeal lymphatic vessels (mLVs) function as the main plumbing pipes for CSF. They confirmed macromolecules in the CSF mainly runs through the basal mLVs. Notably, the team also revealed that the brain’s major drainage system, specifically basal mLVs are impaired with aging. Their findings have been reported in the journal Nature on July 24. Throughout our body, excess fluids and waste products are removed from tissues via lymphatic vessels. It was only recently discovered that the brain also has a lymphatic drainage system. mLVs are supposed to carry waste from the brain tissue fluid and the CSF down the deep cervical lymph nodes for disposal. Still scientist are left with one perplexing question — where is the main exit for the CSF? Though mLVs in the upper part of the skull (dorsal meningeal lymphatic vessels) were reported as the brain’s clearance pathways in 2014, no substantial drainage mechanism was observed in that section. “As a hidden exit for CSF, we looked into the mLVs trapped within complex structures at the base of the skull,” says Dr. Ji Hoon Ahn, the first author of this study. The researchers used several techniques to characterize the basal mLVs in detail. They used a genetically engineered lymphatic-reporter mouse model to visualize mLVs under a fluorescence microscope. By performing a careful examination of the mice skull, they found distinctive features of basal mLVs that make them suitable for CSF uptake and drainage. Just like typical functional lymphatic vessels, basal mLVs are found to have abundant lymphatic vessel branches with finger-like protrusions. Additionally, valves inside the basal mLVs allow the flow to go in one direction. In particular, they found that the basal mLVs are closely located to the CSF. Dr. Hyunsoo Cho, the first author of this study explains, “All up, it seemed a solid case that basal mLVs are the brain’s main clearance pathways. The researchers verified such specialized morphologic characteristics of basal mLVs indeed facilitate the CSF uptake and drainage. Using CSF contrast-enhanced magnetic resonance imaging in a rat model, they found that CSF is drained preferentially through the basal mLVs. They also utilized a lymphatic-reporter mouse model and discovered that fluorescence-tagged tracer injected into the brain itself or the CSF is cleared mainly through the basal mLVs. Jun-Hee Kim, the first author of this study notes, “We literally saw that the brain clearance mechanism utilizing basal outflow route to exit the skull. It has long been suggested that CSF turnover and drainage declines with ageing. However, alteration of mLVs associated with ageing is poorly understood. In this study, the researchers observed changes of mLVs in young (3-month-old) and aged (24~27-months-old) mice. They found that the structure of the basal mLVs and their lymphatic valves in aged mice become severely flawed, thus hampering CSF clearance. The corresponding author of this study, Dr. Koh says, “By characterizing the precise route for fluids leaving the brain, this study improves our understanding on how waste is cleared from the brain. Our findings also provide further insights into the role of impaired CSF clearance in the development of age-related neurodegenerative diseases.” Many current therapies for Alzheimer’s disease target abnormally accumulated proteins, such as beta-amyloid. By mapping out a precise route for the brain’s waste clearance system, this study may be able to help find ways to improve the brain’s cleansing function. Such breakthrough might become quite a sensational strategy for eliminating the buildup of aging-related toxic proteins. “It definitely warrants more extensive investigation of mLVs in patients with age-related neurodegenerative disease such as Alzheimer’s disease prior to clinical investigation,” adds Professor Koh.
2019.07.25
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Deciphering Brain Somatic Mutations Associated with Alzheimer's Disease
Researchers have found a potential link between non-inherited somatic mutations in the brain and the progression of Alzheimer’s disease Researchers have identified somatic mutations in the brain that could contribute to the development of Alzheimer’s disease (AD). Their findings were published in the journal Nature Communications last week. Decades worth of research has identified inherited mutations that lead to early-onset familial AD. Inherited mutations, however, are behind at most half the cases of late onset sporadic AD, in which there is no family history of the disease. But the genetic factors causing the other half of these sporadic cases have been unclear. Professor Jeong Ho Lee at the Graduate School of Medical Science and Engineering and colleagues analysed the DNA present in post-mortem hippocampal formations and in blood samples from people aged 70 to 96 with AD and age-matched controls. They specifically looked for non-inherited somatic mutations in their brains using high-depth whole exome sequencing. The team developed a bioinformatics pipeline that enabled them to detect low-level brain somatic single nucleotide variations (SNVs) – mutations that involve the substitution of a single nucleotide with another nucleotide. Brain somatic SNVs have been reported on and accumulate throughout our lives and can sometimes be associated with a range of neurological diseases. The number of somatic SNVs did not differ between individuals with AD and non-demented controls. Interestingly, somatic SNVs in AD brains arise about 4.8 times more slowly than in blood. When the team performed gene-set enrichment tests, 26.9 percent of the AD brain samples had pathogenic brain somatic SNVs known to be linked to hyperphosphorylation of tau proteins, which is one of major hallmarks of AD. Then, they pinpointed a pathogenic SNV in the PIN1 gene, a cis/trans isomerase that balances phosphorylation in tau proteins, found in one AD patient’s brain. They found the mutation was 4.9 time more abundant in AT8-positive – a marker for hyper-phosphorylated tau proteins– neurons in the entorhinal cortex than the bulk hippocampal tissue. Furthermore, in a series of functional assays, they observed the mutation causing a loss of function in PIN1 and such haploinsufficiency increased the phosphorylation and aggregation of tau proteins. “Our study provides new insights into the molecular genetic factors behind Alzheimer’s disease and other neurodegenerative diseases potentially linked to somatic mutations in the brain,” said Professor Lee. The team is planning to expand their study to a larger cohort in order to establish stronger links between these brain somatic mutations and the pathogenesis of Alzheimer’s disease. (Figure 1. Bioinformatic pipeline for detecting low-level brain somatic mutations in AD and non-AD.) (Figure 2. Pathogenic brain somatic mutations associated with tau phosphorylation are significantly enriched in AD brains.) (Figure 3. A pathogenic brain somatic mutation in PIN1 (c. 477 C>T) is a loss-of-function and related functional assays show its haploinsufficiency increases phosphorylation and aggregation of tau.)
2019.07.19
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